True Risk Research Articles

Hybrid therapy with ablation + subcutaneous ICD for secondary prevention of sudden cardiac death in ischemic heart disease

Abstract Background The aim of the prospective Ventricular Tachycardia Ablation- Subcutaneous ICD (VTAbl-SICD) Trial was to provide data on the efficacy and safety of a novel hybrid management strategy that combines VT ablation (VTAbl) with S-ICD implantation in patients who present with scar-related VT. The rate of appropriate therapy in patients with S-ICD may be a quite fairest surrogate of true residual sudden death (SD) risk compared to transvenous ICD (TV-ICD). More specific data on ischemic heart disease – the prominent cause of VT with the better results of VTAbl – may give arguments for questioning current practices in the future. Methods 32 patients with post ischemic scar-related sustained VT/VF were included. Patients underwent VTAbl with subsequent (or previous prophylactic n=8) S-ICD implant and were followed for 2-years. We evaluate the occurrence of appropriate and ICD therapies once ablated, as well as cardiovascular (CV) readmissions or death. We also compared to 64 propensity-score matched patients implanted with a secondary prevention TV-ICD (enrolled in the Ranolazine in High-Risk Patients With Implanted Cardioverter-Defibrillators (RAID) trial). Results Mean age was 57±12 years (28 males, 87%) (53% hypertension, 31% diabetes and 47% congestive heart failure with NYHA 1.6±1). Mean LVEF was 39±9%.There were no major complications associated with the ablation and implant procedures. Propensity-score matched patients implanted with a secondary prevention TV-ICD displayed similar clinical characteristics. At 16.5±8.6 months FU, appropriate ICD therapy occurred in 5 patients (15%) in the VTAbl-SICD group, significantly lower compared to the TV-ICD group (34 pts, 53%) (p<0.001). This corresponded to 2-year cumulative probability of 20% vs. 71% in the VTAbl-SICD vs. TV-ICD groups, respectively (log-rank p<0.001; Figure 1) and a significant 83% reduction in the risk of appropriate ICD therapy associated with VTAbl-SICD (HR= 0.17 [95% CI 0.07 - 0.39; p<0.001). Two of the patients who received appropriate ICD therapy in the VTAbl-SICD group may have had unrecognized transient causes of VT (torsades de pointes or unrecognized ischemia), letting 3 out of 32 (10%) with possible aborted SD caused by VT recurrences. There were no cases of untreated symptomatic VT. The rate of CV readmissions was similar in the VTAbl-SICD (41%) vs. TV-ICD group (44%) (p=0.7), whereas mortality was significantly lower in the VTAbl-SICD- vs.TV-ICD- group (0% vs. 17%, respectively; p<0.001) Conclusions Our findings suggest that VT ablation in ischemic heart disease patients allow reaching a low residual true risk for SD, which should now be evaluated in terms of cost-effectiveness compared to ablation + S-ICD implantation. Concommitant S-ICD implantation seems to be a safe alternative to TV-ICD without ablation.Appropriate ICD therapy-free KM

Assessing the effectiveness and mechanisms of Fe/PS, Fe/H2O2, and O3 treatment for water disinfection: Spotlight on VBNC bacteria

Advanced oxidation processes (AOPs) exhibit significant potential for water disinfection due to their generation of large quantities of highly oxidizing free radicals. However, the neglect of viable but nonculturable (VBNC) cells obscures their true disinfection efficacy and potential environmental health risks. Therefore, the study evaluated the disinfection effectiveness and mechanisms of typical AOPs, including Fe/H2O2, Fe/persulfate (PS), and O3, from the perspective of the production of VBNC bacteria. The results indicate that Fe/PS exhibits the strongest bacterial inactivation rate (99.94%), and the cells lose their ability to reactivate. Fe/H2O2 and O3 induce more cells to enter the VBNC state compared to Fe/PS. Moreover, different AOPs result in varying levels of free radical production and utilization efficiency, with SO4•− and O3 exhibiting greater selectivity in deactivating bacteria compared to HO•. The inhibition of VBNC bacteria production by Fe/PS treatment may be attributed to the combined action of HO• and SO4•− on microorganisms, leading to oxidative stress and metabolic disruption in bacteria through the inhibition of biofilm formation and aminoacyl-tRNA biosynthesis (p < 0.05), thereby causing direct bacterial death rather than entry into the VBNC state. In contrast, Fe/H2O2 and O3 result in the upregulation of the metabolism of alanine, aspartate, and glutamate, as well as styrene degradation capacity by the bacteria, leading to the production of more VBNC bacteria. Overall, the study offers insights into mitigating potential biological risks in water disinfection and developing environmentally friendly and efficient disinfection technologies.

