Severity of gallstone, sludge or microlithiasis induced pancreatitis - all of the same?

BACKGROUND/AIM: Severity of microlithiasis and sludge-induced pancreatitis in comparison to gallstone-induced pancreatitis has never been studied for a lack of definition. In order to understand whether bile duct obstruction or other mechanisms contribute to biliary pancreatitis severity we performed a monocentric, retrospective cohort study. METHODS: In this retrospective cohort study 263 patients with acute biliary pancreatitis treated at a tertiary care center from 2005 to 2021 were stratified according to the recent consensus definition for microlithiasis and sludge. The gallstone-pancreatitis cohort was compared to microlithiasis, sludge and suspected stone passage pancreatitis cohorts in terms of pancreatitis outcome, liver function and EUS/ERCP results using one-way ANOVA and Chi2 test. Multinomial logistic regression analysis was performed to correct for bias. RESULTS: Microlithiasis and sludge-induced pancreatitis classified according to the revised Atlanta classification, did not present with a milder course than gallstone-induced pancreatitis (p = 0.62). Microlithiasis and sludge showed an increase in bilirubin on the day of admission to hospital, which was not significantly different from gallstone-induced pancreatitis (p = 0.36). The likelihood of detecting biliary disease on EUS resulting in bile duct clearance was highest on the day of admission and day 1, respectively. CONCLUSION: Microlithiasis and sludge induce gallstone-equivalent impaired liver function tests and induce pancreatitis with similar severity compared with gallstone-induced acute biliary pancreatitis.

Penicillin Allergy Testing and Delabeling for Patients Who Are Prescribed Penicillin: A Systematic Review for a World Health Organization Guideline.

Secondary prevention with penicillin aims to prevent further episodes of acute rheumatic fever and subsequent development of rheumatic heart disease (RHD). Penicillin allergy, self-reported by 10% of the population, can affect secondary prevention programs. We aimed to assess the role for (i) routine penicillin allergy testing and the (ii) safety of penicillin allergy delabeling approaches in this context. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, ISRCTN, and CPCI-S to identify the relevant reports. We found 2419 records, but no studies addressed our initial question. Following advice from the WHO-Guideline committee and experts, we identified 6 manuscripts on allergy testing focusing on other populations showing that the prevalence of allergy confirmed by testing was low and the incidence of life-threatening reactions to BPG was very low (< 1-3/1000 individuals treated). A subsequent search addressed penicillin allergy delabeling. This found 516 records, and 5 studies addressing the safety of direct oral drug challenge vs. skin testing followed by drug administration in patients with suspected penicillin allergy. Immediate allergic reactions of minor severity were observed for a minority of patients and occurred less frequently in the direct drug challenge group: 2.3% vs. 11.5%; RR = 0.25, 95%CI 0.15-0.45, P < 0.00001, I2 = 0%. No anaphylaxis or deaths were observed. Severe allergic reactions to penicillin are extremely rare and can be recognized and dealt by trained healthcare workers. Confirmation of penicillin allergy diagnosis or delabeling using direct oral drug challenge or penicillin skin testing seems to be safe and is associated with a low rate of adverse reactions.

Cardiac resynchronization therapy in inotrope-dependent heart failure: a meta-analysis.

