Higher Risk Of Events Research Articles

Effectiveness of the GRACE risk score according to troponin elevation in patients admitted with non-ST elevation acute coronary syndrome: a post-hoc analysis of the UKGRIS cluster RCT

Abstract Background In the United Kingdom GRACE Risk Score (UKGRIS) phase 3 parallel group cluster randomised controlled trial, the Global Registry of Acute Coronary Events (GRACE) risk score (GRS) did not improve adherence to guideline recommended management or reduce cardiovascular events at 12 months in patients admitted with suspected non ST elevation acute coronary syndrome (NSTEACS) compared with standard care.(1) Troponin elevation in the context of NSTEACS is associated with high risk of adverse clinical events, including myocardial infarction, heart failure and death,(2) and in this population the GRS may impact on outcomes. Purpose To investigate the effectiveness of the GRS compared with standard care according to troponin elevation in patients admitted with NSTEACS. Methods Post-hoc analysis of primary and secondary outcome measures according to troponin elevation on admission of the UKGRIS trial across 42 sites in England. Patients aged ≥18 years admitted with suspected NSTEACS and a minimum follow-up of 24 months were eligible. Primary outcome measures were use of guideline recommended management and time to the composite of cardiovascular death, non-fatal myocardial infarction, new onset heart failure hospital admission, and readmission for cardiovascular event. Secondary measures included the duration of hospital stay, EQ-5D-5L (five domain, five level version of the EuroQoL index), and the composite endpoint components. Results A total of 3050 patients were randomised in UKGRIS, of whom 2602 had troponin elevation. The effect of GRS compared with standard care on the uptake of guideline recommended care was greater for participants with troponin elevation (odds ratio 1.34, 95% CI 0.84 to 2.13) compared to those without (0.88, 0.52 to 1.47) (Table 1). There was an interaction between troponin elevation and effect of GRS versus standard care on guideline uptake (relative odds ratio 1.52, 95% CI 1.16 to 2.00, P < 0.01). The time to the first composite event was not improved by the GRS among participants with (hazard ratio 0.86, 95% CI 0.67 to 1.12) or without troponin elevation (1.19, 0.80 to 1.77) (Figure 1), with no interaction (relative hazards ratio 0.73, 95% CI 0.51 to 1.03, P = 0.07), and none of the individual components of the composite outcome had a significant interaction between randomisation to GRACE and troponin elevation. Baseline adjusted EQ-5D-5L utility at 12 months and duration of hospital stay at 24 months were not statistically significantly different for the two trial arms among participants with or without troponin elevation. Conclusions For suspected NSTEACS, the effect of the GRS compared with standard care on uptake of recommended processes was greater in those with elevated troponin than in those without. However, this did not translate to a reduction in the composite primary outcomes or secondary outcomes at 24 months.

Typical profile of a patient with atrial fibrillation in the Russian population based on medical registries. A systematic review

Aim. To compare clinical and anamnestic characteristics of patients with atrial fibrillation (AF) included in three large international stu­dies assessing the efficacy and safety of therapy with direct oral anti­coagu­lants, with the profile of a typical Russian patient with AF in clinical practi­ce, established by medical registries in the Russian Federation (RF).Material and methods. A systematic review of scientific publications was con­ducted. The search was conducted in the E-library and Google Scholar databases. Publications from 8 registries of patients with AF, con­ducted in the Russian Federation from 2012 to 2023, were found, which present the clinical and anamnestic characteristics of patients. All studies included in the analysis meet the generally accepted require­ments for medical registries. The systematic review protocol was pre­viously recorded in the PROSPERO electronic database (CRD42024512425).Results. A Russian patient with AF is a patient with a large number of cardiovascular pathologies and a high risk of thromboembolic events. According to the analysis, Russian patient with AF has an average age of ~70 years. Most patients have a diagnosis of hypertension, heart failure, while from one third to half of patients have a diagnosis of chronic kidney disease. From 20 to 30% of patients have a history of myocardial infarction and every fifth patient has type 2 diabetes.Conclusion. In all countries around the world, including the Russian Fe­deration, for many years, medical registries have been one of the main sources of information on the characteristics of patients with AF and the disease course. They can supplement the available data from randomized clinical trials with real-world data. Comparison of clinical and anamnestic characteristics of patients in randomized clinical trials of direct oral anticoagulants with characteristics of patients in the Russian registries shows that patients included in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K An­tagonism for Prevention of Stroke and Embolism Trial in Atrial Fib­rillation (ROCKET AF trial) were most similar to Russian patients with AF.

