Higher Risk Of Adverse Events Research Articles

Characteristics of depression treatment in men with testosterone deficiency

BACKGROUND: Treatment of depression in men with testosterone deficiency is particularly challenging because of the overlap between the symptoms of depression itself and those associated with testosterone deficiency, which requires the development of additional diagnostic and therapeutic approaches. AIM: To enhance the effectiveness of comprehensive treatment of depression in men with testosterone deficiency. MATERIALS AND METHODS: The study involved 140 male participants (aged 18–65 years) diagnosed with depressive episodes and recurrent depressive disorder according to the International Classification of Diseases, 10th revision. Patients were divided into the main group (testosterone levels below 12.1 nmol/l) and the control group (normal testosterone levels). The main group (n=90) was further divided into three therapeutic subgroups of 30 patients each: receiving sertraline monotherapy, testosterone monotherapy, and combined sertraline and testosterone treatment. The control group included men with depression and normal testosterone levels (n=50), who received sertraline only. RESULTS: Depression in men in the context of testosterone deficiency has distinct clinical features, both phenomenologically and syndromally. The severity of the depressive syndrome in men with testosterone deficiency is lower (17.0 [16.0; 18.75] points on the HDRS scale) than in patients with normal testosterone levels (19.0 [18.0; 22.0] points on the HDRS scale), and the depressive episode tends to occur later in life (47.0 [42.0; 55.0] years) compared to those with normal levels of testosterone (29.5 [24.25; 40.0] years) and is less likely to be recurrent than in those with normal testosterone levels (29.5 [24.25; 40.0] years). The study of the efficacy and safety of depression therapy in the context of testosterone deficiency shows that a combined approach to the treatment of depression in men with testosterone deficiency has both advantages (considering the specifics of patients by normalizing testosterone levels and erectile function) and disadvantages (relatively higher risk of adverse events) compared to sertraline monotherapy. CONCLUSION: The identified characteristics of the course and treatment of depression in the context of reduced testosterone levels allowed for the development of a more effective therapeutic and diagnostic algorithm.

Post-Ischemic Stroke Cardiovascular Risk Prevention and Management

Cardiac death is the second most common cause of death among patients with acute ischemic stroke (IS), following neurological death resulting directly from acute IS. Risk prediction models and screening tools including electrocardiograms can assess the risk of adverse cardiovascular events after IS. Prolonged heart rate monitoring and early anticoagulation therapy benefit patients with a higher risk of adverse events, especially stroke patients with atrial fibrillation. IS and cardiovascular diseases have similar risk factors which, if optimally managed, may reduce the incidence of recurrent stroke and other major cardiovascular adverse events. Comprehensive risk management emphasizes a healthy lifestyle and medication therapy, especially lipid-lowering, glucose-lowering, and blood pressure-lowering drugs. Although antiplatelet and anticoagulation therapy are preferred to prevent cardiovascular events after IS, a balance between preventing recurrent stroke and secondary bleeding should be maintained. Optimization of early rehabilitation care comprises continuous care across environments thus improving the prognosis of stroke survivors.

Safety of treating acute pulmonary embolism at home: an individual patient data meta-analysis.

Home treatment is considered safe in acute pulmonary embolism (PE) patients selected by a validated triage tool (e.g. simplified PE severity index score or Hestia rule), but there is uncertainty regarding the applicability in underrepresented subgroups. The aim was to evaluate the safety of home treatment by performing an individual patient-level data meta-analysis. Ten prospective cohort studies or randomized controlled trials were identified in a systematic search, totalling 2694 PE patients treated at home (discharged within 24 h) and identified by a predefined triage tool. The 14- and 30-day incidences of all-cause mortality and adverse events (combined endpoint of recurrent venous thromboembolism, major bleeding, and/or all-cause mortality) were evaluated. The relative risk (RR) for 14- and 30-day mortalities and adverse events is calculated in subgroups using a random effects model. The 14- and 30-day mortalities were 0.11% [95% confidence interval (CI) 0.0-0.24, I2 = 0) and 0.30% (95% CI 0.09-0.51, I2 = 0). The 14- and 30-day incidences of adverse events were 0.56% (95% CI 0.28-0.84, I2 = 0) and 1.2% (95% CI 0.79-1.6, I2 = 0). Cancer was associated with increased 30-day mortality [RR 4.9; 95% prediction interval (PI) 2.7-9.1; I2 = 0]. Pre-existing cardiopulmonary disease, abnormal troponin, and abnormal (N-terminal pro-)B-type natriuretic peptide [(NT-pro)BNP] at presentation were associated with an increased incidence of 14-day adverse events [RR 3.5 (95% PI 1.5-7.9, I2 = 0), 2.5 (95% PI 1.3-4.9, I2 = 0), and 3.9 (95% PI 1.6-9.8, I2 = 0), respectively], but not mortality. At 30 days, cancer, abnormal troponin, and abnormal (NT-pro)BNP were associated with an increased incidence of adverse events [RR 2.7 (95% PI 1.4-5.2, I2 = 0), 2.9 (95% PI 1.5-5.7, I2 = 0), and 3.3 (95% PI 1.6-7.1, I2 = 0), respectively]. The incidence of adverse events in home-treated PE patients, selected by a validated triage tool, was very low. Patients with cancer had a three- to five-fold higher incidence of adverse events and death. Patients with increased troponin or (NT-pro)BNP had a three-fold higher risk of adverse events, driven by recurrent venous thromboembolism and bleeding.

