Total Events Research Articles

Comparative Efficacy and Safety of Intramedullary Lengthening Nails vs. Alternative Techniques for Femoral Limb Lengthening: A Systematic Review and Meta-Analysis.

Limb lengthening procedures are performed for various indications, including limb length discrepancies (LLDs) and short stature. This systematic review and meta-analysis compares the efficacy and safety of the newer motorized intramedullary lengthening nails (MILNs) with the traditional alternative techniques (ATs) for femoral limb lengthening. We conducted a comprehensive literature search in the Medline, Embase, Cochrane, Web of Science, and Scopus databases, inclusive of all dates through July 1, 2023, and without language restrictions. Factors mediating outcomes included problems, obstacles, complications, total adverse events, healing/consolidation index, time to full weight-bearing, lengthening accuracy, percentage of lengthening goal achieved, and duration of hospital stay. Effect sizes were quantified using STATA 17.0. Statistical algorithms employed were random effects model standardized mean differences (SMDs) for continuous outcomes and log risk ratios (RRs) for dichotomous outcomes, both with 95% confidence intervals (CIs). Our meta-analysis included 10 studies comparing MILN with AT: 180 femurs in the MILN group and 160 femurs in the AT group. This was exclusively comprised of retrospective cohort studies. When compared with AT, limb lengthening procedures utilizing MILNs had significantly lower problems (log RR, -1.35; 95% CI, -1.93 to -0.77; p < 0.001), complications (log RR, -0.56; 95% CI, -0.90 to -0.22; p = 0.001), and total adverse events (log RR, -0.69; 95% CI, -1.17 to -0.21; p = 0.005), as well as a superior bone healing index (SMD, -0.80; 95% CI, -1.32 to -0.28; p = 0.003). However, no significant differences were found in obstacles, percentage of lengthening goal achieved, lengthening accuracy, time to full weight-bearing, and duration of hospital stay. Limb lengthening with MILNs vs. AT may offer more favorable patient outcomes, lowering risk for problems, complications, and total adverse events, while optimizing the bone healing/consolidation index. However, the limitation of nonrandomized retrospective studies and high heterogeneity should be acknowledged. Level II (meta-analysis of cohort studies). See Instructions for Authors for a complete description of levels of evidence.

TQB2450 with or without anlotinib as maintenance treatment in subjects with locally advanced/unresectable non-small cell lung cancer that have not progressed after prior concurrent/sequential chemoradiotherapy (R-ALPS): study protocol for a randomized, double-blind, placebo-controlled, multicenter phase III trial.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). TQB2450 (benmelstobart) is a novel humanized immunoglobulin G1 monoclonal antibody against programmed death-ligand 1 (PD-L1). Anlotinib, an oral multitargeted anti-angiogenic agent with potential synergy with ICIs, has shown efficacy in relapsed and advanced NSCLC. Accumulating preclinical data suggest a synergism between immunological and anti-angiogenic therapies through the improvement of the immune microenvironment of the tumor. In this study, we hypothesized that the combination of TQB2450 and anlotinib as maintenance treatment would enable further improvements in the outcomes of patients with locally advanced/unresectable NSCLC without driver mutations that have not progressed after definitive chemoradiotherapy. The Radiotherapy and Anlotinib Let PD-L1 Superb (R-ALPS) study is a randomized, double-blind, placebo-controlled, multicenter phase III study (Clinicaltrials.gov identifier, NCT04325763). A total of 534 eligible participants will be randomized to receive TQB2450 (1,200 mg) plus anlotinib (8 mg), or TQB2450 (1,200 mg) plus placebo, or placebo as maintenance therapy. Progression-free survival (PFS), assessed by the independent review committee is the primary endpoint. The secondary endpoints include additional measures of efficacy, safety, and biomarkers. An interim analysis of the effectiveness will be conducted when 70% (286 cases) of the total PFS events have been reached. The development of the R-ALPS study will contribute to a deeper insight into the interplay between immunotherapy and anti-angiogenic therapy and thus might expand the treatment options available to patients with locally advanced or unresectable NSCLC. Clinicaltrials.gov identifier: NCT04325763. Date of registration: May 27, 2020. Protocol version: Version 4.0, Sep 16, 2022 (https://classic.clinicaltrials.gov/ct2/show/NCT04325763).

