Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database.

BACKGROUND: The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research. METHODS: Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50 years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software. RESULTS: Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49 years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men. CONCLUSION: The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.

The role of Cardiotrophin-1 and echocardiography in early detection of subclinical diabetic cardiomyopathy in children and adolescents with type 1 diabetes mellitus.

OBJECTIVES: To assess the role of Cardiotrophin-1 (CT-1) and echocardiography in early detection of subclinical Diabetic Cardiomyopathy (DCM) in children with type 1 Diabetes Mellitus (T1D). METHODS: This case-control study included two groups of children and adolescents aged between 7 and 18. Group (1) included forty patients with T1D (duration > 5 years) regularly followed at the children's hospital of Cairo University, and Group (2) included forty age and sex-matched healthy subjects as a control group. The serum level of CT-1 was measured, and conventional echocardiography, tissue Doppler imaging (TDI), and 2D speckle tracking echocardiography were performed. RESULTS: The level of CT-1 in the cases ranged from 11 to 1039.4 pg/ml with a median (IQR) of 19.4 (16.60-25.7) pg/ml, while its level in the control group ranged from 10.8 to 162.6 pg/ml with a median (IQR) of 20.2 (16.2-24.8) pg/ml. CT-1 levels showed no statistically significant difference between cases and controls. Patients had significantly higher mean left ventricle E/E' ratio (p<0.001), lower mean 2D global longitudinal strain (GLS) of the left ventricle (LV) (p<0.001), and lower mean GLS of the right ventricle (RV) (p<0.001) compared to controls. Ofpatients with diabetes, 75 % had LV diastolic dysfunction, 85 % had RV diastolic dysfunction, 97.5 % had LV systolic dysfunction, and 100 % had RV systolic dysfunction. CONCLUSIONS: Non-conventional echocardiography is important for early perception of subclinical DCM in patients with T1D. CT-1 was not specific for early detection of DCM.

Effect of Pemafibrate on the Lipid Profile, Liver Function, and Liver Fibrosis Among Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are prevalent conditions linked to obesity and metabolic disturbances, with potential complications such as cirrhosis and cardiovascular risks. This systematic review and meta-analysis aimed to evaluate the efficacy of pemafibrate, a drug targeting fat and sugar metabolism genes, in treating patients with MASLD/MASH. Methods: Databases such as MEDLINE, Web of Science, Cochrane Library, and Scopus were searched until September 2023 to identify relevant studies. Selected studies underwent a thorough quality assessment using tools like Risk of Bias 2 tool (ROB-2) and the National Institutes of Health (NIH) Quality Assessment Tools. Comprehensive meta-analysis software was used for statistical evaluations, with a focus on lipid profiles, liver function tests, and fibrosis measurements. Results: A total of 13 studies were included; 10 of them were included in the quantitative analysis. Our findings showed that pemafibrate significantly decreased low-density lipoprotein cholesterol (LDL-C) (effect size (ES) = -9.61 mg/dL, 95% confidence interval (CI): -14.15 to -5.08), increased high-density lipoprotein cholesterol (HDL-C) (ES = 3.15 mg/dL, 95% CI: 1.53 to 4.78), and reduced triglycerides (TG) (ES = -85.98 mg/dL, 95% CI: -96.61 to -75.36). Additionally, pemafibrate showed a marked reduction in liver enzyme levels, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), with significant effect sizes and P values. For liver stiffness outcomes, pemafibrate decreased AST to platelet ratio index (APRI) (ES = -0.180, 95% CI: -0.221 to -0.138). Conclusions: Pemafibrate, with its enhanced efficacy and safety profile, presents as a pivotal agent in MASLD/MASH treatment. Its lipid-regulating properties, coupled with its beneficial effects on liver inflammation markers, position it as a potentially invaluable therapeutic option.

The effect of shortening vasoactive drug durations alongside endoscopic therapy in esophageal variceal bleeding: an updated systematic review and meta-analysis.

