Minor Events Research Articles

Analysis of Adverse Reactions Associated with the Use of Crataegus-Containing Herbal Products

Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of Crataegus-containing products in humans. Methods: A scoping review of the literature about adverse reactions associated with Crataegus-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation’s global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. Results: The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes ‘gastrointestinal disorders’, ‘skin and subcutaneous tissue disorders’, ‘general disorders and administration site conditions’, ‘cardiac disorders’ or ‘nervous system disorders’. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. Conclusions: The results of our study provide deeper insight in the adverse reaction profile of Crataegus-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure.

The “Lochkovian-Pragian Event” re-assessed: New data from the low latitude shelf of peri-Gondwana

In the late Lochkovian a regression is documented in several areas of the world, followed by a transgression in the early Pragian. Connected with the eustatic variation, a minor extinction event occurred (“Lochkovian-Pragian Event”), affecting several fossil groups, a strong reduction of carbonate production and sedimentary facies changes. The Carnic Alps are a key area for studying this event, because lower Devonian rocks are widely exposed, representing diverse sedimentary environments from shallow water to relatively deep shelf. Fourteen sections were measured along the Carnic Alps across the Lochkovian-Pragian boundary. In the shallower part of the basin, both the Polinik and the Seekopf formations span the boundary, but evident erosional surfaces are observable in the field at the Lochkovian-Pragian boundary. Above the unconformity, at places the so-called megaclast horizon is present in the Seekopf Formation. In intermediate settings the Rauchkofel Fm. Is unconfomably followed by the Kellerwand Fm., and different parts of the upper Lochkovian and lower Pragian are missing in the various sections. In the deeper parts of the basin the transition from the La Valute Fm. To the Findenig Fm. Is slightly diachronous from the latest Lochkovian to the earliest Pragian; however, conodonts and tentaculitids are rare in the marly boundary beds, preventing a precise chronostratigraphic calibration of these levels. At places, evidence of subaerial exposure at the formational boundary is documented. In general, the hiatus seems to be larger in the western part of the Carnic Alps, in correspondence with the shallower parts of the succession, suggesting a sea level drop in the late Lochkovian, followed by a transgression in the Pragian. Data from the Carnic Alps are compared with those of other regions of North Gondwana to demonstrate that the sea-level variation at the Lochkovian-Pragian boundary are of global importance

Clinical and peri procedural outcomes using reduced dose prasugrel vs standard dose ticagrelor in elderly patients of acute coronary syndrome undergoing PCI

Abstract Introduction The novel antiplatelet agent prasugrel is generally not indicated in elderly(>75-years) patients in standard dose(60 mg loading and 10 mg maintenance) however, there is a scarce data on safety and efficacy of reduced dose prasugrel(30 mg loading and 5 mg maintenance dose) among elderly patients undergoing elective PCI. Some previous studies have raised concerns regarding the differences in pharmacodynamic and pharmacokinetic responses to prasugrel in asian ethnicities. The efficacy and safety of reduced dose prasugrel in elderly patients has not been investigated. Therefore, in this study we have compared the efficacy and safety of a reduced dose prasugrel with standard dose ticagrelor in elderly Indian patients undergoing elective PCI for acute coronary syndrome (ACS). Purpose To study the periprocedural and intermediate term clinical outcomes using reduced dose prasugrel versus standard dose ticagrelor in elderly Indian patients of acute coronary syndrome undergoing PCI. Methods This was a single centre, randomised, prospective cohort study. Based on the previous reference studies, at 95% level of significance and 80% of power, the sample size was calculated as 73 in each group. Study was conducted from May 2021 to October 2022 (18 months). Patients >75 years of age with ST-segment–elevation (STE) or Non ST elevation (NSTE) ACS treated with PCI were included. The study was approved by the institutional ethics review board. Participants were assigned to receive a standard dose of ticagrelor (180 mg loading followed by 90 mg twice daily, n=73) or a reduced dose prasugrel (30 mg loading followed by 5 mg once daily, n=73). The primary efficacy end point of the study was a composite of major adverse cardiac events (MACE) including cardiovascular mortality , non fatal MI and stroke. The secondary safety end points were major and minor bleeding events. Patients were followed up at 15 days, 3 months and 6 months. Results The baseline clinical and demographic characteristics were comparable in the both groups. The composite of primary efficacy end points at 6 months occurred significantly more in ticagrelor group vs reduced dose prasugrel group(13.7% vs 4.1% P value=0.05) and composite of secondary safety end point were comparable in both the groups(21.9% vs 16.4% respectively, p=0.44). Dyspnoea was seen more frequently in standard dose ticagrelor group as compared to reduced dose prasugrel group (15.1% vs. 6.8% respectively, p value=0.133). Conclusion The results of our study indicate that the reduced dose prasugrel is safe in elderly patients, has similar bleeding events as compared to standard dose ticagrelor group and is better tolerated. The reduced dose prasugrel is significantly more efficacious as compared to standard dose ticagrelor in elderly patients in terms of reduced MACE events. Although large scale randomized studies may be warranted in such populations to draw a broader conclusion.Baseline characteristicsEnd results

