High-risk Cohort Research Articles

Social connection and its prospective association with adolescent internalising and externalising symptoms: an exploratory cross-country study using retrospective harmonisation.

Social connection factors play a key role for young people's mental health. It is important to understand how their influence may vary across contexts. We investigated structural (e.g. household size), functional (e.g. social support) and quality (e.g. feeling close) social connection factors in relation to adolescent internalising and externalising symptoms, comparing two countries Brazil and the United Kingdom (UK). We pooled data from the UK Millennium Cohort Study (MCS) and the Brazilian High Risk Cohort Study (BHRCS). We included 12 social connection variables, identified through retrospective harmonisation and lived experience expert involvement. We tested measurement invariance and conducted multiple regressions to analyse associations between the social connection factors (age 14) and later internalising and externalising difficulties (age 17.5) in both cohorts. We investigated country-level interactions and used weights to account for attrition, survey design, population representativeness and sample size. We found pooled main associations with later internalising symptoms for 'living with half-siblings' (p < .001), 'moving address' (p = .001), 'mother marital status' (p < .001-.003), 'bullying' (p = .001), 'being bullied' (p < .001) and 'difficulties keeping friends' (p < .001). For externalising, we found main associations with 'household size' (p = .041), 'moving address' (p = .041), 'mother's marital status' (p = .001-.013), 'bullying others' (p < .001) and 'being bullied' (p < .001). Country-level interactions suggested higher internalising symptoms were associated with 'household size' (p = .001) in Brazil and 'being bullied' (p < .001) in MCS. Additionally, 'half-siblings in household' (p = .003), 'poor mother-child relationship' (p = .018), 'single mother' (p = .035), 'bullying' (p < .001) and 'being bullied' (p < .001) were more strongly linked to externalising difficulties in MCS. Social connection factors, mostly structural, contributed to adolescent internalising and externalising difficulties in both countries. Factors relating to bullying and family composition seem to play a stronger role in each country. Cultural and socioeconomic factors might explain these differences. Future research should investigate cross-regional differences to meaningfully inform global mental health efforts.

Role of routine uterine artery Doppler at 18-22 and 24-28 weeks' gestation following routine first-trimester screening for pre-eclampsia.

To assess the performance of mean uterine artery pulsatility index (UtA-PI) at 18-22 and 24-28 weeks of gestation in the prediction of pre-eclampsia (PE) and small-for-gestational age (SGA), and its role in reassessing the risk of PE and SGA in pregnancies screened for PE in the first trimester. This was a retrospective observational cohort study of 4464 women with singleton pregnancy screened routinely for PE in the first trimester, using the Gaussian algorithm, from March 2019 to May 2021, and who underwent UtA-PI assessment at 18-22 gestational weeks. Women were categorized as low risk or high risk based on the risk index obtained after first-trimester screening for PE. In high-risk patients, UtA-PI was also assessed at 24-28 weeks of gestation. Sensitivity, specificity, positive predictive value, negative predictive value (NPV), positive likelihood ratio, negative likelihood ratio and area under the receiver-operating-characteristics curve were calculated to assess the performance of UtA-PI at 18-22 and 24-28 weeks in predicting PE and SGA in the high-risk group. In all participants, different UtA-PI percentiles at 18-22 or 24-28 weeks, or their combination, were analyzed to explore their role in reassessing the risk of PE and SGA following first-trimester PE screening. The performance of UtA-PI at 18-22 and 24-28 weeks in the high-risk group was good for predicting preterm PE and preterm SGA, and excellent for predicting early-onset PE and early-onset SGA, with an NPV of > 97% for all outcomes. In the low-risk group, UtA-PI ≥ 95th percentile at 18-22 weeks' gestation identified a subgroup of pregnancies with a significantly higher risk of preterm SGA compared to the low-risk group. In the high-risk group, UtA-PI < 60th percentile at 18-22 weeks' gestation, UtA-PI < 85th percentile at 24-28 weeks' gestation, and UtA-PI < 85th percentile at 24-28 weeks' gestation in women with UtA-PI ≥ 60th percentile at 18-22 weeks, identified subgroups of pregnancies with a risk of PE and SGA comparable to that of the low-risk group. The performance of UtA-PI at 18-22 and 24-28 gestational weeks in high-risk pregnancies identified during first-trimester screening for PE is similar to that in the general population. The risk of PE and SGA in a high-risk cohort can be reassessed by measuring UtA-PI at 18-22 weeks, 24-28 weeks or both, allowing adjustment of follow-up, particularly de-escalation of care. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Enhanced neurobiological biomarker differentiation for attention-deficit/hyperactivity disorder through a risk-informed design.

