Major Adverse Events Research Articles

Prediction model of in-hospital cardiac arrest using machine learning in the early phase of hospitalization.

In hospitals, the deterioration of a patient's condition leading to death is often preceded by physiological abnormalities in the hours to days beforehand. Several risk-scoring systems have been developed to identify patients at risk of major adverse events; however, such systems often exhibit low sensitivity and specificity. To identify the risk factors associated with in-hospital cardiac arrest (IHCA), we conducted a retrospective cohort study at a tertiary medical center in Taiwan. Four machine learning algorithms were employed to identify the factors most predictive of IHCA. The support vector machine model was discovered to be the most effective at predicting IHCA. The ten most critical physiological parameters at 8 h prior to the event were pulse rate, age, white blood cell count, lymphocyte count, body temperature, body mass index, systolic and diastolic blood pressure, platelet count, and use of central nervous system-active medication. Using these parameters, we can enhance early warning and rapid response systems in our hospital, potentially reducing the incidence of IHCA in clinical practice.

Cryoablation of Primary Breast Cancer in Patients Ineligible for Clinical Trials: A Multiinstitutional Study.

BACKGROUND. Breast cancer cryoablation clinical trials have strict inclusion criteria that exclude patients with potentially treatable disease. OBJECTIVE. The purpose of this study was to evaluate the safety and outcomes of breast cancer cryoablation without surgical excision in patients ineligible for prospective cryoablation clinical trials due to unfavorable patient or tumor characteristics. METHODS. This retrospective study included women who underwent cryoablation of biopsy-proven unifocal primary breast cancer with locally curative intent, without surgical excision, despite being ineligible for (and thus excluded from) cryoablation clinical trials, across seven institutions between January 1, 2000, and August 26, 2021. Adverse events (AEs) were recorded. Cryoablation procedures were classified as technically successful if they were not prematurely terminated and achieved intended treatment parameters and if the first follow-up imaging examination showed no evidence of residual disease. The results of follow-up biopsies were recorded. Ipsilateral breast tumor recurrences (IBTRs) diagnosed during follow-up were identified and classified as true recurrence or new primary disease. A competing-risk model was used to estimate the cumulative incidence of IBTR accounting for death before IBTR as a competing risk. RESULTS. The final study sample included 112 patients (median age, 71 years). A total of seven of 112 (6.3%) patients had a minor AE; no moderate or major AEs occurred. A total of 110 of 112 cryoablation procedures (98.2%) were technically successful. During a median follow-up of 2.0 years, 22 of 110 patients (20.0%) underwent biopsy for suspicious imaging findings in the ipsilateral breast, which yielded benign concordant findings in nine of 22 patients (40.9%) and IBTR in 12 of 22 patients (54.5%). Overall, 12 of 110 patients (10.9%) experienced IBTR, including seven with true recurrence and five with new primary disease; three of 12 patients (25.0%) with IBTR had received earlier adjuvant or neoadjuvant therapy. When death was accounted for as a competing risk, the cumulative incidence of IBTR was 5.3%, 12.2%, and 18.2% at 1, 2, and 3 years, respectively. CONCLUSION. In select individuals with unfavorable patient or tumor characteristics, breast cancer cryoablation provides a safe alternative to surgery and has good outcomes. These findings may be particularly relevant in patients who are also poor surgical candidates. CLINICAL IMPACT. Breast cancer cryoablation can be safely applied in a larger patient populations than those defined by clinical trial inclusion criteria.

Treatment of Reactive Arthritis with Biological Agents.

Reactive arthritis (ReA) is an inflammatory joint condition triggered by an infection elsewhere in the body, and this review aims to provide a comprehensive synthesis of recent studies including case reports and case series to determine whether biologics are a treatment option. Recent studies indicate that biological agents, including anti-TNF agents (infliximab, adalimumab, etanercept), anti-IL17 (secukinumab), and anti-IL6 (tocilizumab), are effective in treating refractory cases of ReA. Evidence suggests these agents are associated with significant clinical improvement. Notably, the data reveal that these biologics are generally well-tolerated, with a low incidence of major adverse events, which supports their safety profile for use in ReA. Biological agents, including anti-TNF, anti-IL17, and anti-IL6 therapies, can be safely and effectively used in the treatment of ReA when conventional therapies fail. It further emphasizes the need for a well-designed controlled trial to provide scientific basis for better informed clinical decisions in cases not responding to conventional treatment.