Genomic and transcriptomic perspectives on the origin and evolution of NUMTs in Orthoptera

Nuclear mitochondrial pseudogenes (NUMTs) result from the transfer of mitochondrial DNA (mtDNA) to the nuclear genome. NUMTs, as “frozen” snapshots of mitochondria, can provide insights into diversification patterns. In this study, we analyzed the origins and insertion frequency of NUMTs using genome assembly data from ten species in Orthoptera. We found divergences between NUMTs and contemporary mtDNA in Orthoptera ranging from 0 % to 23.78 %. The results showed that the number of NUMT insertions was significantly positively correlated with the content of transposable elements in the genome. We found that 39.09 %-68.65 % of the NUMTs flanking regions (2000 bp) contained retrotransposons, and more NUMTs originated from mitochondrial rDNA regions. Based on the analysis of the mitochondrial transcriptome, we found a potential mechanism of NUMT integration: mitochondrial transcripts are reverse transcribed into double-stranded DNA and then integrated into the genome. The probability of this mechanism occurring accounts for 0.30 %-1.02 % of total mitochondrial nuclear transfer events. Finally, based on the phylogenetic tree constructed using NUMTs and contemporary mtDNA, we provide insights into ancient evolutionary events such as species-specific “autaponumts” and “synaponumts” shared among different species, as well as post-integration duplication events.

Multicenter retrospective cohort study demonstrates superior safety profile of indobufen over aspirin for Post-CABG antiplatelet therapy.

Coronary artery bypass grafting (CABG) is essential for treating coronary artery disease, with postoperative aspirin crucial to prevent graft restenosis. However, its gastrointestinal side effects may limit tolerability in some patients. Indobufen presents a potential alternative, but its safety and efficacy need further validation. This study aimed to compare the efficacy and safety of indobufen versus aspirin in patients' post-CABG. This retrospective observational study included 39 patients who underwent CABG at two centers from January to December 2023. Patients were retrospectively assigned to two groups based on the antiplatelet therapy they received: the indobufen group (n = 19) and the aspirin group (n = 20). The primary endpoint was a composite of non-fatal myocardial infarction, stroke, and revascularization due to acute coronary syndrome in the intention-to-treat population. Postoperative data on platelet count, hemoglobin, D-dimer, activated partial thromboplastin time (APTT), and hospital stay length were collected. Transfusion rate, bleeding, thrombotic events, and gastrointestinal adverse reactions were compared between the two groups. Over the 8-to-18-month follow-up period, 5 patients (25%) in the aspirin group reached the primary endpoint, while none in the indobufen group did, a difference that was statistically significant (p = 0.02). Although the rates of non-fatal myocardial infarction, revascularization, stroke, and thrombotic events were higher in the aspirin group, these differences did not reach statistical significance. Importantly, the total bleeding events were markedly lower in the indobufen group (15.79% vs. 55%, p = 0.011), with major bleeding events also significantly reduced in the indobufen group (0% vs. 20%, p = 0.04). Both groups showed no significant differences were observed in postoperative hospital stay, hemoglobin, and D-dimer levels between the groups. However, the indobufen group demonstrated significantly lower platelet count and APTT. The average daily cost of indobufen was 27.8 times higher than that of aspirin. Indobufen demonstrates a comparable antiplatelet effect to aspirin and offers significant advantages in reducing gastrointestinal adverse reactions and bleeding risk. It can be considered a preferable alternative for patients who cannot tolerate or have contraindications to aspirin. Further large-scale clinical trials are needed to confirm its potential as the first-choice antiplatelet therapy post-CABG.

Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure with Mildly Reduced and Preserved Ejection Fraction: a Prespecified Analysis of The FINEARTS-HF Trial.

The effect of treatments for heart failure may vary among patients according to left ventricular ejection fraction (LVEF). In the FINEARTS-HF, the nonsteroidal MRA finerenone reduced the risk of cardiovascular death and total worsening heart failure events in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). We examined the effect of finerenone according to LVEF in FINEARTS-HF. FINEARTS-HF was a randomized, placebo-controlled trial examining the efficacy and safety of finerenone in patients with heart failure and LVEF &#x226540%. The treatment effect of finerenone was examined in prespecified analyses according to LVEF categories (<50%, ≥50 to <60%, and ≥60%) and with LVEF as a continuous variable. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. Baseline LVEF data were available for 5993 of the 6001 participants in FINEARTS-HF. Mean and median LVEF were 53 ± 8% and 53% (IQR 46% -58%), respectively. LVEF was <50% in 2172 (36), between 50 to <60% in 2674 (45%), and ≥60% in 1147 (19%). Patients with a higher LVEF were older, more commonly female, were less likely to have a history of coronary artery disease, and more frequently had a history of hypertension and chronic kidney disease compared to those with a lower LVEF. Finerenone reduced the risk of cardiovascular death and total heart failure events consistently across LVEF categories: LVEF <50% rate ratio (RR) = 0.84 (95% CI 0.68, 1.03), LVEF ≥50 to <60% RR = 0.80 (0.66, 0.97) and LVEF ≥60% RR = 0.94 (0.70, 1.25); p interaction = 0.70. There was no modification of the benefit of finerenone across the range of LVEF when analyzed as a continuous variable (p interaction = 0.28). There was a similar consistent effect of finerenone on reducing the total number of worsening heart failure events (continuous p interaction = 0.26). In patients with HFmrEF/HFpEF, finerenone reduced the risk of cardiovascular death and worsening heart failure events, irrespective of LVEF.

