Outcomes In Low-risk Patients Research Articles

Course and predictors of excellent response to therapy in patients with differentiated thyroid cancer at long-term follow-up.

To investigate the long-term outcomes of differentiated thyroid cancer (DTC) and the predictive factors for excellent and incomplete responses to therapy on long-term follow-up of patients. A retrospective chart review and analysis was carried out at King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Demographic, histological, and therapeutic data were collected from patients older than 13 years at the time of diagnosis, with a minimum follow-up of 18 months. Outcomes were divided into excellent, indeterminate, biochemically incomplete, and structurally incomplete responses. Odds ratios (ORs) for predictors of incomplete response at the last visit were determined. We first tested associations univariately with incomplete responses, and then variables with significant associations were included in a multivariable logistic model. Among 230 patients with DTC, 61.7% had excellent responses to therapy on long-term follow-up, and 24.3% had incomplete biochemical and structural responses. The median follow-up was 4.6 years. Factors significantly associated with incomplete response to therapy in the multivariate analysis (p<0.05) were age >55 years (OR=5) and lymph node (OR=3.4) and distant metastases (OR=29). Older age did not affect the outcome in low-risk patients with DTC but was significantly associated with incomplete responses in those with intermediate risk (p=0.04) and high risk (p=0.003). We strongly advocate incorporating age into recurrence risk assessment for patients with DTC.

Outcomes in low-risk patients before and after an institutional policy offering 39-week elective induction of labor

Objective Elective induction of labor versus expectant management at 39 weeks gestation in low-risk nulliparous patients was shown in the ARRIVE randomized trial of over 6000 patients to decrease risks of cesarean delivery without significant change in the composite perinatal outcome. We aimed to pragmatically analyze the effect of offering elective induction of labor (eIOL) to all low-risk patients. Methods Retrospective cohort study of low-risk nulliparous and multiparous patients delivering live, non-anomalous singletons at a single center at greater than or equal to 39 0/7 weeks gestational age. Those with prior or planned cesarean delivery, ruptured membranes, medical comorbidities, or contraindications to vaginal delivery were excluded. Patients were categorized as before (pre-eIOL; 1/2012–3/2014) or after (post-eIOL; 3/2019–12/2021) an institution-wide policy offering eIOL at 39 0/7 weeks. Births occurring April 2014 to December 2018 were allocated to a separate cohort (during-eIOL) given increased exposure to eIOL as our center recruited participants for the ARRIVE trial. The primary outcome was cesarean birth. Secondary outcomes included select maternal (e.g. chorioamnionitis, operative delivery, postpartum hemorrhage) and neonatal morbidities (e.g. birthweight, small- and large-for gestational age, hypoglycemia). Characteristics and outcomes were compared between the pre and during-eIOL, and pre and post-eIOL groups; adjusted OR (95% CI) were calculated using multivariable regression. Subgroup analysis by parity was planned. Results Of 10,758 patients analyzed, 2521 (23.4%) were pre-eIOL, 5410 (50.3%) during-eIOL, and 2827 (26.3%) post-eIOL. Groups differed with respect to labor type, age, race/ethnicity, marital and payor status, and gestational age at care entry. Post-eIOL was associated with lower odds of cesarean compared to pre-eIOL (aOR 0.83 [95% CI 0.72–0.96]), which was even lower among those specifically undergoing labor induction (aOR 0.58 [0.48–0.70]. During-eIOL was also associated with lower odds of cesarean compared to pre-eIOL (aOR 0.79 [0.69–0.90]). Both during and post-eIOL groups were associated with higher odds of chorioamnionitis, operative delivery, and hemorrhage compared to pre-eIOL. However, only among post-eIOL were there fewer neonates weighing ≥4000 g, large-for-gestational age infants, and neonatal hypoglycemia compared to pre-IOL. Conclusion An institutional policy offering eIOL at 39 0/7 to low-risk patients was associated with a lower cesarean birth rate, lower birthweights and lower neonatal hypoglycemia, and an increased risk of chorioamnionitis and hemorrhage.

Expanding the utility of robotics for pancreaticoduodenectomy: a 10-year review and comparison to international benchmarks in pancreatic surgery.

