Analysis of immune-related adverse events in gastrointestinal malignancy patients treated with immune checkpoint inhibitors.

Immune checkpoint inhibitors are becoming an increasingly common treatment for advanced gastrointestinal cancer, but the possibility of immune-related adverse events has raised concerns. This study aimed to evaluate the risks of immune-related adverse events between patients who received immune checkpoint inhibitors and those who received chemotherapy among different types of gastrointestinal cancer. The study utilized data from the multicenter TriNetX database in the United States covering the period between 2015 and 2022. Hazard ratios and 95% confidence intervals were used to describe the relative hazard of immune-related adverse events based on comparing time-to-event rates. Our study revealed that the incidence of immune-related adverse events was significantly higher in patients who received immune checkpoint inhibitors and chemotherapy compared to those who received chemotherapy only in treating gastrointestinal cancer. CTLA-4 inhibitors tended to have a higher rate of immune-related adverse events compared to PD-1/PD-L1 inhibitors. Our study found a lower mortality rate among patients who developed immune-related adverse events compared to those who did not after propensity score matching (HR, 0.661; 95% CI 0.620-0.704; p < .01). We provide important real-world data on the incidence and impact of immune-related adverse events in patients with advanced gastrointestinal cancer treated with immune checkpoint inhibitors. Our study's results support clinicians in making informed decisions about the potential benefits and risks of immune checkpoint inhibitor therapy for patients with gastrointestinal cancer.

Reduction of cardiovascular complications during delivery hospitalization in patients undergoing bariatric procedures.

BACKGROUND: The global surge in obesity presents a significant health challenge, leading to increased adoption of bariatric surgery as an intervention. However, the correlation between bariatric surgery and cardiovascular outcomes during subsequent pregnancies remains unclear. The aim of our study was to determine the prevalence of cardiovascular complications during delivery hospitalizations in patients with bariatric procedure. METHODS: We performed a retrospective analysis utilizing the National Inpatient Sample database to examine data from delivery admissions of pregnant women with obesity and a history of bariatric surgery. These admissions were identified using International Classification of Diseases (ICD) codes from 2009 to 2019. In comparing pregnant individuals who had undergone bariatric surgery with those with obesity but had no such surgical history, we assessed the prevalence of cardiovascular complications. RESULTS: Our study included 3,027,987 pregnancies in individuals with obesity and an additional 117,350 pregnancies following bariatric surgery. Compared to patients without bariatric surgery, post-surgery patients were older (32.84 years vs 29.02 years), primarily White (59.0%), and mostly treated in large urban hospitals. Cardiovascular outcomes showcased reduced odds of congestive heart failure [Adjusted odds ratios (AOR) 0.11, 95% confidence intervals (CI) 0.01-0.74], gestational hypertensive complications (AOR 0.55, 95% CI 0.53-0.59), and cardiac arrhythmia (AOR 0.76, 95% CI 0.64-0.89) in the post-surgery group, with no significant difference in peripartum cardiomyopathy rates (AOR 0.72, 95% CI 0.29-1.76) and no instances of stroke or acute MI. Perinatally, the surgery cohort had higher odds of preterm birth (AOR 1.30, 95% CI 1.24-1.38) and fetal growth restriction (AOR 2.47, 95% CI 2.32-2.63) but fewer incidents of being large for gestational-age (AOR 0.35, 95% CI 0.32-0.38). As bariatric surgery became increasingly recognized as a significant factor in certain complications, its prevalence among the study population increased from 2009 to 2019. CONCLUSION: In summary, our research indicates that bariatric surgery is associated with a decreased risk of cardiovascular complications during delivery. This study highlights how insights from bariatric surgery outcomes could shape clinical guidelines for managing obesity in pregnant women.

Analyzing the utility of renal replacement therapy to manage hepatorenal syndrome in alcoholic hepatitis without liver transplantation: a nationwide analysis.

