Safety of procedural sedation in emergency department settings among the adult population: a systematic review and meta-analysis of randomized controlled trials.

Procedural sedation and analgesia (PSA) are a common practice in emergency departments (EDs), aiming to alleviate pain, anxiety, and discomfort during various medical procedures. We have undertaken a systematic review and meta-analysis with the aim of assessing the incidence of adverse events associated with PSA, including those related to individual drugs and various drug combinations. The study adhered to PRISMA guidelines for a systematic review and meta-analysis of adverse events in ED sedation. A comprehensive search strategy was employed across ten databases, supplemented by searches on clinicaltrials.gov and manual reviews of reference lists. Data extraction focused on medication administration and adverse events. The study considered four types of adverse events: cardiac, respiratory, gastrointestinal, and neurological. Only randomized controlled trials (RCTs) focusing on PSA administered to adult patients within the ED setting were included. The statistical analysis employed OpenMeta Analyst to conduct a one-arm meta-analysis, with findings presented alongside their corresponding 95% Confidence Intervals. Forest plots were constructed to combine and evaluate results, and sensitivity analyses were performed to identify sources of heterogeneity. From a literature search of 4246 records, 32 RCTs were deemed suitable for this meta-analysis. The analysis included 6377 procedural sedations. The most common adverse event was hypoxia, with an incidence rate of 78.5 per 1000 sedations (95% CI = 77.5-133.5). This was followed by apnea and hypotension, with incidence rates of 31 (95% CI = 19.5-41.8) and 28.1 (95% CI = 17.4-38.9) per 1,000 sedations, respectively. Agitation and vomiting each occurred in 15.6 per 1,000 sedations (95% CI = 8.7-22.6). Severe adverse events were rare, with bradycardia observed in 16.7 per 1,000 sedations, laryngospasm in 2.9 per 1,000 sedations (95% CI = - 0.1 to 6), intubation in 10.8 per 1,000 sedations (95% CI = 4-17), and aspiration in 2.7 per 1,000 sedations (95% CI = - 0.3 to 5.7). Ketamine is found to be the safest option in terms of respiratory adverse events, with the lowest rates of apnea and hypoxia, making it the least respiratory depressant among the evaluated drugs. Etomidate has the least occurrence of hypotension when used alone. Propofol has the highest incidence of hypotension when used alone and ranks second in hypoxia-related adverse events after midazolam. Using combinations of sedating agents, such as propofol and ketamine, has been found to offer several advantages over single drugs, especially in reducing adverse events like vomiting, intubation difficulty, hypotension, bradycardia, and laryngospasm. The combination significantly reduces the incidence of hypotension compared to using propofol or ketamine individually. Despite the regular use of procedural sedation, it can sometimes lead to serious adverse events. Respiratory issues like apnea and hypoxia, while not common, do occur more often than cardiovascular problems such as hypotension. However, the least frequent respiratory complications, which can also pose a threat to life, include laryngospasm, aspiration, and intubation. These incidents are extremely rare.

Association between acute peripancreatic fluid collections and early readmission in acute pancreatitis: A propensity-matched analysis.