Morphologic patterns observed in prostate biopsy cases with discrepant grade group and molecular risk classification.

Molecular-based risk classifier tests are increasingly being utilized by urologists and radiation oncologists to guide clinical decision making. The Decipher prostate biopsy test is a 22-gene RNA biomarker assay designed to predict likelihood of high-grade disease at radical prostatectomy and risk of metastasis and mortality. The test provides a risk category of low, intermediate, or high. We investigated histologic features of biopsies in which the Grade Group (GG) and Decipher risk category (molecular risk) were discrepant. Our institutional urologic outcomes database was searched for men who underwent prostate biopsies with subsequent Decipher testing from 2016 to 2020. We defined discrepant GG and molecular risk as either GG1-2 with high Decipher risk category or GG ≥ 3 with low Decipher risk category. The biopsy slide on which Decipher testing was performed was re-reviewed for GG and various histologic features, including % Gleason pattern 4, types of Gleason pattern 4 and 5, other "high risk" features (e.g., complex papillary, ductal carcinoma, intraductal carcinoma [IDC]), and other unusual and often "difficult to grade" patterns (e.g., atrophic carcinoma, mucin rupture, pseudohyperplastic carcinoma, collagenous fibroplasia, foamy gland carcinoma, carcinoma with basal cell marker expression, carcinoma with prominent vacuoles, and stromal reaction). Follow-up data was also obtained from the electronic medical record. Of 178 men who underwent prostate biopsies and had Decipher testing performed, 41 (23%) had discrepant GG and molecular risk. Slides were available for review for 33/41 (80%). Of these 33 patients, 23 (70%) had GG1-2 (GG1 n = 5, GG2 n = 18) with high Decipher risk, and 10 (30%) had GG ≥ 3 with low Decipher risk. Of the 5 GG1 cases, one case was considered GG2 on re-review; no other high risk features were identified but each case showed at least one of the following "difficult to grade" patterns: 3 atrophic carcinoma, 1 collagenous fibroplasia, 1 carcinoma with mucin rupture, and 1 carcinoma with basal cell marker expression. Of the 18 GG2 high Decipher risk cases, 2 showed GG3 on re-review, 5 showed large cribriform and/or other high risk features, and 10 showed a "difficult to grade" pattern. Of the 10 GG ≥ 3 low Decipher risk cases, 5 had known high risk features including 2 with large cribriform, 1 with IDC, and 1 with Gleason pattern 5. In GG1-2 high Decipher risk cases, difficult to grade patterns were frequently seen in the absence of other known high risk morphologic features; whether these constitute true high risk cases requires further study. In the GG ≥ 3 low Decipher risk cases, aggressive histologic patterns such as large cribriform and IDC were observed in half (50%) of cases; therefore, the molecular classifier may not capture all high risk histologic patterns.

Executive gender and capital structure: New evidence from rebalancing events

Existing literature shows that female-led companies exhibit lower leverage compared to their male-led counterparts, a trend frequently attributed to the traditional view of higher risk aversion among women. We explore firms with female CFOs at or close to their optimal leverage and find that their capital structure is no different than that of firms with male CFOs. We argue that female CFOs reveal their true preferences and risk appetite during significant capital structure adjustments and find that their tolerance for risk aligns closely with that of their male counterparts. Our study challenges the conventional narrative by demonstrating that the financing decisions of top executives are likely not influenced by gender-based psychological differences.