Background: The recommended duration of vasoactive drugs in esophageal variceal bleeding (EVB) spans 2-5 days. Prior meta-analyses of randomized trials include only a few studies that compared short vs. long vasoactive drug durations approximating this time range, including older management techniques, and only assessed variceal rebleeding at 5 days. We identified several additional randomized controlled trials (RCTs) assessing rebleeding at various durations, with updated management of EVB. Methods: We performed an updated systematic review and meta-analysis assessing the effect of shortening the vasoactive drug duration by 48-72 h. The primary outcome was rebleeding within 5 days. Secondary outcomes included rebleeding, mortality due to rebleeding, and all-cause mortality within 4-6 weeks (extended period) with subgroup analysis by vasoactive drug and type of endoscopic therapy. Length of stay, blood transfusion requirements and terlipressin-related adverse events were additional secondary outcomes. Results: Our comprehensive search strategy and screening process yielded 14 RCTs with 1060 patients (75.1% male): 7 trials used terlipressin, 4 octreotide, and 3 somatostatin. Shortened durations combined with band ligation led to similar rebleeding, with a trend towards less rebleeding when populations with more severe liver disease were excluded. There was greater rebleeding and mortality over an extended period when shorter durations were combined with sclerotherapy. Longer durations were associated with a longer hospital stay and, for terlipressin, more adverse events. Conclusions: Shorter vasoactive drug durations combined with band ligation in selected populations appear safe. Higher powered RCTs are needed, involving patients with different degrees of severity of EVB and liver disease.

Refugees have cancer too.

Managing cancer under ideal conditions is a daunting prospect, to say the least. Treating cancer in conflict areas, war zones or being a refugee with cancer, facing complex political, economic and health-related threats presents a colossal global challenge. Managing such patients requires close coordination with international bodies, nongovernmental organisations and national governments, mitigating the burden of cancer care provision to patients and host countries alike.

Prevalence of depression and anxiety among newly diagnosed cancer patients: a single centre experience in the Middle East.

Failure to identify and treat depression and anxiety affecting 10% of patients with cancer, increases the disease burden. This study aimed to assess the psychological well-being of newly diagnosed patients in a tertiary healthcare centre in Lebanon. In this cross-sectional study, data were collected for 187 adult patients, from medical records and interviews using standardised questionnaires (Personal health questionnaire-9 (PHQ-9) and generalised anxiety disorder-7). Karnofsky performance status was also assessed, and incidence was calculated using descriptive statistics, chi-square, and T-tests. The rates of moderate or severe anxiety, minimal anxiety, mild depression, moderate or severe depression, and suicidality are 14.9%, 35.6%, 40.7% 22.7% and 6.2%, respectively. Participants with a past history of seeking help from mental health services (OR: 3.978, CI: (1.680-9.415), p = 0.002), those developing cancer-related complications (OR: 3.039, CI: (1.187-7.777), p = 0.020), and those who had an Eastern Cooperative Oncology Group of ≥2 (OR: 5.306, CI: (1.582-17.797), p = 0.007) were independently associated with depression (diagnosed with PHQ-9) in multivariate logistic regression analysis. Patients with cancer exhibit higher evidence of depression and anxiety and should have a thorough psychiatric history and additional psychiatric care.

Neoadjuvant Chemo-Immunotherapy for Early-Stage Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Importance: Randomized clinical trials (RCTs) with neoadjuvant immune checkpoint inhibitors (ICIs) plus chemotherapy (ICI-chemotherapy) for patients with early-stage non-small cell lung cancer (NSCLC) have reported consistent associations with event-free survival (EFS) and pathologic complete response (pCR) pending longer follow-up for overall survival data. Objective: To assess the pooled benefit of ICI-chemotherapy in 2-year EFS and pCR among patients with NSCLC and examine the impact of clinical, pathologic, and treatment-related factors. Data Sources: Full-text articles and abstracts in English were searched in EMBASE, PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews through November 1, 2023, and in oncology conference proceedings from January 1, 2008, to November 1, 2023. Study Selection: Phase 2 or 3 RCTs with neoadjuvant ICI-chemotherapy with or without adjuvant ICIs vs neoadjuvant chemotherapy alone with or without placebo or observation in patients with previously untreated NSCLC staged IB to IIIB were included. Data Extraction and Synthesis: Data extraction of prespecified data elements was performed by 2 reviewers using a structured data abstraction electronic form. A random-effects model was used for meta-analysis. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. Main Outcomes and Measures: Two-year EFS and pCR were the outcomes of interest in patients who received neoadjuvant ICI-chemotherapy (experimental arm) or neoadjuvant chemotherapy alone (control arm). Aggregated pooled hazard ratios (HRs) for time-to-event outcomes (2-year EFS) and risk ratios (RRs) for dichotomous outcomes (pCR) with their respective 95% CIs were calculated. Results: Eight trials with 3387 patients were included, with some concerns of risk of bias as assessed by the Cochrane Collaboration method, mainly related to outcomes measurements. Neoadjuvant ICI-chemotherapy was associated with improved 2-year EFS (HR, 0.57; 95% CI, 0.50-0.66; P < .001) and increased pCR rate (RR, 5.58; 95% CI, 4.27-7.29; P < .001) in the experimental vs control treatment arms. This association was not significantly modified by the main patient characteristics; tumor- or treatment-related factors, including tumor programmed cell death ligand 1 (PD-L1) status; type of platinum-compound chemotherapy; number of cycles of neoadjuvant ICI-chemotherapy; or addition of adjuvant ICIs. Patients whose tumor cells were negative for PD-L1 were at higher risk of relapse (HR, 0.75; 95% CI, 0.62-0.91) than were those with low (HR, 0.61; 95% CI, 0.37-0.71) or high PD-L1 (HR, 0.40; 95% CI, 0.27-0.58) (P = .005). Conclusions and Relevance: In this systematic review and meta-analysis of neoadjuvant ICI-chemotherapy RCTs in patients with early-stage NSCLC, 3 cycles of neoadjuvant platinum-based ICI-chemotherapy were associated with a meaningful improvement in 2-year EFS and pCR.