BACKGROUND: Patients with acute pancreatitis (AP) frequently experience hospital readmissions, posing a significant burden to healthcare systems. Acute peripancreatic fluid collection (APFC) may negatively impact the clinical course of AP. It could worsen symptoms and potentially lead to additional complications. However, clinical evidence regarding the specific association between APFC and early readmission in AP remains scarce. Understanding the link between APFC and readmission may help improve clinical care for AP patients and reduce healthcare costs. AIM: To evaluate the association between APFC and 30-day readmission in patients with AP. METHODS: This retrospective cohort study is based on the Nationwide Readmission Database for 2016-2019. Patients with a primary diagnosis of AP were identified. Participants were categorized into those with and without APFC. A 1:1 propensity score matching for age, gender, and Elixhauser comorbidities was performed. The primary outcome was early readmission rates. Secondary outcomes included the incidence of inpatient complications and healthcare utilization. Unadjusted analyses used Mann-Whitney U and χ 2 tests, while Cox regression models assessed 30-day readmission risks and reported them as adjusted hazard ratios (aHR). Kaplan-Meier curves and log-rank tests verified readmission risks. RESULTS: A total of 673059 patients with the principal diagnosis of AP were included. Of these, 5.1% had APFC on initial admission. After propensity score matching, each cohort consisted of 33914 patients. Those with APFC showed a higher incidence of inpatient complications, including septic shock (3.1% vs 1.3%, P < 0.001), portal venous thrombosis (4.4% vs 0.8%, P < 0.001), and mechanical ventilation (1.8% vs 0.9%, P < 0.001). The length of stay (LOS) was longer for APFC patients [4 (3-7) vs 3 (2-5) days, P < 0.001], as were hospital charges ($29451 vs $24418, P < 0.001). For 30-day readmissions, APFC patients had a higher rate (15.7% vs 6.5%, P < 0.001) and a longer median readmission LOS (4 vs 3 days, P < 0.001). The APFC group also had higher readmission charges ($28282 vs $22865, P < 0.001). The presence of APFC increased the risk of readmission twofold (aHR 2.52, 95% confidence interval: 2.40-2.65, P < 0.001). The independent risk factors for 30-day readmission included female gender, Elixhauser Comorbidity Index ≥ 3, chronic pulmonary diseases, chronic renal disease, protein-calorie malnutrition, substance use disorder, depression, portal and splenic venous thrombosis, and certain endoscopic procedures. CONCLUSION: Developing APFC during index hospitalization for AP is linked to higher readmission rates, more inpatient complications, longer LOS, and increased healthcare costs. Knowing predictors of readmission can help target high-risk patients, reducing healthcare burdens.

Outcomes of Upper Gastrointestinal Bleeding in Hospitalized COVID-19 Patients in the United States: A Propensity-score Matched Analysis of a Large National Database.

Patients with cirrhosis that are hospitalized with COVID-19 infection have been found to have worse outcomes. No comparative study has been conducted between gastrointestinal (GI) bleeding in patients with cirrhosis who are diagnosed with COVID-19. We utilized the National Inpatient Sample (NIS) database to perform a retrospective analysis of 24, 050 patients diagnosed with cirrhosis and COVID-19. The identified patients were separated into variceal bleeding, nonvariceal bleeding, and no (or neither) GI bleeding groups. After performing propensity sample matching and multivariate analysis of mortality, we found no significant differences in mortality among the three groups. However, the variceal bleed group had a shorter length of stay (5.67 days lower than the no-bleed group). Esophagogastroduodenoscopy (EGD) with intervention was associated with reduced mortality in the variceal and nonvariceal bleeding groups. Acute kidney injury was a strong predictor of mortality in both bleeding groups. A native American race was found to be associated with higher mortality in the nonvariceal bleeding group. Our study suggests that there are various pathophysiological processes among the three groups, with no significant mortality differences with cirrhosis complications of GI bleeding.

Groove pancreatitis: From enigma to future directions-A comprehensive review.

Groove pancreatitis (GP) is a rare and clinically distinct form of chronic pancreatitis affecting the pancreaticoduodenal groove comprising the head of the pancreas, duodenum, and the common bile duct. It is more prevalent in individuals in their 4-5th decade of life and disproportionately affects men compared with women. Excessive alcohol consumption, tobacco smoking, pancreatic ductal stones, pancreatic divisum, annular pancreas, ectopic pancreas, duodenal wall thickening, and peptic ulcers are significant risk factors implicated in the development of GP. The usual presenting symptoms include severe abdominal pain, nausea, vomiting, diarrhea, weight loss, and jaundice. Establishing a diagnosis of GP is often challenging due to significant clinical and radiological overlap with numerous benign and malignant conditions affecting the same anatomical location. This can lead to a delay in initiation of treatment leading to increasing morbidity, mortality, and complication rates. Promising research in artificial intelligence (AI) has garnered immense interest in recent years. Due to its widespread application in diagnostic imaging with a high degree of sensitivity and specificity, AI has the potential of becoming a vital tool in differentiating GP from pancreatic malignancies, thereby preventing a missed or delayed diagnosis. In this article, we provide a comprehensive review of GP, covering the etiology, pathogenesis, clinical presentation, radiological and endoscopic evaluation, management strategies, and future directions. This article also aims to increase awareness about this lesser known and often-misdiagnosed clinical entity amongst clinicians to ultimately improve patient outcomes.