Robotic pancreaticoduodenectomy (RPD) is an emerging alternative to open pancreaticoduodenectomy (OPD). Although RPD offers various theoretical advantages, it is used in less than 10% of all pancreaticoduodenectomies. The aim of this study was to report our 10-year experience and compare RPD outcomes with international benchmarks for OPD. A retrospective review of a prospectively maintained institutional database was performed of consecutive patients who underwent RPD between January 2011 and December 2021. Patients were categorized into low-risk and high-risk groups according to the selection criteria set by the benchmark study. Their outcomes were compared to the international benchmark cut off values. Outcomes were then evaluated over time to identify improvements in practice and establish a learning curve. Of 201 RPDs, 36 were low-risk and 165 high-risk patients. Compared to the OPD benchmarks, outcomes of low-risk patients were within the cutoff values. High-risk patients were outside the cutoff for blood transfusions (26% vs. ≤ 23%), overall complications (78% vs. ≤ 73%), grade I-II complications (68% vs. ≤ 62%), and readmissions (22% vs ≤ 21%). Oncologic outcomes for high-risk patients were within benchmark cutoffs. Cases at the end of the learning curve included more pancreatic cancer (42% from 17%) and fewer low-risk patients (10% from 24%) than those at the beginning. After 41 RPD there was a decline in conversion rates and operative time. Between 95 and 143 cases operative time, transfusion rates, and LOS declined significantly. Complications did not differ over time. RPD yields results comparable to the established benchmarks in OPD in both low- and high-risk patients. Along the learning curve, RPD evolved with the inclusion of more high-risk cases while outcomes remained within benchmarks. Addition of a robotic HPB surgery fellowship did not compromise outcomes. These results suggest that RPD may be an option for high-risk patients at specialized centers.

Heart failure outcomes in low-risk patients with atrial fibrillation: a case-control study of 680523 Swedish individuals.

Knowledge of long-term outcomes in patients with atrial fibrillation (AF) remains limited. We sought to evaluate the risk of new-onset heart failure (HF) in patients with AF and a low cardiovascular risk profile. Data from the Swedish National Patient Register were used to identify all patients with a first-time diagnosis of AF without underlying cardiovascular disease at baseline between 1987 and 2018. Each patient was compared with two controls without AF from the National Total Population Register. In total, 227811 patients and 452712 controls were included. During a mean follow-up of 9.1 (standard deviation 7.0) years, the hazard ratio (HR) for new-onset HF was 3.55 [95% confidence interval (CI) 3.51-3.60] in patients compared with controls. Women with AF (18-34years) had HR for HF onset 24.6 (95% CI 7.59-80.0) and men HR 9.86 (95% CI 6.81-14.27). The highest risk was within 1year in patients 18-34years, HR 103.9 (95% CI 46.3-233.1). The incidence rate within 1year increased from 6.2 (95% CI 4.5-8.6) per 1000 person-years in young patients (18-34years) to 142.8 (95% CI 139.4-146.3) per 1000 person-years among older patients (>80years). Patients studied had a three-fold higher risk of developing HF compared with controls. Young patients, particularly women, carry up to 100-fold increased risk to develop HF within 1year after AF. Further studies in patients with AF and low cardiovascular risk profile are needed to prevent serious complications such as HF.

Outcomes in Low-Risk Patients Before and After an Institutional Policy Offering 39-Week Elective Inductions [ID: 1379269

