Low-risk Stratum Research Articles

Culex quinquefasciatus Density Associated with Socioenvironmental Conditions in a Municipality with Indeterminate Transmission of Lymphatic Filariasis in Northeastern Brazil

Lymphatic filariasis (LF) is a neglected tropical disease associated with poverty and poor environmental conditions. With the inclusion of vector control activities in LF surveillance actions, there is a need to develop simple methods to identify areas with higher mosquito density and thus a higher consequent risk of W. bancrofti transmission. An ecological study was conducted in Igarassu, which is in the metropolitan region of Recife, Pernambuco, Brazil. The mosquitoes were captured in 2060 houses distributed across 117 census tracts. The vector density index (VDI), which measures the average number of lymphatic-filariasis-transmitting mosquitoes per number of houses collected in the risk stratum, was constructed. Moreover, the social deprivation indicator (SDI) was constructed and calculated through principal component factor analysis. An average of 242 female C. quinquefasciatus were found in the high-risk stratum, while the average in the low-risk stratum was 108. The overall VDI was 6.8 mosquitoes per household. The VDI for the high-risk stratum was 13.2 mosquitoes per household, while for the low/medium-risk stratum, it was 5.2. This study offers an SDI for the density of C. quinquefasciatus mosquitoes, which can help reduce the costs associated with data collection and allows for identifying priority areas for vector control actions.

Novel MAGIC composite scores using both clinical symptoms and biomarkers best predict treatment outcomes of acute GVHD

AbstractAcute graft-versus-host disease (GVHD) grading systems that use only clinical symptoms at treatment initiation such as the Minnesota risk identify standard and high-risk categories but lack a low-risk category suitable to minimize immunosuppressive strategies. We developed a new grading system that includes a low-risk stratum based on clinical symptoms alone and determined whether the incorporation of biomarkers would improve the model’s prognostic accuracy. We randomly divided 1863 patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) who were treated for GVHD into training and validation cohorts. Patients in the training cohort were divided into 14 groups based on similarity of clinical symptoms and similar nonrelapse mortality (NRM); we used a classification and regression tree (CART) algorithm to create three Manhattan risk groups that produced a significantly higher area under the receiver operating characteristic curve (AUC) for 6-month NRM than the Minnesota risk classification (0.69 vs 0.64, P = .009) in the validation cohort. We integrated serum GVHD biomarker scores with Manhattan risk using patients with available serum samples and again used a CART algorithm to establish 3 MAGIC composite scores that significantly improved prediction of NRM compared to Manhattan risk (AUC, 0.76 vs 0.70, P = .010). Each increase in MAGIC composite score also corresponded to a significant decrease in day 28 treatment response (80% vs 63% vs 30%, P < .001). We conclude that the MAGIC composite score more accurately predicts response to therapy and long-term outcomes than systems based on clinical symptoms alone and may help guide clinical decisions and trial design.

Mortality Risk Assessment Using the REVEAL 2.0 Score in Pulmonary Hypertension Secondary to Left Heart Disease.

Pulmonary hypertension (PH) frequently complicates the course of patients with left heart disease (PH-LHD) and is associated with worse clinical outcomes. Mortality calculators for PH-LHD are lacking, and it is unclear whether any risk prediction tools originally derived from other forms of PH can accurately predict outcomes in patients with PH-LHD. We retrospectively analyzed data from 161 patients diagnosed with PH-LHD referred to our pulmonary hypertension center from 2016 to 2022. We calculated the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) risk score and categorized patients as low, intermediate, or high-risk. We assessed survival at 1 and 3 years using Kaplan-Meier and Cox proportional hazards, as well as classification performance using a concordance index. At the first outpatient visit, 15% of patients were stratified as low-risk, 27% as intermediate, and 57% as high-risk. Cumulative 1-year survival rates were 100%, 94%, and 91% for the low, intermediate, and high-risk strata, respectively. Cumulative 3-year survival rates were 96%, 89%, and 70% for the low, intermediate, and high-risk strata, respectively. We found no difference in outcomes at 1 year between risk groups. High-risk patients had an increased risk of death at 3 years using REVEAL 2.0 (HR 5.32, p < 0.001). However, while REVEAL 2.0 accurately discriminated high-risk patients, the hazard ratio was not statistically different between patients classified as intermediate-risk compared to low-risk. REVEAL 2.0 accurately predicted 3-year survival in PH-LHD patients with high-risk features. However, the mortality risk between patients classified as intermediate-risk was not different from the low-risk stratum, suggesting inaccurate classification for this group of patients.

Baseline Stroke Risk and Efficacy of Dual-Antiplatelet Therapy: A Post Hoc Analysis of the POINT Trial.