Association between glycated albumin and adverse outcomes in patients with heart failure.

Diabetes mellitus is a traditional risk factor for heart failure (HF), and glycated albumin (GA) is a marker to assess short-term glycemic control. Whether GA has prognostic significance in patients with HF remains unclear. A total of 717 patients with HF were enrolled in the prospective cohort study. Patients were grouped by the normal upper limit of GA (17%). Kaplan-Meier analysis and Cox proportional hazards regression were used to evaluate the association between GA and prognosis. During a mean follow-up of 387 days, 232 composite endpoint events of hospitalization for HF or all-cause death occurred. Kaplan-Meier analysis showed a higher rate of adverse events in the higher GA group (GA >17%; log-rank test P < 0.001). GA was an independent predictor of adverse events, both as a continuous variable (per 1% change: hazard ratio [HR] 1.03, 95% confidence interval [CI] 1.00-1.06, P = 0.030) and as a categorical variable (GA >17%: HR 1.36, 95% CI 1.03-1.80, P = 0.032). Restricted cubic splines showed a linear association between GA and adverse events (P for non-linearity = 0.231). There was no significant difference in adverse outcome risk between those with diabetes and GA ≤17% and those without diabetes, whereas the prognosis was worse in those with diabetes and GA >17% (HR 1.56, 95% CI 1.16-2.11, P = 0.004). Compared to the group with normal levels of GA and glycated hemoglobin, the group with GA >17% and glycated hemoglobin >6.5% had a higher risk of adverse events (HR 1.49, 95% CI 1.06-2.10, P = 0.022). GA was an independent predictor of HF prognosis. Combining GA and glycated hemoglobin might improve the predictive power of adverse outcomes in patients with HF.

Improving Interpreter Access in the Pediatric Emergency Department: A Quality Improvement Initiative.

An increasing proportion of the population in the United States have limited English proficiency (LEP). Hospitals that receive federal funding must offer interpreter services. However, access is often lacking for patients. Patients with LEP are at higher risk for adverse events, and the Emergency Department is a particularly high-risk environment for these events. This quality improvement initiative took place from April 2021 to August 2022 in an urban, tertiary care Pediatric Emergency Department. A driver diagram informed four Plan-Do-Study-Act cycles, and data were collected through medical record review, patient surveys, and staff surveys. We tracked outcomes using run and control chart data. During the study period, the proportion of patients with LEP reporting "always" having an interpreter was unchanged (no centerline shift-control chart rules). Documentation of interpreter use for encounters with patients with LEP improved. Preferred language documentation and documentation of the need for an interpreter in the electronic medical record showed no change. Process measure data for staff-reported use of professional interpreters significantly increased, and the use of ad hoc interpreters decreased significantly. Length of stay did not change for English or LEP patients. This quality improvement initiative improved appropriate documentation of LEP and decreased use of nonqualified interpreters, although no change occurred in the proportion of patients who reported always having an interpreter. Patient satisfaction was unaffected.

Development and Validation of the Hospital-to-Home-Health Transition Quality (H3TQ) Index: A Novel Measure to Engage Patients and Home Health Providers in Evaluating Hospital-to-Home Care Transition Quality: A Novel Measure to Engage Patients and Home Health Providers in Evaluating Hospital-to-Home Care Transition Quality.

