Risk Estimates Research Articles

Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABABR Antibodies: Implications for Return to Driving.

Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABABR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months. This would render them eligible for noncommercial driving according to driving regulations in several countries. This retrospective multicenter cohort study analyzed follow-up data from patients aged 15 years or older with seizures resulting from NMDAR-, LGI1-, CASPR2-, or GABABR-AIE, who had been seizure-free for ≥3 months. We used Kaplan-Meier (KM) estimates for the seizure recurrence risk at 12 months for each antibody group and tested for the effects of potential covariates with regression models. We included 383 patients with NMDAR-, 440 with LGI1-, 114 with CASPR2-, and 44 with GABABR-AIE from 14 international centers. After being seizure-free for 3 months after an initial seizure period, we calculated the probability of remaining seizure-free for another 12 months (KM estimate) as 0.89 (95% confidence interval [CI] 0.85-0.92) for NMDAR, 0.84 (CI 0.80-0.88) for LGI1, 0.82 (CI 0.75-0.90) for CASPR2, and 0.76 (CI 0.62-0.93) for GABABR. Taking a <20% recurrence risk within 12 months as sufficient, patients with NMDAR-AIE and LGI1-AIE could be considered eligible for noncommercial driving after having been seizure-free for 3 months.

The Association of Guideline-Directed Prophylaxis with Postoperative Nausea and Vomiting in Pediatric Patients: A Single-Center, Retrospective Cohort Study.

Guidelines for postoperative nausea and vomiting (PONV) prophylaxis in pediatric patients recommend escalation of the number of antiemetics based on a preoperative estimate of PONV risk. These recommendations have been translated into performance metrics, most notably by the Multicenter Perioperative Outcomes Group (MPOG), used at over 25 children's hospitals. The impact of this approach on clinical outcomes is not known. We performed a single-center, retrospective study of pediatric general anesthetic cases from 2018 to 2021. PONV risk factors were defined using MPOG definitions: age ≥3 years, volatile use ≥30 minutes, PONV history, long-acting opioids, female ≥12 years, and high-risk procedure. Adequate prophylaxis was defined using the MPOG PONV-04 metric: 1 agent for 1 risk factor, 2 agents for 2 risk factors, and 3 agents for 3+ risk factors. PONV was defined as documented postoperative nausea/emesis or administration of a rescue antiemetic. Given the nonrandomized allocation of adequate prophylaxis, we used Bayesian binomial models with propensity score weighting. A total of 14,747 cases were included, with PONV in 11% (9% adequate prophylaxis versus 12% inadequate). Overall, there was evidence for reduced incidence of PONV with adequate prophylaxis: weighted median odds ratio 0.82 (95% credible interval, 0.66-1.02; probability of benefit, 0.97) and weighted marginal absolute risk reduction 1.3% (-0.1% to 3.1%). In unweighted estimates, there was an interaction between sum of risk factors and the association of adequate prophylaxis with PONV, with reduced incidence in patients with 1 to 2 risk factors (probability of benefit 0.96 and 0.95) but increased incidence in patients with 3+ risk factors receiving adequate prophylaxis (probability of benefit 0, 0.01, and 0.03 for 3, 4, and 5 risk factors). This was attenuated by weighting, with persistent benefit in 1 to 2 risk factors (probability of benefit 0.90 and 0.94) but equalization of risk in 3+ risk factors. Guideline-directed PONV prophylaxis is inconsistently associated with incidence of PONV across the guideline-defined risk spectrum. This phenomenon, and its attenuation with weighting, is consistent with 2 points: dichotomous risk-factor summation ignores differential effects of individual components, and prognostic information might exist beyond these risk factors. PONV risk at a given sum of risk factors is not homogeneous, but rather is determined by the unique composition of risk factors and other prognostic attributes. These differences appear to have been identified by clinicians, prompting use of more antiemetics. Even after accounting for these differences, however, addition of a third agent did not further reduce risk.

Eligibility for lipid-lowering therapy when applying systemic coronary risk estimation 2 (SCORE2) according to guidelines on apparently healthy middle-aged individuals.