Extracorporeal membrane oxygenation in critically ill patients with active hematologic and non-hematologic malignancy: a literature review.

Combined progress in oncology and critical care medicine has led to new aspirations and discussions in advanced life support modalities in the intensive care unit. Over the last decade, extracorporeal membrane oxygenation, previously considered unsuitable for oncologic patients, has become increasingly popular, with more diverse applications. Nevertheless, mortality remains high in critically ill cancer patients, and eligibility for extracorporeal membrane oxygenation can be extremely challenging. This scenario is even more difficult due to the uncertain prognosis regarding the underlying malignancy, the increased rate of infections related to intensive care unit admission, and the high risk of adverse events during extracorporeal membrane oxygenation support. With advances in technology and better management involving extracorporeal membrane oxygenation, new data on clinical outcomes can be found. Therefore, this review article evaluates the indicators for extracorporeal membrane oxygenation in different types of oncology patients and the possible subgroups that could benefit from it. Furthermore, we highlight the prognosis, the risk factors for complications during this support, and the importance of decision-making based on a multidisciplinary team in the extracorporeal membrane oxygenation indication.

Efficacy of Bile Acid Sequestrants in the Treatment of Bile Acid Diarrhea: A Meta-Analysis of Randomized Controlled Trials.

Bile acid sequestrants (BASs) have often been used for bile acid diarrhea (BAD) but carry a high risk of adverse events. New generations of BASs show promising results; however, their efficacy remains unclear. This systematic review and meta-analysis was conducted using PubMed, Cochrane, and Embase to assess randomized controlled trials (RCTs) published up to November 2023 to retrieve studies that measured the parameters before and after the administration of BASs. The outcomes assessed were cessation or improvement in diarrhea, fecal consistency, abdominal cramping, frequency of diarrhea, and adverse events. Risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled using a random-effects model. Statistical analyses were conducted using RStudio version 4.1.2. The protocol was prospectively registered with PROSPERO (CRD42023445444). Seven RCTs with a total of 311 patients were included, of which 168 (54%) were randomized to BASs. Among BAS-treated patients, 101 (60.1%) received colesevelam, 40 (23.8%) received chenodeoxycholate, 18 (10.7%) received cholestyramine, and 9 (5.3%) received colestid. BASs were associated with a significant improvement in the cessation of diarrhea (RR 3.27; 95% CI 2.08 to 5.15; P ≤ .05) and liquid stool to normal fecal consistency (RR 2.69; 95% CI 1.56 to 4.65; P ≤ .05), as well as an increase in abdominal cramps (RR 5.27; 95% CI 1.21 to 22.93; P ≤ .05). There were no differences in urgency, adverse events, or nausea between groups. These findings indicate that BASs are effective in the treatment of BAD, as indicated by the improvement or cessation of diarrhea episodes.

Minimalist approach to left atrial appendage occlusion through three-dimensional intracardiac echocardiography: Procedural steps and single-center experience

Atrial fibrillation (AF), the most prevalent arrhythmia worldwide, is associated with an annual risk of ischemic stroke of up to 5%, with approximately 98% of thrombi originating from the left atrial appendage (LAA). Direct oral anticoagulants or vitamin K antagonists remain the gold standard for preventing systemic thromboembolism in patients with AF. LAA occlusion (LAAO) is an alternative stroke prevention technique for patients with AF who cannot tolerate long-term anticoagulation. Percutaneous LAAO typically employs a multimodal imaging approach with contrast fluoroscopy and transesophageal echocardiography (TEE) for visualization, device selection and deployment, and complication monitoring. TEE is also used for follow-up imaging. However, it necessitates general anesthesia or deep sedation and is associated with a high risk of adverse events. Three-dimensional intracardiac echocardiography (3D ICE) has been proposed as a viable alternative to TEE for LAAO procedures. In this review, we summarized the current evidence regarding ICE guidance in LAAO procedures. We also presented a case series of consecutive patients presenting at our center who underwent LAAO, which was performed by a single operator using a minimalist approach of moderate sedation, 3D ICE, and same-day discharge. We also presented a summary of the minimalist approach to LAAO using 3D ICE and detailed procedural steps of 3D ICE catheter manipulation for successful LAAO intervention.