High-risk transient ischemic attacks and minor ischemic strokes are followed by a variable risk of ischemic stroke. We aimed to determine how baseline stroke risk modified the efficacy of clopidogrel-aspirin (referred to here as dual-antiplatelet therapy [DAPT]) for transient ischemic attack and minor ischemic stroke. We performed an unplanned secondary analysis of the POINT trial (Platelet-Oriented Inhibition in New Transient Ischemic Attack and Minor Ischemic Stroke). We first evaluated the associations of the CHA2DS2-VASc and stroke prognosis instrument II (SPI-II) scores with the risk of incident ischemic stroke and major hemorrhage (intracranial hemorrhage or major systemic hemorrhage). We then tested for heterogeneity of the relative and absolute treatment effect of DAPT relative to aspirin across low- and high-risk patient subgroups. A total of 4841 trial participants were included in this analysis, with 2400 participants assigned to treatment with short-term DAPT and 2430 participants to treatment with aspirin and placebo. The dichotomized SPI-II score, but not the CHA2DS2-VASc score (P=0.18), was associated with the risk of incident ischemic stroke. A high-risk SPI-II score (>3) was associated with greater risk of incident ischemic stroke (hazard ratio of incident ischemic stroke relative to low-risk SPI-II score of 1.84 [95% CI, 1.44-2.35]; P<0.001) and numerically greater risk of major hemorrhage though not meeting statistical significance (hazard ratio, 1.80 [95% CI, 0.90-3.57]; P=0.10). The relative risk reduction with DAPT was similar across SPI-II strata (Pinteraction=0.31). The absolute risk reduction for ischemic stroke with DAPT compared with aspirin was nearly 4-fold higher (2.80% versus 0.76%; number needed to treat, 31 versus 131) in the high-risk SPI-II stratum relative to the low-risk stratum. The absolute risk increase for major hemorrhage with DAPT compared with aspirin was 3-fold higher (0.84% versus 0.30%; number needed to harm, 119 versus 331) in the high-risk SPI-II stratum relative to the low-risk stratum. Stratification by baseline stroke risk identifies a patient subgroup that derives greater absolute benefit from treatment with DAPT. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00991029.

Simplified risk stratification based on cardiopulmonary exercise test: A Spanish two-center experience.

A simplified 4-strata risk stratification approach based on three variables is widespread in pulmonary arterial hypertension (PAH)at follow-up. This study aimed to assess the impact of replacing the 6-min walk test (6MWT)with the peak 02 uptake evaluated by the cardiopulmonary exercise test (CPET)on risk stratification by this scale. We included 180 prevalent patients with PAH from two reference hospitals in Spain, followed up between 2006 and 2022. Patients were included if all the variables of interest were available within a 3-month period on the Spanish Registry of Pulmonary Arterial Hypertension (REHAP):functional class (FC);NT-proBNP;6MWT; and CPET. The original 4-strata model (NT-proBNP,6MWT, FC) identified most patients at low or intermediate-low risk (36.7% and 51.1%, respectively). Notably, the modified scale (NT-proBNP,CPET, FC) improved the identification of patients at intermediate-high risk up to 18.9%, and at high risk up to 1.1% in comparison with the previous 12.2% and 0.0% in the original scale. This new model increased the number of patients correctly classified into higher-risk strata (positive NRI of 0.06), as well as classified more patients without events in lower-risk strata (negative NRI of 0.04). The proposed score showed a slightly superior prognostic capacity compared with the original model (Harrel's C-index 0.717 vs. 0.709). Using O2 uptake instead of distance walked in the 6MWT improves the identification of high-risk patients using the 4-strata scale. This change could have relevant prognostic implications and lead to changes in the specific treatment of PAH.

Applicability and validation of different prognostic scores in allogeneic hematopoietic cell transplant (HCT) in the post-transplant cyclophosphamide era

We investigated the predictive capacity of six prognostic indices [Karnofsky Performance Status (KPS), Hematopoietic Cell Transplant-Specific Comorbidity Index (HCT-CI), Disease Risk Index (DRI), European Bone Marrow Transplantation (EBMT) and Revised Pre-Transplantation Assessment of Mortality (rPAM) Scores and Endothelial Activation and Stress Index (EASIX)] in 205 adults undergoing post-transplant cyclophosphamide (PTCy)-based allo-HCT. KPS, HCT-CI, DRI and EASIX grouped patients into higher and lower risk strata. KPS and EASIX maintained appropriate discrimination for OS prediction across the first 2 years after allo-HCT [receiver operating characteristic curve (area under the curve (AUC) > 55 %)]. The discriminative capacity of DRI and HCT-CI increased during the post-transplant period, with a peak of prediction at 2 years (AUC of 61.1 % and 61.8 %). The maximum rPAM discriminative capacity was at 1 year (1-year AUC of 58.2 %). The predictive capacity of the EBMT score was not demonstrated. This study validates the discrimination capacity for OS prediction of KPS, HCT-CI, DRI and EASIX in PTCy-based allo-HCT.

AGCT1531: Evaluating the utility of circulating microRNA in the management of children, adolescents, and adults with malignant germ cell tumors.