BACKGROUND: Hepatorenal syndrome (HRS) frequently complicates alcoholic hepatitis (AH) and portends poor survival in this population. Published literature indicates mixed benefits from renal replacement therapy (RRT) for HRS refractory to medical management. Therefore, we sought to assess the utilization of RRT in AH and clinical outcomes at a national level. METHODS: Using the International Classification of Diseases, Tenth Revision (ICD-10) codes, we identified adult patients with AH with a coexisting diagnosis of HRS from the National Readmission Database 2016 through 2019. Mortality, morbidity, and resource utilization were compared. We compared proportions using the Fisher exact test and computed adjusted P-values based on multivariate regression analysis. Analyses were performed using Stata, version 14.2, considering a two-sided P < 0.05 as statistically significant. RESULTS: A total of 73 203 patients with AH were included in the analysis (mean age 46.2 years). A total of 3620 individuals had HRS diagnosis (5%), of which 14.7% (n: 532) underwent RRT. HRS patients receiving RRT had a higher mortality rate than those who did not (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI]: 1.3-2.6, P: 0.01), along with higher resource utilization. Only those patients with HRS who underwent liver transplantation (LT) experienced a mortality reduction (24.4% for those not receiving RRTs and 36.5% for those receiving RRT). CONCLUSIONS: RRT is associated with higher mortality and morbidity when offered to patients with AH and HRS, who do not undergo LT. Therefore, our results suggest careful selection of AH patients when deciding to initiate RRT for HRS.

Systematic Review With Meta-Analysis: Chronic Opioid Use Is Associated With Esophageal Dysmotility in Symptomatic Patients.

INTRODUCTION: We aimed to conduct a systematic review and meta-analysis to assess the impact of chronic opioid exposure on esophageal motility in patients undergoing manometric evaluation. METHODS: Multiple databases were searched through October 2022 for original studies comparing the manometric results of patients who have used chronic opioids (for >90 days) with those who do not. The primary outcomes were esophageal dysmotility disorders. Three high-resolution manometry parameters were conducted as secondary outcomes. A random-effects model was applied to calculate the odds ratio (OR) and means difference (MD) along with a 95% confidence interval (CI). RESULTS: Nine studies were included in this meta-analysis. Opioid use was associated with higher esophageal dysmotility disorders, including distal esophageal spasm (pooled OR 4.84, 95% CI 1.60-14.63, P = 0.005, I 2 = 96%), esophagogastric junction outflow obstruction (pooled OR 5.13, 95% CI 2.11-12.43, P = 0.0003, I 2 = 93%), and type III achalasia (pooled OR 4.15, 95% CI 2.15-8.03, P < 0.0001, I 2 = 64%). No significant differences were observed for hypercontractile esophagus, type I achalasia, or type II achalasia. The basal lower esophageal sphincter pressure (MD 3.02, 95% CI 1.55-4.50, P < 0.0001, I 2 = 90%), integrated relaxation pressure (MD 2.51, 95% CI 1.56-3.46, P < 0.00001, I 2 = 99%), and distal contractile integral (MD 640.29, 95% CI 469.56-811.03, P < 0.00001, I 2 = 91%) significantly differed between the opioid use and nonopioid use group. However, opioid use was associated with a lower risk of ineffective esophageal motility (pooled OR 0.68, 95% CI 0.49-0.95, P = 0.02, I 2 = 53%). DISCUSSION: Chronic opioid exposure is associated with an increased frequency esophageal dysmotility disorders. Our results revealed that opioid use is significantly associated with type III achalasia but not with type I and II achalasia. Therefore, opioid treatment should be taken into account as a potential underlying risk factor when diagnosing these major esophageal motor abnormalities.

Tip-in Versus Conventional Endoscopic Mucosal Resection for Colorectal Neoplasia: A Systematic Review and Meta-analysis.