Evaluation of Alternative Treatment Strategies for Bile Acid Malabsorption in Inflammatory Bowel Disease Patients: A Network Meta-Analysis.

Background: Bile acid malabsorption (BAM) is characterized by chronic watery diarrhea resulting from excessive bile acids in the feces. BAM is often an overlooked cause of chronic diarrhea, with its prevalence not being sufficiently researched. This review aimed to assess existing literature that explores diverse treatment strategies, to review the published studies that examine the various therapies for BAM patients, emphasizing their influence on clinical results. Methods: We conducted a comprehensive review of various databases, including PubMed, Scopus, Web of Science, Cochrane Database, and EMBASE. Our criteria for inclusion focused on randomized controlled studies (RCTs) that evaluated the effectiveness of different treatment options for patients with BAM. To rank the treatments, we adopted the frequentist approach through the "netrank" function of the network meta-analysis (NMA). Moreover, we utilized the "netsplit" function in the NMA to separate direct and indirect evidence. Our analysis was carried out using RStudio version 1.4.1717 (2009 - 2021 RStudio, Inc.), and we used the "netmeta" and "meta" packages for NMA. Results: We found seven relevant articles involving 213 participants, the average age being approximately 50 years, including 53 males and 92 females. Of the drugs examined, tropifexor was proved to be the most effective in raising the fibroblast growth factor 19 (FGF19) levels and reducing the 7 alpha-hydroxy-4-cholesten-3-one (C4) levels, compared to the placebo (mean difference (MD) = 335.30, 95% confidence interval (CI) (334.86, 335.74), MD = -24.60, 95% CI (-25.37, -23.83); respectively). Compared to colesevelam and the placebo, liraglutide was more efficient in decreasing fecal bile acid concentration (liraglutide; MD = -19, 95% CI (-37.61, -0.39)). Conclusions: Tropifexor has been identified as the most successful medication in mitigating BAM symptoms. To ensure more accurate results, there is a need for randomized controlled clinical trials that involve a larger participant pool.

Instrumental activities of daily living in older patients with metastatic prostate cancer: results from the meet-URO network ADHERE prospective study.

Instrumental activities of daily living (IADL) are significant health indicators closely related to executive functions and able to detect mild cognitive impairment. A decline in IADL usually precedes ADL limitation, including taking medications, and may therefore predict a cognitive decline. We aimed to investigate the association of patients' IADL score with other clinical factors, with a particular focus on the presence of a caregiver, and the impact on adherence to androgen receptor pathway inhibitors (ARPIs) and survival outcomes within the Meet-URO 5-ADHERE study. It was a large prospective multicentre observational cohort study monitoring adherence to ARPIs in 234 metastatic castrate-resistant PC (mCRPC) patients aged ≥ 70. We observed an association between impaired IADL and lower geriatric G8 scores (p < 0.01), and lower adherence to ARPIs whether assessed by pill counting (p = 0.01) or self-reported by the patient himself (p = 0.03). The combination of an IADL < 6 and the absence of a caregiver resulted in a significantly high risk of non-adherence to the ARPIs at the multivariable analysis (HR 9.23, 95% confidence interval 2.28-37.43, p = 0.01). IADL alongside the geriatric G8 scales represent essential tools to identify frail and less auto-sufficient patients who are extremely vulnerable particularly if not supported by a caregiver and have the highest risk of nonadherence to ARPIs.