Left Atrial Strain as a Predictor of Early Anthracycline-Induced Chemotherapy-Related Cardiac Dysfunction: A Pilot Systematic Review and Meta-Analysis.

Background: Chemotherapy-related cardiac dysfunction (CTRCD) significantly affects patients undergoing anthracycline (AC) therapy, with a prevalence ranging from 2% to 20%. Reduced left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain (LV GLS) are prognostic parameters for CTRCD detection. Our study aimed to investigate the role of emerging parameters such as left atrial strain (LAS). Methods: We searched multiple databases for studies comparing LAS changes post-AC versus pre-AC therapy in patients with cancer. Primary outcomes included left atrial reservoir strain (LASr), left atrial conduit strain (LAScd), and left atrial contractile strain (LASct). RevMan (v5.4) was used to pool the standardized mean difference (SMD) under a random effects model, with p < 0.05 as the threshold for statistical significance. Results: In an analysis of 297 patients across five studies, AC therapy significantly lowered LASr (SMD = -0.34, 95% CI:-0.55, -0.14, I2 = 0%, p = 0.0009) and LAScd (SMD = -0.41, 95% CI: -0.59, -0.23, I2 = 0%, p < 0.00001) levels. Conversely, LASct demonstrated no significant change (SMD = 0.01, 95% CI: -0.21, 0.23, I2 = 9%, p = 0.95). AC therapy also significantly reduced LV GLS (SMD = -0.31, 95% CI: -0.51, -0.11, I2 = 0%, p = 0.003). While not statistically significant, LVEF decreased (SMD = -0.20, 95% CI: -0.42, 0.03, I2 = 0%, p = 0.09), and left atrial volume index trended higher (SMD = 0.07, 95% CI: -0.14, 0.27, I2 = 0%, p = 0.52) after AC therapy. Conclusions: AC treatment led to reduced LAS and LV GLS values, indicating its potential as an early CTRCD indicator. Larger trials are required to fully explore their clinical significance.

Gender and Racial Differences in the Provision of Palliative Care Services Among Critically ill Necrotizing Fasciitis and Septic Shock Geriatric Patients: Analysis of a Nationwide Database in the United States.

Introduction: Necrotizing fasciitis (NF) and sepsis shock (SS) are both severe and life-threatening conditions requiring specialized care, including palliative care (PC), to optimize comfort. However, data on the utilization of PC in this population, including racial and gender differences, are limited. Methods: We used the National Inpatient Sample (NIS) database from 2016 to 2020 to extract data on patients with NF and SS as well as PC utilization. Chi-squared tests and multivariate linear regression models were utilized to analyze relationships between categorical and continuous variables, respectively. Multivariable logistic regression was used to determine adjusted odds ratios (aORs) and 95% confidence intervals (CI) for various outcomes among various gender and racial groups. Mann-Kendall trend test was used to assess mortality trends over time. Results: Among the 11,260 patients with NF and SS, 2,645 received PC whereas 8,615 did not. Female patients had significantly higher odds of receiving PC versus males (aOR: 1.42, 95% CI 1.27-1.58). No significant racial differences in PC utilization were observed. Patients receiving PC had higher odds of in-hospital mortality (aOR: 1.18, 95% CI 1.03-1.35). No significant trend in in-hospital deaths was observed over the study period. PC was associated with significantly shorter length-of-stay and lower costs. Conclusion: Our study provides comprehensive insights, and identifies gender differences in PC utilization in NF and SS patients. Further research must aim to refine delivery strategies and address potential differences in PC.

Efficacy and Safety of Endoscopic Through-the-Scope Suture System for Gastrointestinal Defects: A Systematic Review and Meta-analysis.