BACKGROUND: Early-stage gastrointestinal neoplasms are frequently treated with conventional endoscopic mucosal resection (C-EMR). However, C-EMR frequently leads to incomplete resection of large colorectal lesions. Tip-in endoscopic mucosal resection (EMR), which was recently introduced for en bloc resection of colorectal neoplasms, minimizes slippage during the procedure. METHODS: We conducted a systematic review and meta-analysis of published studies that compared Tip-in EMR with conventional EMR. We searched several electronic databases and included studies that reported on the primary outcomes of en bloc resection rate and complete resection rate, as well as secondary outcomes such as procedure time and procedure-related complications (including perforation and delayed bleeding rate). We used a random effects model to calculate odds ratios (ORs) with 95% CIs for dichotomous data and weighted mean differences with 95% CIs for continuous data. We also conducted several sensitivity analyses to assess the robustness of our findings. RESULTS: A total of 11 studies involving 1244 lesions (684 in the Tip-in EMR group and 560 in C-EMR group) were included in the meta-analysis. Our meta-analysis showed that compared with conventional EMR, Tip-in EMR significantly increased the en bloc resection rate in patients with colorectal neoplasia (OR=3.61; 95% CI, 2.09-6.23; P <0.00001; I2 =0%) and had a higher complete resection rate (OR=2.49; 95% CI, 1.65-3.76; P <0.0001; I2 =0%). However, the procedure time and rates of procedure-related complications did not differ significantly between the 2 groups. CONCLUSIONS: Tip-in EMR outperformed C-EMR for both the en bloc and complete resection of colorectal lesions with similar rates of procedural complications.

Anatomical location, risk factors, and outcomes of lower gastrointestinal bleeding in colorectal cancer patients: a national inpatient sample analysis (2009-2019).

PURPOSE: This study aimed to investigate the incidence, predictors, and impact of lower gastrointestinal bleeding (LGIB) on inpatient mortality among colorectal cancer patients, due to its clinical significance and potential influence on patient outcomes. METHODS: We conducted a retrospective analysis of data from the National Inpatient Sample database between 2009 and 2019, including 2,598,326 colorectal cancer patients with and without LGIB. Univariate and multivariate logistic regression analyses were performed to determine predictors of LGIB and its association with inpatient outcomes. RESULTS: The highest incidence of LGIB was observed in rectal cancer patients (3.8%), followed by distal colon cancer patients (1.4%) and proximal colon cancer patients (1.2%). Several factors were significantly associated with LGIB, including older age; male sex; certain racial such as Black, Hispanic, and Asia/Pacific Islander patients; or lower socioeconomic status. Multivariate analysis identified independent predictors of LGIB, such as severe sepsis, use of anticoagulants, long-term use of aspirin or antiplatelet drugs, palliative care, malnutrition, cachexia, chemotherapy or immunotherapy, metastasis, alcohol abuse, hypertension, obesity, and family history of digestive cancer. No significant difference in inpatient mortality was observed between patients with and without LGIB. CONCLUSION: Our study underscores the importance of considering colorectal cancer location and identified risk factors for LGIB assessment. Clinicians should address modifiable risk factors and healthcare disparities. Future research should explore underlying mechanisms, targeted interventions, and long-term outcomes beyond inpatient mortality.

Systematic review and meta-analysis of cold snare polypectomy and hot snare polypectomy for colorectal polyps.

BACKGROUND AND AIM: Cold snare polypectomy (CSP) has become increasingly utilized to resect colorectal polyps, given its efficacy and safety. This study aims to compare CSP and hot snare polypectomy (HSP) for resecting small (< 10 mm) and large (10-20 mm) colorectal lesions. METHODS: Relevant publications were obtained from Cochrane Library, Embase, Google Scholar, PubMed, and Web of Science databases. The publication search was limited by English-language and human studies. Pooled mean difference and odds ratios (ORs) were calculated for outcomes of interest. RESULTS: Twenty-three studies were included in this meta-analysis. Pooled OR of delayed post-polypectomy bleeding (DPPB) in the CSP group versus the HSP group was 0.29 (P = 0.0001, I2  = 29%). Subgroup analysis according to lesion size showed a significant reduction in the DPPB rate in lesion sizes 10-20 mm (pooled OR 0.08, P = 0.003, I2  = 0%) and < 10 mm (pooled OR 0.35, P = 0.001, I2  = 27%). Pooled OR of major bleeding in the CSP group was 0.23 (P = 0.0004, I2  = 0%). Subgroup analysis by lesion size revealed a significant decrease in the rate of major bleeding in the CSP group for both lesion sizes 10-20 mm (pooled OR 0.11, P = 0.04) and < 10 mm (pooled OR 0.26, P = 0.003). Complete resection, en bloc resection, and recurrence rate were comparable in the two groups. CONCLUSIONS: Cold snare polypectomy was associated with a lower rate of DPPB and lower risk of major bleeding compared with HSP in both small and large polyps. CSP should be considered as the polypectomy technique of choice for colorectal polyps.