Patients requiring skilled home health care (HH) after hospitalization are at high risk of adverse events. Human factors engineering (HFE) approaches can be useful for measure development to optimize hospital-to-home transitions. To describe the development, initial psychometric validation, and feasibility of the Hospital-to-Home-Health-Transition Quality (H3TQ) Index to identify patient safety risks. Development : A multisite, mixed-methods study at 5 HH agencies in rural and urban sites across the United States. Testing : Prospective H3TQ implementation on older adults' hospital-to-HH transitions. Populations Studied : Older adults and caregivers receiving HH services after hospital discharge, and their HH providers (nurses and rehabilitation therapists). The H3TQ is a 12-item count of hospital-to-HH transitions best practices for safety that we developed through more than 180 hours of observations and more than 80 hours of interviews. The H3TQ demonstrated feasibility of use, stability, construct validity, and concurrent validity when tested on 75 transitions. The vast majority (70%) of hospital-to-HH transitions had at least one safety issue, and HH providers identified more patient safety threats than did patients/caregivers. The most frequently identified issues were unsafe home environments (32%), medication issues (29%), incomplete information (27%), and patients' lack of general understanding of care plans (27%). The H3TQ is a novel measure to assess the quality of hospital-to-HH transitions and proactively identify transitions issues. Patients, caregivers, and HH providers offered valuable perspectives and should be included in safety reporting. Study findings can guide the design of interventions to optimize quality during the high-risk hospital-to-HH transition.

Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial.

Thin-cap fibroatheroma (TCFA) lesions are associated with a high risk of future major adverse cardiovascular events. However, the impact of other optical coherence tomography-detected vulnerability features (OCT-VFs) and their interplay with TCFA in predicting adverse events remains unknown. We aimed to evaluate the individual as well as the combined prognostic impact of OCT-VFs in predicting the incidence of the lesion-oriented composite endpoint (LOCE) in non-ischaemic lesions in patients with diabetes mellitus (DM). COMBINE OCT-FFR (ClinicalTrials.gov: NCT02989740) was a prospective, double-blind, international, natural history study that included DM patients with ≥1 non-culprit lesions with a fractional flow reserve>0.80 undergoing systematic OCT assessment. OCT-VFs included the following: TCFA, reduced minimal lumen area (r-MLA), healed plaque (HP), and complicated plaque (CP). The primary endpoint, LOCE - a composite of cardiac mortality, target vessel myocardial infarction, or clinically driven target lesion revascularisation up to 5 years - was analysed according to the presence of these OCT-VFs, both individually and in combination. TCFA, r-MLA, HP and CP were identified in 98 (25.3%), 190 (49.0%), 87 (22.4%), and 116 (29.9%) patients, respectively. The primary endpoint rate increased progressively from 6.3% to 55.6% (hazard ratio 15.2, 95% confidence interval: 4.53-51.0; p<0.001) in patients without OCT-VFs as compared to patients with concomitant HP, r-MLA, CP, and TCFA. The coexistence of TCFA with other OCT-VFs resulted in an increased risk of the LOCE at 5 years. In DM patients with non-ischaemic lesions, TCFA was the strongest predictor of future LOCE events. However, lesions that present additional OCT-VFs are associated with a higher risk of adverse events than OCT-detected TCFA alone. Further randomised studies are warranted to confirm these findings and their potential clinical implications.

Implementing geriatric assessment for dose optimization of CDK 4/6 inhibitors in older breast cancer patients (IMPORTANT trial): A pragmatic randomized-controlled trial.

TPS1132 Background: Current evidence from both randomized trials and real-world evidence studies suggests that older patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer derive clinical benefit from the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy. However, a higher risk for adverse events due to CDK4/6 inhibitors among older patients is evident, leading to a trend of initiating CDK4/6 inhibitors at a lower dose in clinical practice, though without evidence. The aim of the present randomized trial is to investigate whether lower initial dose of CDK4/6 inhibitors combined with endocrine therapy is comparable to full dose in older patients with advanced HR+/HER2-breast cancer that are assessed as vulnerable/frail based on comprehensive geriatric assessment (CGA). Methods: We designed a multi-national, open-label, pragmatic randomized controlled trial with non-inferiority approach. Patients ≥70 years old with advanced HR+/HER2- breast cancer with no curative intention, no prior treatment in an advanced setting, and suitable to receive a combination of CDK4/6 inhibitors plus endocrine therapy according to treating physician, are eligible for study inclusion. After informed consent, included patients fill out a self-administered CGA tool and categorized accordingly to fit, vulnerable, or frail, depending on the number of impaired CGA domains. Fit patients receive full dose of CDK4/6 inhibitors and endocrine therapy whereas vulnerable/frail patients are randomized to either -1 level lower CDK4/6 inhibitor dose or full dose and endocrine therapy. The randomization is stratified by type of CDK 4/6 inhibitor, type of endocrine therapy, and level of vulnerability. The treating physician decides on the choice of CDK4/6 inhibitor (abemaciclib, ribociclib, palbociclib) and endocrine therapy (aromatase inhibitors, fulvestrant). The primary endpoint is time to treatment failure whereas secondary endpoints include overall treatment utility, progression-free survival, overall survival, time to chemotherapy initiation, toxicity, quality-of-life, time to quality-of-life deterioration and cost-effectiveness. The evaluation of disease progression, toxicity assessment, and the follow-up strategy resembles clinical practice to enhance the pragmatic design approach of IMPORTANT trial. The trial also enables a hybrid decentralized approach where the initial patient visit is in-person whereas the visits for efficacy and toxicity evaluation can be performed digitally according to local practices. In total, 495 patients are planned to be included to allow 346 vulnerable/frail patients to be randomized. Enrollment: The trial is open for recruitment since February 2024 with a recruitment period of 30 months. Clinical trial information: NCT06044623 .

