Carbon Nanodots Inhibit Tumor Necrosis Factor-α-Induced Endothelial Inflammation through Scavenging Hydrogen Peroxide and Upregulating Antioxidant Gene Expression in EA.hy926 Endothelial Cells.

Carbon nanodots (CNDs) are a new type of nanomaterial with a size of less than 10 nanometers and excellent biocompatibility, widely used in fields such as biological imaging, transmission, diagnosis, and drug delivery. However, its potential and mechanism to mediate endothelial inflammation have yet to be explored. Here, we report that the uptake of CNDs by EA.hy926 endothelial cells is both time and dose dependent. The concentration of CNDs used in this experiment was found to not affect cell viability. TNF-α is a known biomarker of vascular inflammation. Cells treated with CNDs for 24 h significantly inhibited TNF-α (0.5 ng/mL)-induced expression of intracellular adhesion molecule 1 (ICAM-1) and interleukin 8 (IL-8). ICAM-1 and IL-8 are two key molecules responsible for the activation and the firm adhesion of monocytes to activated endothelial cells for the initiation of atherosclerosis. ROS, such as hydrogen peroxide, play an important role in TNF-α-induced inflammation. Interestingly, we found that CNDs effectively scavenged H2O2 in a dose-dependent manner. CNDs treatment also increased the activity of the antioxidant enzyme NQO1 in EA.hy926 endothelial cells indicating the antioxidant properties of CNDs. These results suggest that the anti-inflammatory effects of CNDs may be due to the direct H2O2 scavenging properties of CNDs and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells. In conclusion, CND can inhibit TNF-α-induced endothelial inflammation, possibly due to its direct scavenging of H2O2 and the indirect upregulation of antioxidant enzyme NQO1 activity in endothelial cells.

Neurocognitive Impact of Exposure to Cannabis Concentrates and Cannabinoids Including Vaping in Children and Adolescents: A Systematic Review.

During adolescence, significant changes unfold in the brain's maturation process. The density of white matter increases, accompanied by the pruning back of gray matter. This critical and vulnerable period becomes especially noteworthy in the context of drug use, as adolescents are extensively exposed to substances such as tobacco, alcohol, and cannabis. The concern is heightened now that cannabis has been legalized for recreational use in many places, leading to increased exposure levels. Additionally, knowledge about the impact of cannabis on neurocognitive development during this stage is limited. This knowledge gap compounds the issue, making it even more concerning. Therefore, a systematic review was carried out based on the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using medical databases such as PubMed, PubMed Central (PMC), Medline, Cochrane Library, Internet Archive Scholar, and Embase-Elsevier for relevant medical literature. The identified articles were reviewed, eligibility criteria were applied, and 19 research articles were identified. The final papers explored the correlation between children's and adolescents' exposure to cannabis-containing compounds and subsequent changes in the central nervous system (CNS). Findings revealed a considerable impact, ranging from transient alterations in mood to permanent cognitive function and sensory processing changes, affecting the deterioration of the quality of life of these individuals in adulthood. Presently, most studies were conducted on animals, and the few studies on humans have considerable limitations, such as the type of study, age of the population, and small samples, among others. For this reason, it is essential for the scientific community and public health organizations, in general, to conduct more studies that demonstrate the true neurobiological impact of this drug and its accessibility to young people and, based on the results, consider its legalization or propose regulations for its use and commercialization.

Single-Layer or Double-Layer Intestinal Anastomosis: A Systematic Review of Randomized Controlled Trials.