ß-Ecdysterone protects SH-SY5Y cells against ß-amyloid-induced apoptosis via c-Jun N-terminal kinase- and Akt-associated complementary pathways.

Recently, the significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to the loss of neuroprotective estrogen after menopause. Does phytoestrogen have the ability to protect against amyloid-ß (Aß) toxicity? The aim of this study was to evaluate hypothesis that ß-ecdysterone (ß-Ecd) protects SH-SY5Y cells from Aß-induced apoptosis by separate signaling pathways involving protein kinase B (Akt) and c-Jun N-terminal kinase (JNK). Here, we demonstrate that phytoestrogen ß-Ecd inhibits Aß-triggered mitochondrial apoptotic pathway, as indicated by Bcl-2/Bax ratio elevation, cytochrome c (cyt c) release reduction, and caspase-9 inactivation. Interestingly, ß-Ecd upregulates Bcl-2 expression in SH-SY5Y cells under both basal and Aß-challenged conditions, but downregulates Bax expression only in Aß-challenged conditions. Subsequently, Akt-dependent NF-κB activation is required for Bcl-2 upregulation, but not Bax downregulation, in response to ß-Ecd, which was validated by the use of LY294002 and Bay11-7082. Notably, ß-Ecd attenuates the Aß-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and JNK activation without altering the basal ASK1 phosphorylation and JNK activation. ROS-scavenging by diphenyleneiodonium (DPI) abrogated the ability of ß-Ecd to alter the activation of ASK1. Simultaneously, inhibition of JNK by SP600125 abolished ß-Ecd-induced Bax downregulation in Aß-challenged SH-SY5Y cells, whereas LY294002 failed to do so. Consequently, ß-Ecd possesses neuroprotection by different and complementary pathways, which together promote a Bcl-2/Bax ratio. These data support our hypothesis and suggest that ß-Ecd is a promising candidate for the treatment of AD.

Emodin suppresses activation of hepatic stellate cells through p38 mitogen-activated protein kinase and Smad signaling pathways in vitro.

The aim of this study was to evaluate the hypothesis that emodin inhibits extracellular matrix (ECM)-related gene expression in activated hepatic stellate cells (HSCs) by blocking canonical or/and noncanonical components of transforming growth factor ß1 (TGFß1) intracellular signaling. Here, we demonstrate that emodin suppressed the gene expression of HSCs activation markers type I collagen, fibronectin, and α-smooth muscle actin, as well as HSCs proliferation. Mechanistically, emodin suppresses TGFß1, TGFß receptor II, TGFß receptor I, and Smad4 gene expression, as well as Smad luciferase activity. Simultaneously, emodin reduced p38 mitogen-activated protein kinase (p38MAPK ) activity but not c-Jun N-terminal kinases and extracellular signal-regulated kinases 1 and 2 phosphorylation in HSC-T6 cells. Interestingly, deprivation of TGFß using a neutralizing antibody abolished emodin-mediated inhibitions of the both Smad transcriptional activity and p38MAPK phosphorylation. Furthermore, emodin-mediated inhibition of HSCs activation could be partially blocked by PD98059 inhibition of p38MAPK or short hairpin RNA-imposed knockdown of Smad4. Conversely, simultaneous inhibition of Smad4 and p38MAPK pathways completely reverses the effects of emodin, suggesting that Smad and p38MAPK locate downstream of TGFß1 and regulate collagen genes expression in HSCs. Collectively, these data suggest that emodin is a promising candidate for the treatment of hepatic fibrosis.

Natural polyphenol: Their pathogenesis-targeting therapeutic potential in Alzheimer's disease.