Variable-RBE-induced NTCP predictions for various side-effects following proton therapy for brain tumors – Identification of high-risk patients and risk mitigation

Background and purposeDisregarding the increase of relative biological effectiveness (RBE) may raise the risk of acute and late adverse events after proton beam therapy (PBT). This study aims to explore the relationship between variable RBE (above 1.1)-induced normal tissue complication probabilities (NTCP) and patient-specific factors, identify patients at high risk of RBE-induced NTCP increase, and assess risk mitigation by incorporating RBE variability into treatment planning. Materials and methodsWe retrospectively analyzed 105 primary brain tumor patients treated with PBT (RBE = 1.1). We calculated differences in estimated NTCP (ΔNTCP) using a variable RBE-weighted dose (DRBE, Wedenberg model) and a constant RBE-weighted dose (DRBE=1.1), across 16 NTCP models. These differences were correlated with patient-specific characteristics. Based on ΔNTCP, patients were classified as high risk (32 %) or low risk (68 %) for adverse events due to RBE-induced NTCP. This classification was compared with alternative classifications based on (a) relevant patient-specific characteristics, (b) DRBE=1.1, and (c) the difference between DRBE and DRBE=1.1 (ΔD), assessing the balanced accuracy. The potential to reduce RBE-induced NTCP through track-end and linear energy transfer (LET) optimization was evaluated in six example patients. ResultsUsing a variable RBE instead of a constant one resulted in NTCP increases (up to 32 percentage points). Variable-RBE-induced NTCP increases were strongly negatively correlated with the distance between the clinical target volume (CTV) and the organ at risk (OAR) for most side-effects, and positively correlated with CTV volume for certain side-effects. High increases were associated with (a) specific patient factors, particularly the proximity of the CTV to OARs, (b) DRBE=1.1, and (c) ΔD, with a balanced accuracy of 0.88, 0.94, and 0.86, respectively. Optimization of track-ends and LET considerably reduced NTCP values, achieving a mean reduction of 31 % for optimized OARs. ConclusionThe risk of variable-RBE-induced NTCP strongly depends on patient-specific factors and the considered side-effect. A small distance between the tumor and OARs notably increases the risk. Integrating biologically-guided objectives into treatment planning can effectively mitigate the risk.

A Systematic Review of Safety and Efficacy of Factor XI/XIa Inhibitors in Patients With ESKD on Hemodialysis

IntroductionFactor XI/XIa (FXI/XIa) has emerged as a potential target for antithrombotic therapy, driven by preclinical evidence showing a role of FXI/XIa inhibition for preventing thrombosis without impeding hemostasis. This is particularly promising for patients at high risk of both thromboembolic events and bleeding, such as patients with end-stage kidney disease (ESKD) on hemodialysis (HD). MethodsWe systematically searched Embase, MEDLINE, and ClinicalTrials.gov for randomized controlled trials evaluating FXI/XIa inhibitors in patients with ESKD on HD, without restricting inclusion to specific comparators or indications. Interventional treatment arms were pooled, and study results were synthesized by fitting random-effects models, calculating odds ratios (OR) and 95% confidence intervals (CI). ResultsFive phase II studies encompassing 1,270 participants were identified, investigating gruticibart, IONIS-FXIRx, osocimab, or fesomersen in the general HD population and using placebo as a comparator. Four studies were fully published and included in the meta-analysis. Use of FXI/XIa inhibitors was associated with an OR of 0.80 (95% CI, 0.47-1.35) for clinically relevant bleeding, 0.51 (95% CI, 0.21-1.28) for major bleeding, and 0.90 (95% CI, 0.49-1.68) for clinically relevant non-major bleeding. The ORs for thromboembolic events and all-cause mortality were 0.66 (95% CI, 0.28-1.56) and 0.46 (95% CI, 0.15-1.40), respectively. ConclusionCurrently available evidence does not indicate a significantly increased bleeding risk of FXI/XIa inhibitors in patients with ESKD on HD compared to placebo. Their efficacy and their association with all-cause mortality need to be investigated in sufficiently powered, randomized controlled phase III trials.

