Recent Advances in Carbon Nanodots: A Promising Nanomaterial for Biomedical Applications.

Carbon nanodots (CNDs) are an emerging class of nanomaterials and have generated much interest in the field of biomedicine by way of unique properties, such as superior biocompatibility, stability, excellent photoluminescence, simple green synthesis, and easy surface modification. CNDs have been featured in a host of applications, including bioimaging, biosensing, and therapy. In this review, we summarize the latest research progress of CNDs and discuss key advances in our comprehension of CNDs and their potential as biomedical tools. We highlighted the recent developments in the understanding of the functional tailoring of CNDs by modifying dopants and surface molecules, which have yielded a deeper understanding of their antioxidant behavior and mechanisms of action. The increasing amount of in vitro research regarding CNDs has also spawned interest in in vivo practices. Chief among them, we discuss the emergence of research analyzing CNDs as useful therapeutic agents in various disease states. Each subject is debated with reflection on future studies that may further our grasp of CNDs.

Breaking It Down: A Systematic Review Unravelling the Impact of Attention Deficit Hyperactivity Disorder and Methylphenidate on Childhood Fractures.

Limb fractures are a common cause of pediatric hospital admissions and surgeries, with a significant prevalence in the United Kingdom across all injury categories. Among psychiatric conditions in children, attention deficit hyperactivity disorder (ADHD) stands out as frequently associated with fractures, particularly those involving extremities. ADHD, with diagnoses prevalent among a significant proportion of school-age children and adolescents, has witnessed a growing global incidence. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 checklist for our systematic literature search, using various databases and specific search terms related to ADHD and fractures. We considered articles from 2018 to 2023, focusing on English language papers with free full-text access. Our selection process used the PRISMA flowchart. We began with 1,890 articles and, after deduplication, title screening, abstract assessment, and quality evaluation included nine research papers in our review. Our primary focus was on examining fracture-related outcomes in individuals with ADHD compared to those without, considering medication status. These studies encompassed various designs, with a focus on the ADHD-fracture relationship and methylphenidate's (MPH) impact. Our study confirms that ADHD increases fracture risk and suggests that MPH may help mitigate this risk. Early ADHD detection is vital for nonpharmacological interventions. Orthopedic surgeons should proactively identify ADHD, while healthcare professionals should offer injury prevention guidance, particularly for at-risk groups.

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.

Systematic Review of the roles of Inositol and Vitamin D in improving fertility among patients with Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among reproductive-age women. As a leading cause of anovulatory infertility, it complicates fertility treatments, including in vitro fertilization. The widely accepted 2003 Rotterdam diagnostic criteria for PCOS include sub-phenotypes based on variations in androgen excess, ovulatory dysfunction, and polycystic ovarian morphology. In this systematic review, we examined the impacts of inositol and vitamin D on fertility in PCOS. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, we used relevant keywords to comprehensively search databases including PubMed, Google Scholar, and MDPI. From an initial pool of 345 articles, 10 met the inclusion criteria. The articles suggest that vitamin D and inositol, particularly myo-inositol and D-chiro-inositol, may represent therapeutic options for PCOS. Vitamin D influences ovarian follicular development, glucose regulation, and insulin sensitivity. When combined with metformin therapy, it is associated with improved menstrual regularity and ovulation. Inositol is crucial for cellular signaling, energy metabolism, glucose regulation, and fertility. This systematic review underscores the importance of investigating inositol and vitamin D within a PCOS management strategy, given the disorder's prevalence and impacts on fertility and metabolic health. Although these agents show promise, additional research could clarify their mechanisms of action and therapeutic benefits. This review emphasizes the need for exploration of effective treatments to improve the quality of life among individuals with PCOS. Inositol and vitamin D represent potential options, but more studies are required to elucidate their roles in the management of this condition.

Finerenone's Impact on Major Adverse Cardiovascular Events in Chronic Kidney Disease and Type 2 Diabetes Mellitus: A Systematic Review.