Alzheimer's disease (AD) is a detrimental neurodegenerative disease affecting the elderly. Clinically, it is characterized by progressive memory decline and subsequent loss of broader cognitive functions. Current drugs provide only symptomatic relief but do not have profound disease-modifying effects. There is an unmet need to identify novel pharmacological agents for AD therapy. Neuropathologically, the characteristic hallmarks of the disease are extracellular senile plaques containing amyloid ß-peptides and intracellular neurofibrillary tangles containing hyperphosphorylated microtubule-associated protein tau. Simultaneously, oxidative stress, neuroinflammation and mitochondrial dysfunction in specific brain regions are early events during the process of AD pathologic changes and are associated with Aß/tau toxicity. Here, we first summarized probable pathogenic mechanisms leading to neurodegeneration and hopefully identify pathways that serve as specific targets to improve therapy for AD. We then reviewed the mechanisms that underlie disease-modifying effects of natural polyphenols, with a focus on nuclear factor erythroid 2-related factor 2 activators for AD treatment. Lastly, we discussed challenges in the preclinical to clinical translation of natural polyphenols. In conclusion, there is evidence that natural polyphenols can be therapeutically useful in AD through their multifaceted mechanism of action. However, more clinical studies are needed to confirm these effects.

Liver cancer wars: plant-derived polyphenols strike back.

Liver cancer currently represents the leading cause of cancer-related death worldwide. The majority of liver cancer arises in the context of chronic inflammation and cirrhosis. Surgery, radiation therapy, and chemotherapy have been the guideline-recommended treatment options for decades. Despite enormous advances in the field of liver cancer therapy, an effective cure is yet to be found. Plant-derived polyphenols constitute a large family of phytochemicals, with pleiotropic effects and little toxicity. They can drive cellular events and modify multiple signaling pathways which involves initiation, progression and metastasis of liver cancer and play an important role in contributing to anti-liver cancer drug development. The potential of plant-derived polyphenols for treating liver cancer has gained attention from research clinicians and pharmaceutical scientists worldwide in the last decades. This review overviews hepatic carcinogenesis and briefly discusses anti-liver cancer mechanisms associated with plant-derived polyphenols, specifically involving cell proliferation, apoptosis, autophagy, angiogenesis, oxidative stress, inflammation, and metastasis. We focus on plant-derived polyphenols with experiment-based chemopreventive and chemotherapeutic properties against liver cancer and generalize their basic molecular mechanisms of action. We also discuss potential opportunities and challenges in translating plant-derived polyphenols from preclinical success into clinical applications.

Harnessing Plant Flavonoids to Fight Pancreatic Cancer.

PURPOSE OF REVIEW: This review draws on the last fifteen years (2009-2024) of published data to summarize the potential effect of plant flavonoids on pancreatic carcinogenesis and discuss the possible mechanisms of action to establish their applicability as anti-cancer agents. RECENT FINDINGS: This review found that the plant flavonoids with anti-pancreatic cancer activity mainly include chalcones, dihydrochalcones, flavanols, flavanones, flavones, isoflavonoids, flavonols, isoflavones, and flavanonols. Most of these flavonoids have anti-proliferative, pro-apoptotic, cell cycle arrest, anti-angiogenic, anti-inflammatory, anti-epithelial-mesenchymal transition, and anti-metastatic properties. Some flavonoids can also regulate autophagy, immune and glucose uptake in the context of pancreatic cancer. Several molecules and signaling pathways are associated with the pharmacological activities of plant flavonoids, including AMP-activated protein kinase, mitogen-activated protein kinases, phosphatidylinositol-3-kinase/protein kinase B, nuclear factor-κB, signal transducer, and activator of transcription 3, Smad3, epidermal growth factor receptor, and vascular endothelial growth factor. This review provides strong evidence that plant flavonoids have potential against pancreatic carcinogenesis in experimental animals through various pharmacological mechanisms. They are a promising resource for use as adjuvant anti-cancer therapy. However, randomized controlled clinical trials with those flavonoids are needed.

Comparative effectiveness of immunotherapy and chemotherapy in patients with metastatic colorectal cancer stratified by microsatellite instability status.