Outcomes and Cost-Effectiveness of an HER-Embedded AI Screener for Identifying Hospitalized Adults at Risk for Opioid Use Disorder.

NCT05745480.

Atherosclerotic vascular lesion in the coal industry workers of average and high fatal risk groups

Introduction. Experts do not take into account the presence of subclinical atherosclerosis when stratifying risk on the SCORE scale, however, it is the main substrate for the occurrence of cardiovascular disasters. Most primary cardiovascular events occur in low cardiovascular risk groups, which requires timely detection of atherosclerosis and preventive measures to preserve the working population's ability to work and reduce the economic burden of treatment of cardiovascular diseases. The study aims to research the incidence of atherosclerosis in workers of the main professions of the coal industry in the South of Kuzbass in groups of medium and high risk of fatal events on the SCORE scale. Materials and methods. We divided the subjects into two groups using the SCORE scale: high-risk (main) — from 5 to 9%, which included 60 people, and moderate-risk group — from 2 to 4% (comparison) — 70 employees. The average age of the first was 50.98±0.43 years, the comparison group was 49.96±0.35 years (p=0.070). The scientists examined the indicators of blood pressure, lipid, carbohydrate and purine metabolism, and performed an ultrasound examination of the main arteries. Results. The incidence of atherosclerotic plaques in at least one vascular basin was 80.0% in the main group and 78.6% in the comparison group, p=0.845. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The frequency of carotid artery atheromas in the high-risk group on the SCORE scale (52.7%) did not significantly differ from the comparison group (54.3%), p=0.862; a similar pattern in the arteries of the lower extremities: 80.0% vs. 70.0%, respectively, p=0.203. The combination of thickening of the intima of vessels and the presence of atheromas tended to be more frequent in the main group — 83.6% compared with those in the comparison group — 70.1%, p=0.076 Limitations. The study is limited by the number of examined patients who underwent periodic medical examination at the Scientific Research Institute of Complex Problems of Hygiene and Occupational Diseases. Conclusion. The incidence of atherosclerosis among employees of coal enterprises turned out to be very high and did not statistically differ in the groups of medium and high fatal risk stratified on the SCORE scale, which requires more thorough screening and measures of enhanced angioprotective prevention, even in people with a low risk of fatal cardiovascular disasters. Ethics. All the subjects signed an informed consent to participate in the study, the Protocol of which corresponded to the requirements of the Bioethical Committee of the Research Institute of Complex Problems of Hygiene and Occupational Diseases, executed in accordance with the Helsinki Declaration of the World Medical Association "Ethical Principles of conducting medical research with human participation as a subject" as amended in 2013 and the "Rules of Good Clinical Practice" approved by the order Ministry of Health of the Russian Federation No. 200n dated April 1, 2016.

