Reduction of Cardiovascular Risk Using Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in Patients With Acute Coronary Syndrome: A Systematic Review.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates blood cholesterol levels by degrading low-density lipoprotein (LDL) receptors from the surface of hepatocytes. Studies have shown that inhibiting this molecule decreases the cardiovascular risk in individuals with atherosclerotic cardiovascular disease (ASCVD) by lowering low-density lipoprotein cholesterol (LDL-C). Two major cardiovascular outcome trials showed that the use of the PCSK9 inhibitors (alirocumab and evolocumab) in patients with recent acute coronary syndrome (ACS) is associated with a lower risk of further cardiovascular (CV) events. Information regarding the use of these monoclonal antibodies for primary prevention has also been reported by these trials. The goal of this systematic review is to describe the mechanism of PCSK9 inhibitors and further discuss their ability to reduce CV risk in high-risk populations. The search strategy was used in a systematic way using PubMed Central, Google Scholar, and ScienceDirect. We included randomized control trials (RCTs), systematic reviews, and narrative reviews in English published in the last five years. Observational studies, case reports, and case studies were excluded. The quality of the studies was evaluated using the Cochrane Collaboration Risk of Bias Tool, Assessment of Multiple Systematic Reviews 2, and Scale for the Assessment of Narrative Review Articles. A total of 10 articles were included in this systematic review. These included an RCT, a systematic review, and eight narrative reviews. Our study suggested that adding PCSK9 inhibitors to background statin therapy for selected patients with high-risk factors demonstrated substantial benefits in reducing overall CV morbidity and mortality after ACS. Multiple studies have demonstrated the short-term safety of low LDL-C levels caused by these drugs. However, long-term safety must be assessed with further studies.

Bempedoic Acid's Use as an Adjunct in Lowering Low-Density Lipoprotein Cholesterol in Patients With Coronary Artery Disease: A Systematic Review.

Coronary artery disease (CAD) is one of the leading causes of death worldwide. Atherosclerosis begins in childhood as fatty streaks, progresses with age, and lifestyle influences the progression of atherosclerotic plaque. Over time, with significant narrowing of the blood vessels, blood flow into the coronary arteries is compromised, resulting in various symptoms of coronary heart disease. Many drugs are used in clinical practice to prevent atherosclerotic cardiovascular events in patients with CAD. This review aims to investigate the efficacy and safety of a non-statin novel lipid-lowering drug, bempedoic acid (BDA), an adenosine triphosphate (ATP) citrate lyase inhibitor, in lowering serum low-density lipoprotein cholesterol (LDL-C) levels among patients with CAD. BDA is a new drug that recently got approval for clinical use. Following its discovery, BDA has been researched in order to investigate its role in the treatment of hypercholesterolemia. A search for studies was conducted using databases such as PubMed, PMC, ScienceDirect, and Google Scholar up until April 30, 2022. This systematic review has followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 11 studies were finalized to explore the role of BDA alone or as an adjunct in lowering serum LDL-C levels in high-risk patients under maximally tolerated statins, statin-intolerant groups, or treatment with other lipid-lowering drugs. These studies are three randomized controlled trials (RCTs), one pre-proof RCT, two systematic reviews and meta-analyses, and five narrative review articles. This review included 8465 participants from recently conducted RCTs and systematic reviews. Another 14014 participants, enrolled for the Cholesterol Lowering via Bempedoic Acid, an Adenosine Triphosphate-Citrate Lyase-Inhibiting Regimen (CLEAR) Outcomes clinical trial, were also included. BDA in combination with ezetimibe showed good evidence of LDL-C lowering effect. Patients on maximally tolerated statin failing to achieve desired LDL-C when treated in combination with BDA showed a significant decrement in serum LDL-C levels, high sensitivity C-reactive protein (HsCRP), and triglyceride. BDA use showed no adverse side effects. The most common side effect seen in several trials was the rise in serum uric acid level. When treating patients with BDA, baseline uric acid levels should be obtained and regular monitoring of uric acid should be done. The CLEAR Outcomes trial, scheduled to be completed by December 2022, will provide further information on BDA. BDA appears to be a promising alternative to currently available secondary lipid-lowering agents.

