High-risk hypertension patients are more susceptible to cardiovascular disease, stroke, and mortality. Monotherapy and triple combination drug therapy are two different approaches to treating hypertension. Monotherapy involves using a single medication to manage hypertension, whereas triple combination therapy involves the simultaneous use of three different antihypertensive medications from different drug classes. Making a fast switch from monotherapy to combination medication is one method to regulate blood pressure (BP) better. It is widely recognized that a significant proportion of individuals with hypertension require combination therapy to manage their condition effectively. This review aims to evaluate the mortality rates across monotherapy and triple combination drug therapy in high-risk hypertension patients. A systematic literature review was conducted across multiple scientific literature repositories. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines for systematic reviews and meta-analyses. Based on the end outcome of each published journal on the effectiveness of triple combination drug therapy as a treatment option for high-risk hypertension patients, there was a notable difference in overall survival, mortality rates, BP reduction, and adherence datasets. Triple combination drug use correlated with increased timeframes for multiple patient survival parameters within the articles shortlisted in this investigation. However, it is crucial for healthcare providers to weigh the risks and benefits of triple combination drug therapy when deciding which treatment approach is best for their patients.

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.

It is well established that people with autism spectrum disorder (ASD) have significantly higher rates of social anxiety, given that most autistic individuals experience socio-communication impairments, a deficit in social competence, and their experience in social engagement situations often leads to discomfort in social settings. Literature also finds that individuals on the spectrum are often at a higher risk of developing social anxiety, which is often misinterpreted as social anxiety disorder (SAD) leading to delays in the clinical diagnosis of ASD. Hence, an improved understanding of specific factors that put ASD individuals at risk of developing social anxiety will aid research to differentiate between social anxiety among individuals with ASD compared to non-ASD individuals facing social anxiety in general. This systematic review study focuses on empirical literature that provides evidence for reasons contributing to social anxiety among individuals with ASD. Following the systematic review methodology, the study evaluates 10 research papers. The results revealed several correlations that can be useful in helping explain why individuals with ASD are at a higher risk of developing SAD. Individuals with ASD often suffer severe social anxiety because they struggle to understand social cues, maintain eye contact, interpret non-verbal cues like facial expressions or body language, or participate in reciprocal conversation. Other cognitive factors include a preference toward predictable situations, intolerance for uncertainty, and a tendency toward rigid thinking patterns. Unpredictability in social settings often heightens anxiety levels in ASD individuals, making them avoid such situations. Other risk factors include emotional recognition impairments and reduced social competence. These findings serve as a guide to developing better intervention strategies to help individuals with ASD to overcome social anxiety.

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.

Diabetes mellitus (DM) and thyroid dysfunction are two disorders that are closely related. This systematic review aimed to investigate the effect of levothyroxine supplementation on diabetic nephropathy in type 2 diabetic patients with co-existing thyroid dysfunction. We explored medical databases such as PubMed, Medline, Multidisciplinary Digital Publishing Institute (MDPI), and Cochrane Library for relevant medical literature. The papers were screened, and 12 research papers involving 10,371 patients were identified after applying eligibility criteria and quality assessment using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The included papers analyzed the effect of aberrant thyroid profile on kidney disease in diabetic individuals and the role that achieving euthyroid status with levothyroxine supplementation could play in diabetic nephropathy. Reduced free triiodothyronine (FT3) was the most common independent factor associated with diabetic microvascular and macrovascular complications. Levothyroxine (LT4) regimen was more effective than the placebo in lowering urinary albumin excretion rate (UAER), low-density lipoprotein cholesterol, and uric acid and decreasing oxidative stress overall. However, replacement therapy's effect may differ in the short and long terms. Thyroid hormone replacement therapy (THRT) may reduce the risk of diabetic nephropathy and cardiovascular disease (CVD) development in hypothyroid patients, but more randomized trials are needed to confirm the effect of THRT.

[This corrects the article DOI: 10.7759/cureus.46630.].