Rates of Cesarean Delivery and Neurologic Complications in Parturients With Cerebrospinal Fluid Shunts [ID 2683661

INTRODUCTION: The effect of parturition on neurologic status in CSF shunt-dependent patients is poorly understood. Cesarean delivery has been proposed as a safer alternative to labor in this population based on limited case reports and retrospective data in the literature; however, the true risk of vaginal delivery has not been adequately described. To our knowledge, this is the first study to estimate national incidence of neurologic complications based on delivery mode in shunt-dependent parturients. METHODS: The Nationwide Readmissions Database (NRD) was queried for obstetric patients undergoing delivery between 2016 and 2018. ICD-10 codes were used to identify delivery mode, preexisting CSF shunt-dependence, obstetric comorbidities, and neurologic complications. Data were weighted per NRD specifications. RESULTS: Of 11,021,188 total deliveries, 1,856 were in shunt-dependent patients. The primary cesarean rate was 41.2% (n=613) versus 20.1% (n=1,823,517) for shunted and non-shunted parturients, respectively. Multivariate analysis confirmed that presence of a shunt independently predicted cesarean delivery (OR 2.4; CI, 2.0–2.9). Intrapartum shunt complication rates were low regardless of delivery mode (vaginal:0.5%, cesarean:0.5%). Additionally, there was no significant difference in rates of brain herniation (P=.82) or CNS infection (P=.15). CONCLUSION: There is no difference in neurologic complication rates between CSF shunt-dependent patients undergoing cesarean and vaginal delivery; however, cesarean delivery is performed at more than twice the rate of the general population. CSF-shunt dependence alone may not be an independent indication for cesarean delivery in the absence of other obstetric indications.

Preoperative risk factors for anastomotic leak after esophagectomy with gastric reconstruction: A 6-year national surgical quality improvement (NSQIP) database analysis

BackgroundAnastomotic leak is a serious complication after esophagectomy that has been associated with worse outcomes. However, identifying patients at increased risk for anastomotic leak remains challenging. MethodsPatients were included from the 2016 to 2021 National Surgical Quality Improvement Project database who underwent elective esophagectomy with gastric reconstruction for cancer. A multivariable logistic regression model was used to identify risk factors associated with anastomotic leak. ResultsA total of 4,331 patients were included in the study, of whom 647 patients experienced anastomotic leak (14.9%). Multivariable logistic regression revealed higher odds of anastomotic leak with smoking (adjusted odds ratio 1.24, confidence interval 1.02–1.51, P = .031), modified frailty index-5 score of 1 (adjusted odds ratio 1.44, confidence interval 1.19–1.75, P = .002) or 2 (adjusted odds ratio 1.52, confidence interval 1.19-1.94, P = .000), and a McKeown esophagectomy (adjusted odds ratio 1.44, confidence interval 1.16–1.80, P = .001). Each 1,000/μL increase in white blood cell count was associated with a 7% increase in odds of anastomotic leak (adjusted odds ratio 1.07, confidence interval 1.03–1.10, P = .0005). Higher platelet counts were slightly protective, and each 10,000/ μL increase in platelet count was associated with 2% reduced odds of anastomotic leak (adjusted odds ratio 0.98, confidence interval 0.97–0.99, P = .001). ConclusionIn this study, smoking status, frailty index, white blood cell count, McKeown esophagectomy, and platelet counts were all associated with the occurrence of anastomotic leak. These results can help to inform surgeons and patients of the true risk of developing anastomotic leak and potentially improve outcomes by providing evidence to improve preoperative characteristics, such as frailty.

Cardiovascular risk prediction - now and the future

Current cardiovascular risk estimation systems that estimate 10-year risk based on cohort studies starting at around age 40 have probably reached their limits based on current methods. The challenges are to develop new systems that will permit personalised risk estimation earlier in life with better estimates of true lifetime risk and likely treatment benefits. We outline approaches to address these issues.

Managing hypertriglyceridemia for cardiovascular disease prevention: Lessons from the PROMINENT trial.

Numerous epidemiological studies have shown that hypertriglyceridemia is a significant risk factor for cardiovascular diseases (CVD). However, large clinical studies on triglyceride-lowering therapy have yielded inconsistent results. In the current review, we reassess the importance of triglyceride-lowering therapy in preventing CVD based on previous literature and the recently published findings of the PROMINENT trial. This narrative review is based on literature and public documents published up to November 2023. Meta-analyses of trials on peroxisome proliferator-activated receptor α agonists and triglyceride-lowering therapy, including the PROMINENT trial, have indicated that triglyceride-lowering therapy can reduce CVD events. Mendelian randomization studies have also indicated that triglyceride is indeed a true risk factor for coronary artery disease, leaving no doubt about its relationship to CVD. Meanwhile, the negative results from the PROMINENT trial were likely due to the insufficient triglyceride-lowering effect, slight increases in low-density lipoprotein cholesterol and apolipoprotein B, and the inclusion of mostly high-intensity statin users as target patients. It is unlikely that adverse events counteracted the effectiveness of pemafibrate on outcomes. Additionally, pemafibrate has shown positive effects on non-alcoholic fatty liver disease and peripheral artery disease. Although the PROMINENT trial did not demonstrate the significance of pemafibrate as a triglyceride-lowering therapy in a specific population, it does not necessarily negate the potential benefits of treating hypertriglyceridemia in reducing CVD events. It is necessary to explore appropriate populations that could benefit from this therapy, utilize data from the PROMINENT trial and other databases, and validate findings in real-world settings.