Efficacy and safety of reduced-dose and slow-infusion intravenous alteplase regimen in patients with acute pulmonary embolism at intermediate-high-risk

Abstract Background In patients with intermediate-high-risk (IHR) pulmonary embolism (PE), full-dose systemic thrombolytic treatment (STT) has been documented to lower the risk of hemodynamic decompensation and mortality, at the expense of an elevated risk of life-threatening bleeding. In this study, we aimed to evaluate the safety of reduced-dose STT regimen while maintaining effective reperfusion. Methods This single-center study comprised 124 retrospectively evaluated patients (female 58.9 % and mean age 55.4+15.8 years) diagnosed with acute PE at IHR status in accordance with European Society of Cardiology (ESC) 2019 acute PE guidelines in whom intravenous (i.v.) alteplase treatments were utilized. Patients fulfilling at least one of the following criteria have been included in the study: systolic blood pressure ≤ 110 mm Hg, heart rate > 100 bpm, SaO2 < 90 % on room air, respiratory rate > 20 breaths per minute, or serum lactate > 2 mmol/L. Exclusion criteria were any contraindication for STT and symptom onset > 14 days. Standard protocol for initial STT was i.v. infusion of alteplase of 25 mg over 4-6 hours. After completion of the infusion, a second STT in the same manner if one of the following criteria were present; heart rate > 100 bpm, SaO2 < 90 % or signs of organ hypoperfusion. Results Syncope and concomitant deep vein thrombosis were documented in 27.4 % and 49.2 % of patients, respectively. Baseline vital measures were as follows; heart rate: 112 +16.6 bpm, systolic blood pressure: 123+14.9 mm Hg, SaO2: 89 % (85-93), serum lactate 2.35 (1.6-2.9) mmol/L. Median alteplase dose and infusion duration were 50 (25-50) mg and 6 (4-10) hours, respectively. There were significant improvements in clinical parameters, pulmonary thrombus burden, pressure strain and right ventricular size and function as assessed by computed tomography and echocardiography (p< 0.001 for all). Minor and major bleeding events occurred in 3.2 % and 4.8 % of patients, respectively. One major bleed was due to cerebellar hemorrhage, but did not require surgery and patient was discharged without sequela. There were 6 (4.8 %) in-hospital deaths in which 2 were attributed to major hemorrhages and 4 due to hemodynamic decompensation. Conclusion In patients with acute IHR PE, reduced-dose and slow-infusion i.v. alteplase regimen seems to be a clinically relevant and safe reperfusion alternative to full-dose STT protocols associated with well-known major bleeding risks.

Implementation of a Standardized Tool for Root Cause Analysis Selection.

This study sought to determine if a standardized root cause analysis (RCA2) selection algorithm, developed by the Veterans Affairs, would select high-risk events for RCA. Physician-entered incident reports for all surgical service admissions and perioperative visits were queried over 12 months in the DATIX Clinical Incident Management System. Independent reviewers assigned potential harm and event frequency scores using an institutional scoring system and then calculated and rounded average scores. These were classified using RCA2 terminology (catastrophic, major, moderate, minor for harm; frequent, occasional, uncommon, remote for frequency). The scores were then evaluated with the standardized Safety Assessment Code Matrix (SAC) algorithm from the National Patient Safety Foundation's RCA2 guidelines to determine Potential Harm Scores. The SAC combines severity and probability to determine the necessity of conducting an RCA. Catastrophic and major high-frequency events (matrix score = 3) were classified as "RCA recommended." The study then compared cases selected for RCAs using the updated RCA2 algorithm against cases selected using a current, institutional-specific RCA selection process. One hundred four cases were reviewed, comprising 20 catastrophic, 48 major harm, 26 moderate harm, and 10 minor harm events. After removing 9 high-variance cases, our institution's current selection process selected 18 cases for RCAs, including 6/20 catastrophic, 8/39 major harm, and 4/36 moderate/minor harm events. Only 17.3% of cases had an RCA completed, while the standardized RCA2 algorithm recommended investigation for 56.7% of patient safety events, based on SAC Matrix scoring. Current RCA selection processes rendered 4 RCAs on low potential harm or low-frequency events, while 45 potential high-frequency, high potential harm events did not complete RCAs. Standardizing the selection of patient safety incidents for RCA using the RCA2 algorithm improves case identification based on the event frequency and potential harm score. Thus, this algorithm has the potential to advance patient safety.