BACKGROUND: Immunotherapy have demonstrated promising outcomes in patients with high microsatellite instability (MSI) (MSI-H) metastatic colorectal cancer. However, the comparative effectiveness of Immunotherapy and chemotherapy for patients with low MSI (MSI-L), and microsatellite stable (MSS) metastatic colorectal cancer remains unclear. AIM: To investigate immunotherapy vs chemotherapy for treatment of MSI-L/MSS metastatic colorectal cancer, and to evaluate the success of immunotherapy against chemotherapy in managing MSI-H metastatic colorectal cancer during a follow-up of 50 months. METHODS: We conducted a retrospective cohort study using the National Cancer Database (NCDB) to evaluate the overall survival (OS) of patients with metastatic colorectal cancer treated with immunotherapy or chemotherapy. The study population was stratified by MSI status (MSI-H, MSI-L, and MSS). Multivariable Cox proportional hazard models were used to assess the association between treatment modality and OS, adjusting for potential confounders. RESULTS: A total of 21951 patients with metastatic colorectal cancer were included in the analysis, of which 2358 were MSI-H, and 19593 were MSI-L/MSS. In the MSI-H cohort, immunotherapy treatment (n = 142) was associated with a significantly improved median OS compared to chemotherapy (n = 860). After adjusting for potential confounders, immunotherapy treatment remained significantly associated with better OS in the MSI-H cohort [adjusted hazard ratio (aHR): 0.57, 95% confidence interval (95%CI): 0.43-0.77, P < 0.001]. In the MSS cohort, no significant difference in median OS was observed between immunotherapy treatment and chemotherapy (aHR: 0.94, 95%CI: 0.69-1.29, P = 0.715). CONCLUSION: In this population-based study using the NCDB, immunotherapy treatment was associated with significantly improved OS compared to chemotherapy in patients with MSI-H metastatic colorectal cancer, but not in those with MSI-L/MSS metastatic colorectal cancer. Further studies are warranted to determine the optimal therapeutic approach for patients with MSI-L/MSS metastatic colorectal cancer.

Cardiovascular complications during delivery hospitalizations in inflammatory bowel disease patients.

BACKGROUND: The relationship between inflammatory bowel disease (IBD) and cardiovascular outcomes among pregnant women has yet to be thoroughly investigated. Our aim is to assess the odds of cardiovascular disease and cardiac arrhythmias during hospital admissions for delivery and identify contributing factors associated with cardiovascular complications in pregnant women with IBD. METHODS: We performed a retrospective analysis of data from the National Inpatient Sample, obtained from delivery admissions of pregnant women with and without IBD, identified via International Classification of Diseases codes, from 2009 to 2019. Using a regression model, we compared the odds of cardiovascular complications between these two groups, adjusting for traditional cardiovascular risk factors as confounding variables. RESULTS: Our study included 71,361 pregnancies with IBD and 41,117,443 pregnancies without this condition. The incidence of IBD in pregnancy rose near three-fold increase over the decade. In comparison to pregnancies without IBD, those involving pregnant patients with IBD exhibited an increased likelihood of encountering cardiovascular complications, with an adjusted odds ratio (AOR) of 1.37 (95% CI, 1.29-1.46). This heightened risk encompasses a range of conditions, including peripartum cardiomyopathy (AOR, 9.45; 95% CI, 3.86-23.15), cardiac arrhythmias (AOR, 2.03; 95% CI, 1.59-2.60), and hypertensive disorders of pregnancy (AOR, 1.51; 95% CI, 1.37-1.66), notably preeclampsia, eclampsia, and the syndrome of hemolysis, elevated liver enzymes, and low platelet count (HELLP syndrome). Pregnancies with IBD were also associated with three-fold higher odds of venous thromboembolism (AOR, 3.91; 95% CI, 1.45-10.48). CONCLUSIONS: Pregnant patients with IBD had an increased odds of cardiovascular complications during delivery admissions, independent of traditional cardiovascular risk factors. Further research is needed to elucidate the underlying mechanisms and develop targeted prevention strategies for this high-risk population.

Cardiovascular complications during delivery hospitalizations in patients with nonalcoholic fatty liver disease in pregnancy.