Fertility and Pregnancy Outcomes in Patients With Adenomyosis: Is Adenomyosis Synonymous With Infertility?

Adenomyosis is a disease related to the presence of endometrial glands and stromal cells within the uterine myometrium that used to be linked to females that are more than 40 years old and multiparous. Nowadays, females are delaying their pregnancies to their third or fourth decade, and as diagnostic approaches evolve, the disease has become a common problem for females who desire pregnancy. The aim of this study is to identify the physio-pathological factors by which adenomyosis causes infertility and pregnancy complications, as well as the possible results from infertility treatments and the most common pregnancy complications that females with adenomyosis face. A systematic review based on a systematic search from PubMed, Cochrane, and ScienceDirect databases from the past five years was done. Papers with free full text available were subject to the removal of duplicates, screening for relevant titles and abstracts, and a quality assessment to identify the risk of bias (RoB). A total of 10 papers were selected for this study; they include systematic reviews and meta-analyses, cohorts, literature review, and a case-control study. After the review of the data, we conclude that infertility may be due to several factors that impair adequate sperm mobility through the uterus and an impaired implantation of a product. After some fertility treatments were performed, females with adenomyosis had a lower rate of clinical pregnancy. The pregnancy complications such as preterm delivery and hypertension problems related to pregnancy had an increased risk for females with adenomyosis, while for others such as intrauterine fetal death and gestational diabetes, the information is still controversial. The main limitation of this study was the lack of information of physio-pathological-related information probably due to only including data from the past five years.

Newly Discovered Cutting-Edge Triple Combination Cystic Fibrosis Therapy: A Systematic Review.

A cystic fibrosis (CF) transmembrane conductor regulator (CFTR) gene modulating triple therapy combining elexacaftor-tezacaftor-ivacaftor (Trikafta) has been recently discovered. Its approval by the Food and Drug Administration (FDA) in 2019 has expanded the target therapy group to individuals aged twelve and up with at least one Phe508del (phenylalanine 508 deletion) mutation in the CFTR gene. This systematic review aims to assess this combination therapy's safety and efficacy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, an in-depth search was performed. The search was done by utilizing databases such as PubMed Central (PMC), Google Scholar, and Science Direct for articles related to this topic. Studies published in the last five years in the English language were chosen preliminarily. Further eligibility criteria and quality assessment tools were employed to assess the risk of bias and finalize ten articles to be used in this review. The chosen articles constituted four randomized control trials (RCTs), four systematic reviews, and two narrative reviews. The last date for data collection was April 24, 2022. Based on the findings of this review, we concluded that by combining three CFTR modulators, this therapy had outperformed all the currently available medications in terms of improving pulmonary function, reducing exacerbations, and enhancing the quality of life of CF patients. In clinical trials, headache and rash were the most common side effects, and laboratory testing to assess liver function is suggested. Long-term safety and effectiveness must be confirmed by the continued review of real-life patient data. Studies done on triple therapy thus far have been promising. Unfortunately, a small proportion of the CF population remains ineligible for any form of CFTR modulator therapy owing to their type of genetic mutation, and this provides ground for further research in this field.

How Residing in a Long-Term Care Facility Affects Suicidal Risk in Patients With Dementia: A Systematic Review.