INTRODUCTION: We aimed to pragmatically analyze the effect of offering elective induction of labor (eIOL) in low-risk patients on perinatal outcomes. METHODS: This was a retrospective cohort study of low-risk nulliparous or multiparous patients delivering live, nonanomalous singletons at a single center at greater than or equal to 39 0/7 weeks’ gestational age (GA). Those with prior or planned cesarean delivery (CD), ruptured membranes, medical comorbidities, or contraindications to vaginal delivery were excluded. Patients were categorized as before (pre-eIOL; January 2012 to March 2014) or after (post-eIOL; March 2019 to December 2021) an institution-wide policy offering eIOL at 39 0/7 weeks. Births from April 2014 to December 2018 were considered to be during-eIOL given increased exposure to eIOL during the period of the ARRIVE trial at our center. The primary outcome was CD. Characteristics and outcomes were compared between the pre- and during-eIOL, and pre- and post-eIOL groups, and adjusted OR (aOR) (95% CI) was calculated using multivariable regression. Subgroup analysis by parity was planned. RESULTS: Of 10,966 patients analyzed, 2,611 (23.8%) were pre-eIOL, 5,486 (50.0%) during-eIOL, and 2,869 (26.2%) post-eIOL. Groups differed with respect to labor type, age, race and ethnicity, marital and payor status, and GA at care entry. Post-eIOL was associated with lower odds of CD compared to pre-eIOL (aOR 0.75 [95% CI 0.66–0.87]), which was consistent for both nulliparas (aOR 0.71 [0.59–0.85]) and multiparas (aOR 0.64 [0.52–0.79]). During-eIOL was also associated with lower odds of CD compared to pre-eIOL (aOR 0.73 [0.65–0.82]). Both during- and post-eIOL groups were associated with higher odds of chorioamnionitis, operative delivery, and hemorrhage compared to pre-eIOL. However, only among post-eIOL were there fewer neonatal birth weights greater than 4,000 g, large-for-GA infants, and hypoglycemia compared to pre-IOL. CONCLUSION: Institutional policy offering eIOL at 39 0/7 to low-risk patients was associated with a lower CD rate and lower birth weights, and an increased risk of chorioamnionitis and hemorrhage.

Identification and Validation of Prognosis-Related Necroptosis Genes for Prognostic Prediction in Hepatocellular Carcinoma.

Background The prediction of hepatocellular carcinoma (HCC) survival is challenging because of its rapid progression. In recent years, necroptosis was found to be involved in the progression of multiple cancer types. However, the role of necroptosis in HCC remains unclear. Methods Clinicopathological parameters and transcriptomic data of 370 HCC patients were obtained from TCGA-LIHC dataset. Prognosis-related necroptosis genes (PRNGs) were identified and utilized to construct a LASSO risk model. The GEO cohorts (GSE54236 and GSE14520) were used for external validation. We evaluated the distribution of HCC patients, the difference in prognosis, and the accuracy of the prognostic prediction of the LASSO risk model. The immune microenvironment and functional enrichment of different risk groups were further clarified. Finally, we performed a drug sensitivity analysis on the PRNGs that constructed the LASSO model and verified their mRNA expression levels in vitro. Results: A total of 48 differentially expressed genes were identified, 23 of which were PRNGs. We constructed the LASSO risk model using nine genes: SQSTM1, FLT3, HAT1, PLK1, MYCN, KLF9, HSP90AA1, TARDBP, and TNFRSF21. The outcomes of low-risk patients were considerably better than those of high-risk patients in both the training and validation cohorts. In addition, stronger bile acid metabolism, xenobiotic metabolism, and more active immune cells and immune functions were observed in low-risk patients, and high expressions of TARDBP, PLK1, and FLT3 were associated with greater drug sensitivity. With the exception of FLT3, the mRNA expression of the other eight genes was verified in Huh7 and 97H cells. Conclusions. The PRNG signature provides a novel and effective method for predicting the outcome of HCC as well as potential targets for further research.

Redefining “low risk”: Outcomes of surgical aortic valve replacement in low-risk patients in the transcatheter aortic valve replacement era

ObjectivesGuidelines suggest aortic valve replacement (AVR) for low-risk asymptomatic patients. Indications for transcatheter AVR now include low-risk patients, making it imperative to understand state-of-the-art surgical AVR (SAVR) in this population. Therefore, we compared SAVR outcomes in low-risk patients with those expected from Society of Thoracic Surgeons (STS) models and assessed their intermediate-term survival. MethodsFrom January 2005 to January 2017, 3493 isolated SAVRs were performed in 3474 patients with STS predicted risk of mortality <4%. Observed operative mortality and composite major morbidity or mortality were compared with STS-expected outcomes according to calendar year of surgery. Logistic regression analysis was used to identify risk factors for these outcomes. Patients were followed for time-related mortality. ResultsWith 15 observed operative deaths (0.43%) compared with 55 expected (1.6%), the observed:expected ratio was 0.27 for mortality (95% confidence interval [CI], 0.14-0.42), stroke 0.65 (95% CI, 0.41-0.89), and reoperation 0.50 (95% CI, 0.42-0.60). Major morbidity or mortality steadily declined, with probabilities of 8.6%, 6.7%, and 5.2% in 2006, 2011, and 2016, respectively, while STS-expected risk remained at approximately 12%. Mitral valve regurgitation, ventricular hypertrophy, pulmonary, renal, and hepatic failure, coronary artery disease, and earlier surgery date were residual risk factors. Survival was 98%, 91%, and 82% at 1, 5, and 9 years, respectively, superior to that predicted for the US age-race-sex–matched population. ConclusionsSTS risk models overestimate contemporary SAVR risk at a high-volume center, supporting efforts to create a more agile quality assessment program. SAVR in low-risk patients provides durable survival benefit, supporting early surgery and providing a benchmark for transcatheter AVR.