Exposure–response relationships of mirvetuximab soravtansine in patients with folate receptor‐α‐positive ovarian cancer: Justification of therapeutic dose regimen

AimsThis study aimed to investigate exposure–response (ER) relationships in efficacy and safety for mirvetuximab soravtansine (MIRV) which is a first‐in‐class antibody–drug conjugate approved for the treatment of folate receptor‐α‐positive platinum‐resistant ovarian cancer.MethodsMIRV was characterized in 4 clinical studies. Exposure metrics for MIRV, its payload and a metabolite were derived from a population pharmacokinetic model. Efficacy was analysed in MIRV‐treated patients (n = 215) in a recent confirmatory, randomized, chemotherapy‐controlled MIRASOL trial and safety was evaluated in patients pooled across all 4 clinical studies (n = 757).ResultsIn the MIRASOL trial (NCT04209855), MIRV demonstrated significant benefit over chemotherapy in progression‐free survival (PFS), objective response rate (ORR) and overall survival (OS). The most common adverse events (AEs) included ocular disorders, peripheral neuropathy and pneumonitis. For PFS, ORR and OS, the trough concentration of MIRV was the predictor consistently found in ER models for efficacy. In contrast, for ocular AEs (as well as the time to onset of ocular AEs) and peripheral neuropathy, the area under the concentration–time curve (AUC) of MIRV was identified as the exposure metric in ER models for safety. No exposure parameters were found to correlate with pneumonitis. Covariates in all models did not show clinically meaningful impact on efficacy or safety. Logistic regression models for ORR and ocular AEs based on AUC of MIRV were used to justify the clinical dose regimen approved for MIRV.ConclusionThe trough concentration of MIRV correlated with efficacy whereas the AUC of MIRV was associated with major AEs. The ER relationships supported the selected therapeutic dose regimen.

Cardiovascular phenotypes in type 2 diabetes: Latent class analysis of the CANVAS Program and CREDENCE trial.

To identify unique clinical phenotypes in type 2 diabetes (T2D) and investigate their treatment response to canagliflozin using latent class analysis. This was a pooled latent class analysis of the individuals in the CANVAS Program and CREDENCE trial. The co-primary endpoints were hospitalization for heart failure (HHF) and the composite of cardiovascular death (CVD) or HHF. Secondary endpoints included three-point major adverse CV events, its individual components, and all-cause mortality. We completed Cox proportional hazards models to evaluate the effect of canagliflozin across phenotypes. Four distinct phenotypes were identified: Phenotype 1 (n = 966, 6.6%), with the lowest prevalence of heart failure, kidney dysfunction and hypertension; Phenotype 2 (n = 4169, 28.7%), primarily comprising females with a high prevalence of atherosclerotic vascular disease (ASCVD); Phenotype 3 (n = 7108, 48.9%), predominately males with a high prevalence of ASCVD; and Phenotype 4 (n = 2300, 15.8%), possessing the highest prevalences of HF and renal dysfunction. A hierarchical increase in the risk of the primary endpoint was observed across the phenotypes, with the highest CV risk observed for Phenotype 4 (hazard ratio for HHF: 7.57 [95% CI: 4.19-13.69]). Canagliflozin significantly reduced HHF and the composite CVD or HHF across phenotypes (all P values for interaction > .05). We identified four clinically distinct T2D phenotypes with differential CV risks. Canagliflozin reduced the risk of CV events, irrespective of the phenotype, emphasizing its broad therapeutic acceptability.