Remote monitoring is an independent predictor of better survival in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators

Abstract Introduction Despite improvements in pharmacotherapy and advancements in invasive techniques, patients with ischemic cardiomyopathy are at high risk of adverse events and death. Strategies aimed at improving prognosis, including patient-centered individualization of care are needed. Remote monitoring (RM) of patients with heart failure, which allows for a continuous assessment of device- and some patient-related parameters, has been shown to reduce the risk of hospitalization and death, although no analyses were focused specifically on patients with ischemic cardiomyopathy after percutaneous coronary intervention (PCI). Purpose To determine whether RM is associated with outcomes in patients with ischemic cardiomyopathy after percutaneous coronary intervention. Methods The clinical, echocardiographic and angiographic data of consecutive patients with ICM and ICD or CRT-D, who had undergone PCI were obtained from the single-centre COMMIT-HF registry. Each consecutive patient with ICM was offered RM at the discretion of the treating physician. The RM center in our facility monitors patients with cardiac implantable devices in all working days. In case of any clinical, or device-related events potentially requiring reaction, patients are telephonically invited to contact healthcare system, either in the local emergency departments, or in our hospital, or outpatient clinic. Patients supervised with RM undergo routine in-person visits in the outpatient device clinic every 12 months. In the conventional arm, routine visits in the outpatient clinic occur every 6 months. The long-term data were acquired from the National Health Fund – the sole Polish healthcare provider. The primary outcome of the study was 36-month all-cause mortality. Results In the years 2009-2017, there were a total of 1019 patients with ICM and ICD, who underwent PCI, and those constituted the study group. Of those, 227 (22.3%) were monitored remotely, while the remaining were treated conventionally. The studied groups did not differ significantly, apart from that the patients with RM had a history of CABG, and had a lower mean left ventricular ejection fraction (LVEF, 26% vs 32%, p&amp;lt;0.001) than subjects without RM, while the percentage of CRT-D devices was significantly higher in patients with RM (36.2% vs 6.2%, p&amp;lt;0.001). The 36-month all-cause mortality rate was 18.9% in patients monitored remotely and 25.3% in subjects without RM (p log rank = 0.028). In the multivariable analysis, RM was identified as an independent predictor of lower mortality. The other variables independently associated with higher survival were lower age, absence of anemia, optimal glomerular filtration rate, and higher LVEF. Conclusions Remote monitoring of patients with ischemic cardiomyopathy is independently associated with lower all-cause mortality in a real-world cohort of patients with ICDs.Baseline characteristicsMultivariable analysis

LVNC or hyper-trabeculated LV, are we missing something?