12273 Do The First 48 Hours Of Hospitalization Require More Vigilance In Geriatric Patients At Risk Of Hypoglycemia?

Abstract Disclosure: S. Ravi: None. H. Afsana: None. Hypoglycemia (HG; blood glucose <70 mg/dL) is a commonly encountered problem in hospitalized patients and is associated with significant morbidity and mortality as well as increased healthcare costs. Elderly patients are particularly vulnerable to HG as they are more likely to have autonomic dysfunction, resulting in fewer discernible symptoms as well as an impaired counterregulatory response, making it more likely that events go undetected and uncompensated. A survey of the literature identifies a number of risk factors for developing HG, including nephropathy, liver disease, infection, cognitive dysfunction, as well as sulfonylurea and long-term insulin use. Given the significant risks posed by HG, we pose the question: how can we do better to identify geriatric patients at high risk of HG events? In this retrospective chart review, data was collected from charts of patients aged 65-99 years with HG, who presented to the ED and were hospitalized for various reasons at a community hospital. Patients were included if a diagnosis of HG was documented in the EMR during hospitalization regardless of diagnosis of Diabetes Mellitus (DM). In 219 total individuals, potential associated variables were analyzed using descriptive statistics, chi-square tests, and Fisher’s exact tests. When data was not complete for any individual variables, the incomplete data was excluded during respective analysis. Among 219 patients, 128 (58.45%) presented at the time of admission, 33 (15.07%) presented within 24 hours after, 15 (6.85%) presented between 24 - 47 hours after, and 43 (19.63%) presented ≥48 hours after admission. Overall, 80.37% of HG events occurred within the first 48 hours of hospitalization. Interestingly there was no significant relationship identified between severity of HG events and HbA1c. The percent distribution identified delayed or missed meals (33%), insulin use (26%), and infection (8%), as the most common potential causes. These findings suggest that it is beneficial to extend the suspicion of HG events to all geriatric patients, regardless of diagnosis of DM. While validated tools have been proposed to identify diabetic patients at risk for HG, fewer studies have been done to identify potential markers of HG risk in all geriatric patients. It may be that the first 48 hours pose a critical period to identifying and better managing these patients’ blood sugars. While use of continuous glucose monitoring in the inpatient setting has been proposed as a potential solution, other cost-effective methods include ensuring timely delivery of meals and food intake, as well as closer finger stick glucose monitoring in the first 48 hours. Higher powered studies across a wider variety of clinical settings are required to further investigate hypoglycemic events in geriatric patients and to synthesize validated assessment tools. Presentation: 6/2/2024

7834 Case Series using intravenous insulin to treat Severe Hypertriglyceridemia

Abstract Disclosure: F. Khan: None. M. Eltayeb: None. J. Ryan: None. M. Murphy: None. Background: Very severe hypertriglyceridemia (>22.4 mmol/L) is associated with high risk of acute pancreatitis and atherosclerotic cardiac events. Conventional treatments tend not to yield immediate results. There is a lack of clinical guidelines for acute very severe HTG; and potential therapeutic options such as insulin, heparin, plasmapheresis, and octreotide have been tested and shown to be effective. We present a series of four cases where intravenous insulin was useful as an emergency treatment for severe HTG. Clinical Cases: Case 1: 48-year-old male was admitted with very severe hypertriglyceridemia with triglycerides levels of 45.3mmol/L (reference range: 0-1.7 mmol/L), new diagnosis Diabetes Mellitus with ketosis and was started on intravenous insulin. After three days of intravenous insulin, triglyceride levels reduced by 47.93%. Case 2: 28-year-old male, admitted with acute pancreatitis secondary to very severe hypertriglyceridemia (66.9mmol/L), a new diagnosis of Diabetes Mellitus with ketosis, was commenced on intravenous insulin. There was a reduction in triglycerides by 77.5% in 3 days and 96.6% in 9 days with intravenous insulin treatment. Case 3: 29-year-old female, admitted with new diagnosis Diabetes Mellitus with ketosis and very severe hypertriglyceridemia (50.67mmol/L) was treated with intravenous insulin. Total triglyceride reduction was 65.8% in 48 hours. Case 4: 27-year-old female, admitted Diabetic Ketoacidosis (DKA), new diagnosis Diabetes Mellitus, very severe hypertriglyceridemia (24.3mmol/L) was treated with intravenous insulin. 65.8% reduction in triglycerides was seen in after 72 hours. Conclusion: These cases show the efficacy of insulin infusion with encouraging results, especially when plasmapheresis is not readily available however larger studies including a randomized controlled trials is needed to confirm the efficacy and safety for the use of intravenous insulin to establish a universal and effective treatment for this severe life-threatening metabolic disorder. Reference: Simha V. Management of hypertriglyceridemia BMJ 2020; 371 :m3109 doi:10.1136/bmj.m3109 Presentation: 6/3/2024

Transcarotid arterial revascularization for symptomatic carotid web

ObjectivesSymptomatic carotid web is an increasingly recognized cause of acute ischemic stroke with a high risk of recurrent ischemic events despite aggressive medical interventions. Surgical interventions including transfemoral carotid artery stenting (TFCAS) and carotid endarterectomy have been described to reduce this risk, but transcarotid arterial revascularization (TCAR) has not been evaluated for this purpose. Materials and MethodsPatients with cerebral ischemia from carotid web underwent TCAR with flow reversal. Patients were monitored for periprocedural complications and assessed at follow-up for clinical evidence of recurrent ischemia. ResultsSix cases over the course of 21 months were identified, 2 males and 4 females with a median age of 59.5 (interquartile range of 39). All underwent technically successful TCAR without periprocedural complications no post-procedural cerebral ischemia over a median follow-up time of 21 months. ConclusionsIn this small series of patients, TCAR provided a safe and effective treatment of carotid webs that had previously caused cerebral ischemia.