TPS5104 Background: Conventional serum tumor markers for malignant germ cell tumors (MGCTs) have limited performance characteristics, especially in non-secreting histologies such as embryonal carcinoma or seminoma. Growing evidence has shown circulating microRNAs (miRNA), particularly miR-371a-3p, to be a more sensitive biomarker, elevated across all MGCT subtypes except teratoma. However, studies to date have been retrospective or non-randomized. If confirmed in prospective clinical trials, circulating miRNA may have the potential to become a universal MGCT biomarker, aiding in diagnosis, prognostication, relapse detection, and prediction of viable disease after chemotherapy. One of the key objectives of AGCT1531 is to test the performance characteristics of circulating miRNA in children, adolescents, and young adults (AYAs) with low-risk and standard-risk MGCTs. AGCT1531 is unique among MGCT trials for including patients across all ages, genders, sites, histologies, and treatments. Methods: AGCT1531 is a prospective clinical trial sponsored by the Children’s Oncology Group (COG), co-designed with United Kingdom, Japan, and India, and supported by all NCTN groups. It has three strata for low-risk tumors, defined as stage I tumors treated with surgery followed by active surveillance: non-seminomatous tumors of any site; testis seminomas; and ovarian immature teratomas. Patients of any age are eligible. Target accruals are 432, 277, and 212 patients, respectively. Key endpoints include overall and event-free survival and longitudinal measurements of circulating miRNA. Serum is collected at intervals aligned with NCCN follow-up guidelines to minimize testing burden. For patients over 11 years old with stage I non-seminomatous tumors, serum is collected at enrollment, months 4, 8, 12, 18, and 24; and (if applicable) at relapse. The trial also has two strata for standard-risk MGCTs: SR1 for children under age 11 years and SR2 for AYAs age 11-25 years. Target accruals are 518 and 595 patients, respectively. Both strata are randomized trials of cisplatin-based versus carboplatin-based regimens, with carboplatin used at doses higher than those previously tested in adult MGCTs. Serum collection is recommended at enrollment, months 6, 12, 18, 24, and (if applicable) at relapse. AGCT1531 was activated in August 2017. The low-risk seminoma stratum was added on November 2021. The trial is currently open at 466 sites across seven countries. For adults with testicular GCTs, data from AGCT1531 can contribute to joint analyses of parallel trials evaluating circulating miR-371a-3p in this population: SWOG1823, ANZUP1906 (CLIMATE), and ANZUP P3BEP. Together, this suite of trials will help validate the utility of circulating miRNA and set the stage for future investigations where miRNA is used to influence real-time management decisions for patients with MGCTs. Clinical trial information: NCT03067181 .

Are Guideline-recommended Risk Classification Schemes in Pulmonary Hypertension Adequately Robust to Guide the Real-world Setting?

Pulmonary hypertension is a complex syndrome that encompasses a diverse group of pathophysiologies predisposed by different environmental and genetic factors. It is not clear to which extent the universal risk classification schemes can be applied to cohorts in individual pulmonary hypertension centers with differing environmental backgrounds, genetic pools, referral networks. To explore whether the recommended risk classification schemes could reliably be used for mortality prediction in an unselected pulmonary hypertension population of a tertiary pulmonary hypertension center. A retrospective cross-sectional study. We retrospectively screened our hospital database for the patients with pulmonary hypertension between 2015 and 2022. The grouping of pulmonary hypertension was made as follows in accordance with current guidelines: Group 1: patients with pulmonary arterial hypertension, Group 2: patients with pulmonary hypertension associated with left heart disease, Group 3: patients with pulmonary hypertension associated with lung disease and/or hypoxia, and Group 4: patients with pulmonary hypertension associated with pulmonary artery obstructions. Then, we compared the predicted and observed mortality rates of four different risk classification schemes (REVEAL, REVEAL-Lite, ESC/ERS and COMPERA). We identified 723 cases in our pulmonary hypertension database, the final study population consisted of 549 patients. The REVEAL, REVEAL-Lite and European Society of Cardiology/European Respiratory Society risk scores significantly underestimated the mortality risk in the low-risk stratum (5.3% vs. 1.9%, P < 0.001; 5.3% vs. 2.9%, P = 0.015 and 6.3% vs. 1%, P < 0.001, respectively) and overestimated the mortality risk in the high-risk stratum (11.8% vs. 25.8%, P < 0.001; 10.4% vs. 25.1%, P < 0.001 and 13.2% vs. 30%, P < 0.001, respectively). Although the COMPERA 4-strata model significantly underestimated the risk in low- and intermediate-low risk strata (4.9% vs. 1.5%, P < 0.001 and 6.8% vs. 2.8%, P = 0.001, respectively), it was accurate in intermediate-high and high-risk groups (10.1% vs. 8.7%, P = 0.592 and 15.6% vs. 22%, P = 0.384, respectively). The analyses limited only to group 1 pulmonary hypertension patients gave similar results. The established risk classification schemes may not perform as good as expected in unselected pulmonary hypertension populations and this may have important implications on management decisions. Tertiary centers should not uncritically accept the published risk prediction models and consider modifying current risk scores according to their own patient characteristics.