Relationship between body mass index and clinical events in patients with atrial fibrillation undergoing percutaneous coronary intervention

Background It is still unclear whether body mass index (BMI) affects bleeding and cardiovascular events in patients requiring oral anticoagulants (OAC) for atrial fibrillation (AF) and antiplatelet agents after percutaneous coronary intervention (PCI) for coronary artery disease (CAD). The aim of this study was to evaluate the relationship between BMI and clinical events in patients who underwent PCI under OAC therapy for AF. Method This was a multicenter, observational cohort study conducted at 15 institutions in Japan. AF patients who underwent PCI with drug-eluting stents for CAD were retrospectively and prospectively included. Patients were divided into the Group 1 (BMI <21.3 kg/m2) and the Group 2 (BMI ≥21.3 kg/m2) according to the first-quartile value of BMI. The primary endpoint was net adverse clinical events (NACE), a composite of major adverse cardiovascular events (MACE) and major bleeding events within one year after index PCI procedure. Results In the 720 patients, 180 patients (25.0%) had BMI value <21.3 kg/m2. While the rates of NACE and MACE were significantly higher in the Group 1 than the counterpart (21.1% vs. 11.9%, p = 0.003 and 17.2% vs. 8.9%, p = 0.004), that of major bleeding did not differ significantly between the 2 groups (5.6% vs. 4.3%, p = 0.54). The cumulative rate of NACE and MACE was significantly higher in the Group 1 than the Group 2 (both log-rank p = 0.002), although that of major bleeding events was equivalent between the 2 groups (log-rank p = 0.41). In multivariable Cox regression analyses, while BMI value <21.3 kg/m2 was not associated with major bleeding events, that cut-off value was an independent predictor for increased NACE and MACE. Conclusions Among the patients undergoing PCI for CAD and requiring OAC for AF, BMI value was a useful indicator to predict major adverse clinical events.

The effect of early initiation of self-management program based on multidisciplinary education in heart failure patients

AimsTo explore the effect of early initiation of self-management based on multidisciplinary education in heart failure (HF) patients.MethodsHF patients in the Cardiology Department of Beijing Hospital were consecutively enrolled from June 2022 to February 2023. In-hospital HF patients from June 2022 to October 2022 were divided into the control group, and HF patients from November 2022 to February 2023 were divided into the cardiac rehabilitation (CR) group. A series of self-management education sessions with cardiologists, pharmacologists, nutritionists, and nurses was initiated early in the CR group. Continuous strengthening education was provided during the 3 months of discharge. Patients in the control group only received education twice during hospitalization. Minnesota Living with Heart Failure Questionnaire (MLHFQ), Pittsburgh sleep quality index (PSQI), anxiety Self-rating anxiety scale (SAS), and Self-rating depression scale (SDS) were compared between the two groups. Major cardiovascular adverse events (MACEs) were recorded during follow-up.ResultsA total of 91 HF patients were enrolled. There were 44 patients in the CR group and 47 in the control group. Compared with before the program, the MLHFQ and SAS scores significantly decreased at 3 months after discharge in both groups. PSQI also showed mild improvement without significant differences in both groups. Furthermore, SDS showed a significant increase in the CR group but within the normal range. MACE occurrences did not show a significant difference.ConclusionEarly initiation of self-management program based on multidisciplinary education may help improve quality of life, sleep quality, and reduce anxiety for hospitalized HF patients.

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.

Real-world data to support post-market safety and performance of embolization coils: evidence generation from a medical device manufacturer and data institute partnership