Presence of Atherosclerosis in Multiple Arterial Beds is Associated with Increased Mortality in Patients Undergoing Endovascular Aortic Aneurysm Repair

Patients with polyvascular disease are considered high risk for major adverse cardiac events (MACEs). This retrospective study utilised the Vascular Quality Initiative (VQI) database to quantify the effect of polyvascular disease on outcomes after endovascular aneurysm repair (EVAR). The VQI database was queried from to 2012 - 2022 for elective EVAR. Patients were identified as having peripheral arterial disease, coronary artery disease, or cerebrovascular disease, and then stratified based on the number of arterial beds involved (one to three). Primary outcomes were peri-operative death and MACEs. Multivariate analysis was performed to find associations between comorbidities and primary outcomes. Of the 21 160 patients with arterial disease included in the study, 83.7% were male and the mean age was 73.73 ± 8.57 years. After stratification, 16 892 patients had atherosclerosis in one arterial bed, 3 869 in two arterial beds, and 399 in three arterial beds. Pre-operatively, patients with atherosclerosis in three arterial beds were more likely to have hypertension, diabetes, and renal failure (all p < .001). Post-operatively, patients with disease in three arterial beds were more likely to experience a post-operative complication (11.5% vs. 8.3% vs. 5.4%; p < .001), including MACE (4.6% vs. 4.1% vs. 2.8%; p < .001) and death (3.0% vs. 2.5% vs. 1.7%; p < .010). On multivariate analysis, polyvascular disease was associated with MACEs (odds ratio 1.54, 95% confidence interval 1.29 - 1.84; p < .001). Kaplan-Meier analysis estimates showed statistically significant differences in survival at approximately the three year follow up (p < .001). In this review of patients undergoing elective EVAR, patients with polyvascular disease experienced worse peri-operative outcomes, including death and MACEs, the latter of which was confirmed on multivariable analysis. These patients should be considered high risk and managed accordingly.

Body temperature, systemic inflammation and risk of adverse events in patients with acute coronary syndromes.

Inflammatory processes can trigger acute coronary syndromes (ACS) which may increase core body temperature (BT), a widely available low-cost marker of systemic inflammation. Herein, we aimed to delineate baseline characteristics of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS) patients stratified by initial BT and to assess its predictive utility towards major adverse cardiovascular events (MACE) after the index ACS. From 2012 until 2017, a total of 1044 ACS patients, 517 with STEMI and 527 with NSTE-ACS, were prospectively recruited at the University Hospital Zurich. BT was measured by digital tympanic thermometer along with high-sensitivity C-reactive protein (hs-CRP) and cardiac troponin-T (hs-cTnT) levels prior to coronary angiography. Patients were stratified according to initial BT and uni- and multivariable regression models were fit to assess associations of BT with future MACE risk. Among patients with STEMI, BT was not predictive of 1-year MACE, but a U-shaped relationship between BT and MACE risk was noted in those with NSTE-ACS (p = .029), translating into a 2.4-fold (HR, 2.44, 95% CI, 1.16-5.16) increased 1-year MACE risk in those with BT >36.8°C (reference: 36.6-36.8°C). Results remained robust in multivariable-adjusted analyses accounting for sex, age, diabetes, renal function and hs-cTnT. However, when introducing hs-CRP, the BT-MACE association did not prevail. In prospectively recruited patients with ACS, initial BT shows a U-shaped relationship with 1-year MACE risk among those with NSTE-ACS, but not in those with STEMI. BT is a broadly available low-cost marker to identify ACS patients with high inflammatory burden, at high risk for recurrent ischaemic events, and thus potentially suitable for an anti-inflammatory intervention. ClinicalTrials.gov Identifier: NCT01000701.

Hematological abnormalities in liver cirrhosis.

