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.

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.

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.

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.

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.

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.

Greasing the Wheels of Pharmacotherapy for Colorectal Cancer: the Role of Natural Polyphenols.

PURPOSE OF REVIEW: The main purpose of this review, mainly based on preclinical studies, is to summarize the pharmacological and biochemical evidence regarding natural polyphenols against colorectal cancer and highlight areas that require future research. RECENT FINDINGS: Typically, colorectal cancer is a potentially preventable and curable cancer arising from benign precancerous polyps found in the colon's inner lining. Colorectal cancer is the third most common cancer, with a lifetime risk of approximately 4 to 5%. Genetic background and environmental factors play major roles in the pathogenesis of colorectal cancer. Theoretically, a multistep process of colorectal carcinogenesis provides enough time for anti-tumor pharmacotherapy of colorectal cancer. Chronic colonic inflammation, oxidative stress, and gut microbiota imbalance have been found to increase the risk for colorectal cancer development by creating genotoxic stress within the intestinal environment to generate genetic mutations and epigenetic modifications. Currently, numerous natural polyphenols have shown anti-tumor properties against colorectal cancer in preclinical research, especially in colorectal cancer cell lines. In this review, the current literature regarding the etiology and epidemiology of colorectal cancer is briefly outlined. We highlight the findings of natural polyphenols in colorectal cancer from in vitro and in vivo studies. The scarcity of human trials data undermines the clinical use of natural polyphenols as anti-colorectal cancer agents, which should be undertaken in the future.

Pulmonary Vasodilator Therapy in Severe Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (Severe PH-COPD): A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease-associated pulmonary hypertension (PH-COPD) results in a significant impact on symptoms, quality of life, and survival. There is scant and conflicting evidence about the use of pulmonary hypertension (PH) specific therapy in patients with PH-COPD. Study Design and Methods: PubMed, OVID, CINAHL, Cochrane, Embase, and Web of Science were searched using various MESH terms to identify randomized controlled trials (RCTs) or observational studies investigating PH-specific therapies in patients with severe PH-COPD, defined by mean pulmonary artery pressure (mPAP) of more than 35 mm Hg or pulmonary vascular resistance (PVR) of more than 5 woods units on right heart catheterization. The primary outcome was a change in mPAP and PVR. Secondary outcomes were changes in six-minute walk distance (6MWD), changes in the brain-natriuretic peptide (BNP), New York Heart Association (NYHA) functional class, oxygenation, and survival. Results: Thirteen studies satisfied the inclusion criteria, including a total of 328 patients with severe PH-COPD. Out of these, 308 patients received some type of specific therapy for PH. There was a significant reduction in mPAP (mean difference (MD) -3.68, 95% CI [-2.03, -5.32], p < 0.0001) and PVR (MD -1.40 Wood units, 95% CI [-1.97, -0.82], p < 0.00001). There was a significant increase in the cardiac index as well (MD 0.26 L/min/m2, 95% CI [0.14, 0.39], p < 0.0001). There were fewer patients who had NYHA class III/lV symptoms, with an odds ratio of 0.55 (95% CI [0.30, 1.01], p = 0.05). There was no significant difference in the 6MWD (12.62 m, 95% CI [-8.55, 33.79], p = 0.24), PaO2 (MD -2.20 mm Hg, 95% CI [-4.62, 0.22], p = 0.08), or BNP or NT-proBNP therapy (MD -0.15, 95% CI [-0.46, 0.17], p = 0.36). Conclusion: The use of PH-specific therapies in severe PH-COPD resulted in a significant reduction in mPAP and PVR and increased CI, with fewer patients remaining in NYHA functional class III/IV. However, no significant difference in the 6MWD, biomarkers of right ventricular dysfunction, or oxygenation was identified, demonstrating a lack of hypoxemia worsening with treatment. Further studies are needed to investigate the use of PH medications in patients with severe PH-COPD.

The Impact of Traction Methods on Endoscopic Submucosal Dissection Efficacy for Gastric Neoplasia: A Systematic Review and Meta-analysis.