BackgroundRecognizing the limitations of pre-market clinical data, regulatory authorities have embraced total product lifecycle management with post-market surveillance (PMS) data to assess medical device safety and performance. One method of proactive PMS involves the analysis of real-world data (RWD) through retrospective review of electronic health records (EHR). Because EHRs are patient-centered and focused on providing tools that clinicians use to determine care rather than collecting information on individual medical products, the process of transforming RWD into real-world evidence (RWE) can be laborious, particularly for medical devices with broad clinical use and extended clinical follow-up. This study describes a method to extract RWD from EHR to generate RWE on the safety and performance of embolization coils.MethodsThrough a partnership between a non-profit data institute and a medical device manufacturer, information on implantable embolization coils’ use was extracted, linked, and analyzed from clinical data housed in an electronic data warehouse from the state of Indiana’s largest health system. To evaluate the performance and safety of the embolization coils, technical success and safety were defined as per the Society of Interventional Radiology guidelines. A multi-prong strategy including electronic and manual review of unstructured (clinical chart notes) and structured data (International Classification of Disease codes), was developed to identify patients with relevant devices and extract data related to the endpoints.ResultsA total of 323 patients were identified as treated using Cook Medical Tornado, Nester, or MReye embolization coils between 1 January 2014 and 31 December 2018. Available clinical follow-up for these patients was 1127 ± 719 days. Indications for use, adverse events, and procedural success rates were identified via automated extraction of structured data along with review of available unstructured data. The overall technical success rate was 96.7%, and the safety events rate was 5.3% with 18 major adverse events in 17 patients. The calculated technical success and safety rates met pre-established performance goals (≥ 85% for technical success and ≤ 12% for safety), highlighting the relevance of this surveillance method.ConclusionsGenerating RWE from RWD requires careful planning and execution. The process described herein provided valuable longitudinal data for PMS of real-world device safety and performance. This cost-effective approach can be translated to other medical devices and similar RWD database systems.

Sepsis-associated acute kidney injury in patients with chronic kidney disease: Patient characteristics, prevalence, timing, trajectory, treatment and associated outcomes.

The features and outcomes of sepsis-associated acute kidney injury (SA-AKI) may be affected by chronic kidney disease (CKD). Accordingly, we aimed to compare SA-AKI in patients with or without CKD. Retrospective cohort study in 12 intensive care units (ICU). We studied the prevalence, patient characteristics, timing, trajectory, treatment and outcomes of SA-AKI with and without CKD. Of 84 240 admissions, 7255 (8.6%) involved patients with CKD. SA-AKI was more common in patients with CKD (21% vs 14%; p < .001). CKD patients were older (70 vs. 60 years; p < .001), had a higher median Charlson co-morbidity index (5 vs. 3; p < .001) and acute physiology and chronic health evaluation (APACHE) III score (78 vs. 60; p < .001) and were more likely to receive renal replacement therapy (RRT) (25% vs. 17%; p < .001). They had less complete return to baseline function at ICU discharge (48% vs. 60%; p < .001), higher major adverse kidney events at day 30 (MAKE-30) (38% vs. 27%; p < .001), and higher hospital and 90-day mortality (21% vs. 13%; p < .001, and 27% vs. 16%; p < .001, respectively). After adjustment for patient characteristics and severity of illness, however, CKD was not an independent risk factor for increased 90-day mortality (OR 0.88; 95% CI 0.76-1.02; p = .08) or MAKE-30 (OR 0.98; 95% CI 0.80-1.09; p = .4). SA-AKI is more common in patients with CKD. Such patients are older, more co-morbid, have higher disease severity, receive different ICU therapies and have different trajectories of renal recovery and greater unadjusted mortality. However, after adjustment day-90 mortality and MAKE-30 risk were not increased by CKD.

Caseload and In-Hospital Outcome of Carotid Surgery Performed during the COVID-19 Pandemic vs. Previous Years: A Single-Centre Analysis.

With the beginning of the COVID-19 pandemic in March 2020, restrictions and challenges for elective and emergency vascular surgery as well as worse outcomes were reported. This study aims to compare our single-centre experience with carotid artery surgery during the pandemic and previous years.Our retrospective analysis included all consecutive patients undergoing carotid surgery for symptomatic and asymptomatic stenosis between January 2017 and December 2021. Caseload, operation specific parameters, and demographic data as well as in-hospital outcome were compared during the COVID-19 pandemic versus previous years.A total of 623 consecutive patients were included. The caseload comparison showed an average of 112 carotid artery surgeries per adjusted year (March 16th to December 31st) from 2017 to 2019, prior to the pandemic. The caseload reduction in the first year of the pandemic (2020) was 36.6% (n=71) and 17.9% (n=92) in the second year (2021). No rebound effect was observed. There was no significant difference (p=0.42) in the allocation of symptomatic and asymptomatic patients (asymptomatic patients: 37.1% prior vs. 40.8% during the pandemic; symptomatic patients: 62.9 vs. 59.2%). Major adverse event rates in years prior to the pandemic were postoperative bleeding requiring revision: n=31 (7.1%); stroke in symptomatic patients: n=9 (3.3%) and stroke in asymptomatic patients: n=4 (2.5%); symptomatic myocardial infarction (MCI): n=1 (0.2%); death: n=2 (0.5%). During the pandemic, major adverse event rates were postoperative bleeding requiring revision: n=12 (6.5%); stroke in symptomatic patients: n=1 (0.9%), stroke in asymptomatic patients: n=1 (1.3%); symptomatic MCI: n=1 (0.5%); death: n=1 (0.5%).Since the beginning of the COVID-19 pandemic in March 2020, there has been a significant reduction in carotid artery surgery performed both in symptomatic as well as in asymptomatic patients. There was no worsening of the outcome of carotid surgery performed during the COVID-19 pandemic, and this remained safe and feasible.