AIMS: The viability of cardiac resynchronization therapy (CRT) in inotrope-dependent heart failure (HF) has been a matter of debate. METHODS AND RESULTS: We searched Medline, EMBASE, Scopus, and the Cochrane Library until 31 December 2022. Studies were included if (i) HF patients required inotropic support at CRT implantation; (ii) patients were ≥18 years old; and (iii) they provided a clear definition of 'inotrope dependence' or 'inability to wean'. A meta-analysis was performed in R (Version 3.5.1). Nineteen studies comprising 386 inotrope-dependent HF patients who received CRT (mean age 64.4 years, 76.9% male) were included. A large majority survived until discharge at 91.1% [95% confidence interval (CI): 81.2% to 97.6%], 89.3% were weaned off inotropes (95% CI: 77.6% to 97.0%), and mean discharge time post-CRT was 7.8 days (95% CI: 3.9 to 11.7). After 1 year of follow-up, 69.7% survived (95% CI: 58.4% to 79.8%). During follow-up, the mean number of HF hospitalizations was reduced by 1.87 (95% CI: 1.04 to 2.70, P < 0.00001). Post-CRT mean QRS duration was reduced by 29.0 ms (95% CI: -41.3 to 16.7, P < 0.00001), and mean left ventricular ejection fraction increased by 4.8% (95% CI: 3.1% to 6.6%, P < 0.00001). The mean New York Heart Association (NYHA) class post-CRT was 2.7 (95% CI: 2.5 to 3.0), with a pronounced reduction of individuals in NYHA IV (risk ratio = 0.27, 95% CI: 0.18 to 0.41, P < 0.00001). On univariate analysis, there was a higher prevalence of males (85.7% vs. 40%), a history of left bundle branch block (71.4% vs. 30%), and more pronounced left ventricular end-diastolic dilation (274.3 ± 7.2 vs. 225.9 ± 6.1 mL). CONCLUSIONS: CRT appears to be a viable option for inotrope-dependent HF, with some of these patients seeming more likely to respond.

Handheld echocardiography for the screening and diagnosis of rheumatic heart disease: a systematic review to inform WHO guidelines.

BACKGROUND: Early detection and diagnosis of acute rheumatic fever and rheumatic heart disease are key to preventing progression, and echocardiography has an important diagnostic role. Standard echocardiography might not be feasible in high-prevalence regions due to its high cost, complexity, and time requirement. Handheld echocardiography might be an easy-to-use, low-cost alternative, but its performance in screening for and diagnosing acute rheumatic fever and rheumatic heart disease needs further investigation. METHODS: In this systematic review and meta-analysis, we searched Embase, MEDLINE, LILACS, and Conference Proceedings Citation Index-Science up to Feb 9, 2024, for studies on the screening and diagnosis of acute rheumatic fever and rheumatic heart disease using handheld echocardiography (index test) or standard echocardiography or auscultation (reference tests) in high-prevalence areas. We included all studies with useable data in which the diagnostic performance of the index test was assessed against a reference test. Data on test accuracy in diagnosing rheumatic heart disease, acute rheumatic fever, or carditis with acute rheumatic fever (primary outcomes) were extracted from published articles or calculated, with authors contacted as necessary. Quality of evidence was appraised using GRADE and QUADAS-2 criteria. We summarised diagnostic accuracy statistics (including sensitivity and specificity) and estimated 95% CIs using a bivariate random-effects model (or univariate random-effects models for analyses including three or fewer studies). Area under the curve (AUC) was calculated from summary receiver operating characteristic curves. Heterogeneity was assessed by visual inspection of plots. This study was registered with PROSPERO (CRD42022344081). FINDINGS: Out of 4868 records we identified 11 studies, and two additional reports, comprising 15 578 unique participants. Pooled data showed that handheld echocardiography had high sensitivity (0·87 [95% CI 0·76-0·93]), specificity (0·98 [0·71-1·00]), and overall high accuracy (AUC 0·94 [0·84-1·00]) for diagnosing rheumatic heart disease when compared with standard echocardiography (two studies; moderate certainty of evidence), with better performance for diagnosing definite compared with borderline rheumatic heart disease. High sensitivity (0·79 [0·73-0·84]), specificity (0·85 [0·80-0·89]), and overall accuracy (AUC 0·90 [0·85-0·94]) for screening rheumatic heart disease was observed when pooling data of handheld echocardiography versus standard echocardiography (seven studies; high certainty of evidence). Most studies had a low risk of bias overall. Some heterogeneity was observed for sensitivity and specificity across studies, possibly driven by differences in the prevalence and severity of rheumatic heart disease, and level of training or expertise of non-expert operators. INTERPRETATION: Handheld echocardiography has a high accuracy and diagnostic performance when compared with standard echocardiography for diagnosing and screening of rheumatic heart disease in high-prevalence areas. FUNDING: World Health Organization. TRANSLATIONS: For the Chinese, French, Italian, Persian, Portuguese, Spanish and Urdu translations of the abstract see Supplementary Materials section.