Abstract Introduction LVNC is a heterogeneous poorly understood entity characterized by prominent myocardial trabeculation.(1) It often overlaps with other phenotypes such as DCM, HCM.(2) Incidence of SCD is highly variable, however it may account for about 50% of all mortality in LVNC.(3) Risk stratification of SCD is a complex matter. Despite that current guidelines recommend following the same principles of 1ry prevention as in DCM based on similar CV mortality risk, it seems of utmost importance to identify additional features which could be specifically associated with LVNC and contributing to a higher risk of adverse events particularly ventricular arrhythmia (VA). Purpose To identify possible high risk features for prediction of ventricular arrhythmia in the form of documented NSVT, VT, or VF in LVNC. Methods This is a retrospective single centre cohort study of patients fulfilling the LVNC defining criteria from 2018 to 2023. Patients’ data were reviewed for family history of cardiomyopathies or SCD, clinical presentation, ECGs data in the form of QRS duration, QTc interval and Tp-e, Holter analysis, CIEDs interrogation if present and MRI data including LVEF, volumes, fibrosis burden and distribution, NC/C ratio, NC / LV global mass ratio, global longitudinal strain"GLS", global circumferential strain "GCS" , global radial strain "GRS" , extent of hypertrabeculation, RV involvement in the form of EF, volumes, hypertrabeculation. Results A total of 42 patients were included (34+/- 17 years of age, 57% males). 5 patients of our cohort were pediatrics. Mean LVEF 45%. LGE was detected in 14% of cases, RV involvement in 38 %. Ventricular arrhythmia were present in 15 patients (35%), of which 6 patients had malignant ventricular arrhythmia. LVEF, NC/LV global mass ratio, LVGLS, LVGCS were found to be significantly correlated with the occurrence of VA with cut-off values of &amp;lt;43%, &amp;gt;31%, &amp;lt;-15 and &amp;lt;-13.5 respectively. While positive FH, RV involvement, pattern, burden of LV fibrosis and ECG parameters didn’t significantly increase the incidence of VA. In a multivariate regression analysis NC to LV global mass ratio was the sole independent predictor of VA ( p value=0.024). ICDs were implanted in 10 cases, 8 were for 1ry prevention based on clinical judgement, 4 of them received appropriate ICD therapy. Conclusion LVNC is associated with increased risk of VA. In addition to clinical assessment and LVEF, CMR can add a different insight for risk stratification. Interestingly, LGE wasn’t associated with significantly increased risk of VA "taking into consideration LGE was found only in 14% of cases" highlighting the potential role the trabeculated myocardium in the pathophysiology of VA by altering the electrical stability of the heart. Finally, these findings could contribute in answering an ongoing question; Should LVNC with its unique characteristics be treated as a special entity with its own high-risk criteria for VA and SCD?LV NC/global mass ration and GLSDemographic,clinical,ECG and MRI data

#1078 Prevalence of iron deficiency in patients admitted to a geriatric unit: analysis according to the stages of chronic kidney disease

Abstract Background and Aims Iron deficiency (ID) is a poor prognostic factor in chronic diseases such as chronic kidney disease (CKD). Indeed, independently of anemia, ID is associated with more rapid clinical worsening of CKD and is a risk factor for mortality in this condition. In older patients, CKD is common and often associated with other comorbidities. Method The CARENFER PA study is a national multicenter study designed to evaluate ID in older patients (&amp;gt;75 years) newly hospitalized in a geriatric unit. The primary endpoint was the prevalence of ID, defined as serum ferritin &amp;lt; 100 µg/L and/or transferrin saturation coefficient (TSAT) &amp;lt;20%. Absolute ID was defined as serum ferritin &amp;lt; 100 µg/L and functional ID as serum ferritin ≥ 100 µg/L and TSAT &amp;lt; 20%. In this analysis, we explored ID prevalence according to the degree of CKD. The Short Physical Performance Battery (SPPB) test was used to identify older patients at high risk of adverse events (e.g., disability, falls, hospitalization, death). Results 888 patients (mean age, 85.2 years; women, 63.5%) from 16 French centers were analyzed. Stages of CKD were: stage I, 3.8%; II, 53.2%; IIIa, 22.3%; IIIb, 13.3%; IV, 6.0% and V, 1.4%. ID prevalence in the entire cohort was 57.6% (495/859). When present, ID was absolute in 56.2% (278/495) of cases and functional in 43.8% (217/495). ID prevalence was 54.3% (265/488) in patients with stages I-II, and 61.9% (227/367) in patients with stages III-V (p = 0.0271). In the subgroup of anemic patients, ID prevalence was 58.9% (112/190) and 65.9% (147/223), respectively (p = 0.14). We assessed, according to the stages of CKD, various factors likely to affect or be associated with ID. Thus, in patients with at least three comorbidities, ID prevalence was 56.9% (74/130) in patients with stages I-II and 64.8% (142/219) with stages III-V (p = 0.14); in patients with heart failure, ID was present in 63.2% (36/57) and 60.3% (76/126), respectively (p = 0.71). If patients received treatments with possible effect on ID/anemia (e.g., anticoagulant, proton pump inhibitors, platelet antiaggregant), ID prevalence was 58.4% (192/329) for stages I-II and 62.7% (188/300) for stages III-V (p = 0.27). In patients with CRP ≥ 12 mg/L, ID prevalence was 73.8% (96/130) and 72.2% (117/162), respectively (p = 0.76). In univariate analysis of the entire cohort, degree of CKD (stages III-V vs. I-II), at least three comorbidities, CRP ≥ 12 mg/L, anemia and low serum albumin were significantly associated with ID. In multivariate analysis, CRP ≥ 12 mg was the only independent predictor of ID (odds ratio, 2.78; 95% CI, 1.92–4.08; p &amp;lt; 0.0001). In patients with stages I-II, physical performances were poor (SPPB score 0-6) in 44.5% (77/173) of patients without ID and 57.5% (119/207) with ID; in patients with stages III-V, SPPB scores were low in 55.6% (60/108) of patients without ID and 63.5% (106/167) with ID. Conclusion ID prevalence is high (over half of patients) in older patients admitted to a geriatric unit—particularly those with CKD—and is associated with inflammation and a low SPPB score. These new data underline the importance of more systematic screening for ID in older patients. Future randomized controlled trials should evaluate the efficacy of iron supplementation on the outcome of older patients with ID.