Translation of biomarkers to clinical practice is hindered by the significant overlap in neurobiological measures between ADHD cases and controls. A risk-informed design can enhance the utility and validation of ADHD biomarkers by highlighting differences between individuals with ADHD and those without at differential risk. Participants were 2511 children and adolescents (aged 6 to 14 years) from the Brazilian High Risk Cohort for Mental Conditions. We calculated risk for ADHD among unaffected individuals using a multivariable clinical and sociodemographic risk model. We compared measures of three proposed ADHD biomarkers (polygenic scores, subcortical volumes, and executive function) between participants with vs. without ADHD, and ADHD vs. without ADHD with a high- vs. low-risk loading for ADHD. Compared to the unaffected group, children and adolescents with ADHD had higher ADHD polygenic scores (cohen's d = 0.17), smaller subcortical volumes (d = - 0.25), and poorer executive function (d = - 0.22). Separating the unaffected group into low- and high-risk subgroups revealed more pronounced differences (Cohen's d = 0.20 to 0.60) and nearly doubled the overlap-free area for these three neurobiological measures between the low-risk group and the other two groups. Upon adjustment for the number of ADHD symptoms, simple ADHD vs. without ADHD differences vanished, while the risk-informed analyses remained significant. Here, we demonstrate that a risk-based design increases effect sizes when comparing candidate biomarkers for ADHD. Our study provides a model that may hold promise for evaluating similar contrasts in other mental disorders and samples.

Pulmonary hypertension as a prognostic marker in low-flow low-gradient aortic stenosis: Insights from invasive hemodynamics and post-TAVR outcomes.

Pulmonary hypertension (PH) is a common and significant comorbidity in patients with low-flow low-gradient (LF-LG) aortic stenosis, impacting prognosis after transcatheter aortic valve replacement (TAVR). Non-invasive tools often fail to capture PH's full clinical impact due to inherent limitations. This study evaluates the prognostic significance of PH measured invasively and explores its implications on post-TAVR outcomes. This retrospective study analyzed 90 patients with symptomatic LF-LG aortic stenosis who underwent TAVR. Pulmonary artery systolic pressure (PASP) was categorized as mild (<35 mmHg), moderate (35-50 mmHg), or severe (>50 mmHg) using invasive right heart catheterization. Key endpoints included 12-month all-cause mortality and heart failure rehospitalization, assessed via Kaplan-Meier survival analysis and Cox proportional hazards modeling. PH was present in 50% of patients, with moderate-to-severe cases showing higher mortality (25% vs. 8%, p < 0.001) and rehospitalization rates (20% vs. 6%, p = 0.02). Baseline PASP emerged as an independent predictor of mortality (HR 1.07 per mmHg, p < 0.001) and rehospitalization (HR 1.04 per mmHg, p = 0.01). Subgroup analyses revealed that patients with concomitant COPD or advanced diastolic dysfunction exhibited worse outcomes, underscoring the role of systemic disease burden. Invasive hemodynamic assessment provides superior prognostic insight for PH in LF-LG aortic stenosis patients. The findings advocate for targeted PH management strategies to improve post-TAVR outcomes and challenge the sole reliance on non-invasive methods in high-risk cohorts.

A gift of life, not immortality: Evaluation of a strategy of heart transplant listing in the older patient with advanced heart failure

Patients 65 years of age or older represent the fastest-growing demographic group added to the U.S. heart transplant (HT) list. While post-HT outcomes appear acceptable, immortal time bias is introduced if adverse outcomes that occur while waiting for HT are not considered. Recent durable left ventricular assist device (dLVAD) technological innovations have engendered the question of whether this patient subgroup would achieve equivalent survival from a strategy of primary dLVAD implant as opposed to HT listing. We identified adults ≥65 years of age listed for HT between 2018-2021, excluding persons with dLVAD support and/or multi-organ listing. Among 1176 patients, 2-year survival from HT listing was 78.4 ± 1.2%, similar to the 71% to 75% reported in The Society of Thoracic Surgeons (STS) Intermacs National Database for older adults. Linkage of the Scientific Registry of Transplant Recipients with STS Intermacs would enable comparative effectiveness analyses of surgical heart failure therapeutic strategies in high-risk patient cohorts.