BACKGROUND: Endoscopic submucosal dissection (ESD) for gastric neoplasms can be challenging due to limited traction and visualization. The efficacy of traction-assisted endoscopic submucosal dissection (TA-ESD) continues to require additional validation. This study aims to explore the safety and efficiency of TA-ESD for early gastric neoplasms located at varying sites, in comparison with conventional endoscopic submucosal dissection (C-ESD). METHODS: We conducted a comprehensive literature search using databases up until August 2022. The outcome measures procedure time, en bloc resection rate, complete resection rate, procedure time, and procedure-related adverse event rate. We calculated pooled mean differences (MDs) and odds ratios (ORs) for these outcomes. RESULTS: The mean procedure time was significantly shorter in the TA-ESD group compared to the C-ESD group (MD - 14.9, 95% CI - 21.78 to - 8.03, I2 = 83%, p < 0.0001). Subgroup analysis revealed that mean procedure times for lesions on the greater curvature and upper/middle of the stomach were significantly shorter in the TA-ESD group - 19.2 min (95% CI - 27.75 to - 10.65, I2 = 12%, p < 0.0001) and - 7.35 min (95% CI - 35.4 to - 1.15, p = 0.04), respectively. The en bloc resection and complete resection rates were comparable between the two groups. The rate of perforation was significantly lower in the TA-ESD group than in the C-ESD group (OR 0.36, 95% CI 0.15-0.85, p = 0.02, I2 = 0%). CONCLUSIONS: This study demonstrates the potential benefits of TA-ESD over C-ESD in treating patients with early-stage gastric tumors, highlighting its safety and efficacy. The findings indicate a significant reduction in procedure times at challenging stomach sites with TA-ESD in comparison to C-ESD.

Maternal and fetal outcomes of acute pancreatitis in pregnancy: a population-based study.

BACKGROUND: Acute pancreatitis during pregnancy can have negative effects on both the mother and the fetus. The primary aim of this study is to evaluate the trends, maternal and fetal outcomes, and associated comorbidities of acute pancreatitis during pregnancy using data from the USA National Inpatient Sample (NIS) database. METHODS: This study is a retrospective analysis of hospital discharge records from the NIS database from 2009 to 2019. RESULTS: Delivery patients with acute pancreatitis faced a higher risk of maternal mortality (AOR 91.02, 95% CI 28.47-291.06), postpartum hemorrhage (AOR 1.59, 95% CI 1.02-2.49), and hypertensive complications (defined as preeclampsia, eclampsia, or HELLP syndrome) (AOR 3.42, 95% CI 2.56-4.56) compared to those without acute pancreatitis. Moreover, we saw an increased incidence of preterm labor (AOR 3.94, 95% CI 3.02-5.12) and fetal death (AOR 3.12, 95% CI 1.76-5.53). Rates of fetal restriction and large fetal size were comparable. Additionally, the acute pancreatitis group showed higher rates of acute kidney injury (4.2% vs. 0.06%; AOR, 31.02, 95% CI 12.50-76.98), severe sepsis (0.8% vs. 0.01%; AOR, 34.49, 95% CI 7.67-155.14), and respiratory failure (2.4% vs. 0.06%; AOR, 20.77, 95% CI (8.55-50.41). There were no significant differences in maternal and perinatal outcomes in biliary pancreatitis after the intervention compared to conservative treatment. CONCLUSION: Acute pancreatitis during pregnancy can have negative effects on both the mother and fetus. Treatment for biliary pancreatitis does not affect maternal and fetal outcomes. An interdisciplinary approach is essential to ensure optimal outcomes for mothers and their offspring in these cases.

Maternal and prenatal outcomes of hemochromatosis in pregnancy: A population-based study.

BACKGROUND: This retrospective study investigated the impact of hemochromatosis on maternal and perinatal outcomes among delivery hospitalizations in the United States between 2010 and 2019, revealing notable trends and associations. METHODS: Utilizing data from over 36 million delivery hospitalizations, we conducted a comprehensive analysis, focusing on maternal complications, perinatal outcomes, and healthcare utilization among women with hemochromatosis compared to those without. RESULTS: Women with hemochromatosis exhibited a longer length of hospital stay (3.27 ± 0.20 days vs. 2.64 ± 0.04 days) and higher total hospital charges ($21,789.66 ± $1124.41 vs. $17,751.63 ± $97.71) compared to those without the condition. There was a significant increase in the prevalence of hemochromatosis among delivery hospitalizations over the studied period, from 1.91 per 100,000 hospitalizations to 8.65 cases per 100,000 hospitalizations. Hemochromatosis patients demonstrated a higher prevalence of hypertensive disorders of pregnancy (aOR: 1.50, 95 % CI: 1.03-2.19) and VTE(aOR: 20.35, 95 % CI: 5.05-82.05).There were no statistically significant differences in rates of peripartum hemorrhage, C-section, preterm birth, fetal growth restriction, large for gestational age infants, and fetal death between the two groups. CONCLUSIONS: Our findings underscore higher hypertensive disorders of pregnancy and VTE among women with hemochromatosis, despite unaffected perinatal outcomes. An increasing trend in hemochromatosis prevalence highlights the need for targeted interventions and cost-effective management strategies. Future research is needed to explore potential racial disparities and understand the rising incidence of hemochromatosis among pregnant women.

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.

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.