Finerenone Improves Outcomes in Patients with Heart Failure with Mildly Reduced or Preserved Ejection Fraction Irrespective of Age: A Prespecified Analysis of FINEARTS-HF.

Background: Finerenone improves outcomes in patients with HF and mildly reduced or preserved ejection fraction (HFmrHF/HFpEF). It is important to understand the efficacy and safety of finerenone in these patients according to age. Methods: The aim of this analysis was to evaluate the interaction between age and the efficacy and safety of finerenone in the FINEARTS-HF trial (Finerenone trial to investigate efficacy and safety compared to placebo in patients with heart failure). A total of 6,001 patients aged 40-97 years were stratified by quartile (Q 1-4) of baseline age: Q1 40-66 years (n=1,581), Q2 67-73 years (n=1,587), Q 3 74-79 years (n=1,421), and Q4 ≧ 80 years (n=1,412). FINEARTS-HF evaluated the impact of age on the efficacy of finerenone with respect to the primary composite outcome of cardiovascular death and total (first and recurrent) HF events, including HF hospitalization or urgent HF event, along with secondary efficacy and safety outcomes. Results: The incidence of primary outcome increased with age. Finerenone reduced the risk of the primary outcome consistently across all age categories: RR (95% CI) Q1 0.70 (0.53- 0.92), Q2 0.83 (0.64-1.07), Q3 0.98 (0.76-1.26), and Q4 0.85 (0.67-1.07); p for interaction =0.27. Similarly, a consistent effect was observed for the components of the primary outcome. The mean increase in Kansas City Cardiomyopathy Questionnaire-total symptom score from baseline to 12 months was greater with finerenone than placebo, with a consistent effect across all age categories: mean placebo-corrected change (95% CI) Q1 2.87 (1.09-4.66), Q2 1.24 (-0.59-3.07), Q3 0.94 (-0.98-2.86), and Q4 1.24 (-0.90-3.38); P-interaction=0.50. Adverse events were similar across all age categories. The odds of experiencing hypotension, elevated creatinine, or hyperkalemia (increased) or hypokalemia (decreased) related to finerenone did not differ by age. Conclusions: In the FINEARTS-HF trial, finerenone reduced the primary outcome and components of the primary outcome, and improved symptoms across a wide age spectrum. In addition, finerenone was safe and well-tolerated, irrespective of age. Trial Registration: URL: https://clinicaltrials.gov Unique Identifiers: NCT04435626 and EudraCT 2020-000306-29.

Efficacy of Rituximab in Autoimmune-Mediated IgG4 Pancreaticobiliary Disease: A Systematic Review and Meta-Analysis.

IgG4 pancreaticobilliary disease (IgG4-PBD) typically shows a rapid improvement with glucocorticoid treatment, yet most patients experience a recurrence. Rituximab (RTX) has emerged as a hopeful approach to prevent relapses in IgG4-PBD. Nevertheless, there is a lack of data on the efficacy and safety of RTX in IgG4-PBD. In this study, we aim to perform a systematic review and meta-analysis to study the pooled efficacy of RTX in this patient population. Multiple databases, including MEDLINE, SCOPUS, and Embase, were searched (in March 2024) using specific terms for studies evaluating the efficacy and safety of RTX in IgG4 pancreatic biliary disease. Outcomes of interest were relapse, remission, partial remission rates, and adverse events. Standard meta-analysis methods were used using the random-effects model. I2% heterogeneity was used to assess the heterogeneity. Twelve studies were included in the study (257 patients). The pooled rate of complete remission was 68% (54% to 80%), I2 =53%, respectively. The pooled relapse rate was 23% (13% to 36%), I2=64%. The pooled rate of total adverse events was 21% (12% to 35%), I2=52%. The pooled partial remission rate is 16% (7% to 32%), I2=25%. The pooled rate of complete and partial remission was 81% (66% to 90%), I2=75%. The pooled infusion reaction and infection were 12% (7% to 18%), I2=0% and 14% (8% to 22%), I2=16%, respectively. RTX therapy appears effective in inducing and maintaining remission of pancreaticobiliary disease with a low rate of side effects. RTX presents as a promising treatment option for patients grappling with recurrent or unresponsive IgG4-related ailments. In addition, RTX emerges as an attractive alternative for individuals intolerant to steroids or experiencing IgG4-related disease relapses. Future studies comparing RTX with other immunomodulators will offer deeper insights into relapse factors and elucidate the appropriateness of utilizing this maintenance treatment following the initial flare.