To estimate the proportion eligible for lipid-lowering therapy (LLT) when using the systemic coronary risk estimation 2 (SCORE2) on apparently healthy individuals. Individuals aged 50-64 years were randomly invited to the Swedish cardiopulmonary bioimage study (SCAPIS, n=30,154). Participants with previous atherosclerotic cardiovascular disease (CVD), diabetes mellitus, or chronic kidney disease were excluded. The 10-year risk of CVD was estimated using the SCORE2 equation and the multicell chart. Eligibility for LLT was estimated according to the 2021 European Society of Cardiology CVD prevention guidelines. Presence of coronary atherosclerosis was determined using coronary computed tomography angiography (CCTA). Among 26,570 apparently healthy individuals, 32% had high, and 4% had very-high 10-year CVD risk, according to the SCORE2 equation. Among high and very-high risk individuals, 99% had LDL-C levels above guideline goals making 35% of the total population eligible for LLT. Of those eligible, undergoing imaging, 38% had no signs of coronary atherosclerosis according to CCTA. Using the SCORE2 chart, 52% of the population were eligible for LLT, of which 44% had no signs of coronary atherosclerosis. In those with high or very-high risk, ongoing LLT was reported in 7% and another 11% received LLT within six months after study participation. Nearly all apparently healthy individuals with high and very-high CVD risk, or 35% of the total population, were eligible for LLT according to guidelines, and a large proportion had no signs of atherosclerosis. Compared with the SCORE2 equation, the SCORE2 chart resulted in more individuals being eligible for LLT.

Occurrence and health risk estimate of organochlorine pesticides in fruits and vegetables matrices.

Occurrence of 20 organochlorine pesticides (OCPs) in 60 organic and non-organic fruits and vegetables matrices was undertaken using QuEChERS Method EN 15662 for sample preparation analyzed by gas chromatography-mass spectrometry (GC-MS/MS). The procedural method was validated by spiking the OCP standard solutions at three fortified levels at 10, 50, and 100 µg/kg wet weight (ww) to the real matrix of fruit and vegetable with good recovery ranging from 75 to 108% with relative standard deviation (RSD) ≤ 11%, and the limits of detection and quantification (LODs and LOQs) were 0.002-0.02μg/kg and 0.004-0.1μg/kg ww, respectively. The assessment of health risks associated with pesticide residues through consumption of vegetables and fruits and the effect of washing and peeling on concentration of various pesticides were also studied. The results showed that the concentration levels of 60% of samples were lower than the LOQs, while the rest was contaminated by OCP residues. Organic fruits and vegetables showed the absence of OCPs, while several of the studied compounds were detected from conventional agriculture. Skin removal (peeling) was the most effective strategy to eliminate or decrease pesticide residues, and should be one of the solutions to reduce the health impact of pesticides in fruits and vegetables. The analysis of health risk assessment was based on the use of the estimated average daily intake (EDI), hazard index (HI), and hazard ratio (HR) for individuals in two weight categories: children (weighing 16.7kg) and adults (weighing 60kg). The HI values were less than 1 suggesting that there was no probable non-carcinogenic health effect, except for heptachlor for children (HI of 1.285). However, the values of HR revealed that children were more susceptible to the carcinogenic health effect associated with consuming contaminated vegetables.

Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.

Pediatric sepsis is a serious issue globally and is a significant cause of illness and death among infants and children. Refractory septic shock and multiple organ dysfunction syndrome are the primary causes of mortality in children with sepsis. However, there is incomplete understanding of mechanistic insight of sepsis associated organ dysfunction. Biomarkers present during the body's response to infection-related inflammation can be used for screening, diagnosis, risk stratification/prognostication, and/or guidance in treatment decision-making. Research on biomarkers in children with sepsis can provide information about the risk of poor outcomes and sepsis-related organ dysfunction. This review focuses on clinically used biomarkers associated with immune dysregulation and organ dysfunction in pediatric sepsis, which could be useful for developing precision medicine strategies in pediatric sepsis management in the future. IMPACT: Sepsis is a complex syndrome with diverse clinical presentations, where organ dysfunction is a key factor in morbidity and mortality. Early detection of organ complications is vital in sepsis management, and potential biomarkers offer promise for precision medicine in pediatric cases. Well-designed studies are needed to identify phase-specific biomarkers and improve outcomes through more precise management.