Hematological abnormalities are common in cirrhosis and are associated with various pathophysiological mechanisms. Studies have documented a prevalence of thrombocytopenia, leukopenia, and anemia in patients with compensated cirrhosis of 77.9%, 23.5%, and 21.1%, respectively. These abnormalities carry significant clinical implications, including considerations for invasive procedures, infection risk, bleeding risk, and prognosis. Previously, cirrhosis was believed to predispose patients to bleeding due to alterations observed in classical coagulation tests such as prothrombin time, partial thromboplastin time, international normalized ratio, and thrombocytopenia. However, this understanding has evolved, and cirrhosis patients are now also acknowledged as being at a high risk for thrombotic events. Hemostasis in cirrhosis patients presents a complex phenotype, with procoagulant and anticoagulant abnormalities offsetting each other. This multifactorial phenomenon is inadequately reflected by routine laboratory tests. Thrombotic complications are more prevalent in decompensated cirrhosis and may correlate with disease severity. Bleeding is primarily associated with portal hypertension, endothelial dysfunction, mechanical vessel injury, disseminated intravascular coagulation, endotoxemia, and renal injury. This review comprehensively outlines hematologic index abnormalities, mechanisms of hemostasis, coagulation, and fibrinolysis abnormalities, limitations of laboratory testing, and clinical manifestations of bleeding and thrombosis in patients with liver cirrhosis.

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD. This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

Efficacy and Safety of Low or Reduced Dose Direct Oral Anticoagulants Versus Dual Antiplatelet Therapy Following Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis.

This meta-analysis aimed to compare the efficacy and safety of low-dose direct oral anticoagulants (DOACs) versus dual antiplatelet therapy (DAPT) in patients undergoing left atrial appendage closure (LAAC). A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, and Scopus, up to August 12, 2024. Studies comparing low-dose DOACs with DAPT in post-LAAC patients were included. The primary outcomes of interest were thromboembolic events, major bleeding, and all-cause mortality. Four studies, including two randomized controlled trials and two observational studies, met the inclusion criteria, with a total of 828 patients (319 in the DOAC group and 509 in the DAPT group). The meta-analysis revealed that patients treated with DOACs had a significantly lower risk of thromboembolic events compared to those receiving DAPT. DOACs were also associated with a significantly reduced risk of device-related thrombosis. Although the risk of stroke was lower in the DOAC group, the difference was not statistically significant. The risk of death did not differ significantly between the two groups. Regarding safety outcomes, patients receiving DOACs experienced fewer bleeding events compared to those on DAPT, with the difference being statistically significant. However, high heterogeneity was reported among the study results for bleeding events. These findings suggest that low-dose DOACs may be a more effective and safer alternative to DAPT for post-LAAC antithrombotic management, particularly in patients at high risk for both thromboembolic and bleeding events. DOACs demonstrated superior efficacy in reducing the risk of stroke, systemic embolism, and other thrombotic complications, while also minimizing bleeding risks.

The CNIC polypill (Acetylsalicylic acid + Atorvastatin + Rampril) in secondary prevention of cardiovascular disease in patients with type 2 diabetes: A comparative analysis with alternative therapeutic approaches

BackgroundPatients with type 2 DM (T2DM) and established cardiovascular disease (CVD) are at high risk of recurrent CV events. We analysed the use of the CNIC-polypill (acetylsalicylic acid, ramipril, and atorvastatin) compared with other therapeutic strategies in patients with T2DM and CVD from the retrospective NEPTUNO study. MethodsPatients were stratified into four therapeutic approaches: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. Outcomes included the 2-year cumulative incidence and risk of recurrent major adverse CV events (MACE) and CV death, risk factors control, medication persistence, and utilisation of healthcare resources and costs. ResultsAfter two years, T2DM patients treated with Monocomponents, Equipotent drugs, or Other therapies had increased recurrent MACE risk compared to CNIC-polypill (11 %, 23 %, and 44 %, respectively; P < 0.05) and shorter median time to CV events (305–377 vs. 396 days; P < 0.05). The CNIC-polypill group achieved a significant 11.2 % increase in patients reaching LDL-c targets <70 mg/dL, outperforming other strategies. It also exhibited superior triglyceride control and a higher proportion achieving the <130/80 mmHg blood pressure goal. The CNIC-polypill cohort displayed significantly higher 24-month persistence (71.5 % vs. 54.7 %–58.3 %, p < 0.05) and lower mean adjusted costs per patient (€5083 vs. €6000–€6523; p < 0.05). In a comparative analysis, T2DM patients had lower baseline LDL-c and total cholesterol levels than non-T2DM counterparts yet experienced a higher incidence of recurrent MACE over two years. ConclusionThe CNIC-polypill (ASA, atorvastatin and ramipril) emerged as a promising treatment for patients with CVD, particularly those with T2DM, offering improved clinical outcomes and economic efficiency.