Several malignant and benign indications may necessitate bowel resection. Despite the emergence of newer techniques, the hand-sewn technique remains popular for the reestablishment of intestinal continuity after resection. This method can achieve anastomosis in one or two layers. Some studies have suggested that the single-layer technique has several potential benefits compared to its rivals while simultaneously maintaining a comparable efficacy and safety profile. Previous reviews have failed to recommend either of these methods over the other due to a lack of high-quality evidence. This review aims to establish which technique provides the best outcomes by reviewing recent relevant trials and comparing both methods. We conducted a systematic review of randomized controlled trials (RCTs) using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. A database search of PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) ultimately returned nine randomized trials published between 2003 and 2023 comparing single-layer intestinal anastomosis (SLIA) and double-layer intestinal anastomosis (DLIA) that fit the inclusion criteria. Overall, results show a dearth of robust trials, and the included studies displayed variable eligibility criteria and materials used for anastomosis. The available evidence, however, does suggest that neither technique is inferior in terms of preventing post-operative complications, but SLIA is less expensive and quicker to perform. The evidence is, however, limited, and further high-quality research is needed.

A Systematic Review of Chemotherapeutic Regimens Used in Pancreatic Cancer.

Pancreatic cancer is a malignant tumor with one of the worst prognosis. Its incidence has been on the rise in recent years. First-line and second-line treatments as well as adjuvant therapies have been employed in clinical trials for pancreatic cancer along with traditional chemotherapy and radiotherapy that has been enhanced. The prognosis of pancreatic ductal adenocarcinoma (PDAC) is still quite bad despite recent improvements in diagnostic and treatment methods. Since most patients are not candidates for treatment with a curative purpose, effective palliative care is crucial. For this systematic review, between December 25, 2022, and January 5, 2023, we searched PubMed, Medline, Cochrane, and Science Direct and discovered 225 relevant articles. The appropriateness of the literature abstracts for the pooled analysis was evaluated using different combinations of keywords such as pancreatic cancer, first- and second-line chemotherapy, palliative chemotherapy, gemcitabine and nab-paclitaxel (GnP), FOLFIRINOX (FFX), and fluorouracil. Eight research studies with a total of 15,236 people, including systematic reviews, meta-analyses, and randomized controlled trials (RCTs), were included. The only treatment of choice for patients without metastatic disease who have clinical staging that suggests resectable or borderline resectable pancreatic cancer (BRPC) should be resection. This research examined how first- and second-line chemotherapeutic regimens (using different drug combinations) affected patients with locally advanced pancreatic cancer (LAPC) or BRPC and how they responded in terms of overall survival (OS), tumor resectability, and progression-free interval. The review concludes by highlighting the results of these therapies. Notably, a growing body of research indicates that the two most popular first-line medication combinations GnP and FFX have similar results in RCTs and in real-world populations. Results of second-line therapy after first-line regime failure are still dismal, and there is still a great deal of doubt regarding the best course of action. More RCTs and real-world evidence studies that address current and innovative regimens, as well as the best order in which to administer them, are required, with a greater emphasis on targeted therapy with fewer side effects.

Discussing the Prognosis and Complications of Transvenous Lead Extraction in Patients With Cardiac Implantable Electronic Devices (CIED): A Systematic Review.

An increase in cardiovascular implantable electronic devices (CIEDs) and undoubtedly the complications brought on by these devices coincide with an increase in cardiovascular disorders, particularly heart rhythm abnormalities. The safest procedure to extract these devices is transvenous lead extraction (TLE). Thus, this systematic review aimed to summarize the possibility of success rates and the common complications that could arise during the surgery. Full-text publications in PubMed, MEDLINE, PubMed Central (PMC), and ScienceDirect were used in this study, which was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Seventeen studies were reviewed for this systematic review after being screened by title, abstract, full-text availability, and quality appraisal assessment. Heart and vascular tears, along with tricuspid regurgitation (TR), are common adverse events. Pulmonary embolism, hemothorax, hemopericardium, and ghost appearance in echo are less common consequences. In addition, the longer the dwelling time of the leads, the greater the chance of infection due to an increase in lead adhesions and fibrous tissue that has made the procedure unsafe as time passes. However, we concluded that TLE is a successful method across all age groups with an excellent probability of clinical and procedural success in a majority of studies.