Parasitic behaviour and developmental morphology of Anastatus japonicus reared on the factitious host Antheraea pernyi.

The egg parasitoid Anastatus japonicus is a key natural enemy in the biological control of various agricultural and forestry pests. It is particularly used against the brown marmorated stink bug Halyomorpha halys and the emerging defoliator pest Caligula japonica in East Asia. It has been proved that the eggs of Antheraea pernyi can be used as a factitious host for the mass production of A. japonicus. This study systematically documented the parasitic behaviour and developmental morphology exhibited by A. japonicus on the eggs of A. pernyi. The parasitic behaviour of A. japonicus encompassed ten steps including searching, antennation, locating, digging, probing, detecting, oviposition, host-feeding, grooming, and resting. Oviposition, in particular, was observed to occur in three stages, with the parasitoids releasing eggs during the second stage when the body remained relatively static. Among all the steps of parasitic behaviour, probing accounted for the longest time, constituting 33.1% of the whole time. It was followed by digging (19.3%), oviposition (18.5%), antennation (9.6%), detecting (7.4%), and the remaining steps, each occupying less than 5.0% of the total event time. The pre-emergence of adult A. japonicus involves four stages: egg (0 to 2nd day), larva (3rd to 9th day), pre-pupa (10th to 13th day), pupa (14th to 22nd day), and subsequent development into an adult. Typically, it takes 25.60 ± 0.30 days to develop from an egg to an adult at 25℃. This information increases the understanding of the biology of A. japonicus and may provide a reference for optimising reproductive devices.

Exploring variations in flood events and casualties over Yamuna River basin, India

ABSTRACT The current study seeks to investigate the temporal and spatial distribution of flood events and casualties in the Yamuna River basin from 1978 to 2014. The data were compiled from the published reports on disastrous weather events and analyzed with simple quantitative methods (sums, averages, and percentages). The analysis revealed the occurrence of a total of 1886 flood events, which resulted in 5481 casualties (148 per year). The years 1995, 2003, 1993, and 1996 were observed as the most devastating years, contributing about 30 percent of the total flood events, while 1978, 1980, 1981, 1995, 2006, and 2013 were the deadliest years in terms of casualties (47 percent). The largest number of flood events and casualties were recorded during June–September months. Considering the event/casualty density and rates, the states of Himachal Pradesh and Uttarakhand experienced the highest event density (0.036 and 0.091) and casualty rates (2.1 and 1.9 persons). These findings will help in identifying and demarcating the worst flood-affected areas over the Yamuna River basin, which can subsequently help in reducing the flood risk and human casualties in these regions after initiating suitable flood mitigation measures.

An Enhanced LPRAFF with Tri-State Inverter Embedded Non-Clock Gating via the CT-GWO Algorithm

Since a long time ago, it has been understood how radiation affects digital circuits, particularly those using the Complementary Metal Oxide Semiconductor (CMOS) model. Total Ionisation Dose (TID) and Single Event Effects (SEE) are the two most significant radiation effects. Depending on the gate input count, the complexity of the circuit will rise, which will worsen the radiation and raise the cumulative dose levels. The incremental dose level affects the circuit parameter failure, which affects how well the logic design functions. Many authors concentrate on minimising the effects of radiation while preventing function loss, but these extra efforts use excess energy. To improve the efficiency of the Low Power Radiation Aware (LPRA) circuit, this paper introduces optimisation concepts in a Flip Flop (FF) architecture named Chaos Theory-based Grey Wolf Optimised FF (CT-GWOFF). First, compute each component's radiation response using a physics-based modelling strategy. To minimise undesirable latches and disable the inverter chain when the input data remain constant, a tri-state inverter, incorporating a non-clocked gating mechanism, is provided. This prevents repeated transitions of delayed clock signals. Moreover, the proposed model is implemented in FFs for simulation purposes, making it more cognizant of radiation effects and power consumption. Using the HSPICE tool, the performance of the suggested circuit design is evaluated at the 16 nm CMOS Predictive Technology Model (PTM).