Spatiotemporal Mapping of Annual Malaria Incidence in Rivers State, Nigeria

Rivers State is the centre of Nigeria's oil industry and has the presence of oil prospectors including expatriates who are at risk of malaria infection. Periodic analysis of epidemiological data will enable malaria control programmers to appraise the interventions carried out over the years and assist in the development of sustainable and adaptive strategies directed from an informed local level. This study, therefore, examined spatiotemporal variations in malaria incidence in the State using Annual Parasite Incidence (API) as an indicator. Monthly reported malaria cases from 2007-2017 at the local government area (LGA) level were retrieved from the Integrated Disease Surveillance Response (IDSR) system of Rivers State Ministry of Health while projected population data for the same period were obtained from the National Bureau of Statistics. API of the LGAs from 2007 to 2017 were computed, integrated into GIS, and subjected to weighted overlay analysis to delineate the risk zones. The eleven-year retrospective study of malaria in Rivers State displayed geographical variations which were statistically significant between the LGAs. Malaria incidence fluctuated throughout the study period. API values increased from 13.746 in 2007 to 34.067 in 2013 and dropped to 8.721 in 2017. All the LGAs recorded API values below 100, indicating a very low malaria burden in a controlled setting. However, none of the LGAs has reached the WHO standard level for the elimination of transmission. Ikwerre, Eleme, Ogu-Bolo and Opobo/Nkoro LGAs were assigned to the very high malaria risk stratum (362.615 to 490.005) whereas Abua-Odual, Akuku-Toru and Degema LGAs were assigned to very low-risk malaria stratum (103.281 to 113.897). The findings of this research will aid stakeholders in evaluating the impact of control strategies employed over the years and possibly, revisit malaria extant interventions for improved malaria control outcomes.

Cardiopulmonary Exercise Testing Contributes to Accurate Risk Assessment in Patients with Low-risk Pulmonary Hypertension

Background: European guidelines for pulmonary arterial hypertension (PAH) stratify the risk using clinical characteristics and complementary studies, including the cardiopulmonary exercise test (CPET). This takes into account 3 parameters: peak O2 con-sumption (peak VO2), its percentage with respect to the predicted VO2, and the minute ventilation/carbon dioxide production (VE/VCO2) slope. However, none of the models that validated this way of stratifying risk included PCPE among their variables. Objectives: To determine what proportion of patients with group I PAH considered to be at low risk and who walk &gt;440 meters in the 6-minute walk test (6MWT) have parameters considered to be of moderate or high risk in the PCPE. Methods: Patients &gt;18 years of age, diagnosed with group I PAH at low risk of events, who walked &gt;440 meters in the 6MWT and had NT-proBNP value &lt; 300 pg/dL were included. A CPET was performed in which the peak VO2, its percentage with respect to the predicted VO2, and the VE/VCO2 slope were recorded. It was determined what proportion of patients presented these parameters in a higher than low risk stratum (peak VO2 consumption ≤15 ml/min/Kg, its percentage with respect to the predicted VO2≤65% and the VE/VCO2 slope ≥ 36).Results: Eighteen patients were included. Despite being low-risk patients with a good functional class, all patients presented a peak VO2 less than 85% of predicted, which determines a deterioration of functional capacity. A single patient (6%) presented the three parameters evaluated at low risk, 8 patients (44%) had at least one altered parameter, 7 patients (39%) presented 2 altered param-eters and in 2 patients (11%) all parameters were altered. The parameters that were most frequently altered were the percentage of predicted peak VO2 and the VE/VCO2 slope in 67% of the cases. Only 4 patients presented a peak VO2 &lt;15 ml/kg/m. No patient presented peak VO2 values or percentage of predicted VO2 in the high-risk category. However, 6 patients (33%) presented a high-risk VE/VCO2 slope. Conclusion: Majority (92%) of the patients considered low risk and who walk more than 440 meters in 6 minutes presented at least one altered variable in the CPET. The VE/VCO2 slope and the percentage of predicted peak VO2 consumption were the most fre-quently altered variables. The VE/VCO2 slope was the only one...

Identification of low and very high-risk patients with non-WNT/non-SHH medulloblastoma by improved clinico-molecular stratification of the HIT2000 and I-HIT-MED cohorts