OBJECTIVE: While the association between metabolic dysfunction-associated steatotic liver disease (MASLD) and long-term cardiovascular risks has been studied, the impact of MASLD on cardiovascular events during delivery hospitalizations remains relatively unexplored. This study aims to examine the prevalence of cardiovascular diseases (CVDs) and cardiac arrhythmias in pregnant patients with MASLD and identify potential risk factors. METHODS: A retrospective analysis of hospital discharge records from the National Inpatient Sample database between 2009 and 2019 was conducted to assess maternal cardiovascular outcomes. Multivariable logistic regression models were employed, and adjusted odds ratios (AOR) were calculated to evaluate the association between MASLD and cardiovascular outcomes during pregnancy. RESULTS: The study sample included 17 593 pregnancies with MASLD and 41 171 211 pregnancies without this condition. Women with MASLD exhibited an increased risk of congestive heart failure [AOR 3.45, 95% confidence interval (CI) 1.04-11.43], cardiac arrhythmia (AOR 2.60, 95% CI 1.94-3.49), and gestational hypertensive complications (AOR 3.30, 95% CI 2.93-3.72). Pregnancies with MASLD were also associated with a higher rate of pulmonary edema (AOR 3.30, 95% CI 1.60-6.81). CONCLUSION: MASLD is an independent risk factor for cardiovascular complications during delivery hospitalizations, emphasizing the necessity for prepregnancy screening and targeted prevention strategies to manage CVD risks in expectant patients with MASLD.

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease: A systematic review and meta-analysis.

Background and study aims Gastroesophageal reflux disease (GERD) is a widespread chronic gastrointestinal condition with an increasing worldwide prevalence. This research was a systematic review and meta-analysis evaluating the efficacy, safety, and long-term outcomes of endoscopic full-thickness plication (EFTP) for the treatment of GERD. Methods A comprehensive search of databases was conducted for studies published up to April 2023. We included randomized controlled trials (RCTs) and prospective observational studies that examined the use of EFTP in treating GERD among adult patients. We calculated pooled effect estimates using a random-effects model. Results EFTP significantly improved GERD Health-Related Quality of Life (GERD-HRQL) scores at 3-, 6-, and 12-month follow-up intervals. A considerable proportion of patients discontinued proton pump inhibitors, with cessation rates of 59% (95% confidence interval [CI]: 0.47-0.71), 68% (95% CI: 0.58-0.78), and 67% (95% CI: 0.46-0.89,) at 3, 6, and 12 months, respectively. At 3 and 6 months, 61% (95% CI: 0.54-0.68) and 66% (95% CI: 0.56-0.76) of patients experienced ≥50% improvement in GERD-HRQL scores. EFTP demonstrated a favorable safety profile, with a low rate of severe adverse events. We observed a 6.76% reduction (95% CI: -14.53-1.02) in the percentage of time with esophageal pH <4, a decrease in DeMeester scores, and fewer total reflux episodes. The average procedure time was 22.75 minutes (95% CI: 22.03-23.48). Subgroup analyses suggest that both the GERDx system and the NDO Plicator are effective and safe in treating GERD. Conclusions The findings from our study reveal that EFTP is a safe and effective treatment for GERD patients who have not responded adequately to conventional therapies. Given its minimally invasive nature, effectiveness, and limited adverse effects, EFTP emerges as a compelling alternative to conventional surgical procedures.

Systematic Review with Meta-analysis: Efficacy and Safety of Upadacitinib in Managing Moderate-to-Severe Crohn's Disease and Ulcerative Colitis.