Postpartum Outcomes in Patients Receiving Venous Thromboembolism Prophylaxis during Antepartum Admission.

We evaluated if venous thromboembolism (VTE) prophylaxis in the inpatient antepartum period was associated with wound hematomas, VTE occurrence, and other adverse outcomes. This study is a secondary analysis of a retrospective cohort of patients who delivered at University of Alabama at Birmingham (UAB). Patients receiving outpatient anticoagulation (AC) were excluded. We grouped patients into those who received inpatient antepartum prophylactic AC and those who did not. The primary outcome was wound hematomas from delivery to 6 weeks postpartum (PP). Secondary outcomes included VTE occurrence and select adverse outcomes, including other wound complications, unplanned procedures, mode of anesthesia, and intensive care unit (ICU) admission. Analyses were performed with no AC group as the reference. A sensitivity analysis excluding those who received inpatient PP AC was performed. Of 1,035 included patients, only 169 patients received inpatient prophylactic AC. They were older, had higher body mass indices, and more comorbidities. Patients receiving inpatient antepartum AC had higher wound hematomas (adjusted odds ratio [aOR] 23.81; 95% confidence interval [CI] 7.04-80.47). They had similar risk for developing VTE as the control group (aOR 2.68; 95% CI 0.19-37.49) but were more likely to have wound complications (aOR 2.36; 95% CI 1.24-4.47), maternal deaths (p < 0.05), and require PP ICU admission (aOR 13.38; 95% CI 4.79-37.35). When excluding those receiving any PP AC, there was no difference in bleeding complications between the two groups and VTE rates remained unchanged. Rates of maternal deaths and PP ICU admissions remained higher in those who received inpatient antepartum AC prophylaxis. In this small cohort study, increased wound hematomas were found in those who received inpatient antepartum AC prophylaxis with no difference in VTE occurrence. While adverse events were increased in the inpatient AC group, this was mostly associated with PP AC prophylaxis. Larger studies should be conducted to describe the true benefits and risks of antepartum AC prophylaxis and determine efficacy of this widely used practice. · Peripartum chemoprophylaxis is associated with increased wound hematomas.. · VTE is rare, despite its association with significant peripartum morbidity/mortality.. · Large studies are needed to guide practices that optimize the risk/benefit ratio of chemoprophylaxis..

An Overview of Pharmacovigilance Practice and Management in Sub-Saharan African Countries

Most sub-Sahara African countries faced with prolonged resource deficiencies suffers specific constraints in establishing a functional and operationally-free pharmacovigilance systems platforms which should guide and in facilitate the generation of vital data to reinforce health information policies and practices. Despite the commendable efforts invested by the different stake holders within such countries to harmonize pharmacovigilance guidelines and regulations, lack of integration and the dependence on pharmacovigilance systems remain major constrains. Other identified difficulties are those associated with the problem of translating data reporting tools into multiple communicable languages, and the inadequacy of the healthcare experts who translates with the patient’s population, the pressure imposed by the short consultation time between a patient and a health practitioner. To add to this, there exist issues of community concern like the increasing use of herbal traditional products with anecdotal therapeutic evidence, low quality, self-medication practices, counterfeit and roadside drugs use, substandard medications that are readily accessible to the population. Some prolonged problems are associated with social and political instability, territorial conflicts, little or no access to drug utilization data, which makes it difficult to reliably estimate the true risks of medication use. Pharmacovigilance activities are still at its infancy due to poor and less trained health personnel, lack of budget allocation for health vigilance from the State financial attributions. In addition to the limited investment in pharmacovigilance activities, there is little collaboration between public health programmes and National Medicines Regulatory Authorities (NMRA), especially during mass drug administration for neglected tropical diseases and mass vaccinations. Frequent spontaneous report in SSA is low and this can hinder robust signal detection analyses. This paper attempts to identify the challenges of the practice of pharmacovigilance in sub-Saharan African countries and its implication in health vigilance in the community. In this paper, we review the specific challenges and areas of progress in pharmacovigilance in SSA.