Chronic pain is a condition that frequently affects patients and communities. There are several treatment options available, including both pharmacological and non-pharmacological. Opioid prescriptions have increased over the past few years, and long-term use of opioids leads to an increased risk of opioid misuse and death due to overdose. This systematic review discusses the effective pain management options in chronic non-cancer pain patients that may help prevent opioid use and misuse. We searched PubMed, PubMed Central (PMC), Medical Literature Analysis and Retrieval System Online (MEDLINE), Multidisciplinary Digital Publishing Institute (MDPI), and Google Scholar for relevant literature. The different results were screened by the application of eligibility criteria, and 15 papers were finalized for review. These papers discussed the different pain management options, physician guidelines, and efforts to reduce opioid misuse, the importance of pill counting, and the involvement of multidisciplinary care teams in pain management. However, most of these papers were reviews over a short duration. The effects of emotions on chronic pain have been discussed along with the multidisciplinary pain rehabilitation treatment options that have improved patients' overall function. The reviewed research demonstrated positive outcomes of spinal cord stimulation in chronic low back pain, thereby reducing opioid use. However, further research is needed to explore more treatment options for chronic pain that can adequately reduce pain and prevent opioid use.

Heart failure with preserved ejection fraction (HFpEF) is a subtype of congestive heart failure distinguished by a normal ejection fraction. Comorbidities associated with its development typically include chronic conditions such as diabetes, hypertension and obesity that restrict the heart's filling pressure. Since heart failure with reduced ejection fraction (HFrEF) has been the subject of much research, physicians have always been faced with the problem of a lack of effective therapeutic interventions when treating patients with HFpEF. In recent years, there has been an increase in the number of research studies to identify effective therapeutic medication for HFpEF. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, which were initially developed to manage diabetes, have shown improvement in clinical outcomes in HFpEF even in the absence of diabetes. This systematic review aimed to gather and analyze evidence from randomized controlled trials and observational studies on the two drug classes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines were followed in the conduct of this comprehensive systematic review. To find all relevant studies, we searched three major medical databases, including Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed (NCBI). We have identified 13 studies on both classes of drugs, some of which have contributed to formulating current guidelines for managing HFpEF. The quality of included studies has been scrutinized using quality assessment tools, including the Cochrane Risk of Bias 2 tool and the Newcastle-Ottawa Scale tool, to ensure transparency and limit bias to lead to more reliable findings. Most studies on SGLT-2 inhibitors demonstrated a significant reduction in hospitalization rates and symptom burden, as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) scores and functional capacity, as measured by a 6-minute walk test distance. GLP-1 receptor agonists have also improved symptom scores and functional capacity, specifically in obese patients, although reductions in hospitalization rates remain unclear. Improvements in functional capacity and symptom scores were observed for both drug classes, though some metrics were not consistently statistically significant across studies. The superiority of one medication over another remains inconclusive due to a lack of trials comparing both drugs. In addition, GLP-1 receptor agonists have been more recently studied, necessitating further research on this drug class to assess long-term outcomes, efficacy in non-obese patients, and combination with SGLT-2 inhibitors.

[This corrects the article DOI: 10.7759/cureus.68760.].