Evaluating an approach for communicating integrated risk scores for melanoma.

Integrated risk scores (polygenic and non-genetic risk factors) can facilitate risk-stratification, to inform targeted melanoma screening. This mixed-methods pilot study assessed satisfaction, attitudes, and psychosocial impact of a protocol for communicating integrated risk for melanoma using questionnaires (baseline and 1-month post-results) and semi-structured interviews. Affected and unaffected adults enroled in ongoing melanoma studies were recruited to receive their integrated risk booklets and attend a genetic counselling appointment. 35/73 consented to participate; 31 and 33 completed baseline and follow-up questionnaires, respectively. Participants rated the information as useful, felt it motivated favourable health behaviours and were satisfied with the quality and content of the booklet. All participants felt highly empowered managing melanoma risk at baseline and follow-up. Most participants were unsure or felt little to no control over preventing future melanomas, which did not change at follow-up (Chi-square p = 0.73). Genetic-specific distress, and uncertainty was low for all participants post-results. Qualitative interviews supported quantitative findings and highlighted importance of access to a clinician for results interpretation and risk-management. In this high-risk cohort, the communication model was acceptable, and did not result in negative psychosocial sequelae. Findings from this study highlight key considerations for effective communication and delivery of integrated risk which can be used to inform future research in more diverse cohorts for melanoma and other common conditions.

Prognostic factors associated with worse outcomes following chemoradiation therapy in patients with anal carcinoma.

Chemoradiation therapy (CRT) is considered as the first line of treatment for patients with squamous cell carcinoma of the anal canal. Following initial CRT, patients who present with either persistent or locally recurrent disease are treated by surgical intervention. The aim of our study is to determine the prognostic factors associated with failure of CRT and overall mortality in patients with anal squamous cell carcinoma (SCC). We performed a 14-year analysis (2004-2017) of the National Cancer Database and included patients diagnosed with non-metastatic SCC of the anal canal who underwent CRT. Baseline patient characteristics including demographics, comorbidities and tumour characteristics were analysed. Outcome measures were needed for operative intervention after 4 months of initiation of CRT (failure of CRT) and 5-year overall mortality. Multivariate logistic regression analysis identified prognostic factors independently associated with failure of CRT. We included a total of 37 615 patients with anal SCC who received CRT. Predictors of operative intervention included male sex, higher Deyo-Charlson Comorbidity Index (DCCI) and higher primary tumour stage. The 5-year overall survival rate was 77.6%, and 2.4% of patients failed CRT, defined as requiring and undergoing surgical intervention within 4 months post-initiation of CRT. Median follow-up time was 47 (95% CI 24-84) months. Independent predictors of overall mortality within the first 5 years of diagnosis were increased age, male sex, Black race, non-insured status, higher DCCI, higher primary tumour grade, and higher primary tumour and lymph node stage. The 5-year survival rate was significantly lower in patients who underwent operative intervention compared to those who received CRT alone (57.4% vs. 78.1%; P < 0.01). Our study showed that male sex, younger age, DCCI of 1 and 3, and increased tumour size were predictive of CRT failure among patients with anal SCC. Increased age, male sex, Black race, non-insured status, increased DCCI, and more aggressive tumour characteristics were associated with increased 5-year overall mortality. More importantly, patients who failed CRT had worse 5-year overall survival. Our findings support increased emphasis on intensive surveillance for these high-risk patient cohorts.