This study aims to review the current literature regarding the association between suicide risk in patients aged 65 years or over with dementia residing in long-term care facilities (LTCs). We also evaluate the most common methods of suicide and protective versus risk factors of nursing home (NH) life on suicide behavior in patients with dementia. Following preferred reporting items for systematic reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the relevant free full-text articles found in PubMed, Pub Psych, Cochrane library, and Science Direct up until April 4, 2022. Medical Subject Heading (MeSH) terms and keywords (nursing home, long-term care facility, suicide, self-injurious behavior, dementia), were used to search for full-text randomized clinical trials (RCTs), cross-sectional, case-control, cohort studies, systematic reviews, and studies published in the English language in the last 12 years, focused on human subjects 65 years and older were selected based on predefined eligibility criteria. The search yielded 57,909 articles, of which 12 studies met our inclusion criteria. The articles were subjected to quality appraisal by two reviewers. We used the Newcastle Ottawa scale (NOS) for quality assessment with a mean score of six for 12 observational studies used in this paper. Of the included reports, six were cross-sectional, five were cohort, and one was case-control. Four articles carefully examine the relationship between dementia and suicide, and all confirm the hypothesis that staying in LTCs reduces the risk of suicide in patients with dementia. However, the rest of the articles generally determine a higher risk of suicide in demented patients and describe male gender, non-Hispanic white race, younger age, newly diagnosed with dementia within one-year, mild dementia, comorbidities, depression, previous history of suicidal behavior, low social support and unstable family relationship as the risk factors of suicide in this population. In comparison, extended stay in NHs and other kinds of LTCs, severe dementia with impaired insight, older age, comorbid schizophrenia, physical disability with limitation and more difficulty preparing and executing a suicide plan, positive and robust social relationships, access to professional caregivers and high frequency of visits from relatives marked as the protective factors. Existing research on suicide risk in long-term care facility residents with dementia is limited. However, due to the increase in dementia rates that require people to reside in NHs and on the other hand, considering the multiple risk factors of suicide in the elderly living in such places, the need for a screening system for identifying people at suicide risk and performing preventive therapeutic and behavioral interventions is well felt.

The Role of Leptin in Systemic Lupus Erythematosus: Is It Still a Mystery?

Systemic lupus erythematosus (SLE) is a chronic inflammatory connective tissue disease with varying clinical manifestations. Recent studies have proposed that leptin may be related to SLE development. This study aims to assess current information regarding the relationship between leptin and SLE. A systematic search was done using PubMed, Google Scholar, ScienceDirect, Epistemonikos, and Cochrane Library databases. Studies published in the English language in the last 10 years were selected based on predefined eligibility criteria. The quality of the studies was evaluated using the Newcastle-Ottawa Scale and the Assessment of Multiple Systematic Reviews 2 tool. A total of 12 studies were included in this systematic review. These included systematic reviews/meta-analyses, cross-sectional studies, and case-control studies. Based on the findings of this review, we conclude thatleptin is significantly elevated in SLE patients; however, it does not seem to correlate with disease activity. The exact mechanism of leptin in the pathogenesis of the disease remains unknown and further research is needed regarding this aspect.

A Systematic Review Comparing Digital Subtraction Angiogram With Magnetic Resonance Angiogram Studies in Demonstrating the Angioarchitecture of Cerebral Arteriovenous Malformations.

In brain arteriovenous malformations (AVMs), there is mismatched communication between arteries and veins, causing a nidal bed between them. This systematic review explores whether a magnetic resonance angiogram (MRA) can be used as a diagnostic imaging tool instead of a digital subtraction angiogram (DSA). Utilizing PubMed, Cochrane, and Google Scholar, as well as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for article selection, a literature search was conducted over the past five years. Eleven studies were included, with a majority of the articles suggesting a potential for consideration. Arterial spin labeling (ASL) versus time-of-flight (TOF) scans was a comparison study, in addition to the study on pseudo-continuous arterial spin labeling (pc-ASL), which proved its high sensitivity in comparison with DSA scans. Other studies included quantitative magnetic resonance angiogram (Q-MRA) measuring the blood flow and susceptibility weighted imaging (SWI) modality. Although promising, digital subtraction angiogram (DSA) scans have diagnostic superiority. In addition, articles discussed follow-up magnetic resonance angiogram (MRA) scans after surgery. Overall, digital subtraction angiogram remains the gold standard due to its superior spatial resolution and hemodynamic properties; these are the key limitations of magnetic resonance studies. MRA has demonstrated its ability to reproduce high-quality diagnostic images for arteriovenous malformation (AVM) angioarchitecture; however, coupled with their limitations, not many studies with large sample sizes over longer periods have been conducted, and we urge more research into it.