The estimated 10-year risk of first-onset cardiovascular disease in Swedish-born and non-Swedish-born primary healthcare patients

BackgroundSCORE2 has been introduced as an updated risk assessment tool for calculating the 10-year risk of first-onset cardiovascular disease (CVD). However, it does not account for ethnicity or socioeconomic status, known to affect CVD risk. This study investigated and compared SCORE2 estimates in Swedish-born and non-Swedish-born primary healthcare patients. The second aim was to examine if several risk factors could explain differences in CVD risk between the groups.MethodsThis was an observational, cross-sectional study. Data were obtained from the 4D Diabetes Project study, providing a total of 444 participants aged between 40 and 69 years. All participants had complete risk variable data necessary for the SCORE2 tool and no history of previous CVD. Descriptive analysis was conducted to compare distributions of risk factors between Swedes and immigrants and odds ratios of risk factors amongst these two groups in correlation to elevated CVD risk were calculated using logistic regression.ResultsSwedish-born patients showed a significantly higher risk of elevated CVD risk estimates (≥ 2.5% CVD risk increase for individuals < 50 years, respectively, ≥ 5% for individuals aged 51–69) than the non-Swedish-born population, even after adjustment for educational level (OR = 1.61, 95% CI 1.08–2.39). Weekly alcohol consumption implicated a risk of being classified as high risk of CVD risk, regardless of country of birth (OR = 1.93 CI 1.25-3.00). However, Swedes accounted for most of the alcohol consumption (62.6% vs. 19.6%). No other explanatory variable showed significance in association with elevated CVD risk.ConclusionsSwedish-born patients were found to be at higher risk of an increased 10-year CVD risk. The association of alcohol consumption with elevated CVD risk needs to be further studied in longitudinal studies in representative populations, notably among Sweden’s diverse ethnic groups.

Implementing absolute cardiovascular disease risk assessment into pathology collection services.

Pathology services represent an ideal setting to integrate absolute cardiovascular disease (CVD) risk estimation when patients attend for routine cholesterol testing. This study aimed to explore the process of implementing CVD risk estimation into point-of-care service delivery by pathology staff to inform future implementation and sustainability. A new service for CVD risk estimation via a self-directed screening station was implemented into 14 pathology service sites across Tasmania, Australia. Before implementation, observations at pathology services (n = 26) and semi-structured interviews were undertaken with 26 pathology staff (88% female, 77% aged 41-60 years) to identify factors that could impact implementation of the service. The process of implementation was then evaluated using participant observations and clinical trial recruitment data. Transcripts and field notes were analysed thematically according to the Medical Research Council Framework and used to develop a programme logic model to understand how the service could be adapted to be successfully integrated into routine workflow at pathology services. Eight key themes were identified during the pre-implementation phase as important factors that could impact upon integration of CVD risk estimation into pathology services. Themes related to factors within the organisation, including available resources, logistics and workflow, as well as having sufficient time to complete the intervention. Additional factors related to the individual motivations of staff, collaborative leadership and patient characteristics. Success of implementation varied among sites, requiring the trialling of different strategies to support uptake of the service and patient recruitment. Implementing CVD risk estimation into point-of-care pathology services required an understanding of the core implementation components specific to each context, and for implementation strategies to be targeted to the individual and organisational contexts. The generated programme logic model may be useful in guiding future implementation endeavours within these services and aiding the selection of apt implementation strategies. ClinicalTrials.gov Identifier: NCT04896021, registered 19/05/2021, https://clinicaltrials.gov/study/NCT04896021.

Estimation of climate and watershed management-induced potential soil loss using the USLE in Demjer watershed, Blue Nile basin, Ethiopia

ABSTRACT This study aimed to predict future soil loss under different climatic scenarios in the Demjer watershed, Blue Nile River Basin. The soil loss was calculated using USLE. The GCMs derived under the RCP4.5 and RCP8.5 for the period 2020–2049 were used. Three LULC scenarios were considered and the projection of the change in rainfall was estimated under the RCP4.5 and RCP8.5 scenarios. The projected mean annual precipitation increased by 6.42 and 5.95% under the RCP4.5 and RCP8.5 scenarios, respectively. The soil loss rate in the future ranged from 0 to 144.7 t ha−1y−1 and from 0 to 142.4 t ha−1y−1 for RCP4.5 and RCP8.5, respectively. Compared to the base period, the soil loss rates increased by 7.6% (RCP4.5) and 7.4% (RCP8.5). This is attributed to increase in rainfall erosivity. The LULC scenario is a major variable in reducing soil erosion rates in the future. That means, soil loss would reduce up to 33.6% of the present soil loss rate, if all the current cultivated lands with slopes >35% are covered by plantations and if open grazing land controlled. Estimation of future soil loss risk could provide evidence for preparing site-specific conservation plans, thereby enabling sustainable use of land.