VKH with APECED in a Two-Year-Old Child: A Rare Concomitant Diagnosis in an Unprecedented Age.

PURPOSE: To present a case of Vogt Koyanagi Harada (VKH) associated with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED) in a two-year-old. CASE PRESENTATION: A two-year-old type 1 diabetic with hypothyroidism presented with impaired fixation. Ocular examination revealed right vitritis, choroiditis, a hyperemic disc, and an area of exudative detachment. At the same time, there was no fundus view in the left eye, and ultrasonographic assessment revealed vitritis and a thickened choroid. Patient developed sunset glow fundus with alopecia, poliosis and vitiligo and a diagnosis of complete VKH with APECED was made. CONCLUSION: APECED is a rare endocrine disorder and has been reported to be associated with VKH twice. Likewise, VKH is commonly present in much older patients; this is the first time ever to be diagnosed in a two-year-old child.

Diagnostic Paracentesis Within 1 Day Is Associated With Reduced Mortality and Length of Hospital Stay in Patients with Cirrhosis and Ascites.

Spontaneous bacterial peritonitis (SBP) is the most common infection in patients with cirrhosis and is associated with high mortality. Although recent literature reports mortality benefits to early diagnostic paracentesis, current guidelines do not offer specific recommendations for how quickly diagnostic paracentesis should be performed in patients with cirrhosis and ascites who are admitted to the hospital. Therefore, we conducted a systematic review and meta-analysis to evaluate outcomes among patients admitted to the hospital with cirrhosis and ascites receiving paracentesis within ≤ 12, ≤ 1 day, and > 1 day. Eight studies with 116,174 patients were included in the final meta-analysis. The pooled risk of in-hospital mortality was significantly lower in patients who underwent early (≤ 12 h or ≤ 1 day) compared to delayed (> 12 h or > 1 day) paracentesis (RR: 0.69, p < 0.00001), and in patients who underwent paracentesis compared to no paracentesis (RR: 0.74, p < 0.00001). On subgroup analysis, in-hospital mortality was significantly lower in both paracentesis within ≤ 12 h (RR: 0.61, p = 0.02) vs. > 12 h, and within ≤ 1 day (RR: 0.70, p < 0.00001) vs. > 1 day. While there was a trend towards decreased mortality in those undergoing paracentesis within ≤ 12 h compared to ≤ 1 day, the difference did not reach statistical significance. The length of hospital stay was significantly shorter by 5.38 days in patients who underwent early (≤ 12 h) compared to delayed (> 12 h) paracentesis (95% CI 4.24-6.52, p < 0.00001). Early paracentesis is associated with reduced mortality and length of hospital stay. We encourage providers to perform diagnostic paracentesis in a timely manner, at least within 1 day of hospital admission, for all patients with cirrhosis and ascites.

Interleukin-8 genetic polymorphism and its relation to Helicobacter pylori infection and Helicobacter pylori-associated gastric diseases.

Helicobacter pylori (H. pylori) infection has a variety of clinical outcomes, and host genetic factors play an important role in this process. Cytokines are important factors in mediating and controlling the inflammatory process during H. pylori infection. Interleukin-8 (IL-8) plays a critical role in the epithelial cell response to H. pylori infection and the development of H. pylori-related gastric disorders. The IL-8 gene has an A/T base pair polymorphism in the promoter region (-251), which has been linked to an increase in interleukin production by gastric epithelial cells. In this context, the goal of our study was to determine the polymorphism in the IL-8 gene and its relation to H. pylori infection and H. pylori-associated gastric diseases. Gastric biopsy specimens were collected from 44 patients with H. pylori infection and 29 patients without H. pylori infection. The rapid urease test and detection of the glmM gene were used to diagnose H. pylori infection. Polymerase chain reaction-restriction fragment length polymorphism was used to identify the polymorphism in the Il-8 gene (at position-251). The presence of the A/A and T/A genotypes of the IL-8 gene was found to be significantly associated with susceptibility to H. pylori infection (p = 0.012 and p = 0.004, respectively). Also, the IL-8 A allele was significantly associated with H. pylori infection in our study (p = 0.002). We did not find a significant association between IL-8 gene polymorphism and a higher risk of gastritis and peptic ulcer disease. In conclusion, IL-8 gene polymorphism at -251 position was significantly associated with H. pylori infection.