The effect of sodium-glucose co-transporter 2 inhibitors on outcomes after cardiac resynchronization therapy.

AIMS: The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. METHODS AND RESULTS: We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0 ± 11.5 years (mean ± standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8 ± 9.9% and QRS duration of 161 ± 29 ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n = 66) and without (n = 308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P = 0.049). CONCLUSIONS: We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.

The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials.

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

Routine Antenatal Echocardiography in High-Prevalence Areas of Rheumatic Heart Disease: A WHO-Guideline Systematic Review.

Background: Rheumatic Heart Disease (RHD) is the most common cause of valvular heart disease worldwide. Undiagnosed or untreated RHD can complicate pregnancy and lead to poor maternal and fetal outcomes and is a significant factor in non-obstetric morbidity. Echocardiography has an emerging role in screening for RHD. We aimed to critically analyse the evidence on the use of echocardiography for screening pregnant women for RHD in high-prevalence areas. Methods: We searched MEDLINE and Embase to identify the relevant reports. Two independent reviewers assessed the reports against the eligibility criteria in a double-blind process. Results: The searches (date: 4 April 2023) identified 432 records for screening. Ten non-controlled observational studies were identified, five using portable or handheld echocardiography, comprising data from 23,166 women. Prevalence of RHD varied across the studies, ranging from 0.4 to 6.6% (I2, heterogeneity >90%). Other cardiac abnormalities (e.g., congenital heart disease and left ventricular systolic dysfunction) were also detected <1% to 2% of cases. Certainty of evidence was very low. Conclusion: Echocardiography as part of antenatal care in high-prevalence areas may detect RHD or other cardiac abnormalities in asymptomatic pregnant women, potentially reducing the rates of disease progression and adverse labor-associated outcomes. However, this evidence is affected by the low certainty of evidence, and lack of studies comparing echocardiography versus standard antenatal care. Prospective Registration: PROSPERO 2022 July 4; CRD42022344081 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=344081. Research question: 'In areas with a high prevalence of rheumatic heart disease, should handheld echocardiography be added to routine antenatal care?'

Effect of wheat straw ash as cementitious material on the mechanical characteristics and embodied carbon of concrete reinforced with coir fiber.

The use of supplementary cementitious materials has been widely accepted due to increasing global carbon emissions resulting from demand and the consequent production of Portland cement. Moreover, researchers are also working on complementing the strength deficiencies of concrete; fiber reinforcement is one of those techniques. This study aims to assess the influence of recycling wheat straw ash (WSA) as cement replacement material and coir/coconut fibers (CF) as reinforcement ingredients together on the mechanical properties, permeability and embodied carbon of concrete. A total of 255 concrete samples were prepared with 1:1.5:3 mix proportions at 0.52 water-cement ratio and these all-concrete specimens were cured for 28 days. It was revealed that the addition of 10 % WSA and 2 % CF in concrete were recorded the compressive, splitting tensile and flexural strengths by 33 MPa, 3.55 MPa and 5.16 MPa which is greater than control mix concrete at 28 days respectively. Moreover, it was also observed that the permeability of concrete incorporating 4 % of coir fiber and 20 % of WSA was reduced by 63.40 % than that of the control mix after 28 days which can prevent the propagation of major and minor cracks. In addition, the embodied carbon of concrete is getting reduced when the replacement level of cement with WSA along with CF increases in concrete. Furthermore, based on the results obtained, the optimum amount of WSA was suggested to be 10 % and that of coir fiber reinforcement was suggested to be 2 % for improved results.

De-escalation of dual antiplatelet therapy for patients with acute coronary syndrome after percutaneous coronary intervention: a systematic review and network meta-analysis.