Analysis of the direct economic impact of smoking-related hospitalizations in Italy.

Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy. We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking. One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively. Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking.

Health risk assessment due to uranium contamination in groundwater: MATLAB based Monte-Carlo simulations

ABSTRACT Uranium contamination is a growing concern due to its inherent toxicity, which poses a significant threat to human health. The health risk assessment due to uranium contamination in groundwater of Mansa district, Punjab (India) is investigated. The LED LF-2a Fluorimeter model by Quantalase (Indore) was used for measurement of uranium concentration in groundwater collected in October 2021 from twenty-six locations. A comparison is conducted between the deterministic and probabilistic approaches since the deterministic approach might either underestimate or exaggerate the risk estimation. Monte-Carlo simulations are used to curtail the associated uncertainties in the data. The simulations are carried out in MATLAB for risk assessment and sensitivity analysis. The deterministic and probabilistic approaches are used to calculate hazard quotient, excess cancer risk and annual effective dose. Using probabilistic approach, the hazard quotient for male and female at 5th percentile is 4.36 and 3.81, respectively. Similarly, the hazard quotient for male and female at 95th percentile is 38.95 and 34.26, respectively. The mean hazard quotient is 18.45 and 15.68 for male and female, respectively, using deterministic approach. The hazard quotient is greater than 1 for both genders (male and female) and excess cancer risk is also higher than 10−4 using both deterministic and probabilistic approaches. The annual effective dose using deterministic approach is 0.23 mSv year−1 whereas using probabilistic approach, the 5th and 95th percentile is 0.56 mSv year−1 and 4.33 mSv year−1, respectively. The sensitivity analysis indicated that the overall risk is more sensitive to concentration of uranium in groundwater and the exposure frequency. This study emphasises on the hazards posed to humans by the ingestion of uranium contaminated groundwater, hence stressing the urgency for taking actions to protect the population of the study area.

A non-stationary bivariate extreme value model to estimate real-time pedestrian crash risk by severity at signalized intersections using artificial intelligence-based video analytics

Vehicle-pedestrian crashes are generally severe due to the vulnerability of pedestrians compared to the occupants of vehicles. However, the estimation of pedestrian crash risk by severity has not been given adequate attention in the field of proactive safety assessments applying traffic conflict techniques. This study proposes a novel analytical framework to estimate real-time pedestrian crash risk by severity at the signal cycle level while incorporating the effect of time-varying exogenous variables. Specifically, the study applies a non-stationary bivariate extreme value model to jointly model the post encroachment time and Delta-V for estimating real-time pedestrian crash risk by severity at individual signal cycles. The proposed framework is tested on 144 h of video data collected from three signalized intersections in Queensland, Australia. The developed bivariate extreme value model has been found to reliably predict severe and non-severe pedestrian crash frequencies compared to the historical crash records of severe and non-severe pedestrian crashes at those signalized intersections. Results suggest that the frequency of pedestrian conflicts per signal cycle and average pedestrian speed in a signal cycle are associated with real-time pedestrian crash risks. In addition, pedestrian conflicts per signal cycle and average vehicle speed per cycle were associated with the interaction severity component of the non-stationary bivariate extreme value model. The proposed proactive estimation of pedestrian crash risk by severity levels can help design time-sensitive countermeasures for vulnerable road users.

Development and validation of RSClin N+ tool for hormone receptor-positive (HR+), HER2-negative (HER2-), node-positive breast cancer.