There is no correlation between differences in adverse events and differences in patient-reported outcome measures in orthopaedic trauma randomized controlled trials: A systematic review

IntroductionA recovery without adverse events is a top priority of orthopaedic trauma patients, however many randomized controlled trials (RCTs) are only powered to detect a difference in patient-reported outcome measures (PROMs). While it may be assumed that differences in major adverse event rates between treatment groups will result in differences in PROMs, this has not been established. The purpose of this study was to perform a systematic review of RCTs to evaluate if differences in these outcomes were correlated. MethodsA systematic search was conducted of online databases to identify RCTs in orthopaedic trauma fracture management that reported both major adverse events and PROMs. Adverse events included secondary surgeries or complications that could negatively affect long-term outcomes (nonunion, chronic regional pain syndrome, etc.). The correlation between a difference (p < 0.05) in adverse events and a difference in PROMs was assessed. ResultsThe systematic review yielded 30 RCTs involving 6,769 patients. The primary outcome was a continuous PROM in 70.0 % (21/30). A difference in major adverse events was reported in 23.3 % (7/30) and a difference in PROMs was reported in 6.7 % (2/30). Studies reporting a difference in adverse events, compared to those that did not, were not more likely to report a difference in PROMs (14.3 % (1/7) vs. 4.3 % (1/23); p = 0.42). ConclusionsThere was no correlation between differences in adverse event rates and differences in PROMs in orthopaedic trauma RCTs. Investigators should consider powering studies to detect differences in the major adverse events that both patients and surgeons wish to avoid. Level of evidenceLevel I

Efficacy and safety of therapeutic alpha-1-microglobulin RMC-035 in reducing kidney injury after cardiac surgery: a multicentre, randomised, double-blind, parallel group, phase 2a trial

Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury. In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30mL/min/1.73m2) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19). Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n=45) and 39.8% (n=35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p=0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3mL/min/1.73m2, 90% CI 0.51-8.12, p=0.06; and MAKE 6.7% (n=6) vs 15.9% (n=14); RR: 0.41, 90% CI: 0.19, 0.88, p=0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group). In this proof-of-concept study, RMC-035 did not reduce AKI 72h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes. Guard Therapeutics.

Evaluation of the Diagnostic Utility of Urine Biomarkers Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) and Insulin-like Growth Factor Binding Protein-7 (IGFBP-7) in Predicting Acute Kidney Injury and Short-term Outcomes among High-risk, Critically Ill Patients in a Tertiary Government Hospital in the Philippines.