Lumen-apposing metal stents for anastomosis creation throughout the gastrointestinal tract: A large single-center experience.

The introduction of lumen-apposing metal stents (LAMSs) has revolutionized the field of therapeutic endoscopic ultrasound. This study aims to evaluate the efficacy and safety of LAMS in creating an endoscopic ultrasound-guided anastomosis between two segments of the gastrointestinal (GI) tract. Data from all consecutive LAMS procedures for anastomosis creation between two segments of the GI, conducted between October 2019 and February 2024, were retrospectively analyzed for technical success (defined as correct deployment of the LAMS in the target), clinical success (defined as achievement of the intended clinical goal), and adverse events. A total of 145 LAMS procedures were performed in 136 patients. Indications for LAMS procedures included the need for endoscopic access to or reversal of surgically excluded segments of the GI tract (n = 73, 50.3%), and the alleviation of any GI outflow obstruction (n = 72, 49.7%). The overall technical and clinical success rates were very high (97.2% and 95.2%, respectively). Adverse events were observed in 20/145 (13.8%) cases, including 11 (7.6%) minor events (AGREE <3) and nine (6.2%) major events (AGREE ≥3). Major events included stent migration (n = 1), persisting fistula (n = 3), and bleeding (n = 4). All adverse events were successfully managed, and there were no procedure-related deaths. Loss of LAMS patency occurred in 4/145 (2.8%) cases and could be endoscopically managed in all cases. The creation of anastomoses with LAMS between two segments of the GI tract appears to be effective and safe, with a low reintervention rate due to loss of LAMS patency.

Comparison of Thromboembolic Complications After Carotid Artery Stenting with and without Using Protection Devices: A Systematic Review and Meta-Analysis Study

Background: This study compared the rate of thromboembolic events during carotid angioplasty and stenting (CAS) with and without embolic protection devices (EPDs). We reviewed literature to find studies comparing embolic event rates during CAS with and without EPDs and conducted a meta-analysis to determine the safer approach.Methods: The Embase, PubMed, and Web of Science databases were thoroughly searched following PRISMA guidelines. Each estimation was executed using random-effects models. The I2 index was used to assess the heterogeneity among the studies. Egger and Begg’s tests were applied to evaluate publication bias. Stata version 14.2 was used for statistical analysis.Results: For 25% of patients, an EPD was used during CAS, and for 75% it was not. Of the patients undergoing CAS, the prevalences of hypertension, diabetes mellitus, coronary artery disease, and cigarette smoking were 81%, 37%, 39% and 43%, respectively. In total, of the patients included 52% were symptomatic and 48% were asymptomatic. The mortality rate reduced from 2% in the no-EPD subgroup to 1% in the EPD subgroup. The occurrence of all other complications was also reportedly higher in patients who did not receive an EPD, including major stroke and myocardial infarction, except for minor events, which were reported to be almost the same in both subgroups.Conclusions: We found that the use of an EPD can help reduce the occurrence of thromboembolic complications of CAS, including myocardial infarction, major stroke, and death. Altogether, our results suggest that the benefits of using an EPD during CAS outweigh its risks.

An Evaluation of the Safety of Half-Dose Direct Oral Anticoagulants Following Total Joint Arthroplasty: A Pilot Study.