508 Background: The RSClin tool was developed to provide estimates of recurrence risk and absolute chemotherapy benefit for patients with HR+/HER2- node-negative breast cancer using the 21-gene recurrence score (RS) and clinicopathologic factors. For patients with node-positive disease, we developed a new tool (RSClin N+) to increase the prognostic and predictive utility of risk estimates by combining RS with clinicopathologic factors and menopausal status. Methods: We used Cox regression to estimate 5-year risk of invasive disease or death (iDFS) and likelihood ratio (LR) tests to compare fit of RSClin N+ with RS alone and clinicopathologic factors (tumor grade, tumor size, positive lymph nodes [N1/N2], age) alone in 5283 node-positive patients treated with chemoendocrine therapy (CET) vs endocrine therapy alone (ET) in the S8814 (n=367: N1=227, N2=140, all postmenopausal) and RxPONDER (n/N1=4916) trials. Data from both studies were pooled and stratified by study for postmenopausal models; premenopausal models were fit only on RxPONDER data. Absolute CET benefit across combination of covariate values was estimated as the difference between ET and CET risk estimates. Validation of RSClin N+ was performed in 592 Nmic/N1 patients in the Clalit registry real-world dataset. Results: For pre- and postmenopausal patients, RSClin N+ provided significantly more prognostic information for iDFS than RS or clinicopathologic factors alone (LR Chi-square p&lt;0.05). In postmenopausal patients, RS and clinicopathologic factors were independently prognostic, but only RS showed interaction with CET benefit (p=0.016). Absolute CET benefit for iDFS ranged from &lt;0.1% to 21.5% as the RS increased from 0 to 50. Table shows examples of risk stratification and predicted benefit by RS within clinical low and high risk patients. In premenopausal patients, both RS and clinicopathologic factors remained prognostic but no interaction was observed between RS and CET.In external validation, RSClin N+ risk estimates were concordant with (Lin’s concordance=0.92) and prognostic for observed risk (HR 1.75; 95% CI 1.38 to 2.20). Conclusions: The RSClin N+ model provides improved estimates of prognostic risk and absolute CET benefit than clinical or genomic data alone in node-positive, HR+/HER2- breast cancer and could be used in patient counseling. [Table: see text]

Population attributable fraction of reproductive factors in triple negative breast cancer by race.

10522 Background: Age-adjusted incidence rates of triple negative breast cancer (TNBC) are higher in African American (AA) women than in non-Hispanic White (White) women. The disproportionate incidence of TNBC in AA women partially drives the 40% higher mortality rate from breast cancer in AA women compared to White women. Several studies have identified lack of breastfeeding and younger age at first birth as risk factors for TNBC. There are large differences in breastfeeding uptake and duration in the US: only 44% of AA women breastfeed for 6 months or longer, compared to 60% of White women. To quantify the contribution of differences in breastfeeding patterns and younger age at first birth to disparities in incidence of TNBC, we calculate the population-attributable fraction (PAF), which is the proportion of the incidence of a disease that may be attributable to a particular exposure. Methods: A systematic review was performed to identify relevant case-control studies. Pooled odds ratios (ORs) for breastfeeding for &lt; 6 months and age at first birth &lt; 25 years were calculated from data extracted from studies using a common effect model. PAF was calculated using the Levin formula. Risk factor population prevalences were extracted from national surveys. Pooled ORs were used as estimates of relative risk (RR). A combined PAF was calculated using the polychoric correlation coefficient between breastfeeding duration and age at first birth to account for contributions of multiple risk factors. Results: Using race specific ORs, the PAF of breastfeeding for &lt; 6 months was 12% (95% confidence interval (CI) 5-20%) among White women and 15% (95% CI 3-26%) among AA women. The PAF of having a child before age 25 was not significantly different from zero for White women (2% (CI -6-11%)) but was significantly different from zero for AA women (21% (CI 5-25%)). The combined PAF was 27% for AA women and 17% for all women in the US. Extrapolating to the US population, we estimated that 4,850 annual cases of TNBC (2,421 among White women and 1,533 among AA women) could be attributed to breastfeeding for &lt; 6 months and age at first birth &lt; 25 years. Conclusions: Given the protective role of breastfeeding against TNBC, policy changes aimed at supporting breastfeeding, addressing structural barriers, and promoting a culture shift could reduce racial disparities in TNBC incidence in the US. [Table: see text]

Clinical and economic benefit of genomic testing strategies to guide the treatment of patients with HR+/HER2- breast cancer in the US.