A national analysis of systemic adverse events of beta-blockers used for glaucoma therapy

Purpose To evaluate systemic complications for timolol, carteolol, levobunolol, and/or betaxalol by using an FDA Federal Adverse Event Reporting System (FAERS) Methods We evaluated FAERS for adverse events associated with β-blocker use for glaucoma. All reported symptoms were reviewed to identify systemic adverse events and to detect safety signals, defined as information on a new or known side effect that may be caused by a medicine. We used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC) as a part of a disproportionality analysis comparing the frequency of β-blocker symptoms with all other adverse event reports. We considered a signal to be detected when all four disproportionality analysis metrics were positive. Results We found 10,500,309 total adverse event reports from the FAERS database 2004-2022Q3, which included 8,793 case reports with a primary suspect of a β-blocker use for glaucoma. 1,838 unique adverse symptoms were reported were associated with β-blocker. Regarding outcomes, there were 165 (1.88%) reports of disability, 671 (7.63%) reports of hospitalisation, and 1,934 (21.99%) reports of some other unspecified complication. Regarding adverse events, the most reported general, cardiac, and respiratory symptoms were respectively dizziness (n = 281), bradycardia (n = 145), and dyspnoea (n = 195). 256 (2.91%) cases of death were reported. We found significant signals on bradycardia (n = 145), complete atrioventricular block (n = 38), and bronchospasm (n = 23). No allergic, endocrine, constitutional, or gastrointestinal symptoms generated positive signals. Conclusion β-blocker use in glaucoma therapy can be rarely associated with serious systemic and life-threatening complications.

Fishing event detection and species classification using computer vision and artificial intelligence for electronic monitoring

Fisheries regulations require detailed catch reporting on commercial fishing vessels. Vital components for the sustainable management of fish stocks include a robust estimate of the number of fish caught and the species composition. Catch recording is often done manually by human observers on fishing vessels. Human observers are costly, and consistent data streams can be subject to observer availability and the weather. On-vessel cameras (electronic monitoring, EM) are a growing alternative to human observers. However, on-land human auditors are required to review hundreds of hours of videos recorded during fishing trips that can last for weeks. In this paper, a framework is presented to automatically detect fish in EM videos, count the total fishing events, and classify the fish species. For this purpose, a deep learning and computer vision-based model is developed to efficiently detect fish and fishers onboard a vessel. Secondly, a vision-based tracking pipeline tracks the detected fish and counts the total fishing events in the videos. Thirdly, the extracted fishing events are classified through a deep learning-based fish species classifier, to provide the distribution of different fish species caught for a fishing trip. For our experiments, the datasets were prepared using the electronic monitoring data of multiple fishing trips of a fishing vessel. The videos were recorded on Australian longline vessels targeting tunas and billfish. For the fish detection task, video frames were extracted and labelled manually to provide a digital ground-truth. For the fish species classification task, hundreds of fish images of multiple species were cropped to provide a training dataset for the fish classifier. For the fish counting task, manual counts for the fishing events of individual fish species were generated for the test fishing trips. The developed fish and fisher detector achieves a mean Average Precision of 87.0 % for fish and 94.0 % for fishers on test video frames. The fishing event detection pipeline achieves an Average Precision of 81.0 % and an Average Recall of 74.5 % on test videos. The fish species classifier achieves an Accuracy (Top-1) of 91.11 % for the classification of cropped fish images and 89.05 % for the classification of extracted fishing events from the videos. Experimental results show that our proposed computer vision and artificial intelligence-based solution for video analysis has great potential to automate the auditing process from electronic monitoring footage and contribute to the sustainable management of fish stocks.

Personality vulnerability to depression, resilience, and depressive symptoms: epigenetic markers among perinatal women.

We examined differences in DNA methylation patterns in the NR3C1 and FKBP5 genes in relation to personality vulnerability to depression, resilience, and perinatal depressive symptoms, whilst also considering possible moderating effects of childhood traumatic events. N = 160 perinatal women were assessed at late pregnancy and 1 year postpartum for personality vulnerability to depression, resilience, depressive symptoms, and childhood traumatic events with self-reported questionnaires. NR3C1 and FKBP5 methylation markers were analyzed via sodium bisulfite sequencing. Associations of methylation markers with the above mentioned variables were tested using multivariable regressions. NR3C1 methylation at CpGs 1, 4 and average methylation sites were negatively associated with resilience; NR3C1 methylation at CpG 2 was positively associated with postpartum depressive symptoms; methylation at CpG 4 was positively associated with prenatal depressive symptoms. The interaction between current distress due to interpersonal traumatic events and NR3C1 CpG sites in relation to personality vulnerability was significant on CpG sites 3 and 4, whereas the interaction between current distress due to total traumatic events and NR3C1 in relation to personality vulnerability was significant on CpG site 2. FKBP5 showed no significant associations with the outcomes. This study identified associations between NR3C1 methylation and resilience as well as perinatal depressive symptoms. Interestingly, an interaction between early trauma and personality vulnerability was noted. Our findings on these specific DNA methylation markers may, if replicated and integrated into risk prediction models, contribute to early diagnosis of mothers at risk, targeted health promotion, and early interventions.