Efficacy of Duloxetine With Arthrocentesis in the Management of TMJ Internal Derangement.

Temporomandibular joint (TMJ) arthrocentesis is one of the most commonly used non-invasive surgical interventions in the treatment of refractory pain and dysfunction associated with internal derangement. Several adjunctive therapies have been used in combination with arthrocentesis in an attempt to increase its efficacy and long-term maintenance. Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor which is used in different chronic pain conditions. This study aimed to assess the efficacy of duloxetine in combination with arthrocentesis compared with arthrocentesis alone. Twenty-eight patients with chronic TMJ pain were included and randomly allocated into 2 groups (control and study groups). The control group included patients who underwent TMJ arthrocentesis only, and the study group included patients who underwent arthrocentesis followed by giving duloxetine (30mg) orally twice daily for 3 months. Pain, maximum mouth opening, and level of anxiety and depression were assessed preoperatively and followed at regular intervals of 1 week, 1 month, 3 months, and 6 months postoperatively. Pain was significantly reduced in both groups at all postoperative intervals and was significantly lower in the study group than the control group at 6 months. Maximum mouth opening increased significantly in both groups, but the difference between them was not significant. Level of anxiety and depression was significantly decreased in both groups, with no statistically significant difference between them. The results of this study indicate that duloxetine in combination with arthrocentesis may provide effective and long-term pain control; however, its use is associated with a higher risk of adverse events.

Machine learning with electrocardiograms to optimize mortality risk stratification in patients with suspected acute coronary syndrome

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung, and Blood Institute (NHLBI) and National Center for Advancing Translational Sciences (NCATS). Background The importance of risk stratification in patients with suspected acute coronary syndrome (ACS) extends beyond diagnosis and immediate treatment. It influences the precision of care delivery and the allocation of resources to those at highest risk of adverse events. Purpose We sought to evaluate the prognostic value of electrocardiogram (ECG) feature-based machine learning models to risk-stratify long-term mortality in those with suspected ACS. Methods This was a multicenter prospective observational cohort study of consecutive, non-traumatic patients evaluated at the emergency department for suspected ACS. The derivation cohort included 4,015 patients from a University Medical Center (age 59±16 years, 47% women, 80% training with 10-fold cross-validation and 20% testing). Ascertainment of all-cause death was based on numerous data sources, including the Centers for Disease Control and Prevention’s National Death Index registry. We trained six machine learning methods for survival analysis using 73 morphological ECG features from presenting prehospital 10-second 12-lead ECGs. We used predicted risk scores in a variational Bayesian Gaussian mixture model to define three risk groups corresponding to low, moderate, and high-risk and compared the resulting classification performance against the HEART score. The external testing cohort included 3,095 patients from a University (age 59±15 years, 44% women). Results The mortality rate was 20.3% in the derivation cohort after an average follow-up period of 3.53 years (IQR 1.75 - 5.32). Extra Survival Trees outperformed other forecasting models during cross-validation. In the internal testing cohort, the derived risk groups were significantly predictive of survival (Kaplan-Meier log-rank test statistic = 121.14, p&amp;lt;0.001), outperforming the classification performance using the HEART score (Figure 1). Our machine learning-based risk stratification model detected &amp;gt;90% of death events missed by low-risk HEART score (Figure 2). Ruling-out the low-risk group, it achieved a negative predictive value of 93.4% with a sensitivity of 85.9% (compared to 89.0% and 75.0%, respectively, for the HEART score). This classification performance generalized well to our external testing cohort. Compared to those in the low-risk group, patients at moderate (OR = 3.62 [1.35-9.74]) and high (OR = 6.12 [2.38-15.75]) risk had significantly higher odds of 30-day cardiovascular death (n=109, 3.5%). Conclusions Using only features from the 10-second 12-lead ECG, we derived and externally validated a machine learning model that stratifies the mortality risk of patients during long-term follow up. This model outperformed current standard of care based on the HEART score. Future work should validate the potential of this decision-support tool in influencing treatment plans and resource allocation.Figure 1.Clustering performanceFigure 2.Sankey diagram

Predictors of Late Adverse Events in Patients with Surgically Treated Type I Aortic Dissection