Acute kidney injury (AKI) is a common complication of critical illness that often leads to increased mortality and morbidity. Biomarkers detect AKI earlier, providing a window of opportunity for timely intervention. Of the recent biomarkers in literature, the cell cycle arrest biomarkers tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP-7) were found to be superior in predicting AKI. Our study aimed to evaluate the diagnostic performance of urine TIMP-2/IGFBP-7 in its ability to predict AKI and major adverse kidney events within 30 days (MAKE30) among high-risk patients for AKI. MAKE30 is a composite outcome comprised of all-cause mortality, use of renal replacement therapy (RRT), or persistent renal dysfunction at hospital discharge truncated at 30 days. We conducted a prospective, cross-sectional study which included 135 adult, non-COVID ICU patients. Baseline urine TIMP-2/IGFBP-7 results were used to dichotomize the population into low risk (<0.3 ng/mL) or high risk (≥0.3 ng/mL) for AKI. Participants were then observed for 30 days and monitored for MAKE30 outcomes. ROC curves were created to calculate the sensitivity, specificity, NPV, PPV, and the AUC of the 0.3 ng/mL cut-off to predict the AKI and MAKE30. Urine TIMP-2/IGFBP-7 cutoff of 0.3 ng/mL predicted AKI with a sensitivity of 82.4%, specificity of 79.2%, PPV of 57.1%, NPV of 93% and AUC of 0.81. MAKE30 was detected with a sensitivity of 62.8%, specificity of 76.1%, PPV of 55.1%, NPV of 81.4% and AUC of 0.69. Elevated levels of urine TIMP-2/IGFBP-7 were found to be associated with AKI (p<0.01), MAKE30 (p<0.01) and all of its subcomponents. Survival or discharge after 30 days were found to be associated with lower urine TIMP-2/IGFBP-7 levels (p<0.01). Urine TIMP-2/IGFBP-7, at its current cut-off at 0.3 ng/mL, can predict the likelihood of developing AKI and major adverse kidney events among high-risk patients for AKI. It can serve as a useful adjunct to existing methods, such as serum creatinine, in the early diagnosis and prognosis of acute kidney injury and expanding the therapeutic window to prevent disease progression and improve outcomes.

Perfecting the pour: A novel co-axial technique with sequential injections for optimising cement delivery during sacroplasty.

Percutaneous sacroplasty is an effective treatment for painful sacral fractures and tumours, however there is no accepted optimal technique for performing this procedure. This study investigated a novel approach to sacroplasty combining co-axial sacral access, sequential cement injections and hypothermic cement manipulation to improve cement delivery. This retrospective study analysed 11 patients who underwent co-axial sacroplasty between April 2023 and March 2024 for treatment of painful insufficiency fractures (n = 5) or malignant sacral tumours (n = 6). All cases were performed using biplane fluoroscopy with conebeam CT navigation for planning and monitoring percutaneous access. Procedural details, technical outcomes, and clinical outcomes including Numerical Rating Scale (NRS) pain and analgesic utilisation on a six-point scale were analysed pre-procedure and at follow-up. Technical success of was achieved in all cases using this technique. The mean injected cement volume was 20.5 ± 6.4 ml. Median pre-procedural NRS pain scores of 8 (IQR 7.25-8) significantly decreased to 0 (IQR, 0-0.25) at follow-up (p <.01). The median preprocedural analgesic utilisation score reduced from 3 (IQR, 2-3) to 0 (IQR, 0-2.5) at follow-up (p <.01). Cement leakage occurred during two cases without associated adverse clinical sequelae. There were no major adverse events. Co-axial sequential injection sacroplasty is a safe and effective technique which allows facilitates controlled delivery of cement. Improved control of cement delivery, including around high-risk structures for cement leakage, offers a potential safety advantage over conventional sacroplasty techniques. Further research comparing technical and clinical outcomes to conventional techniques is warranted.

Hepatic and splenic venous access tract closure using the VASCADE vascular closure system following percutaneous intervention in patients with CHD.

Hepatic and splenic venous access are specialised techniques used to perform diagnostic and interventional procedures in the cardiac catheterisation laboratory. Bleeding events are the most commonly reported complication following hepatic or splenic venous access. The VASCADE Vascular Closure System (Cardiva Medical Inc. Santa Barbara, CA) is an approved device for closure of femoral vascular access tracts in patients ≥18 years of age. We report our experience using VASCADE to close the hepatic or splenic venous access site in the cardiac catheterisation laboratory. This is a single centre retrospective review of all patients who had percutaneous hepatic or splenic venous access obtained in the cardiac catheterisation laboratory from March 1, 2022 through October 30, 2023 and underwent tract closure with VASCADE. Ten patients (six male) underwent 16 procedures (median age and weight 3.5 years and 12.5 kg) with 15 hepatic and two splenic veins accessed. Successful closure of the access tracts with VASCADE was performed in all patients. There were no major adverse events related to closure of the access sites with VASCADE. VASCADE can be used following transhepatic and trans-splenic venous access in the cardiac catheterisation laboratory to safely close the access tract and potentially reduce the risk of post-procedural bleeding complications. Further evaluation in a larger cohort of patients is needed to ensure VASCADE is safe for use and provides adequate haemostasis following hepatic or splenic venous access, particularly in children.