Chronic kidney disease (CKD) impacts about 10% of adults globally and substantially elevates the risk of major adverse cardiovascular events (MACE), such as heart attacks, strokes, cardiovascular-related deaths, and hospital admissions due to heart failure. The interplay between CKD and cardiovascular disease (CVD) leads to poor health outcomes. Nevertheless, there is a scarcity of systematic reviews focusing on the effectiveness of finerenone, a new non-steroidal mineralocorticoid receptor antagonist (MRA), in lowering these risks. In this systematic review, we aim to evaluate the impact of finerenone on reducing MACE in individuals with CKD and type 2 diabetes mellitus (T2DM). CKD pathophysiology involves hyperglycemia, hypertension, and dyslipidemia, leading to glomerular hyperfiltration, inflammation, and fibrosis. Traditional treatments, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and sodium-glucose cotransporter-2 inhibitors (SGLT2i), often fall short in preventing cardiovascular events. Steroidal MRAs like spironolactone and eplerenone, while effective in reducing proteinuria, are limited by hyperkalemia risks. Finerenone offers a more selective mechanism, reducing sodium retention, inflammation, and fibrosis, with a lower risk of hyperkalemia. We searched five electronic databases comprehensively, identifying studies consistently demonstrating that finerenone significantly reduces MACE and improves renal outcomes by reducing albuminuria and slowing the fall in estimated glomerular filtration rate (eGFR). However, limitations include study heterogeneity, short follow-up periods, and potential publication bias. In conclusion, finerenone shows promise as a therapeutic option for CKD and T2DM, reducing MACE and improving renal outcomes. Further research is needed to understand its long-term benefits and safety across diverse populations.

Challenges and Elements Hindering the Adoption of Enhanced Recovery After Surgery (ERAS) Protocols in Colorectal Surgery and Their Resolutions: A Systematic Review.

This systematic review focuses on the various aspects of Enhanced Recovery After Surgery (ERAS) implementations, such as the various barriers, facilitators, and the role of teamwork. A systematic search was performed in PubMed, PubMed Central (PMC), and the Cochrane Library for studies published between the years 2018 and 2023. Inclusion criteria encompassed studies assessing the various factors hindering the implementation of ERAS protocols on patients undergoing colorectal surgery. It collectively highlights the importance of a multidisciplinary approach, continuing education, supervision, and patient involvement in achieving a successful implementation. Important findings include the positive impact of a performance improvement team, audits and feedback, and patient-centered approaches in reducing hospital length of stay, reducing inflammation, and improving patient outcomes. In addition, the study emphasizes the challenges of complete adherence to all ERAS components and suggests a simplified protocol to improve implementation. This paper also seeks to understudy the hurdles encountered during the adoption of the ERAS protocol and studies the various fundamental components of the protocol.

The Role of Alpha-Synuclein and Tubulin-Associated Unit (Tau) Proteins in the Diagnosis, Prognosis, and Treatment of Parkinson's Disease: A Systematic Review.

Parkinson's disease (PD) is a degenerative neurological disorder resulting from the death of dopaminergic neurons, which, in turn, results in impaired motor and cognitive functions. Early diagnosis is important in achieving a good prognosis for PD. Currently, the only approved way to diagnose PD is through medical history, current symptoms, and neurological examination. This, however, can only happen after PD progresses far enough in patients. Biomarkers in cerebrospinal fluid (CSF) and blood plasma, however, may provide insight into the early progress of PD and potentially concurrent dementia, which can also aid in the development of novel treatments. Specifically, this systematic review explores alpha-synuclein (α-syn) and tubulin-associated unit (Tau) proteins and analyzes their potential roles as biomarkers while also touching on nilotinib and immunotherapy as potential treatment options. PubMed, PubMed Central (PMC), Medline, and Cochrane Library serve as the databases for relevant literature, upon which eligibility criteria and quality checks - Assessment of Multiple Systematic Review (AMSTAR) tool, Newcastle-Ottawa Quality Assessment Scale, Cochrane risk-of-bias assessment 2 (RoB2), and Scale for the Assessment of Narrative Review (SANRA) - were applied. The remaining literature examines the various aspects of PD and Parkinson's disease dementia (PDD) and associated biomarkers. From 10 studies, 2,361 participants, both PD patients and healthy controls (HCs), were assessed and compared. Various assessment scales, such as the Unified Parkinson's Disease Rating Scale part III (UPDRS III), were used to ascertain the severity or progression of PD in patients while also seeking a noticeable correlation with α-syn and total Tau (t-Tau). The lack of standardized clinical testing has led to conflicting reports. Thus, while the articles generally agree on the potential efficacy of α-syn and Tau protein analysis in the diagnosis, prognosis, and treatment of PD and PDD, they also argue for further testing and trials.