OBJECTIVES: To compare dual antiplatelet therapy (DAPT) de-escalation with five alternative DAPT strategies in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). DESIGN: We conducted a systematic review and network meta-analysis (NMA). Parallel-arm randomised controlled trials (RCTs) comparing DAPT strategies were included and arms of interest were compared via NMA. Partial ranking of each identified arm and for each investigated endpoint was also performed. SETTING AND PARTICIPANTS: Adult patients with ACS (≥18 years) undergoing PCI with indications for DAPT. SEARCH METHODS: A comprehensive search covered several databases (PubMed, Embase, Cochrane Central, MEDLINE, Conference Proceeding Citation Index-Science) from inception to 15 October 2023. Medical subject headings and keywords related to ACS, PCI and DAPT interventions were used. Reference lists of included studies were screened. Clinical trials registers were searched for ongoing or unpublished trials. INTERVENTIONS: Six strategies were assessed: T1 arm: acetylsalicylic acid (ASA) and prasugrel for 12 months; T2 arm: ASA and low-dose prasugrel for 12 months; T3 arm: ASA and ticagrelor for 12 months; T4 arm: DAPT de-escalation (ASA+P2Y12 inhibitor for 1-3 months, then single antiplatelet therapy with potent P2Y12 inhibitor or DAPT with clopidogrel); T5 arm: ASA and clopidogrel for 12 months; T6 arm: ASA and clopidogrel for 3-6 months. MAIN OUTCOME MEASURES: Primary outcome: Cardiovascular mortality. SECONDARY OUTCOMES: bleeding events (all, major, minor), stent thrombosis (ST), stroke, myocardial infarction (MI), all-cause mortality, major adverse cardiovascular events (MACE). RESULTS: 23 RCTs (75 064 patients with ACS) were included. No differences in cardiovascular mortality, all-cause death, recurrent MI or MACE were found when the six strategies were compared, although with different levels of certainty of evidence. ASA and clopidogrel for 12 or 3-6 months may result in a large increase of ST risk versus ASA plus full-dose prasugrel (OR 2.00, 95% CI 1.14 to 3.12, and OR 3.42, 95% CI 1.33 to 7.26, respectively; low certainty evidence for both comparisons). DAPT de-escalation probably results in a reduced risk of all bleedings compared with ASA plus full-dose 12-month prasugrel (OR 0.49, 95% CI 0.26 to 0.81, moderate-certainty evidence) and ASA plus 12-month ticagrelor (OR 0.52, 95% CI 0.33 to 0.75), while it may not increase the risk of ST. ASA plus 12-month clopidogrel may reduce all bleedings versus ASA plus full-dose 12-month prasugrel (OR 0.66, 95% CI 0.42 to 0.94, low certainty) and ASA plus 12-month ticagrelor (OR 0.70, 95% CI 0.52 to 0.89). CONCLUSIONS: DAPT de-escalation and ASA-clopidogrel regimens may reduce bleeding events compared with 12 months ASA and potent P2Y12 inhibitors. 3-6 months or 12-month aspirin-clopidogrel may increase ST risk compared with 12-month aspirin plus potent P2Y12 inhibitors, while DAPT de-escalation probably does not.

Boosting-based ensemble machine learning models for predicting unconfined compressive strength of geopolymer stabilized clayey soil.