Efficacy of Adenosine Versus Verapamil in Terminating Acute Attacks of Paroxysmal Supraventricular Tachycardia: A Systematic Review.

Paroxysmal supraventricular arrhythmias are a group of common rhythm disturbances that are often prevalent, frequently recurrent, sporadic, and life-threatening. These arrhythmias are precipitated by factors such as age, sex, and associated comorbidities. Typically, patients with paroxysmal arrhythmias are asymptomatic during evaluation, and the condition is often detected incidentally. Symptoms associated with these arrhythmias include palpitations, fatigue, light-headedness, chest discomfort, dyspnea, presyncope, and, less commonly, polyuria and serious psychological distress. In terms of treatment, common modalities include antiarrhythmic drug therapy and catheter ablation. When selecting drug therapy, factors such as comorbidities, patient-specific modifiers, preferences, follow-up frequency, and cost-effectiveness are taken into account. For long-term treatment, calcium channel blockers are often used instead of adenosine, while adenosine is preferred for acute attacks due to its higher efficacy. Comparatively, adenosine and verapamil are commonly used drugs in the emergency setting to treat paroxysmal supraventricular tachycardia (PSVT). Adenosine exhibits a faster onset of action, but adverse effects occur more commonly, whereas verapamil has a slower onset of action and a lower incidence of adverse effects. We searched for articles from PubMed, PubMed Central (PMC), and Science Direct, and these articles were reviewed systematically. After applying the search strategy to these databases, 195 articles were identified. Fourteen of these were finalized for review. The efficacy of adenosine versus verapamil in terminating acute attacks of PSVT is reviewed in our article.

Exploring Circulating Tumor DNA (CtDNA) and Its Role in Early Detection of Cancer: A Systematic Review.

There is a significant increase in the need for an efficient screening method that might identify cancer at an early stage and could improve patients' long-term survival due to the continued rise in cancer incidence and associated mortality. One such effort involved using circulating tumor DNA (ctDNA) as a rescue agent for a non-invasive blood test that may identify many tumors. A tumor marker called ctDNA is created by cells with the same DNA alterations. Due to its shorter half-life, it may be useful for both early cancer detection and real-time monitoring of tumor development, therapeutic response, and tumor outcomes. We obtained 156 papers from PUBMED using the MeSH approach in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) criteria and ten articles from additional online resources. After removing articles with irrelevant titles and screening the abstract and full text of the articles that contained information unrelated to or not specific to the title query using inclusion and exclusion criteria, 18 out of 166 articles were chosen for the quality check. Fourteen medium to high-quality papers were chosen out of the 18 publications to be included in the study design. The reviewed literature showed no significant utility of ctDNA in detecting early-stage tumors of size less than 1 cm diameter. Still, the ideal screening test would require the assay to detect a size <5 mm tumor, which is nearly impossible with the current data. The sensitivity and specificity of the assay ranged from 69% to 98% and 99%, respectively. Furthermore, CancerSEEK achieves tumor origin localization in 83% of cases, while targeted error correction sequencing (TEC-Seq) assays demonstrate a cancer detection rate ranging from 59% to 71%, depending on the type of cancer. However, it could be of great value as a prognostic indicator, and the levels are associated with progression-free survival (PFS) and overall survival (OS) rates, wherein the positive detection of ctDNA is associated with worse OS compared to the tumors detected through standard procedures, with an odds ratio (OS) of 4.83. We conclude that ctDNA could be better applied in cancer patients for prognosis, disease progression monitoring, and treatment outcomes compared to its use in early cancer detection. Due to its specific feature of recognizing the tumor-related mutations, it could be implemented as a supplemental tool to assess the nature of the tumor, grade, and size of the tumor and for predicting the outcomes by pre-operative and post-operative evaluation of the tumor marker, ctDNA, and thereby estimating PFS and OS depending on the level of marker present. A vast amount of research is required in early detection to determine the sensitivity, specificity, false positive rates, and false negative rates in evaluating its true potential as a screening tool. Even if the test could detect the mutations, an extensive workup for the search of tumor is required as the assay could only detect but cannot localize the disease. Establishing the clinical validity and utility of ctDNA is imperative for its implementation in future clinical practice.