Sarcopenia is a risk factor for post-transjugular intrahepatic portosystemic shunt hepatic encephalopathy and mortality: A systematic review and meta-analysis.

BACKGROUND/AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is a commonly performed procedure in patients with liver cirrhosis to treat portal hypertension-related conditions, including variceal bleeding and refractory ascites. However, while the increased risk of hepatic encephalopathy (HE) after TIPS is important to consider when determining whether a patient is a good candidate for TIPS, currently there is no widely used method to predict the development of post-TIPS HE, although the model for end-stage liver disease (MELD) score is used to predict post-TIPS mortality. We conducted a systematic review and meta-analysis to evaluate sarcopenia as a risk factor for HE and mortality in patients undergoing TIPS. METHODS: A comprehensive search strategy was used to identify reports of post-TIPS HE and mortality in sarcopenia vs. non-sarcopenia patients with liver cirrhosis who received TIPS in March 2023. Open Meta Analyst was used to compute the results. RESULTS: Twelve studies with 2056 patients met inclusion criteria and were included in the final meta-analysis. Sarcopenia was associated with a significantly higher post-TIPS HE rate than non-sarcopenia (risk ratio [RR]: 1.68, 95% CI: 1.48-1.92, p < 0.00001, I2 = 65%), as well as a significantly higher post-TIPS mortality rate (RR: 1.73, 95% CI: 1.14-2.64, p < 0.00001, I2 = 87%). CONCLUSION: Patients with sarcopenia have a significantly increased risk of post-TIPS HE and mortality. Presence of sarcopenia should be considered when weighing the risks and benefits of performing TIPS in patients with cirrhosis. Further studies are needed to determine the clinical utility of important risk factors such as sarcopenia on post-TIPS outcomes.

Folfirinox vs. Gemcitabine + Nab-Paclitaxel as the First-Line Treatment for Pancreatic Cancer: A Systematic Review and Meta-Analysis.

Background: The efficacy and safety of Folfirinox (FFX) or gemcitabine + nab-paclitaxel (GnP) to be used as the first-line drugs for pancreatic cancer (PC) is yet to be established. We conducted an analysis of retrospective studies to assess the efficacy and safety of these two regimens by comparing their survival and safety outcomes in patients with PC. Methods: We conducted an extensive review of two electronic databases from inception till February 2023 to include all the relevant studies that compared FFX with GnP published and unpublished work. Retrospective studies were only included. Overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs), while objective response rate (ORR) and safety outcomes were pooled using odds ratios (ORs) with 95% confidence interval (CI) using the random effects model. Results: A total of 7,030 patients were identified in a total of 21 articles that were shortlisted. Pooled results concluded that neither FFX nor GnP was associated to increase the OS time (HR: 0.93, 95% CI: 0.83 - 1.04; P = 0.0001); however, FFX was more likely associated with increased PFS when compared to GnP (HR: 0.88, 95% CI: 0.81 - 0.97; P < 0.0001). ORR proved to be non-significant between the two regimens (OR: 0.90, 95% CI: 0.64 - 1.27; P = 0.15). Safety outcomes included neutropenia, anemia, thrombocytopenia and diarrhea. GnP was more associated with diarrhea (OR: 1.96, 95% CI: 1.22 - 3.15; P = 0.001), while FFX was seen to cause anemia (OR: 0.70, 95% CI: 0.51 - 0.98; P = 0.10) in PC patients. Neutropenia and thrombocytopenia were in-significant in the two drug regimens (OR: 1.10, 95% CI: 0.92 - 1.31; P = 0.33 and OR: 0.83, 95% CI: 0.60 - 1.13; P = 0.23, respectively). Conclusion: FFX and GnP showed a significant difference in increasing the PFS, while no difference was observed while measuring OS. Safety outcomes showed that FFX and GnP shared similar safety profiles as FFX was associated with hematological outcomes, while GnP was more associated with non-hematological outcomes.

Hepatic encephalopathy with proton pump inhibitor use in post tips patients: a systematic review and meta-analysis.