Proton pump inhibitors (PPIs) have been the first-line drug of choice for acid-peptic diseases for a long time. While literature is abundant on the efficacy of the drug, the adverse effects of this drug, especially in the gastrointestinal (GI) system, have been a topic of ongoing research interest. The long-term safety profile remains controversial. PPIs have been found to cause polyps, malignancies, and pre-cancerous conditions such as intestinal metaplasia, enteric infections such as Clostridium difficile, and microscopic colitis. Furthermore, long-term use is seen to be associated with decreased iron absorption and disruption in gut microbiota. This systematic review aims to perform a qualitative synthesis of the literature on the long-term adverse effects of PPIs on the GI system. This review utilized the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, PubMed Central (PMC), MEDLINE (Medical Literature Analysis and Retrieval System Online), MDPI (Multidisciplinary Digital Publishing Institute), and EBSCO (Elton B. Stephens Company) Library databases were searched for data published in the past 15 years, between 2010 and 2024, using Medical Subject Headings (MeSH) and keywords, and a total of 260 articles were identified. The PubMed search, which included articles from MEDLINE and PMC, yielded 216 results; the MeSH search included 11 articles. EBSCO and MDPI searches retrieved nine and 24 articles, respectively. After applying the eligibility criteria and performing qualitative synthesis, 50 articles were shortlisted. 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 Newcastle-Ottawa Scale (NOS) for observational studies, and JBI critical appraisal checklist for case reports, were used. This review will help clinicians evaluate the risk-benefit factors of PPI use on a case-by-case basis, help mitigate unnecessary long-term prescription of PPI, and reduce the incidence of unwanted adverse events.

Obesity is a prominent health issue across the globe that causes negative reproductive consequences like decreased fertility. Even its effects on the success of in vitro fertilization (IVF) have drawn interest, with some studies indicating that BMI was linked to IVF failure. In this systematic review, we attempt to bring together the data regarding the impact of obesity on IVF outcomes. It also intends to quantify the adverse effects of female partner obesity on key IVF measures such as implantation, clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR), and to understand the mechanism of these adverse effects in obese women. A literature search was undertaken in PubMed/Medline, PubMed Central, Cochrane Library, Science Direct, and MDPI for studies comparing the effects of obesity (BMI ≥ 30 kg/m²) on IVF results. These studies included randomized controlled trials, cohort studies, case studies, literature reviews, and case-control studies. From the databases, we were able to select 533 relevant articles. The studies were evaluated, eligibility standards were followed, and 13 papers were considered. We collected data, and analyses of implantation rates, CPR, LBR, and MR were narratively reviewed because the studies were heterogeneous. This review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and the quality was assessed using the Cochrane Risk of Bias 2 scale for randomized trials and the Newcastle-Ottawa Scale for observational studies. A total of 13 studies, including participants, were included in the analysis. Obesity was consistently correlated with lower implantation, reduced CPR and LBR, and higher MR than women with normal BMI. To be precise, every five-unit increase in BMI was associated with a 5-7% reduction in CPR and LBR and a 9% rise in MR, underscoring the significant impact of obesity on IVF outcomes. In terms of mechanisms, metabolic disturbances in the oocytes, reduced endometrial response, and chronic inflammation were identified as the primary causes of these poor outcomes in obese women. In addition, interventions to reduce weight, such as diet and bariatric surgery, had an impact on the success of IVF. Obesity has a significant negative effect on IVF success, both in terms of oocyte quality and endometrial responsiveness. In overweight women who are seeking fertility treatment, weight control must be part of preconception treatment. However, further studies are needed to determine effective weight loss interventions and to better understand the mechanisms underlying IVF success in this group.

[This corrects the article DOI: 10.7759/cureus.64766.].

A precarious complication of thyrotoxicosis, or thyroid storm, is the increased risk of cardiomyopathy, which leads to circulatory collapse and cardiopulmonary arrest. It is crucial to promptly identify this condition to prevent significant deterioration of the left ventricular function and cardiogenic shock. This article seeks to examine published research that emphasizes the connection between thyroid storm and beta-blocker usage in relation to cardiogenic collapse and provides management recommendations. The search was performed on September 9, 2022, using PubMed, Science Direct, and Google Scholar libraries. A systematic exploration was carried out using the keywords Thyroid Storm AND cardiogenic Shock AND cardiac arrest AND beta blocker. The use of beta blockers as part of thyroid storm management was linked to the development of cardiogenic collapse and cardiac arrest. Ultra-short-acting beta-blockers like esmolol were a safer option than propranolol in treating patients with a thyrotoxic storm.

Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a rare disorder that most commonly affects the posterior part of the brain. Two common causes of PRES are hypertension and autoimmune diseases such as systemic lupus erythematosus (SLE). This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations and aimed at finding the association between hypertension and PRES in SLE patients. We searched medical databases such as PubMed, PubMed Central (PMC), Cochrane Library, and Multidisciplinary Digital Publishing Institute (MDPI) for relevant medical literature. The identified papers were screened, subjected to inclusion and exclusion criteria, and ran through quality appraisal tools, after which 16 papers were finalized. The finalized papers explored the roles of hypertension in SLE patients diagnosed with PRES. In this review, we identified a link between hypertension and PRES-SLE patients. We aimed to explain the role of hypertension in the development of PRES in SLE patients. This study also explains the different treatment modalities to be used for treating the patients presenting with PRES and differentiates other neuropsychiatric illnesses commonly present in SLE patients from PRES. It's important to make an accurate clinical diagnosis by understanding the clinical features and neuroimaging results of PRES for future care since it may even be incurable in some circumstances.

Multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR TB) is a global concern, with 450,000 new cases and 191,000 deaths in 2021. TB and chronic kidney disease (CKD) have been associated since 1974, with suggested explanations such as oxidative stress, malnutrition, dysfunction in vitamin D metabolism, and a compromised cell-mediated immune response. End-stage renal failure patients are more likely to acquire drug resistance due to poor adherence, adverse drug reactions, and inappropriate dose adjustment. We then aim to evaluate the therapeutic outcome of multidrug-resistant TB of the lungs in patients who require hemodialysis in terms of successful treatment (cured and treatment completed) and the associated factors for a favorable outcome. Our secondary goal is to identify unfavorable treatment outcomes (treatment failed, patient died, or patient lost to follow-up) and the underlying associated factors. We conformed to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Guidelines for this systematic review. We included adults (>19 years old) with chronic kidney disease who needed hemodialysis and had microbiologically confirmed multidrug-resistant pulmonary TB, excluding patients who had a renal allograft transplant, were on peritoneal dialysis, had extrapulmonary TB, were children and pregnant patients. We searched PubMed, MEDLINE, PubMed Central, ScienceDirect, Public Library of Science (PLOS), and Google Scholar. Keywords were combined with the Boolean "AND" operator to gather results as well as the medical subject heading (MeSH) search strategy. After screening study articles by reading their titles and abstracts, the following tools were used to assess the risk of bias: the Newcastle-Ottawa scale for observational studies, the Assessment of Multiple Systematic Reviews (AMSTAR) checklist for systematic reviews, and the Joanna Briggs Institute (JBI) assessment tool for case reports. Primary and secondary outcomes were assessed, and a conclusion was made. We gathered 21,570 studies from the databases between 2013 and 2023, with 30,062 total participants. There were eight eligible studies for review. Patients with CKD, particularly those on dialysis, are at increased risk of TB due to a combination of factors that contribute to immunosuppression. TB reactivation is common in chronic renal failure patients. Diagnostic samples such as sputum and pleural fluid had lower sensitivity rates compared to tissue samples, which led to delays in diagnosis and treatment and, most importantly, contributed to drug resistance. All new dialysis patients should undergo interferon-gamma release assay testing. TB-infected patients with severe renal disease (eGFR 30 ml/min) had increased morbidity and mortality; however, the use of directly observed treatment, short-course (DOTS), and renal-dose adjustment of anti-TB medications significantly reduced these risks. Drug-induced hepatitis and cutaneous reactions were common adverse effects of anti-TB medications. A therapeutic drug monitoring guideline is required to reduce these adverse events and even mortality. Additional research is required to assess the safety and efficacy of therapeutic regimens, as well as their outcomes, in this population with multidrug-resistant TB.