Background Total joint arthroplasty (TJA) patients on preoperative anticoagulation therapy present a challenge for adult reconstructionsurgeons. The goal in managing such patients is to limit bleeding complications associated with administering the medications while preventing medical complications from withholding them. At our institution, we began a protocol in 2017 that utilizes a half-dose direct oral anticoagulant (DOAC) regimen for one week followed by resuming of the full-dose regimen in select patients who underwent TJA. This study investigated the 90-day safety profile associated with this protocol compared to previous literature. Methodology A retrospective review of 898 patients from a single institution was conducted including allpatients receiving a half-dose DOAC protocol for one week followed by resuming of the full-dose regimen after total knee and total hip arthroplasty between 2017 and 2022. Data were collected on patient demographics, type of surgery, and DOAC dosage. Ninety-day complications were collected and separated into reduced dose complications of DOAC (such as cerebrovascular accidents (CVAs) or venothrombotic events (VTEe)) and DOAC therapy-related complications (including wound and bleeding complications). Results In the total hip arthroplasty (THA) subgroup (n = 396, 44.10%), there were four major VTE occurrences, aligning with therange seen in historical protocols. Deep vein thrombosis (DVT) and pulmonary embolism (PE) incidents were three and one, respectively, both within the historical range. In the total knee arthroplasty (TKA) subgroup of 502 (55.90%) patients, there were seven major VTE events, with five DVTs and two PEs, also aligning with historical ranges. Medical complications in the THA group included no CVA events and one myocardial infarction, with the latter slightly higher than the historical range. In the TKA group, there were two medical complications, both being CVAs. Regarding bleeding complications, THA patients showed four major bleeding incidents, two blood transfusions, and two hemorrhages, with these numbers comparable to or lower than historical ranges. There were seven minor bleeding events. For TKA, there were two major bleeding events, two blood transfusions, no hemorrhages, and five minor bleeding events. Wound complications in THA included five surgery-related complications, two cases of wound dehiscence, and three infections. TKA patients experienced 17 surgery-related complications, six cases of wound dehiscence, and 11 infections. Conclusions This study suggests that the half-dose DOAC protocol in patients undergoing TJA is non-inferior to historical full-dose DOACprotocolswarranting further investigation to generalize across broader populations.

Procedural Sedation and Analgesia in an Australian Emergency Department: Results of the First 3 Months of a Procedural Sedation Registry

Background: Procedural sedation and analgesia (PSA) is commonly performed in emergency departments (EDs) to reduce anxiety, discomfort, or pain during a procedure. The primary goal of PSA is to produce a state of relaxation and drowsiness without eliminating the patient’s protective reflexes. Despite the discovery of new techniques and medications to deliver PSA, there is a paucity of research evaluating PSA in EDs over the last decade. We aim to describe the current practice of PSA in an Australian tertiary mixed ED with 75,000 presentations per year. Methods: A retrospective study of the initial 3 months of a PSA registry, which was part of the Tasmanian Emergency Care Outcomes Registry, was analyzed; Results: All told, 80 consecutive cases were entered over a 3-month period, with pediatric patients (&lt;14 years old) making up 35% of all cases. Joint reductions (17, 39%) and fracture reductions (13, 29%) were the most common indications for the adult population, whilst fracture reductions (9, 36%), laceration repairs (7, 28%), and other distressing procedures (7, 28%) were the most common indications in the pediatric cohort. Pharmacological approaches also differed between groups, with ketamine (25, 92%) preferred in the pediatric cohort whilst the combination of propofol and fentanyl (22, 42%) was preferred in the adult cohort. No adverse events were recorded in the pediatric cohort whilst 6 (8%) minor events occurred in the adult population, with no severe events occurring for either cohort. PSA also occurred more frequently at 0900–1000 and the incidence was reduced between 0000 and 0800. Conclusions: PSA is commonly performed in our tertiary mixed ED and is both safe and effective, with non-severe complication rates similar to those in the reported literature. Severe complications are rare and therefore a larger cohort will be required to assess this aspect. The approach to ED PSA is also different between pediatric and adult populations and therefore research needs to differentiate both populations.

Safety of Sofosbuvir-Based Direct-Acting Antivirals for Hepatitis C Virus Infection and Direct Oral Anticoagulant Co-Administration.