Seismic trend analysis: a data mining approach for pattern prediction

&lt;span lang="EN-US"&gt;In the global context, seismic movements represent a constant for the population due to geophysical variability and other factors that make them possible, carrying with them the risk of losing innocent lives. The main purpose of our research is to apply data mining techniques to prevent seismic events of any magnitude to anticipate and mitigate future events. In the development of the research, we applied knowledge discovery database methodology. The clustering analysis results revealed the following: cluster 0 encompassed 45 items, with average magnitude of 0.230, representing 15.5% of the total events. Cluster 1 comprised 56 items with average magnitude of 0.156, equivalent to 19.2% of the total. Cluster 2, the largest, consisted of 94 items with average magnitude of 0.156, constituting 32.3% of the total seismic events. Cluster 3 was composed of 54 items, with average magnitude of 0.155, representing 18.3% of the total. Lastly, cluster 4 included 42 items, with average magnitude of 0.155, representing 14.5% of the total. In conclusion, cluster 3 emerged as the most significant, with 94 events and average magnitude of 0.141, equivalent to 32.3% of the total seismic events. This discovery underscores the need to utilize data mining techniques for earthquake prediction, enabling proactive measures against potential events, which are frequent in various geographic areas.&lt;/span&gt;

Low-Intensity Heparin Infusion Compared With High-Intensity Heparin Infusion Dosing in Patients With Mechanical Mitral Valves: A Retrospective Cohort Study.

Patients with a mechanical mitral valve have an increased risk of thrombosis, and guidelines recommend a higher international normalized ratio goal for vitamin K antagonists-based anticoagulation. Guidelines provide recommendations for bridging with unfractionated heparin; however, there is no clear guidance on the heparin infusion intensity that should be used. This study was a retrospective, single-center, cohort study of patients aged ≥18 years or older with a mechanical mitral valve admitted from June 2019 to September 2022 who were maintained on a singular heparin infusion intensity nomogram for at least 48 hours. The patients were stratified into either a low- or a high-intensity heparin infusion nomogram. The exclusion criteria included non-nomogram heparin infusions and patients within 30 days of valve implantation. The primary outcome of this study was a composite of all bleeding events (major, clinically significant nonmajor, and minor bleeding). The secondary outcomes included bleeding events, analyzed individually, and thrombotic events. Seven total bleeding events were observed between the 2 groups, with 1 minor bleeding event in the low-intensity group and 6 bleeding events in the high-intensity group. One thrombotic event occurred in the high-intensity group. No statistically significant differences were found between the primary and secondary outcomes. Future studies are necessary to guide heparin infusion intensity selection in patients with mechanical mitral valves.

Increased kidney stone risk following total pancreatectomy with islet autotransplantation

Background/objectivesChronic pancreatitis (CP) is associated with increased risk of calcium-oxalate kidney stones, likely due to enteric hyperoxaluria. However, the risk of kidney stones for patients with CP after total pancreatectomy with islet autotransplantation (TPIAT) is unknown. We aimed to evaluate kidney stone risk in patients with CP after TPIAT. MethodsA retrospective analysis of 629 patients who underwent TPIAT was conducted to identify patients who developed kidney stones post-TPIAT. Kaplan-Meier analysis estimated time to first event. An Anderson-Gill proportional-hazards analysis of all kidney stone events described key clinical associations. ResultsMean age at TPIAT was 33 years (SD 15.3, range 3–69); 69.8 % (n = 439) were female. The estimated chance of any kidney stone episodes by 5 years post-TPIAT was 12.8 % (95 % CI: 8.8–16.6 %); by 10 years, 23.2 % (CI: 17.5–28.6 %); by 15 years, 29.4 % (CI: 21.8–36.2 %). Significant associations with kidney stones post-TPIAT included older age (HR 1.25 per 10 years), smoking history (HR 1.72), mild chronic kidney disease (HR 1.96), renal cysts (HR 3.67), pre-TPIAT kidney stones (HR 4.06), family history of kidney stones (HR 4.10), and Roux-en-Y reconstruction (HR 2.68). Of the 77 patients who developed kidney stones, 34 (44.1 %) had recurrent episodes. Of 143 total kidney stone events, 35 (24.5 %) required stone removal, 79 (55.2 %) resolved spontaneously, and 29 (20.3 %) were missing this data. ConclusionsPatients with CP post-TPIAT commonly have kidney stones: nearly 3 in 10 have ≥1 kidney stone episodes within 15 years. Clinicians should be aware of this risk and counsel patients on prevention.

Finerenone in Patients With a Recent Worsening Heart Failure Event: The FINEARTS-HF Trial.