INTRODUCTION: Hepatic encephalopathy (HE) after Trans-jugular intrahepatic portosystemic shunt (TIPS) is a common clinical problem. According to recent studies, Proton pump inhibitor (PPI) use can serve as an independent risk factor for HE. We performed a systematic review and meta-analysis to analyze the association between HE with PPI use versus without PPI use in patients undergoing TIPS. EVIDENCE ACQUISITION: We conducted a comprehensive literature search from inception through February 15th, 2022 on MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases. Odds ratio (OR) was calculated when comparing dichotomous variables of patients with HE vs no HE in PPI use versus no PPI use in post TIPS patients. A 95% confidence interval (CI) and P values (<0.05 considered significant) were also generated. EVIDENCE SYNTHESIS: The search strategy yielded a total of 27 articles. We finalized four studies with a total of 825 patients. There was statistically significant difference in TIPS patients with HE in PPI users versus non-PPI users (OR 3.39 [1.79-6.43], P<0.01, I2=55.5%). Pooled mean average days to hospitalization was 215.2 days to hospitalization for hepatic encephalopathy in non-PPI users compared to 139.5 days in PPI users. CONCLUSIONS: Our study determines that there is a higher risk of post-TIPS HE in patients on PPI therapy vs. patients not receiving PPI therapy. We recommend using PPIs at a lower tolerable dose where necessary. Larger studies are needed to draw stronger conclusions.

Evaluating the diagnostic accuracy of magnetic resonance imaging in distinguishing strictures in Crohn's disease: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis sought to assess the diagnostic accuracy of magnetic resonance imaging (MRI) in distinguishing fibrotic from inflammatory strictures in Crohn's disease (CD) patients. METHODS: A rigorous and systematic exploration of five key databases yielded studies that met predefined criteria. Data were extracted for a comprehensive meta-analysis using MetaDiSC and MetaDTA software, providing diagnostic accuracy measures. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was utilized for evaluating the methodological quality and potential bias within the studies. RESULTS: The systematic review involved the evaluation of 7437 records, culminating in the inclusion of 22 studies. In detecting fibrotic strictures in CD patients, MRI exhibited a pooled sensitivity of 85.20% (95% CI: 76.10-91.20%) and specificity of 96.00% (95% CI: 87.80-98.70%). For differentiating fibrotic strictures from inflammatory stenosis, the sensitivity was 81.5% (95% CI: 70.2-89.20%), and the specificity was 97.2% (95% CI: 90.0-99.3%). In terms of assessing the severity of strictures, sensitivity stood at 90.4% (95% CI: 78.1-96.1%) and specificity at 89.4% (95% CI: 57.4-98.2%). The consistency of the diagnostic accuracy was observed across different geographical locations and the various reference tests applied in the studies. CONCLUSIONS: The results of this meta-analysis underscore the robust diagnostic accuracy of MRI in detecting fibrotic strictures, distinguishing between fibrotic and inflammatory strictures, and evaluating stricture severity in CD patients. These findings support the integration of MRI into standard diagnostic protocols for patients with CD. Further large-scale, multicenter trials are warranted to confirm these results and to identify any potential limitations associated with the application of MRI in this clinical setting.

Continuous vs. intermittent terlipressin infusion for portal hypertension: a systematic review and meta-analysis.

Background: Portal hypertension, a major complication of chronic liver disease, often leads to life-threatening variceal bleeding, managed effectively with vasoactive drugs like terlipressin. However, the most optimal method of terlipressin administration, continuous versus intermittent infusion, remains a subject of debate, necessitating this systematic review and meta-analysis for evidence-based decision-making in managing this critical condition. Methods: This systematic review and meta-analysis adhered to the PRISMA standards and explored multiple databases until 6 April 2023, such as MEDLINE through PubMed, Scopus, Web of Science, and CENTRAL. Independent reviewers selected randomized controlled trials (RCTs) that met specific inclusion criteria. After assessing study quality and extracting necessary data, statistical analysis was performed using Review Manager (RevMan), with results presented as risk ratios (RR) or mean differences. Results: Five RCTs (n=395 patients) were included. The continuous terlipressin group had a significantly lower risk of rebleeding (RR=0.43, P=0.0004) and treatment failure (RR=0.22, P=0.02) and fewer total adverse effects (RR=0.52, P<0.00001) compared to the intermittent group. However, there were no significant differences between the two groups in mean arterial pressure (P=0.26), length of hospital stays (P=0.78), and mortality rates (P=0.65). Conclusion: This study provides robust evidence suggesting that continuous terlipressin infusion may be superior to intermittent infusions in reducing the risk of rebleeding, treatment failure, and adverse effects in patients with portal hypertension. However, further large-scale, high-quality RCTs are required to confirm these findings and to investigate the potential benefits of continuous terlipressin infusion on mortality and hospital stays.