10584 Background: Multiple testing technologies are available to inform treatment decisions for hormone receptor positive (HR+) and human epidermal growth factor receptor 2 negative (HER2-) early-stage breast cancer, including tumor profiling and germline genetic testing (GGT). The 21-gene assay provides an estimate of distant recurrence risk and potential clinical benefit of chemotherapy. GGT identifies pathogenic variants which inform lifetime cancer risk as well may inform therapy options. This study explored the potential synergy of utilizing both tests by assessing the cost-effectiveness of this strategy compared to no testing from a societal perspective. Methods: A health economic model was developed using best practices to assess a patient cohort with HR+/HER2-, node-negative (N0) or node-positive (N1) breast cancer that was guided to surgical and adjuvant treatment by GGT ( ATM, BRCA1/2, CDH1, CHEK2, PALB2, PTEN,and TP53) and the 21-gene assay. Treatment effectiveness was informed by clinical trials (TAILORx and RxPONDER); costs for treatment, monitoring, and health utilities were sourced from literature. Clinical expert opinion and guidelines informed current US clinical practice. The base case analysis evaluated lifetime total costs, life-years, and quality-adjusted life years (QALYs) versus no testing. Scenario and sensitivity analyses were performed to evaluate model robustness. Results: The testing strategy was dominant (lower cost and higher QALYs gained) compared to no testing leading to a QALY improvement of 0.286 and cost savings of $16,463 in the N0 population (Table) and a 0.099 QALY improvement and $299 cost savings in the N1 population. Scenario analyses indicated that while the 21-gene assay was the primary driver of results, there were synergistic effects when tests were combined. Sensitivity analysis supported cost-effectiveness at most willingness-to-pay thresholds and identified the probability of chemotherapy and rate of distant recurrence as the most impactful model inputs. Conclusions: Using a testing strategy including both the 21-gene assay and GGT enables optimization of treatment decisions in early HR+/HER2- breast cancer, improving patient outcomes at reduced costs. [Table: see text]

Outcomes of Near-Total and Subtotal Resection of Sporadic Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

To evaluate tumor control and facial nerve outcomes after gross-total (GTR), near-total (NTR), and subtotal resection (STR) of sporadic vestibular schwannomas (VS). PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were searched in August 2021 through inception following PRISMA guidelines. English language articles reporting tumor control and facial nerve outcomes of adults (≥18 years) with NTR and STR of VS were evaluated. Study characteristics, demographics data, tumor characteristics, type of surgical intervention, and outcome measures on tumor control and facial nerve function were collected. Pooled relative risk (RR) estimates for tumor recurrence and facial nerve outcomes were calculated and stratified by extent of resection. From an initial search of 2504 articles, 48 studies were included in the analysis. When comparing 1108 patients who underwent NTR to 3349 patients with GTR, the pooled RR of recurrence in the NTR cohort was 2.94 (95% confidence interval [CI] 1.65-5.24, P = .0002). When comparing 1016 patients who underwent STR to 6171 patients with GTR, the pooled RR of recurrence in the STR cohort was 11.50 (95% CI 6.64-19.92, P < .0001). Estimates for risk of tumor regrowth for less-than-complete resection are presented. There was no elevated risk of adverse facial nerve outcome (defined as House-Brackmann grade III and above) in each category of extent of resection compared to GTR. Extent of resection predicts risk of tumor recurrence/regrowth following microsurgical resection. Favorable facial nerve outcome should be weighed against the increased risk of regrowth and the potential need for further treatment.

Atypicality index as an add-on to combined first-trimester screening for chromosomal aberrations.