Calciphylaxis is a rare but potentially life-threatening disease that is not yet completely understood. It occurs mainly in patients with chronic kidney disease termed calcific uremic arteriolopathy (CUA) but also affects patients with normal renal function. Although this disease's pathogenesis is unclear, it is associated with the dysregulation of calcium and phosphate and subsequent calcification of peripheral arterioles. Calciphylaxis has up to 80% mortality, even with multidisciplinary and multimodal treatment modalities. The available literature identified some relevant risk factors associated with the development of calciphylaxis, but the authors differ significantly in risk profiling. Moreover, most papers on calciphylaxis are observational studies, namely case series, case reports, cohort, and cross-sectional studies. Although recently available articles mentioned some risk factors, the studies mainly focused on diagnosis, treatment, and prognosis with limited emphasis on structured risk profiling. In addition, experimental and systemic review studies on risk factors associated with calciphylaxis are lacking. Thus, this systematic review's primary focus is to determine risk factors associated with developing calciphylaxis in patients with chronic kidney disease. We searched electronic databases from 2018 to 2024 for articles that contained relevant risk factors linked with the development of calciphylaxis using the keywords calciphylaxis, chronic kidney disease, and risk factors. We identified 486 articles, removed duplicate papers from selected articles, applied inclusion and exclusion criteria, and conducted a quality assessment test. Two independent authors performed data extraction manually, and we compared the results for consistency and accuracy. Twenty-two articles met the eligibility criteria, but only 16 articles passed the quality assessment appraisal and were included in the systematic review. We identified 1,739 patients: 664 (38.2%) and 1075 (61.81%) were males and females, respectively. A total of 1373 (78.95%) were on dialysis, and 926 (53.25%) were diabetics. Caucasians and patients with obesity were 695 (37.90%) and 613 (35.25%), respectively. At the time of diagnosis, 599 (34.45%), 311 (17.90%), and 278 (15.99%) were on vitamin K antagonists (VKA), vitamin D, and calcium phosphate binders. The number of patients with elevated parathyroid hormone was 196 (11.27%). Our study found no experimental or systematic reviews that primarily focused on risk factors associated with the development of calciphylaxis. Our research indicated that dialysis is the most frequent risk factor linked to the development of calciphylaxis. Other risk factors include being caucasian, female gender, obese, diabetic mellitus (DM), having elevated parathyroid hormone, and use of VKA (warfarin), vitamin D, and calcium phosphate binders. These findings are consistent with the evidence seen in most of the articles we reviewed. However, the papers we studied are mainly observational mono-centered research articles, with the majority having a small sample size. Thus, we recommend a multicenter, large-scale experimental study to assess risk factors and profiling for the development of calciphylaxis in patients with chronic kidney disease.

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.

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 β-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. β-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 β-blockers in decreasing mortality in critically ill populations such as sepsis and septic shock patients.

Achalasia is a rare esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and absence of peristalsis, leading to significant swallowing difficulties and other symptoms. Traditional treatment options, including Heller myotomy (HM) and pneumatic dilation (PD), have been effective but are associated with risks such as perforation and gastroesophageal reflux disease (GERD). Peroral endoscopic myotomy (POEM) has emerged as a minimally invasive alternative, potentially offering several advantages over conventional methods. This systematic review aims to compare the efficacy, safety, and long-term outcomes of POEM versus HM in the treatment of achalasia. We systematically reviewed studies that compared POEM with HM in achalasia patients, focusing on key outcomes such as myotomy length, operative time, treatment success rates, and complication rates. The review included 15 studies comprising four randomized controlled trials, 10 cohort studies, and one case-control study. The results consistently showed that POEM achieved longer myotomy lengths and shorter operative times compared to HM. POEM also demonstrated higher or comparable treatment success rates, with a uniform definition of success based on achieving an Eckardt score of ≤3. However, the complication rates, particularly the incidence of GERD, varied between the two procedures, highlighting the need for careful patient selection and long-term follow-up. POEM offers a promising alternative to HM for the treatment of achalasia, with advantages in terms of reduced invasiveness, shorter operative times, and potentially higher treatment success rates. However, further high-quality research is necessary to fully establish its long-term efficacy and safety compared to conventional treatments.

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.