Molecular groups of medulloblastoma (MB) are well established. Novel risk stratification parameters include Group 3/4 (non-WNT/non-SHH) methylation subgroups I–VIII or whole-chromosomal aberration (WCA) phenotypes. This study investigates the integration of clinical and molecular parameters to improve risk stratification of non-WNT/non-SHH MB. Non-WNT/non-SHH MB from the HIT2000 study and the HIT-MED registries were selected based on availability of DNA-methylation profiling data. MYC or MYCN amplification and WCA of chromosomes 7, 8, and 11 were inferred from methylation array-based copy number profiles. In total, 403 non-WNT/non-SHH MB were identified, 346/403 (86%) had a methylation class family Group 3/4 methylation score (classifier v11b6) ≥ 0.9, and 294/346 (73%) were included in the risk stratification modeling based on Group 3 or 4 score (v11b6) ≥ 0.8 and subgroup I–VIII score (mb_g34) ≥ 0.8. Group 3 MB (5y-PFS, survival estimation ± standard deviation: 41.4 ± 4.6%; 5y-OS: 48.8 ± 5.0%) showed poorer survival compared to Group 4 (5y-PFS: 68.2 ± 3.7%; 5y-OS: 84.8 ± 2.8%). Subgroups II (5y-PFS: 27.6 ± 8.2%) and III (5y-PFS: 37.5 ± 7.9%) showed the poorest and subgroup VI (5y-PFS: 76.6 ± 7.9%), VII (5y-PFS: 75.9 ± 7.2%), and VIII (5y-PFS: 66.6 ± 5.8%) the best survival. Multivariate analysis revealed subgroup in combination with WCA phenotype to best predict risk of progression and death. The integration of clinical (age, M and R status) and molecular (MYC/N, subgroup, WCA phenotype) variables identified a low-risk stratum with a 5y-PFS of 94 ± 5.7 and a very high-risk stratum with a 5y-PFS of 29 ± 6.1%. Validation in an international MB cohort confirmed the combined stratification scheme with 82.1 ± 6.0% 5y-PFS in the low and 47.5 ± 4.1% in very high-risk groups, and outperformed the clinical model. These newly identified clinico-molecular low-risk and very high-risk strata, accounting for 6%, and 21% of non-WNT/non-SHH MB patients, respectively, may improve future treatment stratification.

Development and Validation of a Risk Assessment Model for Pulmonary Nodules Using Plasma Proteins and Clinical Factors

Deficiencies in risk assessment for patients with pulmonary nodules (PNs) contribute to unnecessary invasive testing and delays in diagnosis. What is the accuracy of a novel PN risk model that includes plasma proteins and clinical factors? How does the accuracy compare with that of an established risk model? Based on technology using magnetic nanosensors, assays were developed with seven plasma proteins. In a training cohort (n= 429), machine learning approaches were used to identify an optimal algorithm that subsequently was evaluated in a validation cohort (n= 489), and its performance was compared with the Mayo Clinic model. In the training set, we identified a support vector machine algorithm that included the seven plasma proteins and six clinical factors that demonstrated an area under the receiver operating characteristic curve of 0.87 and met other selection criteria. The resulting risk reclassification model (RRM) was used to recategorize patients with a pretest risk of between 10%and 84%, and its performance was assessed across five risk strata (low,≤ 10%; moderate, 10%-34%; intermediate, 35%-70%; high, 71%-84%; very high, > 85%). Stratification by the RRM decreased the proportion of intermediate-risk patients from 26.7%to 10.8%(P< .001) and increased the low-risk and high-risk strata from 16.8%to 21.9%(P< .001) and from 3.7%to 12.1%(P< .001), respectively. Among patients classified as low risk by the RRM and Mayo Clinic model, the corresponding true-negative to false-negative ratios were 16.8 and 19.5, respectively. Among patients classified as very high risk by the RRM and Mayo Clinic model, the corresponding true-positive to false-positive ratios were 28.5 and 17.0, respectively. Compared with the Mayo Clinic model, the RRM provided higher specificity at the low-risk threshold and higher sensitivity at the very high-risk threshold. The RRM accurately reclassified some patients into low-risk and very high-risk categories, suggesting the potential to improve PN risk assessment.

The implications of the Fetal Medicine Foundation 35- to 36-week preeclampsia prediction competing-risk model on timing of birth