OBJECTIVE: Recently, a through-the-scope suturing (TTSS) system has received FDA approval and has been evaluated for closing mucosal defects postintervention. We hereby performed a systematic review and pooled meta-analysis of available studies to assess the safety and efficacy of this intervention. METHODS: We queried the following databases through April 26, 2023: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, and Web of Science Core Collection. Endoscopists utilizing TTSS for the following reasons were included: endoscopic mucosal resection, endoscopic submucosal dissection, peroral endoscopic myotomy, perforation, fistula closure, and/or stent fixation. The outcomes assessed were technical success, primary clinical success (closure of defect without additional intervention), and overall clinical success (closure of defect with/without additional intervention). Random effects model with the DerSimonian Laird approach was used to report event rates expressed as proportions with a 95% CI. RESULTS: A total of 12 studies with 512 patients (mean age of 61.5 ± 18.4 y, 54.6% females) were included. The technical success rate was 96.0% (CI: 94.3%-97.7%). The primary clinical success rate was 74.8% (CI: 65.5%-84.1%). The overall clinical success rate was 95.4% (CI: 92.6-98.2%). Only 1 mortality case unrelated to intervention was reported. CONCLUSION: The TTSS appears safe and effective for closing mucosal defects after therapeutic endoscopic interventions. Further cost-effective studies should be performed comparing with endoclips for use in clinical settings.

Safety and efficacy of biliary suprapapillary metal and plastic stents in malignant biliary obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Biliary drainage is vital in managing malignant biliary obstruction (MBO). Suprapapillary stenting has emerged as a viable alternative to transpapillary stenting and is performed using inside plastic (iPS) or metal stents (iMS). This meta-analysis aims to evaluate the outcomes of suprapapillary stent placement for MBO. METHODS: The Embase, PubMed, and Web of Science databases were systematically searched to include all studies published before September 31, 2023, that reported on the outcomes of suprapapillary stents placed for MBO. Using the random-effect model, the pooled, weight-adjusted event rate estimate for the clinical outcomes was calculated with 95% confidence intervals (CIs). RESULTS: Twenty-eight studies were included, with a total of 1401 patients. The pooled clinical success rate was 98.9%. A subgroup analysis yielded non-significant differences between the iPS and iMS groups (99.3% vs. 98.6%, respectively; P = 0.44). The pooled incidence rate of adverse events (AE) with suprapapillary stents was 9.5%. In a subgroup analysis, the incidence of AEs with iPS was 10.7% compared to 9% in the iMS group without a statistical difference (P = 0.32). The most common adverse event was cholangitis (2.2%), followed by pancreatitis (1.1%), cholecystitis (0.5%), and bleeding (0.12%). CONCLUSION: When technically feasible, suprapapillary stenting for MBO is a viable endoscopic option with a high clinical success rate and acceptable adverse event rates. Both iPS and iMS exhibit similar efficacy.

Clinicopathologic patterns and survival patterns among prostate carcinosarcoma patients in the United States: An analysis of SEER database.

INTRODUCTION: Prostatic carcinosarcoma comprises <1% of all prostate neoplasms. The literature on this disease is limited to a few case studies, primarily due to the rarity of this malignancy. We aimed to investigate the demographic, clinical, and histologic factors, prognosis, and survival of prostatic carcinosarcoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with prostatic carcinosarcoma from 2000-2018. Demographic and clinical data, including age, race, sex, tumor grade, stage, tumor size, lymph node status, metastasis, and treatment modalities, were recorded. RESULTS: Prostatic carcinosarcoma had a median age of 72 years at diagnosis, with a majority of cases among White individuals (93%). When reported, the histologic grade comprised moderately differentiated (3.3%), poorly differentiated (56.7%), and undifferentiated/anaplastic (40%) subtypes. In patients with reported data, tumor size varied between 2-5 cm (15.8%) and >5 cm (84.2%). Distant metastasis most commonly occurred in the liver (12.5%) and lung (12.5%), followed by the bone (8.3%). The most common treatment performed was surgery with radiation (32.4%). The five-year overall survival was 11.9%. CONCLUSIONS: Prostatic carcinosarcoma affects men in the seventh decade of life. Regional and distant tumor stage is considered an indicator of survival. Prostate carcinosarcoma is rare; due to its aggressive nature, a deeper understanding, and an improved personalized therapeutic approach are necessary for improving patient outcomes in this challenging arena of oncology.