Desfechos Adversos Perinatais Associados A Escolaridade Materna

Objective: To compare different levels of education with adverse perinatal outcomes in low-risk patients. Methodology: Cross-sectional study, puerperae were randomly selected, usual risk, attended in the public network, with single gestation. The evaluated puerperae were divided into 3 groups, according to education: primary or less, secondary and higher or more. The outcomes evaluated were cesarean section, neonatal ICU, low 1st minute Apgar, prematurity, and low birth weight. The calculation of the odds ratio had a 95% confidence interval. Results: the population was divided into 3 groups, 187 (52.9%) puerperal women with primary education or less, 437 (60.5%) patients with secondary education and 98 (13.6%) patients with higher education or more. Maternal characteristics differed in terms of age, previous pregnancies, normal deliveries, previous cesarean sections, age of 1st pregnancy, number of prenatal visits, income, number of people living in the household, and tobacco use. In the newborn profile, there was a difference only regarding cesarean sections. After calculating the odds ratio, it was seen that patients with primary education or less had a lower propensity to perform a cesarean section (0.511 95%CI 0.290-0.900), as well as patients with secondary education (0.530 95%CI 0.322-0.873), both compared to the population with higher education or more. In the other outcomes, no significance was observed. Conclusion: Primary and secondary education proved to be protective factors for cesarean section. No difference was found regarding prematurity, low birth weight, need for neonatal ICU and low 1st minute Apgar score.

Abstract PS6-41: Mammaprint and blueprint as prognostic indicators for elderly patients with early stage breast cancer