Preeclampsia is associated with increased risks of life-threatening, -altering, and -ending complications. Assessment of risk for preeclampsia at 35 to 36 weeks' gestation by the Fetal Medicine Foundation 36-week competing-risk model identifies approximately 75% of women who will develop term preeclampsia, at a 10% screen-positive rate. This study aimed to assess whether the Fetal Medicine Foundation 36-week model can provide personalized guidance to women about the probable timing of their delivery, whether or not they develop pregnancy hypertension. In this prospective nonintervention screening study at 2 maternity hospitals in England, women who did not have preeclampsia (American College of Obstetricians and Gynecologists definition) and were attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation underwent assessment of risk for preeclampsia, including maternal demographic characteristics, medical history, mean arterial pressure, and serum placental growth factor and soluble fms-like tyrosine kinase-1. Fetal Medicine Foundation 36-week model risk categories for subsequent preeclampsia were defined as: A, ≥0.500; B, 0.20 to 0.499; C, 0.05 to 0.199; D, 0.020 to 0.049; and E, <0.020. Obstetrical records were examined for all women to identify their gestational age at delivery, and whether they experienced a spontaneous onset of labor (irrespective of mode of delivery) or had a medically indicated birth (either induction of labor or unlabored cesarean delivery). The cumulative incidence of delivery and risk ratios, for all deliveries and for spontaneous deliveries, was assessed. Among 29,035 women with singleton pregnancies, 1.0%, 2.9%, 3.3%, 5.0%, 9.9%, and 77.9% were in A, B, C, D, and E risk strata, respectively. In the A (vs E) stratum, 71.95% (vs 33.52%) of births were medically indicated. Compared with women in stratum E, women in higher risk strata were more likely to deliver, and to deliver following spontaneous labor, before their due date. For example, of the women in stratum A (vs E), 14.2% (vs 1.1%; risk ratio, 12.5 [95% confidence interval, 9.45-15.35]), 48.5% (vs 5.1%; risk ratio, 8.47 [7.48-9.35]), 69.6% (vs 15.5%; risk ratio,3.86 [3.59-4.08]), and 90.1% (vs 44.8%; risk ratio, 6.72 [4.53-9.95]) gave birth before 37 0/7, 38 0/7, 39 0/7, and 40 0/7 weeks, respectively. For women in stratum A (vs E), when censored for medically indicated births, spontaneous labor occurred more commonly before 37 0/7 (risk ratio, 4.31 [1.99-6.57]), 38 0/7 (risk ratio, 3.71 [2.48-4.88]), 39 0/7 (risk ratio, 2.87 [2.22-3.46]), and 40 0/7 (risk ratio, 1.42 [1.14-1.77]) weeks. Women in higher-risk strata gave birth earlier, and more frequently following medically indicated delivery, compared with those in lower-risk strata. Importantly, the proportion of women who gave birth following spontaneous onset of labor before their due date was also greater in higher-risk than in lower-risk women. The Fetal Medicine Foundation 36-week competing-risk model incorporates biomarkers of placental aging, including angiogenic imbalance; these results imply that a fetoplacental response to placental aging may be an important trigger for the onset of labor at term.

A single-center multidisciplinary study analyzing thyroid nodule risk stratification by comparing the thyroid imaging reporting and data system (TI-RADS) and American thyroid association (ATA) risk of malignancy for thyroid nodules

ObjectivesThe thyroid imaging reporting and data system (TI-RADS) and 2015 American Thyroid Association (ATA) guidelines are two well-known risk stratification systems for classifying thyroid nodules based on cancer risk. This study aims to evaluate the diagnostic efficacy of these two systems in predicting malignancy in patients undergoing thyroid surgery. MethodsWe studied data on 120 individuals who were scheduled to undergo surgery for benign or malignant nodular diseases of the thyroid gland between October 2017 and October 2019. The TI-RADS category and ultrasound pattern based on ATA guidelines were assigned to dominant thyroid nodule categories by two experienced radiologists blinded to patients’ previous thyroid ultrasonography and fine-needle aspiration biopsy results. A pathologist with experience in thyroid diseases blinded to patients’ sonographic and clinical data reviewed the thyroidectomy specimens. ResultsA total of 120 patients, 88 women and 32 men, were included in our study. Final histopathological results were as follows: 50% (n=60) papillary thyroid carcinoma, 36.6% (n=44) benign nodular thyroid diseases, 4.1% (n=5) follicular adenoma, 2.5% (n=3) hurtle cell adenoma, 1.7% (n=2) follicular thyroid carcinoma, 1.7% (n=2) medullary thyroid carcinoma, 1.7% (n=2) hurtle cell carcinoma, and 1.7% (n=2) follicular tumor of uncertain malignancy potential. The sensitivity, specificity, positive predictive value, and negative predictive value for TI-RADS were 80%, 56%, 72%, and 67%, respectively, and that for ATA were 80%, 64%, 76%, and 69%, respectively. ConclusionThe TI-RADS and ATA showed similar rates of sensitivity, specificity, NPV, and PPV. Our observed risk of malignancy was higher than expected for the ACR TI-RADS 3–5 categories and the very low, low, and intermediate suspicion risk strata in the ATA guidelines. We found no difference between observed and expected malignancy risk for the ACR TI-RADS 2’s and ATA's high suspicion categories.

Thrombotic Risk Stratification and Intensive Statin Therapy for Secondary Prevention of Coronary Artery Disease - Insights From the REAL-CAD Study.