Abstract 3626: Day 21 early bone marrow response does not offer high concordance with response bone marrow in the induction chemotherapy setting of FLT3 mutant acute myeloid leukemia

Abstract Purpose: Day 14 early bone marrow biopsies are routinely initiated to determine need for reinduction chemotherapy, but poorly predict true response and risk overtreatment. Day 21 (D21) bone marrow biopsies have been performed in the context of trials utilizing FLT3-targeted therapies in combination with induction chemotherapy (Stone et al. NEJM 2017). However, the utility of D21 bone marrow responses is not well defined. Methods: We retrospectively identified 26 newly diagnosed FLT3 mutant AML patients who underwent induction chemotherapy with midostaurin and Next Generation Sequencing (NGS) of bone marrow aspirate within a week of diagnosis. Results: 19/26 (73%) of patients had both D21 and response bone marrow biopsy. Of the remaining 7 patients, 4 patients did not have D21 bone marrow, 2 died of unrelated complications prior to response bone marrow, and 1 did not have recovery marrow available for assessment. Our cohort included 13 (50%) men with a median age of 57 years (range, 21 - 73 years). All patients had ECOG of 0 - 1. 96% of cases were de novo AML and 81% had normal cytogenetics. FLT3 ITD mutations were detected in 17 (65%) patients with a median FLT3 ITD ratio of 0.305 (range, 0.03 - 1) and median FLT3 VAF of 23.8% (range, 3.2 - 80.6%). 7 patients (26.9%) underwent additional allogeneic stem cell transplant. In the 19 patients evaluable for analysis, 13/13 (100%) patients with blast % ≤ 5 at D21 achieved a complete response (CR) based on recovery marrow. 4/6 (67%) patients with blast % &amp;gt; 5 at D21 which were considered to have residual disease based on pathology review (median blast % 11 (range, 6 - 17%) ultimately achieved a CR. The 2 patients that did not achieve a CR has a blast % of 29% and 9% on D21 marrow. Thus, the positive predictive value of D21 early bone marrow response corresponding with the response bone marrow was only 33% in our patient cohort. Of the 4 patients that did not have D21 marrow but had recovery marrows available for review, the CR rate was 100%. No other significant differences in initial disease characteristics were seen. There were no differences proportion of co-mutations in NPM1, DNMT3A, TP53, IDH2, and IDH1, and higher FLT3 ITD ratio nor FLT3 VAF corresponded with ability to clear D21 bone marrow. Additionally, there were no differences in minimal residual disease (MRD) and overall survival (OS) between the groups. Conclusions: Our study suggests early bone marrow response in the context of FLT3-mutant disease is not dependent on inherent disease characteristics and does not correspond to overall response to targeted induction chemotherapy. The utility of these marrows in is this population needs to be studied further in a larger cohort to better understand the clinical necessity to avoid unnecessary cost/procedures to patients and even more importantly unnecessary reinductions. Citation Format: Vincent Lok, Su Bin Hahn, Nikesh N. Shah, Daniel A. Kerr, Ivan M. Borrello, Eduardo M. Sotomayor, David M. Swoboda. Day 21 early bone marrow response does not offer high concordance with response bone marrow in the induction chemotherapy setting of FLT3 mutant acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3626.

On Trust Recommendations in the Social Internet of Things – A Survey

The novel paradigm Social Internet of Things (SIoT) improves the network navigability, identifies suitable service providers, and addresses scalability concerns. Ensuring trustworthy collaborations among devices is a key aspect in SIoT and can be realized through trust recommendations. However, the outcome of trust recommendations depends on multiple factors related to the context-dependent nature of SIoT and practical constraints brought by the devices and networks embedded in the SIoT. While the existing literature has proposed numerous trust recommendation models to assess the trustworthiness of devices in various scenarios, researchers have not sufficiently examined the required features for trust recommendations in the SIoT. Consequently, trust recommendation models may inaccurately assess the true risk of device interactions. In this literature survey, we investigate the context-dependent features and recommendation methods used for the SIoT using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. We propose a novel taxonomy to categorize trust recommendation models according to their input features and design. Our findings reveal limited attention is given to the context-dependent features, constraints of the information environment, and limited inference capabilities that impede more precise trust recommendations. Finally, we present the research gaps and outline future directions to enable trustworthy inter-domain operations within the SIoT.