Probing the Relationship Between the Human Gut Microbiome and Prospects of Prostate Cancer: A Systematic Review.

Prostate neoplasia is one of the most commonly occurring neoplasias in males and has a high mortality rate. Prostate cancer (PCA) risk factors include tall stature, male sex, known family history, obesity, high blood pressure, lack of fitness, higher levels of testosterone for a long time, increasing age, and ethnicity are well known. The association and role of the gut microbiota in different diseases in our body have been highlighted recently. Therefore, finding the influence of gut microbiota on the prostatic cells can be useful for preventing prostatic neoplasia and/or reducing its severity. We aimed to assess its impact on PCA risk. We thoroughly searched databases for the relevant literature for our systematic review. The final research papers analyzed how bacteria played a role in the risk of PCA, either through inflammation or the production of metabolites that increase/decrease the risk of PCA. Based on the studies reviewed, we found that some gut bacteria play a role in the formation of PCA. In contrast, some bacteria can help prevent PCA, but the metabolism of the dietary components is the major factor for PCA.

Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) Immunotherapy: A Promising Breakthrough in Cancer Therapeutics.

The advent of immune checkpoint inhibitors has revolutionized cancer therapy by leveraging the body's immune system to combat malignancies effectively. Among these groundbreaking agents, programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have emerged as pivotal therapeutic approaches. PD-L1, a key protein expressed on the surface of various cells, including cancer cells, plays a central role in immune regulation by interacting with the programmed cell death protein 1 (PD-1) receptor on T-cells leading to immune suppression. The substantial increase in PD-L1 expression on cancer cell surfaces has driven the exploration of PD-1/PD-L1 inhibitors as potential immunotherapeutic agents. These inhibitors are monoclonal antibodies designed to impede the PD-L1 and PD-1 interaction and disrupt the immunosuppressive signal, thereby reinvigorating the anti-tumor immune response mediated by activated T-cells. Clinical trials investigating PD-1/PD-L1 inhibitors have demonstrated remarkable efficacy in the treatment of diverse advanced or metastatic cancers, including leukemia, non-small cell lung (NSCLC), hepatocellular, melanoma, gastric, colorectal, and breast cancers, among others. Regulatory approvals have been granted for both monotherapy and combination therapy with other cancer treatments, encompassing chemotherapy and additional immune checkpoint inhibitors. While PD-1/PD-L1 inhibitors have exhibited significant success, they are not devoid of challenges. The emergence of intrinsic or acquired resistance, as well as immune-related adverse events, warrants thorough investigation and management. Consequently, researchers have embarked on combination trials to augment the therapeutic potential of PD-1/PD-L1 inhibitors and surmount resistance mechanisms.

Protective Effects of Long-Term Usage of Cyclo-Oxygenase-2 Inhibitors on Colorectal Cancer in Genetically Predisposed Individuals and Their Overall Effect on Prognosis: A Systematic Review.