It is unknown whether beneficial effects of higher-dose statins on cardiovascular events are different according to the thrombotic risk in patients with chronic coronary syndrome (CCS). The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study is a randomized trial comparing 4 mg and 1 mg pitavastatin in patients with CCS. This study categorized 12,413 patients into 3 strata according to the CREDO-Kyoto thrombotic risk score: low-risk (N=9,434; 4 mg: N=4,742, and 1 mg: N=4,692), intermediate-risk (N=2,415; 4 mg: N=1,188, and 1 mg: N=1,227); and high-risk (N=564; 4 mg: N=269, and 1 mg: N=295). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina. Cumulative 4-year incidence of the primary endpoint was significantly higher in the high-risk stratum than in the intermediate- and low-risk strata (11.0%, 6.3%, and 4.5%, P<0.0001). In the low-risk stratum, the cumulative 4-year incidence of the primary endpoint was significantly lower in the 4 mg than in the 1 mg group (4.0% and 4.9%, P=0.02), whereas in the intermediate- and high-risk strata, it was numerically lower in the 4 mg than in the 1 mg group. There was no significant treatment-by-subgroup interaction for the primary endpoint (P-interaction=0.77). High-dose pitavastatin therapy compared with low-dose pitavastatin therapy was associated with a trend toward lowering the risk for cardiovascular events irrespective of the thrombotic risk in patients with CCS.

Calibrating Readmission Risk Prediction Models for Determining Post-discharge Follow-up Timing.

The soaring hospital readmission rates are straining the already limited financial resources in the US health system. Meanwhile, timely outpatient follow-up, an efficient and cost-effective intervention following hospital discharge, has been shown to reduce the readmission risk. However, the current and projected shortage of physicians in primary and specialty care poses a unique dilemma in transitional care planning: optimizing the utilization of post-discharge follow-up to reduce readmission rate while limiting the strain on the limited pool of outpatient physicians. The ideal solution would entail a strategy whereby patients at higher risk for readmission are stratified towards earlier outpatient follow-up and vice versa. This article explores the utility of Institution-specific readmission risk prediction algorithms for assessing patient population for diverse administrative, clinical and socioeconomic risk factors and further classifying the hospital’s patient population into high- and low-risk strata, so that appropriate risk-concordant timing of follow-up can be assigned at the time of hospital discharge, with earlier follow-up assigned to high readmission risk strata. This stratification shall help ensure judicious and equitable human resource allocation while simultaneously reducing hospital readmission rates.

Outcomes of children with well-differentiated fetal hepatoblastoma treated with surgery only: Report from Children's Oncology Group Trial, AHEP0731

BackgroundHepatoblastoma (HB) requires surgical resection for cure, but only 20–30% of patients have resectable disease at diagnosis. Patients who undergo partial hepatectomy at diagnosis have historically received 4–6 cycles of adjuvant chemotherapy; however, those with 100% well-differentiated fetal histology (WDF) have been observed to have excellent outcomes when treated with surgery alone. Patients and methodsPatients on the Children's Oncology Group non randomized, multicenter phase III study, AHEP0731, were stratified based on Evan's stage, tumor histology, and serum alpha-fetoprotein level at diagnosis. Patients were eligible for the very low risk stratum of surgery and observation if they had a complete resection at diagnosis and rapid central histologic review demonstrated HB with 100% WDF histology. ResultsA total of 8 eligible patients were enrolled on study between September 14, 2009 and May 28, 2014. Outcome current to 06/30/2020 was used in this analysis. The median age at enrollment was 22.5 months (range: 8–84 months) and the median AFP at enrollment was 714 ng/ml (range: 18–77,747 ng/mL). With a median follow-up of 6.6 years (range: 3.6–9.8 years), the 5-year event-free (EFS) and overall survival (OS) were both 100%. ConclusionThis report supports that HB with 100% WDF histology completely resected at diagnosis is curable with surgery only. The development of evidence-based surgical guidelines utilizing criteria based on PRETEXT group, vascular involvement (annotation factors), tumor-specific histology and corresponding biology will be crucial for optimizing which patients are candidates for resection at diagnosis followed by observation. Level of evidencePrognosis study, Level I evidence.

19-OR: KidneyIntelX Association with Clinical Outcomes in Diabetic Kidney Disease