Patients with heart failure (HF) and a recent worsening heart failure (WHF) event are known to be at high risk of recurrent hospitalization and death, regardless of ejection fraction. This study examined the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone in relation to the recency of a WHF event. FINEARTS-HF (FINerenone trial to investigate Efficacy and sAfety superioR to placebo in paTientS with Heart Failure) was a randomized, double-blind, placebo-controlled trial of finerenone in patients with HF and left ventricular ejection fraction≥40%. In this prespecified analysis, we assessed the risk of cardiovascular (CV) events and response to finerenone vs placebo in relation to the time from WHF to randomization (during or within 7days, 7days to 3months, >3months, or no prior WHF). The primary outcome was a composite of total (first and recurrent) WHF events and CV death, analyzed using a proportional rates method. Of 6,001 patients validly randomized to finerenone or placebo, 1,219 (20.3%) were enrolled during (749 [12.5%]) or within 7days (470 [7.8%]), 2,028 (33.8%) between 7days and 3months, and 937 (15.6%) >3months from a WHF event; 1,817 (30.3%) had no prior history of WHF. Rates of the primary composite outcome varied inversely with time since WHF, with >2-fold higher risk in those enrolled during or within 7days of WHF compared with those enrolled >3months from WHF or without prior WHF (risk ratio [RR]: 2.13; 95%CI: 1.82-2.55). Compared to placebo, finerenone appeared to lower the risk of the primary composite to a greater extent in those enrolled within 7days of WHF (RR: 0.74; 95%CI: 0.57-0.95) or between 7days and 3months of WHF (RR: 0.79; 95%CI: 0.64-0.97) than in those >3months from WHF or without prior WHF (RR: 0.99; 95%CI: 0.81-1.21); however, no definitive treatment-by-time interaction could be confirmed (P = 0.07). Greater absolute risk reductions with finerenone were accordingly seen in those with recent WHF (Ptrend=0.011). The risk of adverse events including hyperkalemia and worsening renal function among patients assigned to finerenone was not increased in those with recent WHF. Compared with those without recent WHF, patients with HF and mildly reduced or preserved ejection fraction who have experienced a recent WHF event are at higher risk for recurrent HF events and CV death; a possible signal of enhanced absolute treatment benefit with finerenone in this population requires further confirmation in future studies. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With HeartFailure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; A study to gather information on the influence of study drug finerenone on the number of deaths and hospitalizations in participants with heart failure EudraCT 2020-000306-29).

Effect of Finerenone on the KCCQ in Patients With HFmrEF/HFpEF: A Prespecified Analysis of FINEARTS-HF

BackgroundPatients with heart failure (HF) are limited by symptoms and have impaired quality of life. The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a patient-reported outcome measure that enables evaluation of the effect of HF and the impact of new therapies on health status in patients with HF. ObjectivesThis prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure) assessed the efficacy and safety of finerenone according to baseline KCCQ Total Symptom Score (TSS) and the effect of finerenone on KCCQ-TSS. MethodsFINEARTS-HF tested the efficacy of the nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone, compared with placebo, in patients with HF with mildly reduced ejection fraction/preserved ejection fraction. The primary endpoint was the composite of cardiovascular death and total worsening HF events. The KCCQ was completed by patients at randomization and at 6, 9, and 12 months after randomization. Change in KCCQ-TSS was a key secondary endpoint. Patients were stratified by KCCQ-TSS tertiles at baseline. The association between KCCQ tertile and clinical outcomes was evaluated using semiparametric proportional-rates models for total events and Cox models for time-to-first-event data, and the effects of finerenone vs placebo on the primary endpoint were assessed across tertiles of KCCQ-TSS. ResultsOf the 6,001 participants in FINEARTS-HF, 5,986 (99.8%) had baseline KCCQ-TSS recorded (median score 69.8 of a possible 100; higher score = better health status). Lower (worse) KCCQ-TSS was associated with a higher risk of the primary endpoint. Finerenone, compared with placebo, reduced the risk of the primary endpoint across the range of KCCQ-TSS: tertile 1 (score 0-<57): RR: 0.82 (95% CI: 0.68-1.00); tertile 2 (57-<81): 0.88 (95% CI: 0.70-1.11); tertile 3 (81-100): 0.88 (95% CI: 0.69-1.14) (Pinteraction = 0.89). Compared with placebo, finerenone significantly improved KCCQ-TSS from baseline with a mean difference at 12 months of 1.62 points (95% CI: 0.69-2.56 points) (P < 0.001). Numerically fewer finerenone-treated patients experienced clinically meaningful deterioration, and more had improvements in KCCQ-TSS. ConclusionsFinerenone significantly reduced HF events and improved health status in patients with HF and mildly reduced ejection fraction/preserved ejection fraction across the spectrum of KCCQ-TSS at baseline. (Study to Evaluate the Efficacy [Effect on Disease] and Safety of Finerenone on Morbidity [Events Indicating Disease Worsening] & Mortality [Death Rate] in Participants With Heart Failure and Left Ventricular Ejection Fraction [Proportion of Blood Expelled Per Heart Stroke] Greater or Equal to 40% [FINEARTS-HF], NCT04435626; Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure; EudraCT 2020-000306-29)

ApoA-I Infusions and Burden of Ischemic Events After Acute Myocardial Infarction: InsightsFrom the AEGIS-II Trial.