The Adoption and Impact of Telemedicine on Health Equity: A Narrative Review From the Jamaican Context.

Telemedicine rose to popularity during the coronavirus disease 2019 (COVID-19) pandemic but is yet to be fully developed. Hence, this study explores the current status of telehealth in Jamaica, looking at its benefits, challenges with its implementation, the regulatory landscape, and solutions to using this technology. Due to the limited research on this topic, a majority of the sources utilized were gray literature with qualitative and quantitative studies. This review seeks to transform policy and practice, promoting telemedicine as a feasible solution for improving Jamaica's healthcare quality and access. By comparing telemedicine in Jamaica to a more developed nation like the United States, the review highlights not only benefits but also major challenges, including healthcare disparities due to the digital divide, less advanced technology, privacy breaches, and significant financing required for telemedicine infrastructure, among other barriers to its integration. The analysis advocates for improvement in various areas, such as cybersecurity measures, advanced training for healthcare professionals, further investments in technological infrastructure, refinement of regulatory frameworks and policies, and incorporation of community-based initiatives. This investigation further highlights the need for additional research to gain insights and a broader perspective.

Efficacy of ß-Blockers in Decreasing Mortality in Sepsis and Septic Shock Patients: A Systematic Review.

Sepsis is a life-threatening condition leading to various organ dysfunction due to an underlying infection. Despite providing appropriate treatment, it is still one of the most common causes of death among patients who are admitted to the intensive care unit (ICU). So, multiple studies have been conducted to identify the potential benefits of various drugs in decreasing mortality in sepsis apart from its traditional treatment options. This study aims to identify whether ß-blockers play a role in decreasing mortality in sepsis and septic shock patients because of their potential benefits on several organ systems. Medical databases such as Google Scholar, Summon, PubMed Medical Subject Headings (MeSH), PubMed, Science Direct, Cochrane Library, and Multidisciplinary Digital Publishing Institute (MDPI) were systematically searched for relevant publications. The identified articles were assessed based on the inclusion and exclusion criteria, and 11 research articles were finalized, for which quality appraisal was done using appropriate appraisal tools. ß-blockers significantly lowered the in-hospital mortality in sepsis and septic shock patients, and they were also associated with better patient outcomes. As there are limited studies, further research needs to be done to explore the role of ß-blockers in decreasing mortality in critically ill populations such as sepsis and septic shock patients.

Exploring the Nexus: A Systematic Review on the Interplay of the Methylenetetrahydrofolate Reductase (MTHFR) Gene C677T Genotype, Hyperhomocysteinemia, and Spontaneous Cervical/Vertebral Artery Dissection in Young Adults.

Ischemic strokes (IS) in young adults often evade early detection, resulting in delayed diagnosis until complications arise. Cervical/vertebral artery dissection, a significant contributor to these strokes, presents with symptoms such as migraine with aura, severe headache, and neck pain, commonly overlooked due to their nonspecific nature. This review investigates early indicators of artery dissections, emphasizing their importance in diagnosis and exploring the correlation between methylenetetrahydrofolate reductase (MTHFR) gene C677T genotype polymorphism, hyperhomocysteinemia (HHCY), and IS in young adults. This systematic review encompasses a thorough analysis of 11 papers, including four observational studies, three case reports, three narrative reviews, and one experimental study, involving 4,840 patients aged 18-45 years. Findings reveal HHCY as a significant contributor to vascular damage and tissue ischemia leading to IS. The MTHFR gene C677T genotype polymorphism is closely associated with HHCY, often contributing to underdiagnosed strokes in young adults. Cervical/vertebral artery dissection may manifest as initial symptoms of neck pain or headache, remaining undiagnosed until imaging is conducted. Importantly, the review suggests that MTHFR gene polymorphism can be mitigated through simple supplementation with vitamin B12 and folates, serving as a valuable tool for primary prevention. Additionally, betaine, a methyl donor, was explored in severe MTHFR gene polymorphism cases resistant to conventional supplementation. In conclusion, recognizing the significance of early signs and symptoms, along with a high clinical suspicion, is crucial for preventing catastrophic outcomes, mortality, and morbidity associated with IS in young adults lacking traditional risk factors. The MTHFR gene C677T genotype polymorphism, a potential genetic cause, can be easily managed with simple measures but is often overlooked or underdiagnosed.