Programming exercise intensity in patients on beta-blocker treatment: the importance of choosing an appropriate method.

AIM: To verify the usefulness of current recommended level of target exercise heart rate (HR) and of different HR-based methods for calculating target HR in patients with and without beta-blocker treatment. METHODS: We studied 53 patients not treated with beta-blocker and 159 patients on beta-blocker treatment. All patients underwent a maximal exercise test with gas analysis, and first ventilatory threshold (VT1 or aerobic threshold), second ventilatory threshold (VT2 or anaerobic threshold), time of exercise, maximum load, metabolic parameters, HR at rest (HRrest), HRpeak, HR at VT1 (HRVT1) and at VT2 (HRVT2), and 75, 80, and 85% of HRmax (HR75%, HR80%, HR85%) were calculated. Exercise HR was also determined using the Karvonen formula, applying 60, 70, and 80% of the heart rate reserve (HRR) (HRKarv0.6, HRKarv0.7, and HRKarv0.8). RESULTS: This study included 102 patients on a beta-blocker and 39 not treated with negative cronotropic effect drugs. Maximum load, metabolic parameters, HRrest, HRpeak, HRVT1, and HRVT2 were significantly lower in patients on beta-blocker treatment. The proportion of patients with a HR75%, HR80%, HR85%, ​​HRKarv0.6, HRKarv0.7, and HRKarv0.8 VT2 was very high and depended on whether patients were on beta-blocker treatment. CONCLUSIONS: Prescribed exercise intensity should be within VT1 and VT2, so that the efficacy and safety is guaranteed. If determining VT1 and VT2 is not possible, HR-based methods can be used, but with caution. In fact, there will be always a proportion of patients training below VT1 or above VT2. On the other hand, recommendations for patients on a beta-blocker should be different from patients not receiving a beta-blocker. Patients not treated with a beta-blocker should exercise at HRKarv0.7 or at HR85%. In patients on a beta-blocker, we recommend preferentially a target HR of HRKarv0.6 or HR80%.

Effects of celecoxib on acid-challenged gastric mucosa of rats: comparison with metamizol and piroxicam.

Selective COX-2 inhibitors have been shown to produce fewer gastrointestinal adverse reactions than classical NSAIDs. Nevertheless, these new agents may worsen and delay the healing of experimentally induced gastric ulcers in animals. In this study, we compared the effects of a selective COX-2 inhibitor (celecoxib), a preferential COX-1 inhibitor (piroxicam), and a nonnarcotic analgesic (metamizol) on normal gastric mucosa of rats and, on the other hand, in a setting of preexisting acute gastric lesions induced by 0.6 N hydrochloric acid. Under normal conditions, only piroxicam produced appreciable gastric lesions. However, after acid challenge the three assayed drugs induced significant macroscopic and microscopic damage. Myeloperoxidase activity as an index of neutrophil infiltration was elevated with celecoxib and piroxicam on normal gastric mucosa. On inflamed mucosa, celecoxib augmented enzymatic activity at the lower dose, which was parallelled by an increase in the interleukin 1beta level. Acid instillaton produced a significant rise in PGE2 content at 7 hr. Drug treatment after acid challenge decreased prostaglandin values in all cases, although to a lesser extent than after single drug dose administration. COX-2 mRNA expression was visible 1 hr after acid application, whereas COX-2 protein could only be detected at 7 hr. Piroxicam increased both expression levels. All NSAIDs enhanced transforming growth factor alpha and epidermal growth factor receptor immunoreactivity around the acid-induced lesions. It is concluded that selective COX-2 inhibitors, like conventional NSAIDs, impair the healing of gastric damage, and therefore special attention should be paid in patients with gastric pathologies.