Longitudinal history of mammographic breast density and breast cancer risk by familial risk, menopausal status, and initial mammographic density level in a high risk cohort: a nested case–control study

BackgroundElevated mammographic density is associated with increased breast cancer risk. However, the contribution of longitudinal changes in mammographic density to breast cancer risk beyond initial mammographic density levels, considering familial breast cancer risk and menopausal status, remains uncertain but holds important clinical implications.MethodsIn a nested case–control study within the Sister Study (323 cases, 899 controls; 12,095 mammograms), a cohort enriched for family history of breast cancer, we examined case–control status in relation to the largest annual change in percent density and dense area using mammograms available spanning 5.4 years, on average, using multivariable logistic regression and to the rate of mammographic density change using linear mixed-effects models. We considered effect modification by: mammographic density level of the earlier mammogram, the extent of family history, Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation (BOADICEA) risk strata, and menopausal status.ResultsCases (diagnosed < 60 years) had greater initial percent density and dense area levels and a slower rate of decline in dense area than controls. Women with stable mammographic density (≤ 10% annual change) had an increased breast cancer risk as compared with women whose largest mammographic density change was > 10% annual decline (e.g., Odds Ratio (OR) 2.34, 95% Confidence Interval (CI) 1.63–3.37 for dense area). Increasing vs. decreasing dense area was also associated with elevated risk, especially in women with the highest dense area levels at the earlier mammogram (OR: 2.56, 95%CI 1.50–4.36). Although generally similar across menopausal and familial risk categories, the associations of MD change with risk appeared stronger in pre-menopausal and lower-risk women.ConclusionsWomen who maintain higher levels of mammographic density (i.e. do not decrease over time) or have increasing mammographic density over time have a higher risk of subsequent breast cancer than women with high mammographic density that decreases over time. These findings suggest potential for incorporating mammographic density trajectories in clinical risk assessment, and the importance of additional breast cancer monitoring in women not experiencing declines in mammographic density over time.

Acute Kidney Injury and Outcomes in Infants, Children, and Adolescents, Supported With Extracorporeal Life Support for Cardiopulmonary Failure

In neonatal and pediatric patients who require extracorporeal life support (ECLS), 60–70% develop acute kidney injury (AKI). Acute kidney injury has been associated with increased morbidity and mortality. We sought to describe our center’s experience with AKI in patients requiring ECLS and its effect on outcomes. We conducted a retrospective single-center study at an academic children’s hospital. All patients 0–18 years of age who required ECLS between January 2014 and December 2019. During the study period, there were 313 ECLS runs. The majority were neonates (66.8%) and 68.7% of runs were veno-arterial. Using Kidney Disease Improving Global Outcomes (KDIGO) criteria, 227 patients (72.5%) developed stage 2 or 3 AKI. The AKI group were younger (median age: 0.9 vs. 11.7 months, p &lt; 0.001), more likely to experience a hemorrhagic complication (46.9% vs. 31.9%, p = 0.0298), and had higher mortality rates (44.9% vs. 24.4%, p = 0.0009). Neonates who required ECLS were more likely to develop stage 2 or 3 AKI (78%) than pediatrics (63%) (p = 0.005). Adjusting for confounders, patients who developed AKI had 2.38 times higher odds of mortality (95% confidence interval [CI]: 1.34–4.25, p = 0.003). We conclude that the majority of patients requiring ECLS develop stage 2 or 3 AKI. Those with AKI were twice as likely to die when controlling for confounding variables. Multicenter and prospective evaluation of this modifiable risk factor is imperative to improve the care of this high-risk cohort.

Comprehensive prediction of outcomes in patients with ST elevation myocardial infarction (STEMI) using tree-based machine learning algorithms

ST elevation myocardial infarction (STEMI), a subtype of acute coronary syndrome, is one of the leading causes of morbidity and mortality. Revascularization using primary percutaneous coronary intervention (PPCI) is the gold standard treatment. Despite the restoration of myocardial blood flow, some patients experience adverse outcomes. Early detection of high-risk patients would facilitate timely management, potentially improving their morbidity, mortality, and quality of life. In-depth characterization of the aortic pressure (AP) waveform may identify a high-risk patient cohort. We present tree-based classifiers and features extracted from the AP signals to identify patients at risk of adverse outcomes.This is a single-center, retrospective cohort study that included 605 eligible STEMI patients [64.2 ± 13.2 years, 71.4 % (432) males] treated with PPCI. Outcomes, including mortality (within 30-day and 1-year), and in-hospital events such as prolonged in-hospital stay (>4 days) for medical reasons, a new diagnosis of heart failure (HF), diuretic use for more than 24 h, intubation-ventilation or BiPAP use, and inotropic and/or vasopressor use, were recorded. We extracted features mainly from denoised AP signals recorded during PPCI, followed by different feature selection algorithms and classification methods to predict outcomes. Various classifiers such as tree-based classifiers, including random forest (RF), adaptive boosting (AdaBoost), extreme gradient boosting (XGBoost), and CatBoost, were used.Using recursive feature elimination (RFE) as the feature selection method and the CatBoost classifier, we achieved a receiver operating characteristic curve's area under the curve (AUC) of 80 % for all outcomes except for the new diagnosis of HF and diuretic use (>24 h). For the new diagnosis of HF and diuretic use (>24 h), the AUC values were 73 % and 79 %, respectively.In conclusion, tree-based classifiers using features extracted from AP traces can effectively identify patients at risk of adverse outcomes in patients with STEMI.