Background: Direct oral anticoagulants (DOACs) are recommended for the management of thrombosis prophylaxis, especially in patients with atrial fibrillation. As substrates of cytochrome P450 (CYP) 3A4 and/or P-glycoprotein, they are implicated in potential drug-drug interactions. NS5A/NS5B inhibitors are direct-acting agents (DAAs) against the Hepatitis C Virus (HCV) infection that exert a mild inhibition of P-glycoprotein without effects on CYP3A4. A DOAC and NS5A/NS5B inhibitor co-administration may lead to an increased risk of bleeding. Real-world data on the concomitant use of DOACs and DAAs are scarce. On this purpose, we perform a retrospective analysis on the risk of vascular adverse events (bleeding and thrombosis) among HCV patients under DOAC/DAA therapy, even in advanced liver disease. Methods: Between May 2015 and April 2023, patients treated with sofosbuvir-based DAA regimens and DOACs were consecutively included in this study from 12 Italian medical centers. Baseline characteristics, especially concerning bleeding risk and liver function, were collected. The occurrence of bleeding events, classified as major and minor, was the primary endpoint. Secondary endpoints were the rate of any thrombotic events and/or the need for discontinuation of one or both treatments. Moreover, a cohort of patients, matched by demographic characteristics (age and sex), that switched to vitamin K antagonists (VKAs) during the antiviral treatment was compared with the DOAC/DAA group. Results: A total of 104 patients were included. Thirty-eight of them (36.5%) were cirrhotic. Atrial fibrillation was an indication for anticoagulation in almost all cases (76%). Rivaroxaban (35.6%) was the most used DOAC, followed by apixaban (26.9%), dabigatran (19.2%) and edoxaban (18.3%). Sofosbuvir/velpatasvir (78.8%) was the most prescribed DAA, and all patients were already on anticoagulant therapy before the start of DAAs. During concomitant DOAC/DAA treatment, no major bleeding events were recorded, while four minor bleeding events occurred, but none resulted in DAA or DOAC discontinuation. At univariate analysis, the only additional risk factor statistically related to bleeding events was the anticoagulant therapy (hazard ratio [HR]: 13.2, 95% confidence interval 1,6-109). Performing an evaluation by a LOGIT binomial analysis with demographic characteristics, the antiplatelet therapy remained statistically associated to bleeding events. No significant differences were found in the rate of clinically relevant bleeding when the main population was compared with the VKA-switched cohort. A single major bleeding event leading to anticoagulation and DAA discontinuation was reported in VKA-switched matched cohort. Conclusions: In our study, the concomitant use of NS5A/NS5B inhibitors with DOAC showed good safety, and the only risk factor associated with bleeding events was the concomitant antiplatelet therapy. These findings support the use of DOACs during sofosbuvir-based HCV treatment, even in advanced liver disease. Replacing DOACs with VKAs does not appear to be of clinical benefit.

COVID-19 venous thromboembolism prophylaxis guidelines in pediatrics

IntroductionSARS-CoV-2 (COVID-19) infection and multisystem inflammatory syndrome in children (MIS-C) are risk factors for venous thromboembolism (VTE). Guidelines for VTE prophylaxis were established at our institution at the beginning of the pandemic. Patients who had any VTE risk factors in addition to COVID-19 met criteria for anticoagulation prophylaxis. Patients who were diagnosed with MIS-C met criteria regardless of additional risk factors. Materials and methodsWe conducted a retrospective review of patients admitted with COVID-19 or MIS-C to determine compliance with VTE prophylaxis guidelines and to evaluate the incidence of VTE and bleeding events in our population. Results and conclusionsAmong a total of 678 patients admitted with COVID-19 or MIS-C, 519 (76 %) patients met criteria for VTE prophylaxis and 348 (65.6 %) started prophylaxis. Logistic regression analysis identified a personal or family history of thrombosis or thrombophilia, diagnosis of MIS-C, admission to the intensive care unit, and presence of a central venous catheter as significantly associated with starting VTE prophylaxis. There were 18 patients who developed VTE. Minor bleeding events occurred in 19 patients (5 %), patient important bleeding, no intervention occurred in 8 patients (2 %), clinically relevant nonmajor bleeding in 8 patients (2 %), and major bleeding in 10 patients (3 %). The incidence of VTE in our patients with COVID-19 and MIS-C is similar to VTE rates at other institutions. We found that universally recognized VTE risk factors were appropriate to include as risk factors for thrombosis in hospitalized children with COVID-19 and MIS-C.

COMPARATIVE STUDY OF CLOPIDOGREL VS PRASUGREL IN PATIENTS UNDERGOING ELECTIVE PERCUTANEOUS CORONARY INTERVENTION (PCI)

Antiplatelet therapy is a cornerstone in managing patients undergoing percutaneous coronary intervention (PCI) to prevent thrombotic complications. Prasugrel and clopidogrel are two commonly used agents, but their comparative efficacy and safety remain a subject of ongoing research, particularly in elective PCI cases. Objective: This study aimed to compare the safety and efficacy of prasugrel and clopidogrel in patients undergoing elective PCI, focusing on clinical outcomes such as minor and major bleeding, stent thrombosis, and mortality. Methods: This retrospective cohort study was conducted at a tertiary care hospital in Pakistan between January and July 2024. A total of 200 patients undergoing elective PCI were included in the study. Patients received either clopidogrel (300 mg or 600 mg) or prasugrel (60 mg) as part of their antiplatelet therapy. Clinical outcomes were assessed, including minor and major bleeding, thrombosis, and death. Statistical analyses were performed using Pearson correlations, chi-square tests, and regression analysis. SPSS software (version 25.0) was used for data analysis, with statistical significance set at p &lt; 0.05. Results: Of the 200 patients, 48.5% were male, and 51.5% were female, with the majority aged between 61 and 70. Prasugrel (60 mg) was the most commonly used loading dose (35.5%). Minor bleeding events were significantly higher in the prasugrel group compared to the clopidogrel group (p = 0.05). However, no significant differences were observed in major bleeding, stent thrombosis, or mortality between the two groups. A positive correlation between minor bleeding and stent thrombosis was noted (p = 0.048), while regression analysis confirmed that prasugrel did not significantly increase the risk of major bleeding or death. Conclusion: Prasugrel was associated with a higher incidence of minor bleeding compared to clopidogrel, but both agents exhibited comparable safety profiles in terms of major bleeding, thrombosis, and mortality in patients undergoing elective PCI. The findings suggest that prasugrel can be considered a safe and effective alternative to clopidogrel in elective PCI, with careful patient selection to minimize bleeding risks.