Do we underestimate risk of cardiovascular mortality due to lead exposure?

BackgroundStudies using data from the National Health and Nutrition Examination Survey-III (NHANES-III) have demonstrated significant prospective associations between blood lead levels and increased mortality. Bone lead represents cumulative lead burden and thus is a better biomarker for assessing chronic impacts, but its in vivo assessment requires special K-x-ray fluorescence (KXRF) instrumentation. Our team recently developed an algorithm predicting bone lead levels from a combination of blood lead levels, age and other socioeconomic and behavioral variables. We examined the associations of our algorithm-estimated bone lead levels and mortality in NHANES-III. MethodsWe included 11,628 adults followed up to December 31, 2019. Estimated tibia lead and patella lead levels were calculated using our prediction algorithms. We used survey-weighted Cox proportional hazards models to compute hazard ratios (HRs) and 95 % confidence intervals (CIs). ResultsDuring the median follow-up of 26.8 years, 4900 participants died (mortality rate = 1398 per 100,000 adults/year). Geometric means (95 % CIs) of blood lead, predicted tibia lead, and predicted patella lead were 2.69 μg/dL (2.54, 2.84), 6.73 μg/g (6.22, 7.25), and 16.3 μg/g (15.9, 16.8), respectively. The associations for all-cause mortality were similar between blood lead and bone lead. However, the associations for cardiovascular mortality were much greater with predicted bone lead markers compared to blood lead: for comparing participants at the 90th vs. 10th percentiles of exposure, HR = 3.32 (95 % CI: 1.93–5.73) for tibia lead, 2.42 (1.56–3.76) for patella lead, 1.63 (1.25–2.14) for blood lead. The population attributable fractions for cardiovascular disease mortality if everyone's lead concentrations were declined to the 10th percentiles were 45.8 % (95 % CI: 28.1–59.4) for tibia lead, 33.1 % (18.1–45.8) for patella lead, and 22.8 % (10.4–33.8) for blood lead. ConclusionsThese findings suggest that risk assessment for cardiovascular mortality based on blood lead levels may underestimate the true mortality risk of lead exposure.

First and Second Stage Risk Factors Associated with Perineal Lacerations.

To determine intrapartum factors associated with perineal laceration at delivery. This was a planned secondary analysis of a multicenter randomized clinical trial of delayed versus immediate pushing among term nulliparous women in labor with neuraxial analgesia conducted in the United States. Intrapartum characteristics were extracted from the medical charts. The primary outcome was perineal laceration, defined as second degree or above, characterized at delivery in women participating in longer term pelvic floor assessments post-delivery. Multivariable logistic regression was used to refine risk estimates while adjusting for randomization group, birth weight, and maternal age. Among the 941 women participating in the pelvic floor follow-up, 40.6% experienced a perineal laceration. No first stage labor characteristics were associated with perineal laceration, including type of labor or length of first stage. Receiving an amnioinfusion appeared protective of perineal laceration (adjusted odds ratio, 0.48; 95% confidence interval 0.26-0.91; P = 0.01). Second stage labor characteristics associated with injury were length of stage (2.01h vs. 1.50h; adjusted odds ratio, 1.36; 95% confidence interval 1.18-1.57; P < 0.01) and a prolonged second stage (adjusted odds ratio, 1.64; 95% confidence interval 1.06-2.56; P < 0.01). Operative vaginal delivery was strongly associated with perineal laceration (adjusted odds ratio, 3.57; 95% confidence interval 1.85-6.90; P < 0.01). Operative vaginal delivery is a modifiable risk factor associated with an increased risk of perineal laceration. Amnioinfusion appeared protective against injury, which could reflect a spurious finding, but may also represent true risk reduction similar to the mechanism of warm perineal compress.

Differences in risk profile associated with varicose veins and chronic venous insufficiency - results from the Bonn Vein Study 1.