The present research employs new boosting-based ensemble machine learning models i.e., gradient boosting (GB) and adaptive boosting (AdaBoost) to predict the unconfined compressive strength (UCS) of geopolymer stabilized clayey soil. The GB and AdaBoost models were developed and validated using 270 clayey soil samples stabilized with geopolymer, with ground-granulated blast-furnace slag and fly ash as source materials and sodium hydroxide solution as alkali activator. The database was randomly divided into training (80%) and testing (20%) sets for model development and validation. Several performance metrics, including coefficient of determination (R2), mean absolute error (MAE), root mean square error (RMSE), and mean squared error (MSE), were utilized to assess the accuracy and reliability of the developed models. The statistical results of this research showed that the GB and AdaBoost are reliable models based on the obtained values of R2 (= 0.980, 0.975), MAE (= 0.585, 0.655), RMSE (= 0.969, 1.088), and MSE (= 0.940, 1.185) for the testing dataset, respectively compared to the widely used artificial neural network, random forest, extreme gradient boosting, multivariable regression, and multi-gen genetic programming based models. Furthermore, the sensitivity analysis result shows that ground-granulated blast-furnace slag content was the key parameter affecting the UCS.

Financial development, resource richness, eco-innovation, and sustainable development: Does geopolitical risk matter?

Financial development and geopolitical risks can significantly affect sustainable development. However, the roles of these factors in sustainable development are rarely investigated. Thus, this study takes into account the role of geopolitical risk while exploring the effects of financial development, natural resource rents, and eco-innovation on sustainable development in the Organization for Economic Co-operation and Development (OECD) countries. To this end, yearly data from 1990 to 2019 is analyzed using advanced econometric tests. The Common Correlated Effects Mean Group (CCEMG) results indicate that financial development and eco-innovation are significantly and positively related to sustainable development. Natural resource rents have a detrimental impact on sustainable development which confirms the presence of the resource curse hypothesis in OECD countries. Furthermore, the results revealed that controlling geopolitical risk is useful in fostering sustainable development. Lastly, the panel Granger causality test unveiled one-way causality from financial development, eco-innovation, natural resource rents, and geopolitical risk to sustainable development. Moreover, causalities are found from geopolitical risk to financial development, eco-innovation and natural resources. These findings suggest that OECD countries should prioritize financial development and eco-innovation policies for sustainable development while mitigating the negative effects of natural resource rents. The geopolitical risk can harm sustainable development, so policymakers should promote international cooperation and risk-sharing.

Stability risk assessment of slopes using logistic model tree based on updated case histories.

A new logistic model tree (LMT) model is developed to predict slope stability status based on an updated database including 627 slope stability cases with input parameters of unit weight, cohesion, angle of internal friction, slope angle, slope height and pore pressure ratio. The performance of the LMT model was assessed using statistical metrics, including accuracy (Acc), Matthews correlation coefficient (Mcc), area under the receiver operating characteristic curve (AUC) and F-score. The analysis of the Acc together with Mcc, AUC and F-score values for the slope stability suggests that the proposed LMT achieved better prediction results (Acc = 85.6%, Mcc = 0.713, AUC = 0.907, F-score for stable state = 0.967 and F-score for failed state = 0.923) as compared to other methods previously employed in the literature. Two case studies with ten slope stability events were used to verify the proposed LMT. It was found that the prediction results are completely consistent with the actual situation at the site. Finally, risk analysis was carried out, and the result also agrees with the actual conditions. Such probability results can be incorporated into risk analysis with the corresponding failure cost assessment later.

Comparison of Mechanical Properties of Non-ridged Versus Ridged Backslabs in Lower Limb Fractures.

Introduction Lower limb fractures frequently require immobilization with backslabs to promote healing. This study investigates a novel approach involving the incorporation of a single ridge to enhance backslab strength while maintaining cost-effectiveness. Objective The aim of this study was to assess the mechanical performance of ridged backslabs in comparison to traditional non-ridged backslabs, specifically focusing on their load-bearing capacity and cost-effectiveness when used in lower limb fractures. Methods This experimental study, conducted between January 2023 and June 2023, compares three groups of backslabs with varying layers (eight, ten, and twelve) that were fabricated, each consisting of four ridged and four non-ridged specimens. These backslabs, constructed from six-inch plaster of Paris rolls, were 190 cm in length. A three-point bending test was conducted on both groups using a Hounsfield H100KS Universal Testing Machine (Tinius Olsen Ltd., Redhill, UK), with a crosshead speed of 5 mm/min and a span distance of 190 mm between supports. Results Significant differences in mean maximum force endured were observed between the ten-layered and twelve-layered flat and ridged backslabs (p-values: 0.003 and 0.004, respectively). Ten-layered ridged backslabs exhibited a 56 N higher load-bearing capacity, while twelve-layered ridged backslabs withstood 73.9 N more force than their flat counterparts, underscoring the superior strength of ridged lower limb backslabs. Conclusion Ridged backslabs outperformed non-ridged backslabs in terms of strength when subjected to external forces. These findings support the potential adoption of ridged backslabs as a lightweight, cost-effective, and robust alternative for immobilization in lower limb fractures.