To compute a set of atypicality indices based on combined first-trimester screening (cFTS) markers and second-trimester estimated fetal weight (EFW), and to demonstrate their potential in identifying pregnancies at reduced or increased risk of chromosomal aberrations following a low-risk cFTS result. The atypicality index quantifies the unusualness of an individual set of measurements relative to a reference distribution and can be computed from any variables or measurements available. A score of 0% on the atypicality index represents the most typical profiles, while a score of 100% indicates the highest level of atypicality. From the Danish Fetal Medicine Database, we retrieved data on all pregnant women seen for cFTS in the Central Denmark Region between January 2008 and December 2018. All pregnancies with a cytogenetic or molecular analysis obtained prenatally, postnatally or following pregnancy loss or termination were identified. A first-trimester atypicality index (AcFTS) was computed based on nuchal translucency (NT) thickness, maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A). Furthermore, a second-trimester index (AcFTS + EFW) was computed from cFTS markers and EFW from a routine second-trimester anomaly scan. All pregnancies were stratified into subgroups based on their atypicality levels and their cFTS risk estimates. The risk of chromosomal aberrations in each subgroup was then compared with the overall prevalence, and a graphical presentation of the multivariate measurement profiles was developed. We retrieved data on 145 955 singleton pregnancies, of which 9824 (6.7%) were genetically examined. Overall, 1 in 122 (0.82% (95% CI, 0.77-0.87%)) of all pregnancies seen for cFTS were affected by a fetal chromosomal aberration, and in screen-negative pregnancies (cFTS trisomy 21 risk < 1 in 100 and/or trisomy 18/13 risk < 1 in 50), 0.41% (95% CI, 0.38-0.44%) were affected. In screen-negative pregnancies with a typical first-trimester profile (AcFTS < 80%), the risk of chromosomal aberrations was significantly reduced (0.28%) compared with the overall risk. The risk of chromosomal aberrations increased with higher atypicality index to 0.49% (AcFTS [80-90%)), 1.52% (AcFTS [90-99%)) and 4.44% (AcFTS ≥ 99%) and was significantly increased in the two most atypical subgroups. The same applied for the second-trimester atypicality index, with risks of chromosomal aberrations of 0.76% and 4.16% in the two most atypical subgroups (AcFTS + EFW [90-99%) and AcFTS + EFW ≥ 99%, respectively). As an add-on to cFTS, the atypicality index identifies women with typical measurement profiles, which may provide reassurance, whereas atypical profiles may warrant specialist referral and further investigation. In pregnancies identified as low risk on cFTS but with a highly atypical distribution of NT, PAPP-A and β-hCG, the risk of a chromosomal aberration is substantially increased. The atypicality index optimizes the interpretation of pre-existing prenatal screening profiles and is not limited to cFTS markers or EFW. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Injury Risk Estimation in Mandible-Related Surgical Procedures: A CBCT Study Based on Vital Interforaminal Anatomical Structures.

The mandibular interforaminal region has been considered safe for surgical procedures; nevertheless, the risk of injury to neurovascular structures, such as the mental foramen (MF) and its related structures (anterior loop [AL] and lingual foramina [LF]) should not be overlooked. The study aimed to evaluate the relative risk of injury to these structures during surgical procedures in the anterior region of the mandible based on cone-beam computed tomography (CBCT) scans. A retrospective cross-sectional and observational study was performed on 250 CBCTs from adults (18-69 years) with dentate jaws. Linear measurements of the MF, AL, and LF were evaluated to estimate the risk of injury to these structures during chin-related surgical procedures. The most frequent distance between the base of the mandible (BM) and MF was 8 mm (30.2%). In addition, 20.4% of the CTs had 6 mm from the vestibular cortical bone to the LF. The commonly found measurement from LF to the apex of the nearest tooth was 7 mm (24.0%); 64.2% of the CTs showed a 2-mm distance between the most distal point of the dental implant site to the most anterior point of the AL. Safety distances for genioplasty techniques (MF to mandible base > 6 mm, 96.6% [CI 95%, 95.0%-98.2%]) were observed. Considering the 5-mm cut-off point between the lower limit of a hypothetical bone graft and the chin, 65.4% (CI 95%, 58.9%-71.9%) of CTs were within this distance. Regarding the safety margin of 8 mm, 85.6% (CI 95%, 80.8%-90.4%) were up to this value. This study found safety margins for genioplasty and chin bone grafting surgical techniques that adopt a 5-mm cut-off point. Further similar studies assessing other surgical methods and employing larger samples from different geographical origins may contribute to this field of investigation.

Feasibility of universal breast cancer risk assessment in a diverse, publicly insured obstetrician gynecology clinic.