Unlocking the Therapeutic Symphony: A Systematic Review Exploring the Role of Levosimendan in the Management of Heart Failure.

Levosimendan, a novel drug, a calcium-sensitizing inotrope, has emerged as a potential therapeutic modulator for heart failure (HF). This review appraises the efficacy and safety of levosimendan in managing HF, in different clinical settings. The study aims to examine the clinical outcomes reported in the selected trials to determine the effectiveness of levosimendan in improving key parameters related to HF. Seven relevant studies encompassing 1200 participants were identified from three databases. Inclusion criteria included clinical trials that investigated the therapeutic efficacy of levosimendan in the treatment of HF, and studies involving both adult and pediatric participants. Exclusion criteria involved studies with insufficient data, studies other than clinical trials, case reports, letters to the editor, conference papers, grey literature, and studies published in a language other than English. Upon evaluating the included studies, it was found that levosimendan shows improved hemodynamics and clinical efficacy in patients with severe septic cardiomyopathy. Levosimendan enhanced right ventricular (RV) function in patients with RV dysfunction after mitral valve (MV) surgeries and decreased the amount of N-terminal pro-B-type natriuretic peptide (NT-ProBNP) in non-ST elevated myocardial infarction (NSTEMI) patients with elevated NT-proBNP, all without increasing the overall cost or duration of hospitalization. Despite variations in study designs and participant characteristics, evidence suggests levosimendan significantly improves left ventricular ejection fraction (LVEF) and exercise tolerance measured by a six-minute walk distance. Notably, its safety profile appears favorable with minimal arrhythmic events and comparable rates of adverse effects to a placebo. This systematic review highlights levosimendan's promising potential for HF management, warranting further research to solidify its clinical role.

Reduction of Hospital-Acquired Infections Through a Nursing Education Program: A Quality Improvement Project on the Sensitization of Nursing Staff Toward Infection Control in Neonates.

Background This study aimed to reduce hospital-acquired infections (HAIs) by at least 50% in our unit through a nursing education program to sensitize the nursing staff toward infection control in neonates. Methodology This pre- and post-intervention observational study was conducted in Liaquat National Hospital's Neonatal Intensive Care Unit (NICU) from October 2021 until March 2023. This observational study was conducted in three phases. In phase I (pre-implementation), all neonates with suspected HAIs were included. In phase II (implementation), the nursing staff dedicated to the NICU were trained. In phase III (post-implementation), all neonates with suspected HAIs were included. Culture-proven bloodstream infections (BSIs), urinary tract infections (UTIs), and ventilator-associated pneumonia (VAP) were the three types of HAIs. The nursing scoring was done by the principal investigator based on a questionnaire. The Shapiro-Wilk test was used to evaluate the normality of all quantitative data across all phases. Results In the pre-implementation phase, there were 24 (10.8%) HAIs, among which 19 (8.6%) were BSIs, one (0.5%) was a catheter-associated urinary tract infection (CAUTI), and seven (3.2%) were VAP. Whereas in the post-implementation phase, there were 12 (5%) HAIs, among which 10 (4.1%) were BSIs, none were CAUTIs, and five (2.1%) were VAP. There was a significant reduction of HAIs in the post-implementation phase (p < 0.01). The difference in the knowledge, assessment, and practice was statistically significant in the post-implementation phase (p < 0.01). Conclusions We established a successful cost-effective intervention to improve the awareness and compliance of NICU nurses with infection control practices. This helped us in reducing HAIs in our NICU.

Impact of pneumothorax on mortality, morbidity, and hospital resource utilization in COVID-19 patients: a propensity matched analysis of nationwide inpatient sample database.