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.

Neuro Navigation Versus Conventional Spinal Techniques in Analyzing Nerve Injury and Anatomical Accuracy: A Systematic Review.

Neuronavigation, a computer-assisted surgical technique, enhances the accuracy of spinal surgery by using medical imaging to guide the surgeon's instruments. This method mitigates the serious complications of screw misplacement, such as dural tears, nerve damage, vascular injuries, and internal organ damage, by integrating pre-operative imaging data with real-time intraoperative sensor readings. Because of this integration, it is possible to visualize the spine in three dimensions, guaranteeing accurate instrument placement and greatly lowering the risk of complications. Despite its growing popularity, the benefits of neuronavigation in spinal instrumentation are debated. While some studies report improved accuracy in pedicle screw placement, others find no significant difference compared to conventional freehand techniques. Further research is required to determine the long-term benefits of neuronavigation, including its impact on patient outcomes, like reduced pain and improved function. This systematic review will evaluate the evidence on the risks and benefits of neuronavigation in spinal instrumentation surgery, compared to conventional techniques.

Contribution of the Gut Microbiome to the Perpetuation of Inflammation in Crohn's Disease: A Systematic Review.

Crohn's disease (CD) is a sub-type of inflammatory bowel disease (IBD) with a characteristic relapsing and remitting inflammation involving the gastrointestinal (GI) tract. Although there are several medications to relieve the symptoms, there is no definite cure for the condition. This paper highlights how CD affects our gut flora, which subsequently leads to the perpetuation of inflammation. This review was conducted according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020 guidelines using PubMed, ScienceDirect, Multidisciplinary Digital Publishing Institute (MDPI), and Google Scholar as sources for relevant literature. After applying the quality appraisal tools, we finalized 11 articles for the paper. Inflammation seen in CD leads to dysbiosis, where there is a reduction in beneficial microbes such as Faecalibacterium and Roseburia species and an increase in pathogenic microbes such as Escherichia and Proteus species. This difference in gut microbes disrupts barrier function and immune processes in the intestine, contributing to the worsening of inflammation seen in CD. Several studies have been carried out to understand this complex relationship between the gut microbiome (GM) and CD, as it may serve as a potential novel therapeutic alternative, necessary as CD's burden is increasing globally.

A Detailed Systematic Review Comparing Patent Foramen Ovale Closure vs Medical Therapy for the Prevention of Recurrent Cryptogenic Stroke.

Cryptogenic stroke refers to a type of ischemic stroke with no identifiable cause despite extensive diagnostic testing. Patent foramen ovale (PFO) treatment modality for the prevention of cryptogenic stroke has been controversial. We undertook this systematic review to compare the efficacy of PFO closure versus medical therapy in preventing recurrent cryptogenic stroke and to provide insight into the most effective treatment modality. Inclusion criteria included patients who had PFO, papers written in English language or had translation available, and papers focusing on medical therapy including drug and surgical treatment for PFO for the prevention of recurrent stroke. Exclusion criteria included articles in which full text could not be obtained and articles in which only one treatment modality was mentioned, either surgical closure or drug therapy. The databases used were PubMed, Cochrane, Embase, and ClinicalTrials.gov. We conducted a bias assessment through the modified Jadad scale for randomized controlled trials (RCTs) and AMSTAR.Ca for meta-analysis and systematic review. The literature search identified a total of 277 papers. After screening, 12 papers were selected for the review. Among these, five were RCTs, five were meta-analyses, one was a systematic review, and one was a systematic review with network meta-analysis. The RCTs included a total of 3,336 participants, while the meta-analyses included 21,813 participants. These finalized papers examined the outcomes of PFO closure compared to medical therapy in preventing recurrent strokes.

Evaluating the Efficacy of a Small Interfering Ribonucleic Acid Molecule, Givosiran, in Treating Acute Intermittent Porphyria: A Systematic Review.