Treatment with PCSK9 monoclonal antibodies is associated with discontinuation of oral lipid lowering therapy.

Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) are recommended for high-risk patients if the low-density lipoprotein cholesterol (LDL-C) targets are not achieved with statins and ezetimibe. We studied persistence and adherence to 1) PCSK9 mAbs and 2) statins and ezetimibe in a nationwide cohort of incident PCSK9 mAb users. Information on all PCSK9 mAb users ≤80 years from 2015 through 2023 were extracted from the Norwegian Drug Registry. Discontinuation was defined as a gap in treatment ≥180 days and ≥90 days. Adherence was measured as the proportion of days covered (PDC) during the initial year of PCSK9 mAb therapy. We analyzed adherence of statins and ezetimibe before and after PCSK9 mAb initiation. Of 4,784 patients initiating PCSK9 mAbs, median age was 63 years, 41% were female, 61% had atherosclerotic disease, and 34% had familial hypercholesterolemia. Within three years after initiation, 17% experienced a PCSK9 mAb treatment gap exceeding 180 days. In the 12-month period preceding PCSK9 mAb initiation, 74% dispensed statins whereas 67% dispensed ezetimibe. These numbers were reduced to 35% for statins and 42% for ezetimibe during the 12-month period after PCSK9 mAb initiation. Atherosclerotic disease, using ≥3 statins previously, and older age were significantly associated with discontinuation of statins and ezetimibe. In this high-risk cohort of incident PCSK9 mAb users, more than 1 out of 2 stopped taking statin treatment whereas 40% discontinued ezetimibe. There is a major potential for improving adherence to oral LLD treatment following initiation of PCSK9 mAb.

Utilization of preoperative EOS imaging to prevent adverse events following total hip arthroplasty

ABSTRACT Introduction Previous studies have demonstrated the use of technology in total hip arthroplasty (THA) provided favorable outcomes. This study sought to describe the effect preoperative two-dimensional low-dose (2DLD) full-body radiographs had on the prevention of adverse outcomes following THA. Methods We reviewed 11,814 cases of patients who underwent primary, elective THA from 2016 to 2021. Patient demographics and clinical data were compared between patients who did or did not have preoperative standing and sitting 2DLD images (29.5% vs. 70.5%, respectively) using Chi-squared test and multivariate logistic regressions. Results The rate of patients with preexisting spinal fusion was higher in the 2DLD cohort (2.2 vs. 0.6%, respectively, p < 0.001). Preoperative 2DLD images were favored in outcomes including length of stay (40.15 vs. 67.16 hours; p < 0.001), rate of discharge to home (94.1 vs. 80.0%; p < 0.001), and 90-day readmission rate (3.5 vs. 6.0%; p < 0.001). Multivariate analysis demonstrated preoperative 2DLD images to be significantly associated with lower odds of dislocation, independent from surgical approach, coexisting spinal fusion, and utilization of dual-mobility implants. Conclusion Preoperative 2DLD images were independently associated with decreased risk for dislocations. Even in a higher risk cohort with spinal fusion, the rate of dislocation in the 2DLD cohort was significantly lower.

Abstract 4138559: Cystatin C Predicts Cardiovascular Events in Patients With Coronary Artery Disease Both Among Patients With and Among Those Without Type 2 Diabetes

Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD). We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM. During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p&lt;0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p&lt;0.001). We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.