Maternal and perinatal outcomes of pregnant patients with colorectal cancer: a population-based study.

PURPOSE: This study aimed to investigate the maternal and perinatal outcomes of pregnant patients with CRC using a large population-based database. METHODS: A retrospective cohort study was conducted using the Nationwide Inpatient Sample (NIS) from 2009 to 2019. Pregnant patients with and without CRC were compared for demographic characteristics, comorbidities, maternal and perinatal outcomes, and hospital burden. RESULTS: The study included 306 pregnancies with CRC and 40,887,353 pregnancies without CRC. Pregnant patients with CRC were older and more likely to be White. A significant association was observed between CRC and a history of inflammatory bowel disease or a family history of gastrointestinal cancer. Pregnant patients with CRC had higher odds of maternal death (AOR 260.99, 95% CI 33.36-2041.64), cardiac arrhythmia (AOR 13.73, 95% CI 4.21-44.76), acute kidney injury (AOR 32.6, 95% CI 5.29-200.77), severe sepsis (AOR 163.98, 95% CI 22.05-1219.65), and respiratory failure (AOR 31.67, 95% CI 4.11-243.98). Furthermore, the CRC group experienced higher odds of cesarean section (AOR 1.78, 95% CI 1.05-3.03), preterm birth (AOR 4.16, 95% CI 2.05-8.47), and intrauterine death (AOR 13.18, 95% CI 3.33-52.16). Distinct differences in maternal and perinatal outcomes were observed based on the location of CRC. Pregnant patients with CRC faced higher hospital charges and had longer hospital stays during delivery hospitalization compared to those without CRC. CONCLUSION: Pregnant patients with CRC are at increased risk for adverse maternal and perinatal outcomes, emphasizing the importance of early detection, timely intervention, and comprehensive management during pregnancy.

The hidden dangers of chronic pancreatitis in pregnancy: Evidence from a large-scale population study.

BACKGROUND: Chronic pancreatitis is a debilitating condition that can affect women of childbearing age, and its impact on maternal and perinatal outcomes is poorly understood. AIMS: Our findings aim to help healthcare providers counsel pregnant women with chronic pancreatitis and make informed clinical decisions. METHODS: In this study, hospital discharge records from the National Inpatient Sample database between 2009 and 2019 were retrospectively analyzed to investigate maternal primary outcomes and primary perinatal outcomes. RESULTS: The study findings suggest an association between chronic pancreatitis and elevated rates of gestational diabetes (AOR 1.63, 95% CI 1.19-2.23) and gestational hypertensive complications(AOR 2.48, 95% CI 1.87-3.29). Pregnancies among women with chronic pancreatitis showed an increased likelihood of preterm labor (AOR 3.10, 95% CI 2.40-4.00) and small for gestational age (AOR 2.40, 95% CI 1.35-3.08). Furthermore, it appears that patients with alcohol-induced chronic pancreatitis present a considerably higher risk of fetal death (OR 17.15, 95% CI 2.29-128.26). The study also revealed that those chronic pancreatitis patients with a history of chronic renal failure could be more prone to developing gestational hypertensive complications (OR 20.09, 95%CI 2.07-194.93). Moreover, associations were observed between chronic pancreatitis pregnancies and lengthier hospital stays as well as elevated hospital costs. CONCLUSIONS: Our research has uncovered a heightened risk of complications associated with chronic pancreatitis for mothers and fetuses. The implications of our findings are critical for healthcare professionals, particularly those involved in preconception counseling.

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.

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.

Infectious Complications After Tocilizumab in Patients with COVID: A Real-World Experience.

Introduction: Controversies remain regarding the safety of tocilizumab in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this study, we seek to describe the infectious complications after tocilizumab in COVID patients and determine the related risk factors. Methods: A single-center retrospective observational study was conducted among adult patients with SARS-CoV-2 infection admitted between 06/01/2020 and 12/31/2021 who received tocilizumab at our institution. Baseline demographics and laboratory values are obtained through reviewing electronic medical records. Risk factors of infectious complications after tocilizumab are identified through regression analysis. Statistics are performed using SPSS. P-value <0.05 is considered statistically significant. Results: Out of the 52 patients identified, infectious complications after tocilizumab were documented in 30 patients (57.7%). The most common infections include pneumonia, urinary tract infections, and bacteremia of unknown sources. Overall mortality was 42.3%. Through multivariate regression analysis, age more than 65, hyperglycemia on admission, and tocilizumab administration more than 2 days after hospital admission are independent risk factors associated with developing infections. Conclusions: In real-world experience, infectious complications are not uncommon in COVID patients who receive tocilizumab. Early use of tocilizumab may be of benefit. More rigorous patient selection and monitoring should be explored in future studies.