Background: The aim of this publication is to demonstrate similarities and differences in the association of risk factors with the prevalence of different manifestations of chronic venous disease (CVD), like varicose veins (VV), venous oedema (C3) and severe chronic venous insufficiency (CVI) in the population-based cross-sectional Bonn Vein Study 1 (BVS). Patients and methods: In the BVS 1 between 13.11.2000 and 15.3.2002, 3.072 participants, 1350 men and 1722 women, from a simple random sample of the general population of the city of Bonn and two rural townships aged 18-79 years were included. The overall response proportion was 59%. All participants answered a standardized questionnaire including information about socio-economic data, lifestyle, physical activity, medical history, and quality of life. Venous investigations were performed clinically and by a standardized duplex examination by trained investigators. The CEAP classification in the version of 1996 was used to classify the findings. Logistic regression models were performed for the association of possible risk factors with VV, venous edema (C3) and severe CVI (C4-C6). The predictive risk (PR) describes the association of the diseases and the possible influencing factors. Results: VV, venous oedema (C3) and severe CVI (C4-C6) have common risk factors like higher age, number of pregnancies, family history of VV and overweight or obesity. Female gender is significantly associated with VV and C3 but not with severe CVI (C4-C6). High blood pressure and urban living are only associated with C3 and C4-C6 disease whereas prolonged sitting is associated with C3 and lower social class with C4-C6 exclusively. Discussion: In many epidemiological studies risk factors were associated with chronic venous disorders in general. Our data show that VV, venous edema and severe CVI may have different risk profiles. Venous edema is more often associated with arterial hypertension and sedentary lifestyle whereas lower social class seems to be a risk factor for severe CVI including venous ulcers. Conclusions: The differences in the association of risk factors to VV, venous edema and severe CVI should be considered if prevention and treatment of chronic venous diseases are planned. As examples, compression stockings could be proposed in sitting profession to prevent oedema, VV patients with risk factors like obesity might benefit from early treatment for VV and obesity. More longitudinal evaluation of risk factors is necessary to evaluate the true risk profile of CVD.

Risk estimation in relation to anxiety and depression for low probability negative events

Foundational cognitive models propose that people with anxiety and depression show risk estimation bias, but most literature does not compute true risk estimation bias by comparing people's subjective risk estimates to their individualized reality (i.e., person-level objective risk). In a diverse community sample (N = 319), we calculated risk estimation bias by comparing people's subjective risk estimates for contracting COVID-19 to their individualized objective risk. Person-level objective risk was consistently low and did not differ across symptom levels, suggesting that for low probability negative events, people with greater symptoms show risk estimation bias that is driven by subjective risk estimates. Greater levels of anxiety, depression, and COVID-specific perseverative cognition separately predicted higher subjective risk estimates. In a model including COVID-specific perseverative cognition alongside anxiety and depression scores, the only significant predictor of subjective risk estimates was COVID-specific perseverative cognition, indicating that symptoms more closely tied to feared outcomes may more strongly influence risk estimation. Finally, subjective risk estimates predicted information-seeking behavior and eating when anxious, but did not significantly predict alcohol or marijuana use, drinking to cope, or information avoidance. Implications for clinical practitioners and future research are discussed.

The art of compensation: How hybrid teams solve collective-risk dilemmas.

It is widely known how the human ability to cooperate has influenced the thriving of our species. However, as we move towards a hybrid human-machine future, it is still unclear how the introduction of artificial agents in our social interactions affect this cooperative capacity. In a one-shot collective risk dilemma, where enough members of a group must cooperate in order to avoid a collective disaster, we study the evolutionary dynamics of cooperation in a hybrid population. In our model, we consider a hybrid population composed of both adaptive and fixed behavior agents. The latter serve as proxies for the machine-like behavior of artificially intelligent agents who implement stochastic strategies previously learned offline. We observe that the adaptive individuals adjust their behavior in function of the presence of artificial agents in their groups to compensate their cooperative (or lack of thereof) efforts. We also find that risk plays a determinant role when assessing whether or not we should form hybrid teams to tackle a collective risk dilemma. When the risk of collective disaster is high, cooperation in the adaptive population falls dramatically in the presence of cooperative artificial agents. A story of compensation, rather than cooperation, where adaptive agents have to secure group success when the artificial agents are not cooperative enough, but will rather not cooperate if the others do so. On the contrary, when risk of collective disaster is low, success is highly improved while cooperation levels within the adaptive population remain the same. Artificial agents can improve the collective success of hybrid teams. However, their application requires a true risk assessment of the situation in order to actually benefit the adaptive population (i.e. the humans) in the long-term.