Abstract 4138555: The ApoB/LDL-C Ratio Predicts Cardiovascular Events in Coronary Artery Disease Patients Independently of Type 2 Diabetes Status

A high ApoB/LDL-C ratio reflects small LDL particle size which like type 2 diabetes (T2DM) is associated with insulin resistance. Whether the ApoB/LDL-C ratio and the presence of T2DM are mutually independent predictors of cardiovascular events is unclear and is addressed in the present study. We enrolled a large high-risk cohort of 1200 patients with coronary artery disease. T2DM was diagnosed according to current ADA guidelines. Prospectively, cardiovascular events were recorded over a mean follow-up period of 10.5±4.9 years. At baseline, the ApoB/LDL-C ratio was significantly higher in patients with T2DM (n=422) than in subjects who did not have T2DM (0.81±0.18 vs. 0.74±0.15 p&lt;0.001). During follow-up, 662 patients suffered cardiovascular events. The Apo B/LDL-C ratio predicted cardiovascular events in univariate analysis (HR=1.11 [1.03-1.20] p= 0.006), and the event rate was higher in patients with than in those without T2DM (62.2% vs. 52.3%; p=0.001). In a multivariate adjusted Cox regression model both the ApoB/LDL-C ratio and T2DM significantly predicted cardiovascular events in a mutually independent manner, with standardized adjusted HRs of 1.11 [1.03-1.20]; p=0.008 and 1.39 [1.18- 1.64]; p&lt;0.001, respectively. We conclude that in subjects with coronary artery disease the ApoB/LDL-C and T2DM are mutually independent predictors of cardiovascular events.

Abstract 4136654: Urine Output Response to a Furosemide Infusion is Associated with Acute Kidney Injury in Infants Following Cardiac Surgery

Background: Acute kidney injury (AKI) following cardiac surgery in infants is common and associated with longer mechanical ventilation times and length of stay. Prior studies have shown that a lack of responsiveness to bolus dose furosemide has been associated with increased incidence of AKI. However, these studies have excluded patients on continuous furosemide infusions who are often younger, more hemodynamically unstable, and at higher risk for AKI. Hypothesis: Decreased urine output after initiation of a furosemide infusion predicts development of AKI. Methods: A retrospective cohort study of infants (&lt;1 year of age) was conducted who underwent cardiac surgery requiring cardiopulmonary bypass from 2020-2023 and were on a furosemide infusion post-operatively. The primary outcome was post-operative AKI as defined using KDIGO (Kidney Disease: Improving Global Outcomes) guidelines. A furosemide response score (FRS) was calculated using the total urine output divided by the total dose of furosemide administered over a given time. Univariate and multivariate analyses were performed, and receiver operating characteristic curves used to determine the discriminatory ability of the FRS with regards to the primary outcome. Results: A total of 155 infants (median age at surgery 9 days) were included. Overall, 77% of infants met definition for the primary outcome of AKI; 32% stage 1, 30% stage 2, and 15% stage 3. Lower FRS at 4, 10, and 24 hours after infusion initiation were associated with AKI development (p&lt;0.0001). Younger age, smaller weight at surgery, lack of pre-operative feedings, pre-operative inotropic use and higher surgical complexity were also associated with a higher risk of AKI. An FRS (mL/mg/kg) cutoff of &lt;11.3 at 4 hours, &lt;25.5 at 10 hours, and &lt;55.3 at 24 hours had good discriminatory ability (area under the curve 0.7-0.75) in predicting AKI stage 2 or 3 (p&lt;0.001). Controlling for the significant univariate variables listed above, the FRS cutoffs remained an independent risk factor for the development of AKI stage 2 or 3, (p&lt;0.01) and were significantly associated with longer mechanical ventilation days and length of stay. Conclusion: Lack of responsiveness to a furosemide infusion (as measured by urine output corrected for dose of furosemide) is associated with the development of AKI in a high-risk cohort of infants. These novel findings may be helpful to predict those at risk and allow for further investigations for modifiable risk factors.

Commencement of Atorvastatin and Ezetimibe Immediately in Patients Presenting with Acute Coronary Syndrome.

Lipids are implicated in the development of coronary atherosclerosis. Achieving a significant reduction in lipid levels remains a crucial aspect of secondary prevention following an acute coronary syndrome event. Novel lipid-lowering therapies now provide clinicians with a variety of therapeutic strategies to choose from and tailor to individual patient needs. This review focuses on evidence supporting the importance of early and intensive lipid-lowering therapy use in patients presenting with acute coronary syndrome, specifically addressing data relating to atorvastatin and ezetimibe use in this high-risk cohort of patients.