Colorectal cancer (CRC) is a major global health concern, accounting for significant cancer-related morbidity and mortality worldwide. Despite advancements in early detection and treatment modalities, the prevention of CRC remains a critical goal. Cyclo-oxygenase-2 (COX-2) is an inducible enzyme involved in the production of pro-inflammatory prostaglandins, which play a crucial role in various cellular processes, including inflammation, cell proliferation, apoptosis, and angiogenesis. Elevated COX-2 expression has been consistently observed in colorectal tumors, indicating their role in the pathogenesis of cancer. COX-2 inhibitors, such as celecoxib and rofecoxib, have been studied as potentially effective treatment modalities due to their ability to decrease prostaglandin levels, which are generally higher in cancer patients. Aberrant prostaglandin production is linked to the adenoma-carcinoma sequence, during which adenomas turn dysplastic and accumulate enough damage to become malignant. COX-2 inhibitors have also been shown to modulate various signaling pathways involved in CRC development, such as wingless-related integration site/ß-catenin (Wnt/ß-catenin), mitogen-activated protein kinase (MAPK), and phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathways. This systematic review aimed to evaluate the protective effects of long-term usage of COX-2 inhibitors on CRC in genetically predisposed individuals and their overall effect on the prognosis of the disease. The researchers conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines and collected data from several databases, including PubMed, PubMed Central, Cochrane Library, and Web of Science. The search strategy combined keywords related to CRC, COX-2 inhibitors, protective effects, and prognosis. They identified 1189 articles and shortlisted 26 full-text articles that met the eligibility criteria. Quality assessment tools, such as the Assessment of Multiple Systematic Review (AMSTAR) for systematic reviews, the Cochrane bias assessment tool for randomized control trials, the scale for the assessment of narrative review articles (SANRA) checklist for narrative reviews, and the Joanna Briggs Institute (JBI) tool for cross-sectional studies and case reports, are used. This review's conclusions will assist in determining the effectiveness of COX-2 inhibitors to prevent CRC. This review may also contribute to developing guidelines for clinicians to manage genetically predisposed individuals with CRC. Furthermore, the results of this review will shed light on the potential of COX-2 inhibitors as a preventive measure against CRC in genetically predisposed individuals.

A Systematic Review of Cystic Fibrosis in Children: Can Non-Medical Therapy Options Lead to a Better Mental Health Outcome?

Cystic fibrosis (CF) is a chronic disorder that begins at an early age, so it is crucial to be aware of the physical and emotional burden placed on individuals suffering from it and their families. It significantly impacts an individual's life; therefore, it is essential to acknowledge the effects of the disease on physical and mental health. Our systematic review aims to highlight the areas of life affected by cystic fibrosis and evaluate various non-medical treatment options that may support the mental health of CF patients. We selected PubMed, Google Scholar, and MEDLINE (Medical Literature Analysis and Retrieval System Online) as our databases. We initially found 146,095 articles and narrowed the number of articles down using filters, exclusion and inclusion criteria, and various combinations of Medical Subheadings (MeSH) and key terms. We decided to use a final count of nine articles for our systematic review. The studies we included highlighted the negative impact of cystic fibrosis on mental health, like depression and anxiety, as well as on sleep, physical health, and overall quality of life. Several non-medical interventions, such as logotherapy, psychological interventions, complementary and alternative medicine, and many more, have been shown to enhance the mental health of many participants. Studies suggested that such therapy options may greatly benefit individuals with cystic fibrosis and their current treatment plan. This review indicates that non-medical therapy options can enhance the mental health of individuals suffering from cystic fibrosis and that it is crucial to bring more attention to preventing and treating mental health issues in cystic fibrosis patients. However, as current data is limited, more research with a larger number of participants over an extended period of time is necessary to better evaluate the efficacy of non-medical interventions on mental health.

Comparing Gefitinib and Traditional Chemotherapy for Better Survival in Patients With Non-Small Cell Lung Cancer: A Systematic Review.