Protein Induced by Vitamin K Absence or Antagonist-II Versus Alpha-Fetoprotein in the Diagnosis of Hepatocellular Carcinoma: A Systematic Review With Meta-Analysis.

Background: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) and α-fetoprotein (AFP) are promising tumor markers for the diagnosis of hepatocellular carcinoma (HCC). Yet, their diagnostic performance differs throughout HCC investigations. The aim of this meta-analysis was to assess the effectiveness of PIVKA-II and AFP in the diagnosis of HCC. Methods: A systematic literature search was performed to identify relevant studies from eight databases, which were published up to February 2023, in order to compare the diagnostic performance of PIVKA-II and AFP for HCC. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic (SROC) curve was performed to assess the diagnostic accuracy of each biomarker. Results: Fifty-three studies were identified. The pooled sensitivity (95% confidence interval (CI)) of PIVKA-II and AFP was 0.71 (0.70 - 0.72) and 0.64 (0.63 - 0.65), respectively in diagnosis of HCC, and the corresponding pooled specificity (95% CI) was 0.90 (0.89 - 0.90) and 0.87 (0.87 - 0.88), respectively. The area under the ROC curve (AUC) of PIVKA-II and AFP was 0.89 (0.88 - 0.90) and 0.78 (0.77 - 0.79), respectively. Subgroup analysis demonstrated that PIVKA-II presented higher AUC values compared to AFP in terms of ethnic group (African, European, Asian, and American patients), etiology (mixed-type HCC, hepatitis C virus (HCV)-related, and hepatitis B virus (HBV)-related) and sample size of cases (≤ 100 and > 100). Conclusion: This study reveals that PIVKA-II is a promising biomarker for identifying and tracking HCC, exhibiting greater accuracy than AFP. Our findings indicate that PIVKA-II outperforms AFP in detecting HCC across diverse racial groups and sample sizes, as well as in cases of HBV-related, HCV-related, or mixed-etiology HCC.

Zinc citrate-coated whey protein nanoparticles alleviate kidney damage and the disturbances in inflammatory gene expression in rats.

This work was conducted to synthesize whey protein nanoparticles (WPNPs) for the coating of zinc citrate (Zn CITR) at three levels and to study their protective role against CCl4 -induced kidney damage and inflammatory gene expression disorder in rats. Seventy male Sprague-Dawley rats were divided into seven groups and treated orally for 4 weeks as follows; the control group, the group treated twice a week with CCl4 (5 mL/kg b.w), the groups received CCl4 plus WPNPs (300 mg/kg b.w); the group received 50 mg/kg b.w of Zn CITR or the three formulas of Zn CITR-WPNPs at low, medium and high doses (LD, MD, and HD). Blood and kidney samples were collected for different assays and histological analyses. The fabricated particles were semispherical, with an average size of 160 ± 2.7, 180 ± 3.1, and 200 ± 2.6 nm and ζ potential of -126, -93, and -84 mV for ZN CITR-WPNPs (LD), Zn CITR-WPNPs (MD), and ZN CITR-WPNPs (HD), respectively. CCl4 significantly increased (p ≤ 0.05) kidney function indices, oxidative stress markers, messenger RNA expression of transforming growth factor-ß1, interleukin (IL)-1ß, IL-10, IL-6, inducible nitric oxide synthase, and tumor necrosis factor-α and significantly decreased (p ≤ 0.05) renal superoxide dismutase, catalase, and glutathione peroxidase along with the histological changes in the kidney tissues. WPNPs, Zn CITR, and Zn CITR loaded WPNPS showed a protective effect against these complications and Zn CITR-WPNPs (LD) was more effective. WPNPs can be used effectively for coating Zn CITR at a level of 7 mg/g WPNPs to be used as a supplement for the protection of the kidney against different toxicants to enhance immunity and avoid harm of excess Zn.