Residual aortic dissection (AD) following DeBakey type I AD repair is associated with a high rate of adverse events that need additional intervention or surgery. This study aimed to identify clinical and early post-operative computed tomography (CT) imaging factors associated with adverse events in patients with type I AD after ascending aorta replacement. This single centre, retrospective cohort study included consecutive patients with type I AD who underwent ascending aorta replacement from January 2011 to December 2017 and post-operative CT within 3 months. The primary outcome was AD related adverse events, defined as AD related death and re-operation due to aortic aneurysm or impending rupture. The location and size of the primary intimal tears, aortic diameter, and false lumen status were evaluated. Regression analyses were performed to identify factors associated with AD related adverse events. A decision tree model was used to classify patients as high or low risk. Of 103 participants (55.43 ± 13.94 years; 49.5% males), 24 (23.3%) experienced AD related adverse events. In multivariable Cox regression analysis, connective tissue disease (hazard ratio [HR] 15.33; p < .001), maximum aortic diameter ≥ 40 mm (HR 4.90; p < .001), and multiple (three or more) intimal tears (HR 7.12; p < .001) were associated with AD related adverse events. The 3 year cumulative survival free from AD related events was lower in the high risk group with aortic diameter ≥ 40 mm and multiple intimal tears (41.7% vs. 90.9%; p < .001). Early post-operative CT findings indicating a maximum aortic diameter ≥ 40 mm and multiple intimal tears may predict a higher risk of adverse events. These findings suggest the need for careful monitoring and more vigilant management approaches in these cases.

Extraction of terminal ileal lipomas to cecum can facilitate endoscopic resection: A case series with video.

Large ileal lipomas over 2 cm can cause symptoms, that may require a resection. Due to the narrow lumen and thin walls of the ileum, endoscopic treatments can have a high risk of adverse events and require technical expertise, thus surgical resection is currently the mainstay of treatment. To overcome the technical challenges, we developed a novel method to endoscopically resect terminal ileal lipomas. The technique involves extracting the lesion into the cecum, which creates sufficient space to maneuver, and a better field of view. The lipoma is resected with endoscopic mucosal resection or endoscopic submucosal dissection. The appearance of the lipoma protruding out of the ileocecal valve resembles that of a tongue sticking out of the mouth, thus we named this the "tongue out technique". To assess the technical feasibility of this method, we retrospectively analyzed seven cases of terminal ileal lipoma that were endoscopically resected using the "tongue out technique" at NTT Medical Center Tokyo between January 2017 and October 2023. Technical success was 100% and en bloc resection was achieved in all cases. The median size was 31 (14-55) mm. Three cases were resected with endoscopic mucosal resection while endoscopic submucosal dissection was performed on the other four cases. There was one case of delayed post-endoscopic mucosal resection bleeding, which was caused by clip dislodgement. There were no perforations. No recurrence of the lipoma or associated symptoms have been observed. This new technique can allow more ileal lipomas to be treated with minimally invasive and organ-preserving endoscopic procedures.

Right heart strain in arrhythmogenic right ventricular cardiomyopathy: Implications for cardiovascular outcome.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular events. To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS)) in patients with definite ARVC and its association with adverse events during follow-up. RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint (sustained ventricular arrhythmia and cardiovascular death) was determined. Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (-11.5 [-13.3 - -10.2]%) versus the no-event group (-15.8 [-17.1 - -14.5]%, P < 0.001), and so was RAGLS (22.8 [21.4 - 27.4]% vs. 31.5 [25.1 - 39.6]%, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fit was improved when RVGLS and RAGLS were applied together rather than alone. RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC.

Opioid use and risks in liver transplant candidates and recipients.

Opioid use is extremely prevalent among cirrhosis and liver transplant (LT) patients, despite concerns regarding opioid-related risks in this population. While there are many theoretical risks of opioids in patients with hepatic dysfunction, there is limited evidence on the effect of opioid use on clinical outcomes in cirrhosis and pre- and post-LT patients specifically. As a result there is significant center-level variability in opioid-related practice and policies. The existing data-largely based on retrospective observational studies-does suggest that opioids are associated with increased health resource utilization pre- and post-LT, and that they may precipitate hepatic encephalopathy (HE) in patients with cirrhosis and increase risk of graft loss and death post-LT. The strongest predictor of opioid use post-LT is opioid use prior to transplant; thus, a focus on safe opioid use in the pre- and peri-transplant periods is essential for minimizing opioid-related harms. We describe three strategies to guide LT providers, including: 1) Improved characterization of pain, mental health symptoms, and opioid and polysubstance use; 2) Minimization of opioid prescriptions for those at highest risk of adverse events; and 3) Safe prescribing strategies for those who do use opioids and for management of opioid use disorder (OUD). Ultimately, our goal is to improve quality of life and transplant outcomes among cirrhosis and LT patients, particularly those living with concurrent pain, mental health, and substance use disorders.