Adverse cardiovascular and kidney outcomes in people with SARS-CoV-2 treated with SGLT2 inhibitors

BackgroundWhether use of SGLT2 inhibitors reduces the risk of cardiovascular and kidney events in people who contracted SARS-CoV-2 infection is not clear.MethodsWe used the healthcare databases of the United States Department of Veterans Affairs to build a cohort of 107,776 participants on antihyperglycemic therapy and had SARS-CoV-2 infection between March 01, 2020 and June 10, 2023. Within them, 11,588 used SGLT2 inhibitors and 96,188 used other antihyperglycemics. We examined the risks of major adverse cardiovascular events (MACE)—a composite of death, myocardial infarction and stroke, and major adverse kidney events (MAKE)—a composite of death, eGFR decline > 50%, and end stage kidney disease after balancing baseline characteristics between groups through inverse probability weighting. Survival analyses were conducted to generate hazard ratio (HR) and absolute risk reduction per 100 person-years (ARR).ResultsOver a median follow up of 1.57 (IQR: 1.05–2.49) years, compared to the control group, SGLT2 inhibitors use is associated with reduced risk of MACE (HR 0.82 (0.77, 0.88), ARR 1.73 (1.21, 2.25)) and reduced risk of MAKE (HR 0.75 (0.71, 0.80), ARR 2.62 (2.13, 3.11)). Compared to the control group, SGLT2 inhibitors use is associated with reduced risk of the secondary outcomes of hospitalization (HR 0.94 (0.90, 0.98), ARR 1.06 (1.36, 1.76)), anemia (HR 0.71 (0.65, 0.76), ARR 2.43 (1.95, 2.90)), and acute kidney injury (HR 0.84 (0.79, 0.89), ARR 1.86 (1.29, 2.42)).ConclusionsAmong people with SARS-CoV-2 infection on antihyperglycemic therapy, compared to those on other antihyperglycemics, those on SGLT2 inhibitors have less risk of adverse cardiovascular and kidney outcomes.

High lipoprotein(a) is a risk factor for peripheral artery disease, abdominal aortic aneurysms, and major adverse limb events.

To summarize evidence from recent studies of high lipoprotein(a) as a risk factor for peripheral artery disease (PAD), abdominal aortic aneurysms (AAA), and major adverse limb events (MALE). Additionally, provide clinicians with 10-year absolute risk charts enabling risk prediction of PAD and AAA by lipoprotein(a) levels and conventional risk factors. Numerous studies support high lipoprotein(a) as an independent risk factor for PAD, AAA, and MALE. The strongest evidence is from the Copenhagen General Population Study (CGPS) and the UK Biobank, two large general population-based cohorts. In the CGPS, a 50 mg/dl higher genetically determined lipoprotein(a) associated with hazard ratios of 1.39 (1.24-1.56) for PAD and 1.21 (1.01-1.44) for AAA. Corresponding hazard ratio in the UK Biobank were 1.38 (1.30-1.46) and 1.42 (1.28-1.59). In CGPS participants with levels at least 99th (≥143 mg/dl) vs, less than 50th percentile (≤9 mg/dl), hazard ratios were 2.99 (2.09-4.30) for PAD and 2.22 (1.21-4.07) for AAA, with a corresponding incidence rate ratio for MALE of 3.04 (1.55-5.98) in participants with PAD. Evidence from both observational and genetic studies support high lipoprotein(a) as a causal risk factor for PAD, AAA, and MALE, and highlight the potential of future lipoprotein(a)-lowering therapy to reduce the substantial morbidity and mortality associated with these diseases.

Characteristics and Outcomes of Children and Young Adults With Sepsis Requiring Continuous Renal Replacement Therapy: A Comparative Analysis From the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK).