Endoscopic Therapy of Gastric Varices: Safety and Efficacy of N-Butyl-2-Cyanoacrylate Injection.

Background Upper gastrointestinal bleeding (UGIB) is a common medical emergency that results in significant morbidity, mortality, and socioeconomic burden. Both types of cardio-fundal varices, gastro-esophageal varix 2 (GOV2) and isolated gastric varices type 1 (IGV1), can cause massive bleeding and often are difficult to treat compared to the other types of gastric varices. Endoscopic variceal band ligation (EVBL) is a less effective treatment modality for gastric varices than esophageal varices and is associated with high re-bleeding rates. N-butyl-2-cyanoacrylate (Histoacryl) injection is an effective and potential treatment option for fundal varices. This study aims to evaluate the safety and efficacy of n-butyl-2-cyanoacrylate injection therapy in cardio-fundal varices. Objective To assess the efficacy and safety of n-butyl-2-cyanoacrylate injection therapy for fundal varices. Methods This retrospective observational cohort study was conducted at the Department of Gastroenterology, Allied Teaching Hospital, Gujranwala, over one year. All patients, irrespective of age and gender, presenting with UGIB and in whom fundal varices were diagnosed on gastroscopy followed by n-butyl 2-cyanoacrylate injection therapy were included in this study. The efficacy and safety of Histoacryl therapy were assessed by analyzing successful hemostasis, frequency of re-bleeding, obliteration, and regression of fundal varices on repeat endoscopy. Adverse events such as re-bleeding and mortality related to fundal variceal treatment were documented. Results A total of 60 patients were included in the study. Of these, 70% had IGV1, while the remaining 30% had GOV2. Hemostasis was achieved in 100% of patients following n-butyl-2-cyanoacrylate injection. Successful obliteration with regression of varices was observed in 91.3% of patients. Various adverse events were observed, with abdominal pain being the most common observed complication in 18.3% of participants. However, only 8.3% of participants developed re-bleeding due to ulcer formation at the injection site, and no death occurred directly due to fundal variceal treatment. Conclusion N-butyl-2-cyanoacrylate injection therapy is a lifesaving, effective, and safe intervention for controlling bleeding from cardio-fundal varices, leading to improved health status and a consequent decrease in episodes of recurrent bleeding. Its side effects are few and infrequent. However, larger-scale studies are needed to further evaluate the safety and effectiveness of n-butyl-2-cyanoacrylate injection therapy. These studies will be crucial in establishing comprehensive guidelines for the management of fundal varices.

Prognosis prediction in cardiac amyloidosis by cardiac magnetic resonance imaging: a systematic review with meta-analysis.