Safety of subcutaneous immunotherapy with Novo-Helisen-Depot in the children: a retrospective analysis from a single center in Northern China.

Little is known about the safety of mite extract product Novo-Helisen Depot (NHD) as subcutaneous immunotherapy (SCIT) in the children with mite allergy especially immediate/late local reaction (LRs). We conducted a retrospective study analyzing the adverse events of the children undergoing subcutaneous immunotherapy with NHD. Adverse events included local and systemic adverse reactions (SRs) at the very early and late stage. The correlation of the basic characteristics, laboratory analysis results, LRs and SRs were analyzed. Two hundred and eighty-seven patients received at least 15 months of subcutaneous immunotherapy with NHD were included in the analysis. Skin-prick testing (SPT) results of D. pteronyssinus was associated with an increased risk of immediate LRs in build-up phase (OR = 1.53, 95% CI: 1.02, 2.37) and delayed LRs in maintenance phase (OR = 1.58, 95% CI: 1.05, 2.46), while SPT results of D. farinae was associated with an increased risk of SRs (OR = 3.22, 95% CI: 1.17, 10.00) and severe SRs (OR = 7.68, 95% CI: 1.13, 109.50). Serum IgE level of D. pteronyssinus was associated with an increased risk of SRs (OR = 1.01, 95% CI: 1.00, 1.03). Patients with both asthma and allergic rhinitis was associated with an increased risk of SR, and severe SRs (P < 0.05). NHD as SCIT is safe. The children with higher SPT level with D. farinae or D. pteronyssinus, higher serum IgE level of D. pteronyssinus, children with both asthma and allergic rhinitis, and the children with treatment interruption had higher risk of adverse events.

Patient-specific ascending aortic intervention criteria.

Ascending aortic aneurysms pose a different risk to each patient. We aim to provide personalized risk stratification for such patients based on sex, age, body surface area and aneurysm location (root versus ascending). Root and ascending diameters, and adverse aortic events (dissection, rupture, death) of ascending thoracic aortic aneurysm patients were analysed. Aortic diameter was placed in context vis-a-vis the normal distribution in the general population with similar sex, age and body surface area, by conversion to z scores. These were correlated of major adverse aortic events, producing risk curves with 'hinge points' of steep risk, constructed separately for the aortic root and mid-ascending aorta. A total of 1162 patients were included. Risk curves unveiled generalized thresholds of z = 4 for the aortic root and z = 5 for the mid-ascending aorta. These correspond to individualized thresholds of less than the standard criterion of 5.5 cm in the vast majority of patients. Indicative results include a 75-year-old typical male with 2.1 m2 body surface area, who was found to be at increased risk of adverse events if root diameter exceeds 5.15 cm, or mid ascending exceeds 5.27 cm. An automated calculator is presented, which identifies patients at high risk of adverse events based on sex, age, height, weight, and root and ascending size. This analysis exploits a large sample of aneurysmal patients, demographic features of the general population, pre-dissection diameter, discrimination of root and supracoronary segments, and statistical tools to extract thresholds of increased risk tailor-made for each patient.

A practical guide to selecting and using new ulcerative colitis therapies.

Several new biologics (mirizikizumab) and small molecules (upadacitinib, ozanimod, etrasimod) are approved for the treatment of moderate-to-severe ulcerative colitis. To date, there are no head-to-head trials to guide positioning and use of these newer agents. From phase III clinical trials, in the biologic experienced patient, induction with ozanimod, etrasimod, and mirizikizumab had lower clinical remission rates, whereas upadacitinib's clinical remission rates remained similar. Indirect evidence using network meta-analysis suggests upadacitinib may be more efficacious than other advanced therapies for the treatment of ulcerative colitis in both the bio-naive and experienced patient. Upadacitinib was found to have the highest risk for adverse events. These newer agents add novel mechanisms of action to the expanding therapeutic armamentarium of advanced therapies to treat ulcerative colitis. Based on expert opinion and available data to date, we propose a practical guide on positioning of these new agents for the treatment of ulcerative colitis. In mild-to-moderate disease, one should consider using ozanimod or etrasimod as first-line agents. In moderate-to-severe disease, we favor using mirizikizumab as first-line agent. In patients who have failed an anti-tumor necrosis factor agent, upadacitinib or mirizikizumab should be considered using patient factors and safety to guide one's decision between these two agents.