Following an acute myocardial infarction (AMI), patients remain at risk for subsequent cardiovascular (CV) events. In the AEGIS-II trial, CSL112, a human apolipoprotein A-I derived from plasma that enhances cholesterol efflux, did not significantly reduce the first occurrence of CV death, myocardial infarction (MI), or stroke through 90days compared with placebo. However, an analysis involving only the first event may not capture the totality of the clinical impact of an intervention because patients may experience multiple events. This prespecified exploratory analysis examines the effect of CSL112 on total burden of nonfatal ischemic events (ie, recurrent MI and stroke) and CV death. A total of 18,219 patients with AMI, multivessel coronary artery disease, and additional CV risk factors were randomized to either 4weekly infusions of 6g CSL112 (n=9,112) or matching placebo (n=9,107). Anegative binomial regression model was applied to estimate the effect of CSL112 compared with placebo on the rate ratio (RR) of ischemic events. For CV death, MI, and stroke, there were numerically fewer total events at 90days (503 vs 545 events; rate ratio [RR]: 0.88; 95%CI: 0.76-1.03, P=0.11), and nominally significantly fewer total events at 180 days (745 vs 821 events, RR: 0.87; 95%CI: 0.77-0.99; P=0.04) and 365days (1,120 vs 1,211 events; RR 0.89; 95%CI: 0.80-0.99; P=0.04). Subsequent events constituted 13% of events at 90days, 17% at 180days, and 22% at 1 year. Similar findings were seen with the total occurrence of nonfatal MI and CV death. When type II MIs, unlikely to be modified by enhancing cholesterol efflux, were excluded, there were nominally significant reductions in the total occurrence of nonfatal MI (excluding type 2) and CV death at all timepoints (90days: RR: 0.81; 95%CI: 0.68-0.97; P=0.02; 180days: RR: 0.82; 95%CI: 0.71-0.95; P< 0.01; 365days: RR: 0.86; 95%CI: 0.76-0.98; P=0.02). In this prespecified exploratory analysis of the AEGIS-II trial, 4weekly infusions of CSL112 among high-risk patients after AMI significantly reduced the total burden of nonfatal ischemic events and CV death at 180 and 365days compared with placebo. (AEGIS-II [Study to Investigate CSL112 in Subjects With Acute Coronary Syndrome]; NCT03473223).

The Safety of Calcium Channel Blockers in Controlling Blood Pressure During Cardiac Surgery: A Meta-analysis of Random Controlled Trials

Background: Intraoperative hypertension is a very common critical condition in cardiac surgery, which may lead to myocardial ischemia, affect the smooth progress of the operation, and even lead to the death of the patient. Therefore, it is necessary to manage perioperative hypertension in cardiac surgery. At present, there are various types of drugs for hypertension control in clinical practice, and it is necessary to select vasoactive drugs suitable for cardiac surgery. Methods: A systematic search was conducted in PubMed (Medline), Embase, and the Cochrane Library databases to compare the safety of calcium channel blockers and other antihypertensive drugs in controlling hypertension during cardiac surgery, with the search ending in July 2024. For continuous variables, we utilized combined weighted mean difference (WMD) with a 95% confidence interval (CI) and risk ratio (RR) with a 95% confidence interval to assess both efficacy and safety. Results: A total of six randomized controlled trials were included, with a total of 1886 patients. There was no significant difference in mortality between calcium channel blockers and other vasodilators (RR=0.75, 95% CI: 0.45,1.26, P =0.28; I2=0%, P=0.75). Also, there was no significant difference in the incidence of atrial fibrillation (RR=1.09, 95% CI: 0.94,1.26, P=0.26; I2=13%, P=0.33). In addition, there were no significant differences in the incidence of myocardial infarction (RR=0.76, 95% CI: 0.41,1.39, P=0.37; I2=0%, P=0.55) and renal insufficiency (RR=0.92, 95% CI: 0.65,1.31, P=0.66; I2=40%, P=0.19) between the two groups. Finally, there was no significant difference in the incidence of total adverse events between the two groups (RR=1.05, 95% CI: 0.87,1.27, P=0.60; I2=0%, P=0.68). Conclusion: Compared with other vasodilators, there is no significant difference in the safety of calcium channel blockers in controlling blood pressure in cardiac surgery.