BACKGROUND: Spontaneous pneumothorax (PTX) is more prevalent among COVID-19 patients than other critically ill patients, but studies on this are limited. This study compared clinical characteristics and in-hospital outcomes among COVID-19 patients with concomitant PTX to provide insight into how PTX affects health care utilization and complications, which informs clinical decisions and healthcare resource allocation. METHODS: The 2020 Nationwide Inpatient Sample was used analyze patient demographics and outcomes, including age, race, sex, insurance status, median income, length of hospital stay, mortality rate, hospitalization costs, comorbidities, mechanical ventilation, and vasopressor support. Propensity score matching was employed for additional analysis. RESULTS: Among 1,572,815 COVID-19 patients, 1.41% had PTX. These patients incurred significantly higher hospitalization costs ($435,508 vs. $96,668, p < 0.001) and longer stays (23.6 days vs. 8.6 days, p < 0.001). In-hospital mortality was substantially elevated for PTX patients (65.8% vs. 14.4%, p < 0.001), with an adjusted odds ratio of 14.3 (95% CI 12.7-16.2). Additionally, these patients were more likely to require vasopressors (16.6% vs. 3.3%), mechanical circulatory support (3.5% vs. 0.3%), hemodialysis (16.6% vs. 5.6%), invasive mechanical ventilation (76.9% vs. 15.1%), non-invasive mechanical ventilation (19.1% vs. 5.8%), tracheostomy (13.3% vs. 1.1%), and chest tube placement (59.8% vs. 0.8%). CONCLUSIONS: Our findings highlight the severe impact of PTX on COVID-19 patients, characterized by higher mortality, more complications, and increased resource utilization. Also, being Hispanic, male, or obese increased the risk of developing concomitant PTX with COVID-19.

Remimazolam for sedation in gastrointestinal endoscopy: A comprehensive review.

Worldwide, a majority of routine endoscopic procedures are performed under some form of sedation to maximize patient comfort. Propofol, benzodiazepines and opioids continue to be widely used. However, in recent years, Remimazolam is gaining immense popularity for procedural sedation in gastrointestinal (GI) endoscopy. It is an ultra-short-acting benzodiazepine sedative which was approved by the Food and Drug Administration in July 2020 for use in procedural sedation. Remimazolam has shown a favorable pharmacokinetic and pharmacodynamic profile in terms of its non-specific metabolism by tissue esterase, volume of distribution, total body clearance, and negligible drug-drug interactions. It also has satisfactory efficacy and has achieved high rates of successful sedation in GI endoscopy. Furthermore, studies have demonstrated that the efficacy of Remimazolam is non-inferior to Propofol, which is currently a gold standard for procedural sedation in most parts of the world. However, the use of Propofol is associated with hemodynamic instability and respiratory depression. In contrast, Remimazolam has lower incidence of these adverse effects intra-procedurally and hence, may provide a safer alternative to Propofol in procedural sedation. In this comprehensive narrative review, highlight the pharmacologic characteristics, efficacy, and safety of Remimazolam for procedural sedation. We also discuss the potential of Remimazolam as a suitable alternative and how it can shape the future of procedural sedation in gastroenterology.

Controversies and Future Directions in Management of Acute Appendicitis: An Updated Comprehensive Review.

Globally, acute appendicitis has an estimated lifetime risk of 7-8%. However, there are numerous controversies surrounding the management of acute appendicitis, and the best treatment approach depends on patient characteristics. Non-operative management (NOM), which involves the utilization of antibiotics and aggressive intravenous hydration, and surgical appendectomy are valid treatment options for healthy adults. NOM is also ideal for poor surgical candidates. Another important consideration is the timing of surgery, i.e., the role of interval appendectomy (IA) and the possibility of delaying surgery for a few hours on index admission. IA refers to surgical removal of the appendix 8-12 weeks after the initial diagnosis of appendicitis. It is ideal in patients with a contained appendiceal perforation on initial presentation, wherein an initial nonoperative approach is preferred. Furthermore, IA can help distinguish malignant and non-malignant causes of acute appendicitis, while reducing the risk of recurrence. On the contrary, a decision to delay appendectomy for a few hours on index admission should be made based on the patients' baseline health status and severity of appendicitis. Post-operatively, surgical drain placement may help reduce postoperative complications; however, it carries an increased risk of drain occlusion, fistula formation, and paralytic ileus. Furthermore, one of the most critical aspects of appendectomy is the closure of the appendiceal stump, which can be achieved with the help of endoclips, sutures, staples, and endoloops. In this review, we discuss different aspects of management of acute appendicitis, current controversies in management, and the potential role of endoscopic appendectomy as a future treatment option.