RADT-30. MANAGEMENT OF PRESUMED PSEUDOPROGRESSION WITH EARLY BEVACIZUMAB IN THE THREE MONTHS AFTER HIGH DOSE RADIATION THERAPY FOR GLIOBLASTOMA

Abstract BACKGROUND Optimal management for symptomatic steroid-refractory pseudoprogression (rPsP) following IMRT for Glioblastoma remains poorly defined. This study examined radiological volumetric response and clinical outcomes following use of early Bevacizumab (earlyBEV), defined as commencing during or within 3 months of IMRT. METHODS Consecutive patients managed with Stupp60Gy IMRT between 2016-2023 for Glioblastoma were analysed for those patients receiving earlyBEV for rPsP. Volumetric analysis was performed with sequential MRI T1gd/T2 sequences using preBEV and postBEV scans. Primary endpoint was volumetric reduction of T1gd/T2 volumes at month+2/3 postBEV. Clinical response, overall survival and pattern of relapse, specifically distant failure was assessed. RESULTS Forty-one (14%) of 289 patients received earlyBEV for rPsP, with median follow-up of 9.9months (q1-3:8-25) for survivors. Compared to remaining 248 patient cohort, earlyBEV had worse initial ECOG0,1 (50%vs76%); less near-total resection (5%vs42%); and less MGMT methylation (35%vs46%). Additionally at diagnosis the initial tumours had larger T1gd and T2 volumes. Median time to commencement of earlyBEV was 1.4months postIMRT; including seven patients during IMRT. All patients responded to BEV, with reduction in symptoms, steroid use and radiological volume, though one died pre-assessment. Median T1gd and T2 volumes before earlyBEV were 37cm3 (q1-3:23-63cm3) and 116cm3 (q1-3:90-148cm3) respectively, which were 95% and 78% larger than at diagnosis. Median survival postBEV was 8.1months (95%CI:7.5-8.6). Median volumes postBEV reduced to 16cm3 (q1-3:8-23cm3) and 41cm3 (29-55cm3); which was a percentage reduction for T1gd and T2 of 57% and 65%. Midline shift reduced from 5mm(q1-3:3-8mm) to zero in two-thirds of patients. Patients requiring earlyBEV had worse survival compared to remaining cohort (p&amp;lt;0.001); with median OS 11.9months (95%CI:10.4-13.5) vs 19.9months (95%CI:18.4-21.5). A component of distant relapse was evident in 48% of earlyBEV vs 34% in remaining cohort. One serious adverse event occurred with fatal intracranial haemorrhage day10 after initial BEV dose. CONCLUSION This study data confirms efficacy of earlyBEV for managing steroid-refractory pseudoprogression, but also the worse prognosis of this high-risk cohort.

Temporal Bone Gunshot Wounds: A Multi-institutional Retrospective Study.

To investigate management practices and outcomes in a retrospective cohort of patients who have sustained temporal bone gunshot wounds (TBGSW). Retrospective chart review. Five participating hospitals. Twenty-two patients met inclusion criteria: experienced a TBGSW, survived ≥30 days following the injury, and were evaluated and managed by a neurotologist between 2019 and 2023. No specific interventions were performed for the purposes of this study. Characteristics, evaluation, management, and outcomes of TBGSW survivors. Patients were found to have a mean age of 33 ± 18 years and were predominantly male (18/22, 81.8%). Majority of patients (17/22, 77.3%) had mastoid injury. Most patients (14/22, 63.6%) had some evidence for vascular injury, most frequently the internal carotid artery (9/22, 40.9%). Almost three-quarters (17/22, 77.3%) of patients had clinical exam findings of facial nerve injury, which was the most common indication for surgery. Otologic surgery was performed in 72.7% (16/22), with delayed adverse events most commonly including cholesteatoma and external auditory canal stenosis. Though evidence for hearing impairment was clinically present in at least 15 of 22 patients (68.2%), hearing rehabilitation was pursued in only two patients. With increasing numbers of TBGSW survivors, there is a growing need for practicing neurotologists to be familiar with the wide spectrum of injury patterns and possible complications to inform clinical management in these patients. Early neurotologic assessment and follow-up beyond the acute period is crucial to minimize morbidity in this high-risk cohort.