Impact of non-invasive oxygen reserve index versus standard SpO2 monitoring on peripheral oxygen saturation during endotracheal intubation in the intensive care unit: Protocol for the randomized controlled trial NESOI2.

In critically ill patients, endotracheal intubation (ETI) is lifesaving but carries a high risk of adverse events, notably hypoxemia. Preoxygenation is performed before introducing the tube to increase the safe apnea time. Oxygenation is monitored by pulse oximeter measurement of peripheral oxygen saturation (SpO2). However, SpO2 is unreliable at the high oxygenation levels produced by preoxygenation and, in the event of desaturation, may not decrease sufficiently early to allow preventive measures. The oxygen reserve index (ORI) is a dimensionless parameter that can also be measured continuously by a fingertip monitor and reflects oxygenation in the moderate hyperoxia range. The ORI ranges from 0 to 1 when arterial oxygen saturation (PaO2) varies between 100 to 200 mmHg, as occurs during preoxygenation. No trial has assessed the potential effects of ORI monitoring to guide preoxygenation for ETI in unstable patients. We designed a multicenter, two-arm, parallel-group, randomized, superiority, open trial in 950 critically ill adults requiring ETI. The intervention consists in monitoring ORI values and using an ORI target for preoxygenation of at least 0.6 for at least 1 minute. In the control group, preoxygenation is guided by SpO2 values recorded by a standard pulse oximeter, according to the standard of care, the goal being to obtain 100% SpO2 during preoxygenation, which lasts at least 3 minutes. The standard-of-care ETI technique is used in both arms. Baseline parameters, rapid-sequence induction medications, ETI devices, and physiological data are recorded. The primary outcome is the lowest SpO2 value from laryngoscopy to 2 minutes after successful ETI. Secondary outcomes include cognitive function on day 28. Assuming a 10% standard deviation for the lowest SpO2 value in the control group, no missing data, and crossover of 5% of patients, with the bilateral alpha risk set at 0.05, including 950 patients will provide 85% power for detecting a 2% between-group absolute difference in the lowest SpO2 value. Should ORI monitoring with a target of ≥0.6 be found to increase the lowest SpO2 value during ETI, then this trial may change current practice regarding preoxygenation for ETI. Trial registration: Registered on ClinicalTrials.gov (NCT05867875) on April 27, 2023.

Assessment and pre-assessment of compound hot and drought events over Yangtze River Basin

Abstract The severe compound hot and drought event (CHDE) in 2022 had serious impacts on water resources, agriculture, power supply, and ecosystems in the Yangtze River Basin (YRB). Have similar spatiotemporally overlapping compound events, like the one observed in 2022, occurred historically in the basin? How can we pre-assess the impacts of such potential events on subseasonal timescales? To address these, regional CHDEs in the YRB since 1961 were systematically identified and comprehensively assessed using a modified Intensity-Area-Duration (IAD) technique and hazard assessment method. Additionally, the subseasonal pre-assessment capability for CHDEs in the YRB using the China Meteorological Administration's third-generation climate model prediction system (CPSv3-S2S) was demonstrated. A total of 140 CHDEs occurred during 1961 to 2022, with the 21st century showing a remarkably high risk of such events. Among these, 2022 was the most intense year, with the event from July 26th to August 30th being unprecedented in severity. CPSv3-S2S effectively forecast this event’s occurrence within a 1-25 lead days, particularly in pre-assessing its extensively impacted area and high-hazard centers in the upper and middle reaches of the main river course. This pre-assessment method serves as a valuable reference in decision-making to anticipate and mitigate risks of hydropower supply shortages and heightened electricity demand during extremely high temperatures in the upstream area.