Predictive Nomogram and Propensity Score Matching in Neuroendocrine Carcinoma of the Tubular Gastrointestinal Tract: A US Population-Based Clinical Outcome Study.

Background: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract (GI-NECs) are rare and associated with worse clinical outcomes. This population-based study aims to highlight key demographics, clinicopathological factors, and survival outcomes in the US population. Methods: Data from 10,387 patients with GI-NECs were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2000 to 2020. Results: Most patients were >40 years old at the time of presentation with a median age of 63 years old, with almost equal ethnic distribution per US population data. The most common primary tumor site was the small intestine (33.6%). The metastatic spread was localized in 34.8%, regional in 27.8%, and distant in 37.3% of cases, and the liver was the most common site of metastasis (19.9%) in known cases of metastases. Most NEC patients underwent surgery, presenting the highest 5-year overall survival of 73.2% with a 95% confidence interval (CI) (95% CI 72.0-74.4%), while chemotherapy alone had the lowest 5-year survival of 8.0% (95% CI 6.4-10.0%). Compared to men, women had a superior 5-year survival rate of 59.0% (95% CI 57.6-60.5%). On multivariate analysis, age > 65 (HR 2.49, 95% CI 2.36-2.54%, p ≤ 0.001), distant metastasis (HR 2.57, 95% CI 2.52-2.62%, p ≤ 0.001), tumor size > 4 mm (HR 1.98, 95%, CI 1.70-2.31%, p ≤ 0.001), esophageal (HR 1.49, 95% CI 0.86-2.58%, p ≤ 0.001), transverse colon (HR 1.95, 95% CI 1.15-3.33%, p ≤ 0.01), descending colon (HR 2.12, 95% CI 1.12, 3.97%, p = 0.02) anorectal sites, and liver or lung metastases were associated with worse survival. Surgical intervention and tumors located in the small intestine or appendix showed a better prognosis. Conclusion: GI-NECs are a group of rare malignancies associated with a poor prognosis. Therefore, epidemiological studies analyzing national databases may be the best alternative to have a more comprehensive understanding of this condition, assess the impact of current practices, and generate prognosis tools.

Insights into calcific aortic valve stenosis: a comprehensive overview of the disease and advancing treatment strategies.

Aortic valve stenosis is a disease characterized by thickening and narrowing of the aortic valve (AV), most commonly due to calcification, which leads to left ventricular outflow obstruction called calcific aortic valve disease (CAVD). CAVD presents as a progressive clinical syndrome with cardiorespiratory symptoms, often with rapid deterioration. The modern-day pathophysiology of CAVD involves a complex interplay of genetic factors, chronic inflammation, lipid deposition, and valve calcification, with early CAVD stages resembling atherosclerosis. Various imaging modalities have been used to evaluate CAVD, with a recent trend of using advanced imaging to measure numerous AV parameters, such as peak jet velocity. Significant improvements in mortality have been achieved with transcatheter AV repair, but numerous therapeutics and modalities are being researched to delay the progression of CAVD. This article aims to provide a comprehensive review of CAVD, explore recent developments, and provide insights into future treatments with various novel modalities.

Genome-wide characterization and analysis of rice DUF247 gene family.

BACKGROUND: The domain of unknown function 247 (DUF247) proteins is involved in plant development and stress response. Rice is an important worldwide cereal crop, although an increasing number of DUF proteins have been identified, the understanding of DUF proteins is still very limited in rice. RESULTS: In this study, we identified 69 genes that encode DUF247 proteins in the rice (Oryza sativa) genome by homology searches and domain prediction. All the OsDUF247 proteins were classified into four major groups (I, II, III and IV) by phylogenetic analysis. Remarkably, OsDUF247 genes clustered on the chromosomes solely show close phylogenetic relationships, suggesting that gene duplications have driven the expansion of the DUF247 gene family in the rice genome. Tissue profile analysis showed that most DUF247 genes expressed at constitutive levels in seedlings, roots, stems, and leaves, except for seven genes (LOC_Os01g21670, LOC_Os03g19700, LOC_Os05g04060, LOC_Os08g26820, LOC_Os08g26840, LOC_Os08g26850 and LOC_Os09g13410) in panicles. These seven genes were induced by various abiotic stress, including cold, drought, heat, hormone treatment, and especially salt, as demonstrated by further experimental analysis. DUF247 proteins contain transmembrane domains located on the membrane, suggesting their significant roles in rice development and adaptation to the environment. CONCLUSIONS: These findings lay the foundation for functional characterizations of DUF247 genes to unravel their exact role in rice cultivars.