Outcomes of emergency colorectal surgery within a non-colorectal split site service-a retrospective cohort study.

Emergency colorectal surgery carries a high risk of morbidity and mortality. Subspecialisation and split-site geographically distinct services may lead to critically unwell patients presenting to a non-colorectal specialist centre requiring urgent on-site intervention. This study aims to determine outcomes of this high-risk patient cohort. An observational retrospective study of emergency colorectal laparotomies at the Royal Infirmary of Edinburgh (RIE) between January 2016 and August 2020 was performed. The primary outcome was 30-day mortality. Secondary outcomes included rate of primary anastomosis, complications and overall mortality. Subgroup analysis of the vascular ischaemia cohort and colorectal surgeon involvement was performed. One hundred and eighteen patients were included. The median NELA (National Emergency Laparotomy Audit) score was 6.4% (IQR 2.5%-16.7%) and the 30-day mortality rate was 22% (26/118). The rate of primary anastomosis was 24.6%. Twenty-five patients had a vascular ischaemic pathology demonstrating a higher median NELA score (14.3%, IQR 5-22.4% vs. non-ischaemic group 5.7%, IQR 1.7-14.2%, p = 0.013) and thirty-day mortality (44%, 11/25 vs. 16.1%, 15/93, p = 0.006) than those without ischaemic pathology. Colorectal surgeon involvement in cases without ischaemia (23/93) was associated with a similar 30-day mortality (13.1% colorectal surgeon vs. 17.1% non-colorectal specialist surgeon, p = 0.755) and rate of primary anastomosis (30.4% colorectal surgeon vs. 31.8% non-colorectal specialist surgeon, p = 1). The high mortality rate described highlights a specific group of unwell patients unfit for transfer. Research registration number: researchregistry7101.

Prognostic value of EMT-related genes and immune cell infiltration in thyroid carcinoma.

The Epithelial-Mesenchymal Transition (EMT) is a very important process involved in cancer invasion and metastasis. Additionally, the Cathepsin K (CTSK) gene is closely related to the degradation of the extracellular matrix, which is a critical component of the EMT. The purpose of this study was to determine the relationships between EMT-related genes and immune cell infiltration and their prognostic value in Thyroid carcinoma (THCA). The effect of the CTSK gene on the aggressive biological features of THCA was assessed. Within the framework of the present study, the THCA cohort was analyzed in detail based on data obtained from The TCGA database in the context of the EMT. The TCGA-THCA cohort was then divided into two groups, namely, high- and low-risk groups, based on the calculated EMT scores. Finally, based on the findings from the Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm, LASSO regression analysis, and Kaplan-Meier plotter, we selected five genes (CTSK, C3ORF80, FBLN2, PRELP and SRPX2) associated with patient prognosis. Furthermore, this study examined the presence of various immune cells within the THCA samples using three distinct algorithms, namely ssGSEA, xCell, and MCPcounter. Additional studies have been conducted to establish the roles of CTSK in THCA cell proliferation and migration using various assays, such as CCK8, colony formation, EdU proliferation, Transwell migration and wound healing assays. Additionally, the involvement of CTSK in the regulation of various EMT-related markers was confirmed using Western blot analysis. Based on EMT scores, TCGA-THCA patients were further divided into two groups, and the study revealed that patients in the high-risk group had a worse prognosis than those in the low-risk group. Among the five genes linked to the prognostic value of EMT (CTSK, C3ORF80, FBLN2, PRELP, and SRPX2), CTSK exhibited notably elevated expression in the high-risk cohort. This group also exhibited pronounced immune cell infiltration, with a marked correlation observed between CTSK expression and the levels of macrophages, MDSCs, and various T-cell subtypes. Furthermore, in vitro studies demonstrated that reducing CTSK expression led to significant reductions in THCA cell viability; clonogenic, proliferative, motility and migratory capacities; and the expression of key EMT-related proteins, including N-cadherin, vimentin, slug, and snail. Our results suggest that the expression of CTSK, a gene associated with the EMT, may be associated with THCA onset and progression and thus may serve as a promising prognostic biomarker.