Current non-small cell lung cancer (NSCLC) treatment consists of various combinations of surgery, chemotherapy, and/or radiation, depending on the tumor stage. Individuals with stage II-IIIa NSCLC undergo surgery, followed by combination chemotherapy containing cisplatin, such as vinorelbine + cisplatin. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), such as gefitinib, act by inhibiting any signaling pathway containing the EGFR mutation and inhibiting the growth of NSCLC. TKI is a treatment option in advanced NSCLC, resulting in more prolonged progression-free survival (PFS). This manuscript aims to evaluate the influence of utilizing gefitinib - either alone or in combination with conventional chemotherapeutic drug regimens upon NSCLC patient profile survival parameters. A systematic literature review was conducted across multiple scientific literature repositories. The review was performed using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020. There were six randomized clinical trials (RCT) and five retrospective studies. The overall consensus based on the end outcome of each published journal on the effectiveness of gefitinib as a treatment option for NSCLC indicated that there was a notable difference in overall survival (OS) and progression-free survival (PFS) and disease-free survival (DFS) datasets. Gefitinib use correlated with increased timeframes for multiple patient survival parameters within articles shortlisted in this investigation. However, more comprehensive investigations are required to validate such correlations. Gefitinib did demonstrate the potential to provide beneficial effects and counteract NSCLC within such patients.

Role of Procalcitonin and C-reactive Protein as Predictors of Sepsis and in Managing Sepsis in Postoperative Patients: A Systematic Review.

Systemic inflammatory response syndrome (SIRS) and sepsis are inflammatory responses to infection or trauma, causing symptoms and adverse outcomes such as organ shutdown and death. Different scoring systems can help in the diagnosis of SIRS and sepsis. Several biomarkers such as C-reactive protein (CRP), procalcitonin (PCT), and white blood cells (WBCs) can serve as predictors of sepsis. Surgery, trauma, and burns are the non-inflammatory causes of SIRS and sepsis. In postoperative patients, both inflammatory and non-inflammatory causes of immune response may co-exist. The role of inflammatory biomarkers in identifying sepsis development, deciding to use antibiotics, and discharging patients needs further exploration and clarity. We searched medical databases such as PubMed/Medline, PMC, ScienceDirect, Cochrane Library, and Google Scholar for relevant medical literature. The identified papers were screened, eligibility criteria were applied, and 15 research papers were identified. The finalized papers explored the roles of CRP and PCT in postoperative patients. Both CRP and PCT are raised in a postoperative patient, and then, gradually, the levels decrease. However, in case of an infection, these levels continue to rise and signify an infection, which may progress to sepsis. The cut-off values can guide decision-making about when to start antibiotics and discharge the patient. PCT was found to be more reliable in identifying the infection and preventing the development of sepsis. Further research is needed to identify the exact cut-off values that can help in decision-making.

Gastrointestinal Microbiota and Breast Cancer Chemotherapy Interactions: A Systematic Review.

Breast cancer is the most common type of cancer in women besides basal cell and squamous cell skin cancer. The current systemic therapy guidelines for this heterogeneous disease are mainly based on the molecular subtypes. However, more research is required to improve rates of therapy resistance and prevent side effects. Previous studies have shown that the human gut microbiota may have an important role in carcinogenesis as well as therapy outcomes, but this factor has not yet been integrated into therapy protocols. This systematic review aims to analyze how response rates and side effect profiles of breast cancer systemic therapies may be affected by the gastrointestinal microbiota. A literature search was performed using multiple databases and keywords related to gastrointestinal microbiota, breast cancer, and anticancer drugs. Studies were excluded if they primarily focused on diseases other than breast cancer. Abstracts, reviews, meta-analyses, and animal experiments were also excluded. After screening, nine studies met all selection criteria and included a total of 566 participants. Most studies described the impact of the gut microbiota on therapy response, but a few additionally discussed chemotherapy side effects, probiotics, or antibiotics. In general, diversity and specific microbiota were linked to chemotherapy response as well as prognosis. Microbiota diversity was also predictive of side effects such as neurological symptoms, weight gain, and constipation. The diversity and composition of gastrointestinal microbiota may serve as biomarkers and provide pathways for the optimization of chemotherapy in breast cancer patients.

A Correlation Between the Pathogenic Processes of Fibromyalgia and Irritable Bowel Syndrome in the Middle-Aged Population: A Systematic Review.