Acute intermittent porphyria (AIP) is a severe multiorgan dysfunction disorder that can be fatal if not treated promptly. The newest treatment modality involving small interfering RNA (siRNA) molecules, givosiran, is administered for AIP. Although it has very beneficial effects in treating attacks of AIP, it comes with an extensive side effect profile that is not fully understood or studied. Hence, this novel drug model treatment's risk-benefit evaluation is still necessary. For relevant medical literature, we explored medical databases such as PubMed/Medline, PubMed Central, Cochrane Library, Internet Archive Scholar, Google Scholar, and Wiley Online Library. The selected papers were screened based on eligibility criteria and filtered through quality appraisal tools, and 13 finalized research papers were included in the study. Of the 13 identified papers, three were clinical trials, and 10 were review articles. The selected papers all discussed the effectiveness and side effects of givosiran in acute and recurrent attacks of AIP. The research papers showed decreased rates of acute attacks of AIP with givosiran and terminating recurrent attacks. But there are certain non-serious side effects, like fatigue and nausea. Also, there are some severe side effects, like pain. There is limited information on renal and liver function impairment using givosiran and the use of givosiran in patients with kidney and liver disease, for which further studies are required.

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.

PCSK-9 Inhibitors and Cardiovascular Outcomes: A Systematic Review With Meta-Analysis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved to treat dyslipidaemia. However, there is a lack of knowledge on the most efficient PCSK9 therapies that target PCSK9 for secondary prevention in subjects at high risk for cardiovascular (CV) events. Thus, this study aimed to assess the efficacy and safety of anti-PCSK9 antibodies in randomized controlled trials (RCTs). A comprehensive review of the available literature was done to identify RCTs that compared the use of PCSK9 inhibitors coupled with placebo or ezetimibe for the secondary prevention of CV events in patients on statin-background therapy. All-cause mortality was the major efficacy endpoint, while severe adverse events were the key safety outcome. A random effects model was used, and data were presented as risk ratio (RR) or risk difference with their corresponding 95% confidence intervals (CI). The heterogeneity of the publications was determined using Cochran's Q test, and publication bias was visually examined using funnel plots. All the chosen studies' quality was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI). Forty-one studies (76,304 patients: 49,086 on evolocumab, and 27,218 on alirocumab) were included, and their years of publication spanned from 2010 to 2023. Overall, no significant differences were observed in CV and all-cause mortality between PCSK9 inhibitors and controls. However, alirocumab use was linked to a reduced risk of all-cause death compared to control, but not evolocumab. Each of the drugs, evolocumab and alirocumab, significantly reduced the risk of myocardial infarction (MI), coronary revascularization, and ischemic stroke. In comparison to the control therapy, the risk of major detrimental sequelae was significantly reduced by alirocumab therapy in the subgroup analysis of each PCSK9 inhibitor, whereas evolocumab treatment did not demonstrate significant differences (RR = 0.88; 95% CI = 0.72-1.04; evolocumab: RR = 0.99; 95% CI = 0.87-1.11). Both evolocumab and alirocumab are well-tolerated, safe medications that significantly lower low-density lipoprotein (LDL) levels.

Safety and Efficacy of Biologic Therapies (Ustekinumab and Vedolizumab) in the Treatment of Inflammatory Bowel Disease (IBD): A Systematic Review.

Inflammatory bowel disease (IBD) is a group of chronic disorders, including Crohn's disease (CD) and ulcerative colitis (UC), that contribute to inflammation of the gastrointestinal tract, manifesting as bloody diarrhea, fecal urgency, bloating, cramping, and weight loss. IBD manifests as an exacerbation of these symptoms, which medications with high side effect profiles can manage; consequently, many novel therapies, including biologics such as ustekinumab and vedolizumab, have been developed over the years. This systematic review aims to assess the safety and efficacy of ustekinumab and vedolizumab in treating inflammatory bowel disease based on a comprehensive analysis of relevant studies. A thorough literature search was conducted to identify randomized controlled trials, post hoc analyses, case reports, observational cohorts, and meta-analyses involving ustekinumab and vedolizumab as treatment in IBD patients. The selected studies were critically evaluated for their methodology, patient characteristics, and outcomes. The analysis involved twelve distinct studies investigating the impact of ustekinumab and vedolizumab on individuals afflicted with inflammatory bowel disease (IBD). The findings revealed a notable trend: ustekinumab displayed a propensity for yielding higher rates of clinical remission in patients with ulcerative colitis (UC). Moreover, one study underscored substantial reductions in endoscopic disease activity in patients with Crohn's disease (CD) who were on ustekinumab. Similarly, ustekinumab exhibited promising outcomes in CD patients, including swift ultrasound responses and the achievement of transmural remission, particularly among those who were new to biologic treatments. In line with this, vedolizumab demonstrated early and considerable symptomatic improvements when used to treat both UC and CD patients. While both biologics showed promising results in inducing and maintaining remission, cautious monitoring is warranted due to the potential adverse events observed in some cases. Further research with larger sample sizes and longer follow-up periods is needed to establish a comprehensive understanding of the medications' effects on IBD patients.