Cardiac involvement is the foremost determinant of the clinical progression of amyloidosis. The diagnostic role of cardiac magnetic resonance (CMR) imaging in cardiac amyloidosis has been established, but the prognostic role of various right and left CMR tissue characterization and functional parameters, including global longitudinal strain (GLS), late gadolinium enhancement (LGE), and parametric mapping, is yet to be delineated. We searched EMBASE, PubMed, and MEDLINE for studies analysing the prognostic use of CMR imaging in patients with light chain amyloidosis or transthyretin amyloidosis cardiac amyloidosis. The primary endpoint was all-cause mortality. A random effects model was used to calculate a pooled odds ratio using inverse-variance weighting. Nineteen studies with 2199 patients [66% males, median age 59.7 years, interquartile range (IQR) 58-67] were included. Median follow-up was 24 months (IQR 20-32), during which 40.8% of patients died. Both tissue characterization left heart parameters such as elevated extracellular volume [hazard ratio (HR) 3.95, 95% confidence interval (CI) 3.01-5.17], extension of left ventricular (LV) LGE (HR 2.69, 95% CI 2.07-3.49) elevated native T1 (HR 2.19, 95% CI 1.12-4.28), and functional parameters such as reduced LV GLS (HR 1.91, 95% CI 1.52-2.41) and reduced LV ejection fraction (EF; HR 1.20, 95% CI 1.17-1.23) were associated with increased all-cause mortality. Unlike the presence of right ventricular (RV) LGE (HR 3.40, 95% CI 0.51-22.54), parameters such as RV GLS (HR 2.08, 95% CI 1.6-2.69), RVEF (HR 1.13, 95% CI 1.05-1.22), and tricuspid annular systolic excursion (TAPSE) (HR 1.11, 95% CI 1.02-1.21) were also associated with mortality. In this large meta-analysis of patients with cardiac amyloidosis, CMR parameters assessing RV and LV function and tissue characterization were associated with an increased risk of mortality.

Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart.

BACKGROUND: DNA methylation (DNAm) age acceleration (AgeAccel) and cardiac age by 12-lead advanced electrocardiography (A-ECG) are promising biomarkers of biological and cardiac aging, respectively. We aimed to explore the relationships between DNAm age and A-ECG heart age and to understand the extent to which DNAm AgeAccel relates to cardiovascular (CV) risk factors in a British birth cohort from 1946. RESULTS: We studied four DNAm ages (AgeHannum, AgeHorvath, PhenoAge, and GrimAge) and their corresponding AgeAccel. Outcomes were the results from two publicly available ECG-based cardiac age scores: the Bayesian A-ECG-based heart age score of Lindow et al. 2022 and the deep neural network (DNN) ECG-based heart age score of Ribeiro et al. 2020. DNAm AgeAccel was also studied relative to results from two logistic regression-based A-ECG disease scores, one for left ventricular (LV) systolic dysfunction (LVSD), and one for LV electrical remodeling (LVER). Generalized linear models were used to explore the extent to which any associations between biological cardiometabolic risk factors (body mass index, hypertension, diabetes, high cholesterol, previous cardiovascular disease [CVD], and any CV risk factor) and the ECG-based outcomes are mediated by DNAm AgeAccel. We derived the total effects, average causal mediation effects (ACMEs), average direct effects (ADEs), and the proportion mediated [PM] with their 95% confidence intervals [CIs]. 498 participants (all 60-64 years) were included, with the youngest ECG heart age being 27 and the oldest 90. When exploring the associations between cardiometabolic risk factors and Bayesian A-ECG cardiac age, AgeAccelPheno appears to be a partial mediator, as ACME was 0.23 years [0.01, 0.52] p = 0.028 (i.e., PM≈18%) for diabetes, 0.34 [0.03, 0.74] p = 0.024 (i.e., PM≈15%) for high cholesterol, and 0.34 [0.03, 0.74] p = 0.024 (PM≈15%) for any CV risk factor. Similarly, AgeAccelGrim mediates ≈30% of the relationship between diabetes or high cholesterol and the DNN ECG-based heart age. When exploring the link between cardiometabolic risk factors and the A-ECG-based LVSD and LVER scores, it appears that AgeAccelPheno or AgeAccelGrim mediate 10-40% of these associations. CONCLUSION: By the age of 60, participants with accelerated DNA methylation appear to have older, weaker, and more electrically impaired hearts. We show that the harmful effects of CV risk factors on cardiac age and health, appear to be partially mediated by DNAm AgeAccelPheno and AgeAccelGrim. This highlights the need to further investigate the potential cardioprotective effects of selective DNA methyltransferases modulators.