Individuals with diabetic kidney disease (DKD) are at risk for progression, heart failure, and death. We assessed the association of KidneyIntelX, a bioprognostictest validated for DKD progression, with a composite time-to-event endpoint of 57% eGFR decline, kidney failure, heart failure hospitalization (HFH) , or death in a posthoc analysis of a subgroup of CANVAS participants with DKD. sTNFR-1, sTNFR-2, and KIM-1 were measured via proprietary assays, and KidneyIntelX scores were calculated using the existing algorithm. Hazard ratios for high vs. low-risk strata for the composite outcome were adjusted for age, sex, race, treatment arm, baseline CVD, HbA1c, SBP, DBP, LDL, BMI) . During 5.6 years follow-up, 282 (22%) of the 1278 CANVAS participants with DKD experienced the outcome (57% decline in eGFR/ESKD 3%, HFH 6%, death 16%) . The adjusted HR for the composite outcome in KidneyIntelX high-risk group was 2.7 (95% CI 1.9 to 3.8) vs. the low-risk group. Canagliflozin reduced the risk for the composite event vs. placebo, with larger absolute risk reductions for the high-risk stratum (11%) , compared to intermediate (6%) or low-risk strata (4%) (p&amp;lt;0.01) . In conclusion, KidneyIntelX successfully risk-stratified adults with DKD for clinical outcomes. Absolute risk reductions with canagliflozin were greatest in the high-risk stratum, thereby potentially allowing its use to identify patients most likely to benefit from treatment. Disclosure G.N.Nadkarni: Advisory Panel; Renalytix, Consultant; AstraZeneca, Reata Pharmaceuticals, Inc., Renalytix, Siemens, Other Relationship; Renalytix, Stock/Shareholder; Renalytix. D.Takale: None. B.Neal: Other Relationship; Janssen Research &amp; Development, LLC. K.W.Mahaffey: Consultant; Novo Nordisk. Y.Yavin: Employee; Janssen Research &amp; Development, LLC. M.K.Hansen: Employee; Janssen Research &amp; Development, LLC. F.Fleming: Employee; Renalytix. H.L.Heerspink: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Chinook Therapeutics Inc., CSL Behring, Gilead Sciences, Inc., Goldfinch Bio, Inc., Janssen Research &amp; Development, LLC, Mitsubishi Tanabe Pharma Corporation, Mundipharma, Traveere Pharmaceuticals, Research Support; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. S.Coca: Advisory Panel; 3ive Labs, Nuwellis, Reprieve Cardiovascular, Consultant; Axon Therapies, Bayer AG, Boehringer Ingelheim International GmbH, Vifor Pharma Management Ltd., Stock/Shareholder; pulseData, Renalytix. Funding Renalytix

FIB-4 and incident severe liver outcomes in patients with undiagnosed chronic liver disease: A Fine-Gray competing risk analysis.

The Fibrosis-4 index (FIB-4) can reliably assess fibrosis risk in patients with chronic liver disease, and advanced fibrosis is associated with severe liver disease (SLD) outcomes. However, CLD is underdiagnosed in primary care. We examined the association between FIB-4 risk strata and the incidence of SLD preceding a CLD diagnosis while considering incident CLD diagnoses as competing risks. Using primary care clinic data between 2007 and 2018, we identified patients with two FIB-4 scores and no liver disease diagnoses preceding the index FIB-4. Patients were followed from index FIB-4 until an incident SLD (a composite of cirrhosis, hepatocellular carcinoma or liver transplantation), CLD or were censored. Hazard ratios were computed using a Fine-Gray competing risk model. Of 20 556 patients, there were 54.8% in the low, 34.8% in the indeterminate, 6.6% in the high and 3.8% in the persistently high-risk FIB-4 strata. During a mean 8.2 years of follow-up, 837 (4.1%) patients experienced an SLD outcome and 11.5% of the sample received a CLD diagnosis. Of patients with an SLD event, 49% received no preceding CLD diagnosis. In the adjusted Fine-Gray model, the indeterminate (HR 1.41, 95% CI 1.17-1.71), high (HR 4.65, 95% CI 3.76-5.76) and persistently high-risk (HR 7.60, 95% CI 6.04-9.57) FIB-4 risk strata were associated with a higher incidence of SLD compared to the low-risk stratum. FIB-4 scores with indeterminate- and high-risk values are associated with an increased incidence of SLD in primary care patients without known CLD.

Perioperative risk prediction using the POSSUM and V-POSSUM models in symptomatic carotid stenosis.

Background: This study aimed to evaluate risk factors for adverse outcomes and perioperative stroke and death in patients with symptomatic carotid stenosis undergoing open endarterectomy (CEA). The second objective was to assess the predictive value of the POSSUM and V-POSSUM models for predicting morbidity and mortality from CEA in symptomatic carotid stenosis. Patients and methods: A retrospective observational study of all patients admitted to a single center who underwent CEA for symptomatic carotid stenosis was performed. 320 patients from 1999 to 2013 were included. Postoperative complications, 30-day survival, and stroke rates were recorded. The observed outcomes were compared to the POSSUM and V-POSSUM expected mortality (observed to expected ratio (O:E)). Results: The mean age was 68.1±10.0 years. 215 patients were male (67%). Risk factors for surgical complications were: age, with a higher risk in both groups of less than 60 years and more than 75 years of age (p=0.04), a higher ASA score (p=0.04), and hyperlipidemia (p=0.017). Risk factors for the combined endpoint stroke or death were a higher ASA category (p<0.001), stroke as indication for CEA (p 0.022), and a high degree of stenosis (p=0.019). For POSSUM predicted mortality, there was a good O:E ratio in the two lowest risk groups, but a 2-fold overprediction of death or stroke in the two high-risk strata. The area under the curve (AUC) was 0.58 (95% CI: 0.43-0.73). The V-POSSUM showed a better fit in the high-risk groups, but an underprediction of mortality in the low-risk strata. Conclusions: Age and comorbid conditions are risk factors for adverse outcomes after CEA. The V-POSSUM model is better than POSSUM to predict postoperative death and stroke after CEA in patients with symptomatic carotid stenosis and a high preoperative physiological score. In patients with low physiological scores, both POSSUM and V-POSSUM show a limited predictive value.