BACKGROUND: In the panorama of therapeutic strategies for inflammatory bowel diseases, oral upadacitinib stands out for its potential to improve short-term and long-term patient outcomes. OBJECTIVE: This meta-analysis aspires to collate and assess the available evidence regarding the efficacy and safety of upadacitinib in managing moderate-to-severe Crohn's disease and ulcerative colitis. METHODS: A meta-analysis was conducted using studies sourced from MEDLINE/PubMed, Cochrane Library, Scopus, and Embase, published from January 2010 to March 2024. Peer-reviewed articles that reported data on the effects of upadacitinib in adult patients with Crohn's disease and ulcerative colitis were included based on established inclusion and exclusion criteria. RESULTS: Eight studies, encompassing a total of 2818 patients treated with upadacitinib, were included. In primary outcomes, for patients with Crohn's disease who were using upadacitinib, the weighted pooled clinical remission rate was found to be 45.8% (95% confidence interval [CI] 0.39-0.52), while for patients with ulcerative colitis who were using upadacitinib, the rate was 25.4% (95% CI 0.17-0.36). The pooled clinical response rate for Crohn's disease was 53.6% (95% CI 0.50-0.57), and for ulcerative colitis it was 72.6% (95% CI 0.69-0.76). The pooled serious adverse event rate was 6.0% (95% CI 0.07-0.09). CONCLUSIONS: Upadacitinib demonstrates significant efficacy in achieving clinical remission and response in patients with moderate-to-severe Crohn's disease and ulcerative colitis, as shown by clinical remission rates of 44.9% and 36.0%, respectively. The treatment also maintains a favorable safety profile with a serious adverse event rate of 7.8%, making it an effective option for those resistant or intolerant to traditional immunosuppressants or tumor necrosis factor antagonists.

Higher body mass index is strongly linked to poor outcomes in adult COVID-19 hospitalizations: A National Inpatient Sample Study.

Aims: The coronavirus disease 2019 (COVID-19) pandemic has resulted in more than 6 million deaths worldwide. Studies on the impact of obesity on patients hospitalized with COVID-19 pneumonia have been conflicting, with some studies describing worse outcomes in patients with obesity, while other studies reporting no difference in outcomes. Previous studies on obesity and critical illness have described improved outcomes in patients with obesity, termed the "obesity paradox." The study assessed the impact of obesity on the outcomes of COVID-19 hospitalizations, using a nationally representative database. Materials and Methods: ICD-10 code U071 was used to identify all hospitalizations with the principal diagnosis of COVID-19 infection in the National Inpatient Database 2020. ICD-10 codes were used to identify outcomes and comorbidities. Hospitalizations were grouped based on body mass index (BMI). Multivariable logistic regression was used to adjust for demographic characteristics and comorbidities. Results: A total of 56,033 hospitalizations were identified. 48% were male, 49% were white and 22% were black. Patients hospitalized with COVID-19 pneumonia in the setting of obesity and clinically severe obesity were often younger. Adjusted for differences in comorbidities, there was a significant increase in mortality, incidence of mechanical ventilation, shock, and sepsis with increased BMI. The mortality was highest among hospitalizations with BMI ≥60, with an adjusted odds ratio of 2.66 (95% Confidence interval 2.18-3.24) compared to hospitalizations with normal BMI. There were increased odds of mechanical ventilation across all BMI groups above normal, with the odds of mechanical ventilation increasing with increasing BMI. Conclusion: The results show that obesity is independently associated with worse patient outcomes in COVID-19 hospitalizations and is associated with higher in-patient mortality and higher rates of mechanical ventilation. The underlying mechanism of this is unclear, and further studies are needed to investigate the cause of this.

Lead toxicity and potential therapeutic effect of plant-derived polyphenols.

BACKGROUND: Due to its unique physical and chemical properties, lead is still used worldwide in several applications, especially in industry. Both environmental and industrial lead exposures remain a public health problem in many developing and rapidly industrializing countries. Plant polyphenols are pleiotropic in their function and have historically made a major contribution to pharmacotherapy. PURPOSE: To summarize available pre-clinical and limited clinical evidence on plant polyphenols as potential antidotes against lead poisoning and discuss toxic mechanisms of lead. METHOD: A comprehensive search of peer-reviewed publications was performed from core collections of electronic databases such as PubMed, Web of Science, Google Scholar, and Science Direct. Articles written in English-language from inception until December 2022 were selected. RESULTS: In this review, we review key toxic mechanisms of lead and its pathological effects on the neurological, reproductive, renal, cardiovascular, hematological, and hepatic systems. We focus on plant polyphenols against lead toxicity and involved mechanisms. Finally, we address scientific gaps and challenges associated with translating these promising preclinical discoveries into effective clinical therapies. CONCLUSION: While preclinical evidence suggests that plant polyphenols exhibit bioprotective effects against lead toxicity, scant and equivocal clinical data highlight a need for clinical trials with those polyphenols.