Irritable bowel syndrome (IBS) is a common pathology in middle-aged patients and a regular consultation in the gastroenterology office. The prevalence is high in females with a ratio of 2:1, and due to its multifactorial etiology, it is difficult to address the symptomatology. On the other hand, fibromyalgia syndrome (FMS) is a chronic widespread pain syndrome also prevalent in the female population, characterized by systemic symptoms. It is proven that 28-59 % of patients with FMS develop IBS at some point in their illness; on the other hand, 32-77% of those with IBS will develop FMS. Our study aims to compile information about the pathogenesis of these diseases and highlight their common processes to target these two illnesses potentially.  This systematic review comprises twenty-three studies published between 2017 and 2022, selected by electronic research with keywords and Medical Subject Headings (MESH) strategy. The articles were taken from PubMed, Pubmed Central (PMC), Medline, and Cochrane libraries and met the inclusion and exclusion criteria and the pertinent quality checklists. Of the reviewed studies, 10 were case-control, six were narrative reviews, three were systematic reviews, three were cross-sectional, and one was a cohort study. They investigated the correlation and similitudes in the pathogenic process between FMS and IBS. There are some similar mechanisms in the physiopathologies of IBS and FMS, where the immune system, especially the mast cells (MCs), along with their products, receptors, the inflammatory cells with their intermediaries, hormones, and neurotransmitters such as serotonin, act together pathologically. Also, the role of the microbiota is very important in this pathogenesis since dysbiosis alters the levels of serotonin in the body and can produce hyperstimulation of the autonomic nervous system. There are common associated factors in IBS and FMS, with evident symptoms presented in both syndromes such as fatigue, pain, hypersensitivity, depression, anxiety, and others, that could be correlated in a certain way. After this systematic review, we can conclude that the most accepted theories of the common pathogenesis are the role of serotonin and MCs with their inflammatory biomarkers, which can affect different parts of the body producing the characteristic symptomatology. Moreover, other pathogenic mechanisms such as the involvement of microbiota and dysregulation of the gut-brain axis have shown promising results, and further investigation should be made to support their role.

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.

Efficacy and Safety of Apatinib in the Treatment of Chemotherapy-Refractory Metastatic Colorectal Cancer: A Systematic Review.

The purpose of this study was to systematically review the current evidence on apatinib and offer a better understanding of its safety and efficacy in metastatic colorectal cancer (mCRC) patients who have not responded to standard chemotherapies. This systematic review was conducted using research from the last 10 years (May 30, 2012, to May 30, 2022) and was obtained from the following databases: PubMed, PubMed Central (PMC), ScienceDirect, and Google Scholar. After removing duplicates, screening titles and abstracts, and applying eligibility criteria and quality appraisal, 11 articles were left for this systematic review (one meta-analysis, eight non-randomized studies, and two traditional reviews). Out of the 11 studies, six were on apatinib monotherapy, while three were on apatinib combination therapy. Apatinib has demonstrated efficacy in the monotherapy and combination therapy trials and has exhibited an acceptable safety profile as the adverse events were predominantly graded 1-2 and could be easily managed. Therefore, apatinib is an encouraging candidate for third-line therapy in chemotherapy-refractory mCRC patients. This conclusion should be confirmed and validated by studies with larger, randomized clinical trials to gain better insight and to directly compare the efficacy and safety of apatinib with all current third-line therapies together so that clinicians can easily assess which treatment modality is superior for chemotherapy-refractory mCRC patients.

Role of Non-pharmacological Interventions and Weight Loss in the Management of Gastroesophageal Reflux Disease in Obese Individuals: A Systematic Review.