Low Versus Standard Intensity Heparin Protocols in Adults Maintained on Extracorporeal Membrane Oxygenation: A Retrospective Cohort Study

Background: Patients maintained on extracorporeal membrane oxygenation (ECMO) often require systemic anticoagulation to prevent circuit clotting and systemic thromboembolic complications. The optimal intensity of anticoagulation to balance the risk of bleeding and prevention of thrombotic complications in this patient population is not well described. Objective: To compare bleeding events in patients on ECMO anticoagulated with standard vs low intensity heparin protocols. Methods: This single-center, retrospective cohort study included adult patients on VA- or VV-ECMO and anticoagulated with low or standard intensity heparin protocols. The primary outcome was the incidence of major bleeding; secondary outcomes included the incidence of minor bleeding, thrombotic complications, heparin-induced thrombocytopenia, in-hospital mortality, time in therapeutic range, anti-Xa correlation with aPTT, intensive care unit and hospital lengths of stay, oxygenator exchanges, and rate of protocol switching. Results: A total of 27 patients (14 low intensity, 13 standard intensity) were included. There were six major bleeding events in the low intensity group and four in the standard intensity group ( P = 0.69); there were four minor bleeding events in the low intensity group and five in the standard intensity group ( P = 0.69). Seven patients in the standard intensity group switched protocols; zero patients in the low intensity group switched protocols ( P = 0.002). There were no differences in any other outcomes. Conclusions: There was no difference in the incidence of any bleeding or thrombotic events when using a low vs standard intensity heparin protocol in patients on ECMO. A low intensity heparin strategy for patients on ECMO may be feasible and safe.

Semaglutide Versus Other Glucagon-Like Peptide-1 Agonists for Weight Loss in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.

Obesity places patients at higher risk for numerous problems, including prediabetes, type 2 diabetes mellitus (T2DM), hypertension, metabolic syndrome, cardiovascular disease, and nonalcoholic fatty liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are antidiabetic drugs that have a recognized effect on weight loss. This systematic review analyzed semaglutide against alternative GLP-1 agonists in facilitating weight loss and evaluated their associated adverse events (AEs) in diabetic patients. A systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed using PubMed, Embase, and Cochrane Library for studies comparing semaglutide and other GLP-1 RAs for weight loss. A narrative synthesis and meta-analysis using SPSS program version 29 were performed to analyze the differences in weight loss between cohorts. Nine studies with 5,445 patients whose mean age was 60.01 years (55.5-70) and mean follow-up of 32.5 weeks (4-58.7) were included. The meta-analysis showed that semaglutide had a greater mean weight loss compared to liraglutide (-6.08, 95% confidence interval (Cl) = -8.40, -3.75) and dulaglutide (-2.85, 95% CI = -5.59, 0.11). Tirzepatide had a greater mean weight loss compared to semaglutide (-3.78, 95% CI = -5.52, -2.04). Common AEs included minor and moderate gastrointestinal events. In conclusion, GLP-1 RAs have shown efficacy in reducing body weight in T2DM patients. Semaglutide, liraglutide, dulaglutide, tirzepatide, and exenatide demonstrated mean weight loss reductions of 4.81 kg, 2.81 kg, 4.03 kg, 9.7 kg, and 1.9 kg, respectively, with high rates of minimal to moderate-severity AEs.Semaglutide demonstrated increased numerical weight loss compared to its comparators (dulaglutide, liraglutide, and exenatide). However, tirzepatide, a dual-agonist, produced greater weight loss compared to semaglutide. The paucity of comparative head-to-head trials prevents a definitive conclusion of the superiority of one GLP-1 RA over another.