e13759 Background: Breast cancer is the most diagnosed cancer among women in the United States. Established breast cancer risk assessment (BCRA) tools can estimate a woman’s lifetime risk and inform the need for enhanced breast screening which can improve cancer-associated morbidity and mortality. Currently, critical disparities exist both in breast cancer prognosis and screening uptake. We aimed to evaluate the feasibility of routine BCRA in a diverse, publicly insured obstetrician gynecology clinic. Methods: All patients presenting to the obstetrician gynecology clinic were offered a BCRA using the Tyrer Cuzick (TC) risk model. Patients completed paper surveys and the information was input into the TC model to generate lifetime risk estimates. Printed evidence-based management guidelines were reviewed with and provided to those at ≥ 20% lifetime breast cancer risk and shared with the patient’s provider. Results: Between June 2023 and February 2024, 300 patients were approached and 208 (69.3%) completed the survey. One hundred seven (51.4%) survey respondents were presenting for obstetrical care and 101 (48.6%) for gynecologic care. Respondents had a median age of 33 years (IQR: 12). Ninety-six (46.2%) responding patients self-identified as Hispanic, 45 (21.6%) as Black, 25 (12.0%) as Asian, 28 (13.5%) as Non-Hispanic White, and 14 (6.7%) did not identify in these categories. One hundred eighty-nine (90.9%) survey respondents were publicly-insured. Ten (4.8%) patients were assisted by an interpreter. Overall, 12 (5.8%) patients had an elevated lifetime breast of breast cancer, defined as ≥ 20% based on the TC model (6 (50.0%) among obstetrical patients and 6 (50.0%) among gynecology patients). All patients at elevated risk were referred to a genetics clinic for counseling on options for enhanced breast surveillance. Conclusions: As leaders in women’s cancer care, gynecologic oncologists can lead and support programs to identify those women at highest risk for cancer, especially among historically underserved populations. Our feasibility study demonstrated that 69.3% of patients were willing to complete a BRCA and this tool identified 5.8% of patients to have a significantly elevated lifetime breast cancer risk. Providers should consider incorporating such tools in gynecologic oncology and obstetrical/gynecology clinics.

Risk of subsequent primary cancers among adult cancer survivors.

10554 Background: Improvements in early detection and clinical management of cancers have led to a significant increase in long-term cancer survivors who may be at an elevated risk of developing a subsequent primary cancer (SPC). As the largest and most comprehensive analysis in Canada, we assessed the risks and patterns of SPC development among 134,693 adult cancer survivors with 852,661 person-years of follow-up. Methods: We used data from the Alberta Cancer Registry (ACR) to identify all first primary cancers (FPC) occurring between 2004 and 2015 to allow for adequate follow-up until December 31, 2020. A SPC was considered as the next primary cancer occurring in a different organ/site. We estimated incidence rates (IR) and standardized incidence ratios (SIR) for SPC development with 95% confidence intervals (CI). IRs were estimated as the observed number of SPC divided by the person-years of follow-up. SIRs were estimated as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the general population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up among the adult cancer survivors. Results: The risk of developing a SPC up to fifteen years after an initial cancer was 16.1% for males and 12.3% for females. These risk estimates varied considerably by initial cancer site. Survivors of initial head and neck cancers had a fifteen-year cumulative incidence of 21.3% and a 2.5-fold relative risk of SPC development. Overall, both males (SIR=1.50) and females (SIR=1.64) had an increased risk of developing a SPC. Both male and female survivors of a FPC were at a significantly increased relative risk of developing a screen-detectable SPC (breast, cervical, colorectal, lung). There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors of early-onset cancers diagnosed between ages 18 to 39. Conclusions: Cancer survivors of nearly every FPC site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and this highlights the need to develop evidence-based guidelines for cancer screening in the growing population of long-term cancer survivors.[Table: see text]

Risk of early clinical deterioration and 30-day mortality in pulmonary embolism intermediate-high-risk patients with patent foramen ovale.

We assess the prognostic role of patent foramen ovale (PFO) for the estimation of 30-day mortality and risk of 48-h clinical deterioration since admission, in intermediate-high-risk pulmonary embolism (PE) patients. A post-hoc analysis of intermediate-high-risk PE patients enrolled in the Italian Pulmonary Embolism Registry (IPER) (Trial registry: ClinicalTrials.gov; No.: NCT01604538) was performed. The entire cohort was divided according to the presence or absence of PFO after transthoracic echocardiography (TTE) evaluation. Among 450 intermediate-high-risk PE patients (mean age 71.4 ± 13.8years, 298 males), PFO was diagnosed in 68 (15.1%) cases. A higher mortality rate (29.4% vs. 3.1%, p < 0.001) as well as occurrence of clinical deterioration within 48h from admission (38.2% vs. 3.6%, p < 0.001) were observed in intermediate-high-risk PE patients with PFO compared to those without multivariate Cox regression analysis showed that the presence of a PFO predicts 30-day mortality (HR: 3.21, 95% CI 3.16-3.27, p < 0.001) and was also associated with a significantly higher risk of 48-h clinical deterioration [HR: 2.24 (95% CI 2.20-2.29), p < 0.0001] in intermediate-high-risk PE patients. The presence of a PFO in intermediate-high-risk PE patients is associated with a higher risk of clinical deterioration within 48h from admission and 30-day mortality.