Pediatric sepsis-associated acute kidney injury (AKI) often requires continuous renal replacement therapy (CRRT), but limited data exist regarding patient characteristics and outcomes. We aimed to describe these features, including the impact of possible dialytrauma (i.e., vasoactive requirement, negative fluid balance) on outcomes, and contrast them to nonseptic patients in an international cohort of children and young adults receiving CRRT. A secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), an international, multicenter, retrospective study. Neonatal, cardiac and PICUs at 34 centers in nine countries from January 1, 2015, to December 31, 2021. Patients 0-25 years old requiring CRRT for AKI and/or fluid overload. None. Among 1016 patients, 446 (44%) had sepsis at CRRT initiation and 650 (64%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (defined as a composite of death, renal replacement therapy [RRT] dependence, or > 25% decline in estimated glomerular filtration rate from baseline at 90 d from CRRT initiation). Septic patients were less likely to liberate from CRRT by 28 days (30% vs. 38%; p < 0.001) and had higher rates of MAKE-90 (70% vs. 61%; p = 0.002) and higher mortality (47% vs. 31%; p < 0.001) than nonseptic patients; however, septic survivors were less likely to be RRT dependent at 90 days (10% vs. 18%; p = 0.011). On multivariable regression, pre-CRRT vasoactive requirement, time to negative fluid balance, and median daily fluid balance over the first week of CRRT were not associated with MAKE-90; however, increasing duration of vasoactive requirement was independently associated with increased odds of MAKE-90 (adjusted OR [aOR], 1.16; 95% CI, 1.05-1.28) and mortality (aOR, 1.20; 95% CI, 1.1-1.32) for each additional day of support. Septic children requiring CRRT have different clinical characteristics and outcomes compared with those without sepsis, including higher rates of mortality and MAKE-90. Increasing duration of vasoactive support during the first week of CRRT, a surrogate of potential dialytrauma, appears to be associated with these outcomes.

Evaluation of Left Ventricular Remodeling and Prognosis after PCI in Acute Myocardial Infarction Using Real-Time, Three-Dimensional Echocardiography Combined with Layer-Specific Strain Imaging

Aim: This study aimed to evaluate left atrial and left ventricular volumes, strains, and strain rates in patients with acute ST-segment elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) using real-time three-dimensional echocardiography and layer-specific strain techniques. The relationships between these parameters and left ventricular remodeling (LVR) and prognosis were also explored. Methods: The study included 217 patients with first-episode STEMI who underwent emergency PCI. Echocardiography and myocardial strain analyses were performed within 24 h post-PCI. Patients were categorized into early and non-early LVR groups based on the increase in left ventricular end-diastolic volume (LVEDV). The occurrence of major cardiovascular adverse events (MACE) was followed up for one-year post-PCI. Differences in clinical data and ultrasound parameters between the groups were compared, and the predictive value of myocardial strain indicators for late LVR was analyzed using a multivariate logistic regression model and receiver operating characteristic (ROC) curves. Results: Early LVR occurred in 54.8% of patients and was characterized by decreased left ventricular systolic function, more segments with abnormal movement, and reduced absolute strain values in the three layers of the left ventricular wall myocardium, with a compensatory increase in left atrial strain rate during the contraction phase. The early LVR group showed a higher incidence of MACE at the one-year follow-up. At 6 months post-PCI, 29.9% of patients developed late LVR, which was not completely related to early LVR. Late LVR was associated with a higher incidence of MACE. The longitudinal strain value of each layer of left ventricular myocardium obtained from layer-specific strain imaging showed predictive value for advanced LVR. Conclusions: More than half of patients with STEMI develop early LVR post-PCI, with a higher incidence of MACE during one-year of follow-up, necessitating attention to early LVR in clinical practice. Late LVR, which develops in some patients after 6 months, is also linked to a higher incidence of MACE. Accurate monitoring of the myocardial deformation function using layer-specific strain imaging is expected to become a reference indicator for clinical diagnosis and treatment. Monitoring the structure and function of the left atrium and mitral valve alongside the LVR is important for prognostic assessment and for formulating diagnostic and treatment plans.