Efficacy and outcomes of bempedoic acid versus placebo in patients with hypercholesterolemia: an updated systematic review and meta-analysis of randomized controlled trials.

Introduction: Bempedoic acid (BA) has shown varied efficacy in managing hyperlipidemia. We conducted the most extensive up-to-date meta-analysis, the first to include recent studies by Nissen et al., which boast the largest sample size. Methods: Literature search was done on Medline, EMBASE, and Cochrane Library. The primary endpoint was a change in low-density lipoprotein-cholesterol (LDL-C) levels, while secondary endpoints encompassed changes in lipid parameters, clinical endpoints, and safety endpoints. The least-square mean (LSM) percent change was utilized for lipid changes, with statistical significance set at P < 0.05. Results: This analysis included 12 randomized control trials with 22,249 participants. BA exhibited a substantial reduction in LDL-C levels [LSM % change, -24.34; 95% confidence interval (CI), -27.80 to -20.88; P < 0.0001], total cholesterol levels (LSM % change, -16.62; 95% CI, -21.70 to -11.54; P < 0.00001) and high-density lipoprotein-cholesterol (HDL-C) levels (LSM % change, -4.22; 95% CI, -5.51 to -2.92; P < 0.00001) compared to the placebo. Conclusions: BA significantly lowers LDL-C, total cholesterol, HDL-C, non-HDL-C, high sensitivity C reactive protein, and apolipoprotein levels.

Efficacy and outcomes of antiplatelet therapy versus oral anticoagulants in patients undergoing transcatheter aortic valve replacement: a systematic review and meta-analysis.

Background: Recent guidelines suggest that antiplatelet therapy (APT) is the standard of care in the absence of long-term oral anticoagulation (OAC) indications in patients post-transcatheter aortic valve replacement (TAVR). The superiority of one method over the other remains controversial. Materials and methods: Several databases, including MEDLINE, Google Scholar, and EMBASE, were electronically searched. The primary endpoint was the all-cause mortality (ACM) rate. Secondary endpoints included cardiovascular death, myocardial infarction (MI), stroke/TIA, haemorrhagic stroke, bleeding events, systemic embolism, and valve thrombosis in post-TAVR patients receiving APT and oral anticoagulants (OACs). Forest plots were generated using Review Manager version 5.4, with a p value less than 0.05 indicating statistical significance. Subgroup analysis was performed to explore potential sources of heterogeneity. Results: Twelve studies were selected. No significant differences were observed in APT and OAC group for ACM [risk ratio (RR): 0.67; 95% CI:0.45-1.01; P=0.05], cardiovascular death [RR:0.91; 95% CI:0.73-1.14; P=0.42], MI [RR:1.69; 95% CI:0.43-6.72; P=0.46], Stroke/TIA [RR:0.79; 95% CI:0.58-1.06; P=0.12], ischaemic stroke [RR:0.83; 95% CI:0.50-1.37; P=0.47], haemorrhagic stroke [RR:1.08; 95% CI: 0.23-5.15; P=0.92], major bleeding [RR:0.79; 95% CI:0.51-1.21; P=0.28], minor bleeding [RR:1.09; 95% CI: 0.80-1.47; P=0.58], life-threatening bleeding [RR:0.85; 95% CI:0.55-1.30; P=0.45], any bleeding [RR:0.98; 95% CI:0.83-1.15; P=0.78], and systemic embolism [RR:0.87; 95% CI:0.44-1.70; P=0.68]. The risk of valve thrombosis was higher in patients receiving APT than in those receiving OAC [RR:2.61; 95% CI:1.56-4.36; P =0.0002]. Conclusions: Although the risk of valve thrombosis increased in patients receiving APT, the risk of other endpoints was comparable between the two groups.