With the increasing prevalence of obesity, the worldwide risk of gastroesophageal reflux disease (GERD) has also increased. Abdominal obesity increases intragastric pressure, disturbing the integrity of the gastroesophageal junction, thus facilitating reflux. Other than obesity, some lifestyle factors also cause GERD, including smoking, consumption of alcohol and caffeine, late-night meals, and high fat intake. This review study aimed to assess the impact of weight loss and lifestyle modifications on GERD. In this systematic review, the databases used were PubMed, PubMed Central (PMC), Science Direct, and Google Scholar. Boolean system and Medical Subject Headings (MeSH) strategy were used to form suitable keywords. Patients from the pediatric and geriatric populations were excluded from the study and quality assessment was done using different assessment tools. A positive association between obesity and GERD was found. It was also found that the long-term use of proton pump inhibitors (PPIs) causes complications, so lifestyle interventions should be used more than PPIs for treating GERD, especially in obese patients. We concluded that weight loss could lead to the resolution of gastroesophageal reflux disease, and therefore, conservative measures, including dietary modifications such as reducing the consumption of alcohol, caffeine, and chocolate, behavioral changes such as smoking cessation and elevation of the head of the bed, and weight loss, should be used as first-line management for GERD. Although awareness has increased regarding the adverse effects of proton pump inhibitors, future studies are required to assess these negative effects.

Bevacizumab-Induced Hypertension as a Potential Physiological Clinical Biomarker for Improved Outcomes in Patients With Recurrent Glioblastoma Multiforme: A Systematic Review.

With the advancement in medicine leading to the discovery of anti-vascular endothelial growth factor drugs, numerous oncologists are now commonly using antiangiogenic medications to improve outcomes and attain disease control. Thus, the significance of prognostic and predictive indicators in patient selection has become increasingly imperative. These biomarkers have the capacity to be highly effective and can easily be implemented in various diagnostic and therapeutic settings on a large scale. Overall, it has the potential of significantly decreasing mortality in a fatal disease and possibly achieving partial or complete remission. Many clinical trials have shown the efficacy of bevacizumab in treating malignancies. However, there are currently no known predictive or prognostic biomarkers for bevacizumab in glioblastoma multiforme (GBM). Several clinical studies have evaluated bevacizumab-induced hypertension as a potential marker in patients with different malignancies, including recurrent glioblastoma multiforme (rGBM). This systematic review was performed to determine the association of bevacizumab-induced hypertension with outcomes in patients with advanced brain cancer and to assess whether hypertension (HTN) can be used as a prognostic factor. The review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines, and the databases were searched from January 2012 to June 2022. This review aimed to evaluate six published studies to investigate the relationship between hypertension and the outcomes of patients with rGBM treated with bevacizumab. Among the included publications, four out of six were retrospective and featured a positive result regarding hypertension being used as an independent predictive factor of survival outcomes in rGBM. However, two studies showed negative results. This can be attributed to the limited subsets of patients and the duration of the studies. In conclusion, bevacizumab-induced hypertension may represent a prognostic factor in patients with rGBM.

A Systematic Review of Apoptosis in Correlation With Cancer: Should Apoptosis Be the Ultimate Target for Cancer Treatment?

Targeting apoptosis in cancer therapy has become increasingly popular, and there has been an increasing debate on whether apoptosis should be one of the main targets of therapy in cancer management. This study demonstrates the definition of apoptosis, the signaling pathways, and the pathogenesis behind it. We also show the correlation between apoptosis and cancer and how cancer can evade apoptosis to develop resistance to therapy. In addition, we illustrate the efficacy of adding pro-apoptotic therapy to conventional radio-chemotherapy cancer treatment. A systematic review was conducted using PubMed, PubMed Central (PMC), and ResearchGate, including papers written in English, focusing on adult and geriatric populations, in literature reviews, systematic reviews, and randomized controlled trials published in the last 25 years with relevance to the question. Based on the findings of this review, we conclude that apoptosis is a very sophisticated programmed cellular death with many signaling pathways. Its evasion should be considered one of the hallmarks of cancer and is responsible for multiple drug resistance (MDR) to cancer therapy. Targeting apoptosis seems promising, especially if combined with radio-chemotherapy.