Development of a modified frailty index for adult spinal deformities independent of functional changes following surgical correction: a true baseline risk assessment tool.

To develop a simplified, modified frailty index for adult spinal deformity (ASD) patients dependent on objective clinical factors. ASD patients with baseline (BL) and 2-year (2Y) follow-up were included. Factors with the largest R2 value derived from multivariate forward stepwise regression were including in the modified ASD-FI (clin-ASD-FI). Factors included in the clin-ASD-FI were regressed against mortality, extended length of hospital stay (LOS, > 8days), revisions, major complications and weights for the clin-ASD-FI were calculated via Beta/Sullivan. Total clin-ASD-FI score was created with a score from 0 to 1. Linear regression correlated clin-ASD-FI with ASD-FI scores and published cutoffs for the ASD-FI were used to create the new frailty cutoffs: not frail (NF: < 0.11), frail (F: 0.11-0.21) and severely frail (SF: > 0.21). Binary logistic regression assessed odds of complication or reop for frail patients. Five hundred thirty-one ASD patients (59.5yrs, 79.5% F) were included. The final model had a R2 of 0.681, and significant factors were: < 18.5 or > 30 BMI (weight: 0.0625 out of 1), cardiac disease (0.125), disability employment status (0.3125), diabetes mellitus (0.0625), hypertension (0.0625), osteoporosis (0.125), blood clot (0.1875), and bowel incontinence (0.0625). These factors calculated the score from 0 to 1, with a mean cohort score of 0.13 ± 0.14. Breakdown by clin-ASD-FI score: 51.8% NF, 28.1% F, 20.2% SF. Increasing frailty severity was associated with longer LOS (NF: 7.0, F: 8.3, SF: 9.2days; P < 0.001). Frailty independently predicted occurrence of any complication (OR: 9.357 [2.20-39.76], P = 0.002) and reop (OR: 2.79 [0.662-11.72], P = 0.162). Utilizing an existing ASD frailty index, we proposed a modified version eliminating the patient-reported components. This index is a true assessment of physiologic status, and represents a superior risk factor assessment compared to other tools for both primary and revision spinal deformity surgery as a result of its immutability with surgery, lack of subjectivity, and ease of use.

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.

Abstract TP252: Forward Head Posturing as a Significant Risk Factor for Posterior Circulation Infarcts

Objective: Forward head posturing (FHP) has been associated with chronic anatomic vertebral artery disturbances possibly leading to posterior circulation ischemia. The data supporting FHP as a true risk factor of posterior circulation stroke has not been well established. We aim to study if patients with severe cervical myalgias and FHP have an increased risk of posterior circulation stroke. Methods: We identified all adult patients with posterior circulation stroke and diagnosis of cervical myalgia at Loyola University Medical Center from January 2018 to January 2023. Information on demographics and comorbidities were also collected. We then identified matched pair case-controls (based on age and gender) with non-stroke cervical myalgia patients in the same 5-year period. We compared the relevant comorbidities, C2 tilt angle, and C2-C7 tilt angle of patients to their matched controls to for statistical difference. Results: 76 patients (38 cases and 38 controls) with an average age of 64 years, including 38 (50%) females met our inclusion criteria. The average C2 tilt of cases was 22.9 degrees compared to 17.7 degrees in controls, and the average C2-C7 tilt of cases was 18.9 degrees in cases compared 10.5 degrees in controls. There were no significant differences between relevant comorbidities (including hypertension, hyperlipidemia, diabetes, atrial fibrillation, hyper-coagulopathy, or body mass index) of cases and controls. There was a significant difference of 5.2 degrees higher C2 tilt and 8.1 degrees higher C2-C7 tilt in cases compared to controls respectively (p-value = 0.03). Conclusion: In this single-center retrospective analysis, we found that after controlling for age, gender, and comorbidities, patients with posterior circulation stroke were more likely to have significantly higher C2 and C2-C7 cervical tilt (worse FHP based on radiographic standards) compared to their matched control counterparts.