Crystals and melt inclusions record deep storage of superhydrous magma prior to the largest known eruption of Cerro Machín volcano, Colombia

Abstract Cerro Machín, a volcano located in the northern segment of the Andes, is considered one of the most dangerous volcanoes in Colombia with an explosive record that involves at least five plinian events. Prior studies focused on the last dome-building eruption have suggested the presence of a water-rich mid-crustal magma reservoir. However, no direct volatile measurements have been published and little work has been completed on the explosive products of the volcano. Here, we study the largest known eruption of Cerro Machín volcano which occurred 3600 yr BP producing dacitic pyroclastic fall deposits that can be traced up to 40 km from the vent. Lapilli pumice clasts have a mineral assemblage of plagioclase, amphibole, quartz, and biotite phenocrysts, with accessory olivine, Fe-Ti oxides, and apatite. The occurrence of Fo89-92 olivine rimmed by high Mg# amphibole and the established high-water contents in the magma imply the presence of magma near or at water saturation at pressures &amp;gt;~500 MPa. Measurements of up to 10.7 wt% H2O in melt inclusions hosted in plagioclase and quartz in the 3600 years BP eruption products support the idea that Cerro Machín is a remarkably water-rich volcanic system. Moreover, this is supported by measurements of ~103 – 161 ppm H2O in plagioclase phenocrysts. The application of two parameterizations of water partitioning between plagioclase and silicate melt allows us to use our water in plagioclase measurements to estimate equilibrium melt water contents of 5 ± 1 – 11 ± 2 wt% H2O, which are in good agreement with the water contents we measured in melt inclusions. Results of amphibole geobarometry are consistent with a magma reservoir stored in the mid-to-lower crust at a modal pressure of 700 ± 250 MPa, corresponding to a depth of ~25 km. Minor crystallization in the shallow crust is also recorded by amphibole barometry and calculated entrapment pressures in melt inclusions. Amphibole is present as unzoned and zoned crystals. Two populations of unzoned amphibole crystals are present, the most abundant indicate crystallization conditions of 853 ± 26 °C (1 se; standard error), and the less abundant crystallized at an average temperature of 944 ± 24 °C (1 se). Approximately 18% of the amphibole crystals are normally or reversely zoned, providing evidence for a minor recharge event that could have been the trigger mechanism for the explosive eruption. Plagioclase crystals also show normal and reverse zoning. The moderate Ni concentrations (&amp;lt;1600 μg/g) in the high-Fo olivine xenocrysts suggest that Cerro Machín primary magmas are generated by inefficient interaction of mantle peridotite with a high-silica melt produced by slab melting of basaltic material. Some sediment input is also suggested by the high Pb/Th (&amp;gt;2.2), Th/La (0.3 – 0.4), and low La/Th (&amp;lt;13; relative to mantle array) ratios. Whole rock chemistry reveals heavy rare earth element (HREE) depletion and Sr enrichment that likely formed during the crystallization of garnet and amphibole in the upper part of the mantle or lower portion of the crust, promoting the formation of water-rich dacitic magma that was then injected into the middle-to-lower crust. Textural and compositional differences in the crystal cargo that erupted during dome-building and plinian events support the idea that large volumes of magma recharge lead to effusive eruptions, while only small recharge events are needed to trigger plinian eruptions at Cerro Machín.

The efficacy of aspirin versus low-molecular-weight heparin for venous thromboembolism prophylaxis after knee and hip arthroplasty: A systematic review and meta-analysis of randomized controlled trials.

The purpose of this study was to assess the efficacy of aspirin versus low-molecular-weight heparin (LMWH) in preventing venous thromboembolism (VTE) following hip and knee arthroplasty. PubMed/Medline, Embase, Cochrane Library and Google Scholar databases were searched from inception till June 2024 for original trials investigating the outcomes of aspirin versus LMWH in hip and knee arthroplasty. The primary outcome was VTE. Secondary outcomes included minor and major bleeding events, and postoperative mortality within 90 days. This review was conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 7 randomized controlled trials with 12,134 participants were included. The mean ages for the aspirin and LMWH cohorts were 66.6 (57.6-69.0) years and 66.8 (57.9-68.9) years, respectively. There was no statistically significant difference in the overall risk of VTE between the aspirin and the LMWH cohorts (odds ratio [OR]: 0.95; 95% confidence interval [CI]: 0.48-1.89; p: 0.877). A subanalysis based on the specific VTE entity (pulmonary embolism [PE] or deep venous thrombosis) showed a significantly higher PE risk for patients receiving aspirin than the LMWH cohort (OR: 1.79; 95% CI: 1.11-2.89; p: 0.017). There was no difference in minor (OR: 0.64; 95% CI: 0.40-1.04; p: 0.072) and major bleeding (OR: 0.77; 95% CI: 0.40-1.47; p: 0.424) episodes across both groups. Furthermore, subanalysis among the total knee arthroplasty group showed that the aspirin cohort was significantly more likely to suffer VTEs than their LMWH counterparts (OR: 1.55; 95% CI: 1.21-1.98; p < 0.001). This study demonstrated a significantly higher risk of PE among patients receiving aspirin compared to LMWH following hip or knee arthroplasty for osteoarthritis. Aspirin was associated with a significantly higher overall VTE risk among patients undergoing knee arthroplasty, in particular. This might suggest the inferiority of aspirin compared to LMWH in preventing VTE following such procedures. Level I.