The Efficacy and Safety of Mechanical Thrombectomy in Posterior Circulation Large Vessel Occlusion as Compared to Anterior Circulation Large Vessel Occlusion: A Systematic Review.

Mechanical thrombectomy (MT) has been established as a standard of care for patients with stroke due to anterior circulation large vessel occlusion (AC-LVO). Due to a lack of robust evidence for the effectiveness of mechanical thrombectomy, intravenous thrombolysis (IVT) is still the only approved first-line acute reperfusion strategy for posterior circulation large vessel occlusion (PC-LVO). This systematic review analyzes and reports on the effectiveness and safety of MT in PC-LVO. A literature review was performed to identify all studies of patients with acute ischemic stroke due to PC-LVO who underwent MT with second-generation devices (stent retrievers and/or aspiration devices) that were reported between January 2017 and January 2023. The primary outcome was functional independence at 90 days, defined as a modified Rankin (mRS) score of ≤2. Secondary outcomes were successful recanalization (modified treatment in cerebral infarction score (mTICI) 2b/3), symptomatic intracerebral hemorrhage (sICH), and mortality at 90 days post-procedure. We looked at 13 studies with a total of 30,407 participants in four meta-analyses and 5951 participants in nine observational studies. In most studies, patients in the PC-LVO group were male and younger than the AC-LVO group. Higher baseline National Institutes of Health Stroke Scale (NIHSS) score, lower rates of IVT, longer onset-to-groin puncture time, lower likelihood of sICH, higher 90-day mortality rates, and higher futile recanalization rates were frequently observed in the PC-LVO group with a large discrepancy in the likelihood of functional independence at 90 days with majority studies showing comparable rates. Hence, in patients with acute ischemic stroke caused by the PC-LVO, successful reperfusion can be achieved via MT, though at the cost of higher mortality rates. Such futile recanalization can be avoided with the refinement of procedures through technical improvements, skills training, and recognition of reliable predictors associated with it, which might help increase the efficacy of MT in PC-LVO. Additionally, future large-scale RCTs comparing patient selection and interventional strategies to avoid futile interventions are also needed.

The Effects of Risperidone on Cognition in People With Autism Spectrum Disorder: A Systematic Review.

Autism spectrum disorder is made up of several disorders, which include autism, Asperger syndrome, and pervasive developmental disorder. Boys are four times more likely to be diagnosed than girls with autism spectrum disorder, and symptoms usually become apparent by the age of three. Autism spectrum disorders' core characteristic features are abnormal interaction, impairment in communication, and stereotyped behaviors with restricted activities and interests. There are also non-core features associated with autism spectrum disorder, and these are aggression, self-injurious behavior, and tantrums. To date, there is no one drug approved to treat the core symptoms of autism spectrum disorder, but antipsychotic drugs such as risperidone have been shown to be effective at treating both core and non-core symptoms in controlled trials using multiple behavioral rating scales such as the Aberrant Behavioral Checklist subscale, the Clinical Global Impression Improvement Scale, the Ritvo-Freeman Real Life Scale, the Children's Yale-Brown Obsessive Compulsive Scale, the Vineland Adaptive Behavior Scale, and the Social Withdrawal Subscale. The safety, efficacy, acceptability, and tolerability of risperidone were assessed in these studies, and weight gain was a common side effect observed, but the outcome was usually mild and self-limiting. The effect of risperidone on cognition was explored in this article. The studies selected for this article were of small sample size and short duration, which presented limitations for treatment with risperidone and an area that needs to be explored further for its contribution to clinical practice.