Impact on ventricular arrhythmic burden of SGLT2 inhibitors in patients with chronic heart failure evaluated with cardiac implantable electronic device monitoring

BackgroundSodium-glucose cotransporter 2 (SGLT2) inhibitors have revolutionized the therapeutic scenario of heart failure, demonstrating favorable effects on mortality and quality of life. Previous studies have yielded conflicting data regarding the effects on ventricular arrhythmias. MethodsA prospective observational study was conducted to investigate the anti-arrhythmic properties of SGLT2 inhibitors evaluating the intra-patient difference in major adverse arrhythmic cardiac events (MAACE) over a six-month period in patients with chronic heart failure who were undergoing continuous monitoring using a cardiac implantable electronic device. ResultsFrom January 2022 to January 2023, 82 patients [median age 63 years (IQR 15), male 87 %] were enrolled in the study, with a median follow-up of 28 weeks (IQR 5). The rate of MAACE at baseline was 11 %, without relevant differences in the follow up in terms of major and minor arrhythmic events. In patients with an arrhythmic phenotype at baseline, a mild but non statistically significant reduction of MAACE (from 36 % to 28 %, p = 0.727) was observed and a significant decrease of non-sustained ventricular tachycardia (from 68 % to 32 %, p = 0.022). ConclusionsOur findings suggest potential anti-arrhythmic properties of SGLT2 inhibitors, evident in patients with arrhythmic events before the initiation of the drug.

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.

Evaluation of anti-XA-guided versus APTT-guided management of intravenous unfractionated heparin in patients requiring a durable ventricular assist device

ObjectiveThe objective of this study was to compare the effectiveness and safety of anti-Xa-guided management versus aPTT-guided management of intravenous (IV) unfractionated heparin (UFH) in patients with a durable ventricular assist device (VAD). Materials and methodsThis was a retrospective study conducted at a single academic medical center. Patients were included if they had a durable VAD and were managed using aPTT-guided UFH management from May 2019 to May 2020 or were managed using anti-Xa-guided UFH management from May 2021 to December 2021. The primary outcome of the study was the median time to goal anticoagulation post-initiation of UFH. Secondary outcomes included the percentage of time within the therapeutic range and the incidence of thromboembolic and bleeding complications. ResultsThe study included 23 patients, 12 of whom were managed using anti-Xa-guided UFH, and 11 were managed using aPTT-guided UFH. The treatment arm using anti-Xa-guided UFH demonstrated a faster time to therapeutic anticoagulation goal range with a median time of 21.3 h [IQR = 12.2–34.8] compared to 37.3 h [IQR = 41–74] in the aPTT-guided UFH treatment arm (P = 0.03). In addition, the anti-Xa-guided UFH arm had a higher percentage of time within the therapeutic range, 76 % [IQR = 64.25–96.25] compared to 53 % [IQR = 41–74] in the aPTT-guided UFH arm (P = 0.04). Both arms had no significant differences in major bleeding events (P = 0.59) or clinically relevant minor bleeding events (P = 0.60) among patients. There was no incidence of thromboembolic events in either treatment arm. ConclusionBased on this single-center experience, anti-Xa-guided UFH management resulted in a faster time to therapeutic anticoagulation and a longer time within the desired therapeutic range. The results suggest that anti-Xa-guided monitoring may be superior to UFH-guided monitoring in patients with a durable VAD.

Half-dose ticagrelor versus standard-dose clopidogrel in a dual antiplatelet regimen for stent-assisted coiling or flow diversion of unruptured intracranial aneurysms: a cohort study

BackgroundIntracranial hemorrhage is the major safety concern of standard-dose ticagrelor (90 mg twice daily) based dual antiplatelet therapy (DAPT). The bleeding avoidance strategy through dose de-escalation has been investigated in...