Abstract Background: Elderly breast cancer (BC) patients are an understudied population, with limited evidence regarding treatment options and outcomes and a lack of research involving prognostic multigene assays for this group. One study in patients 65-89 years old with an Oncotype DX Recurrence Score ≥ 26 concluded that gene expression profiling tests have limited utility in elderly patients, and should only be used for patients aged 65-74 with no/low to moderate comorbidities and not for patients ≥ 75. In this study, the 70-gene risk of distant recurrence signature, MammaPrint (MP), and 80-gene molecular subtyping signature, BluePrint (BP), were evaluated in both the neoadjuvant and adjuvant settings in elderly patients with early stage BC. Methods: This analysis included 211 BC patients classified as cT2-4N0-3M0 (T2 &amp;gt; 3.5 cm if N0) who received neoadjuvant chemotherapy and enrolled in the Multi-Institutional Neoadjuvant Therapy MammaPrint Project (MINT) study from 2011-2016. Lymph node (LN) involvement was established following neoadjuvant treatment. The second analysis included 517 early stage BC patients with 0-3 positive LNs who enrolled in the community based cohort study (COPPER) from 2009-2016. Patients were given adjuvant treatment following standard of care. Patients from both cohorts were divided into age at diagnosis groups: &amp;lt; 65, 65-74, and &amp;gt; 74. MP stratified patients into either Low Risk (LR) or High Risk (HR) groups. BP classified patient samples into Luminal, HER2, or Basal subtype. Kaplan Meier analysis and log-rank test were used to assess differences in overall survival (OS) and distant metastasis free survival (DMFS). Clinical risk assessment based on the MINDACT trial algorithm was performed. Results: From MINT, 35 patients were ≥ 65 years old; 80% were HR and 20% were LR. Pathological complete response (pCR) was achieved in 36% (10/28) of elderly HR patients, of whom 70% were HER2 and 30% were Basal by BP. Nodal downstaging occurred in 55% (11/20) of LN positive elderly HR patients, of whom 64% (7/11) achieved pCR. BP classified patients with nodal downstaging as HER2 (55%), Basal (36%), or Luminal (9%). Importantly, pCR and nodal downstaging were more likely to be achieved in HR tumors and correlated with BP subtype in both young and elderly patients. From the COPPER cohort, 77% of HR patients 65-74 years old received chemotherapy (CT), whereas 74% of LR patients omitted CT. Of patients &amp;gt; 74, 49% of HR patients received CT, whereas 75% of LR patients omitted CT. OS and DMFS probabilities indicated good survival outcomes in LR patients that omitted CT and HR patients that received CT, with no significant difference between age groups. A majority of HR patients treated with CT and over 1/3 of LR patients that omitted CT had high clinical risk. Interestingly, among all patients that had a metastasis event, mortality was less likely to occur in patients that received dose dense AC (doxorubicin and cyclophosphamide). Conclusion: MP and BP may identify HR elderly patients who are likely to achieve nodal downstaging and pCR. Elderly patients were safely spared or assigned adjuvant CT based on MP results independent of clinical risk. Furthermore, these data are in line with previous studies that suggest similar survival benefits between older and younger patients who are candidates for aggressive CT regimens. MP and BP elucidate information about tumor biology and provide prognostic value, which may help inform treatment decisions, independent of patient age. MINTAge group&amp;lt; 6565-74&amp;gt; 74MP resultHRLRHRLRHR# of patients152242177% of patients with pCR35% (53/152)033% (7/21)043% (3/7)# of LN+ patients103181456% of LN+ patients with nodal downstaging49.5% (51/103)22% (4/18)50% (7/14)067% (4/6)% of LN+ patients with pCR &amp; nodal downstaging65% (33/51)071%(5/7)050%(2/4)COPPERAge group&amp;lt; 6565-74&amp;gt; 74MP resultHRLRHRLRHRLR# of patients1409988665569# of patients received CT121256813278# of patients omitted CT116717492052# of patients with unknown treatment873489Groups treated based on MPHR treated with CTLR omitted CTAge group&amp;lt; 6565-74&amp;gt; 74&amp;lt; 6565-74&amp;gt; 745-yr DMFS probability (95% CI)91% (80.2-96.7)87% (60.2-91.4)87% (55.2-96.6)100%98% (84.3-99.7)94% (75.9-98.5)5-yr OS probability (95% CI)94% (80.2-98.2)96% (83.4-98.9)86% (54.7-96.5)100%98% (84.3-99.7)97% (80.4-99.6)% Clinical high risk83% (100/121)76% (52/68)63% (17/27)34% (23/67)37% (18/49)35% (18/52) Citation Format: Peter W. Blumencranz, Mehran Habibi, Lisa Blumencranz, Andrea Menicucci, Shiyu Wang, Amy Truitt, William Audeh, Jolanta L. Baginski, Steven Shivers, Geza Acs, Charles E. Cox, MINT Investigators Group. Mammaprint and blueprint as prognostic indicators for elderly patients with early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-41.

An Antithymocyte Globulin-Free Conditioning Regimen Using Fludarabine and Cyclophosphamide Is Associated with Good Outcomes in Patients Undergoing Matched Related Family Donor Transplantation for Aplastic Anemia

Allogeneic hematopoietic stem cell transplantation (HSCT) using fludarabine (Flu)-based conditioning regimens are being increasingly being used in patients with aplastic anemia (AA). We describe an antithymocyte globulin (ATG)-free conditioning regimen consisting of Flu and cyclophosphamide (Cy) in patients undergoing matched related donor (MRD) HSCT for AA. Between 2004 and 2019, 212 patients underwent MRD HSCT using Flu (30 mg/m2/day for 6 days) and Cy (60 mg/kg/day for 2 days) for conditioning. The graft source was peripheral blood stem cells in all patients. Graft-versus-host disease (GVHD) prophylaxis consisted mainly of cyclosporine and methotrexate, although 41 patients received post-transplantation Cy as part of a study. Engraftment occurred in 91% of patients at a median of 16 days, whereas 4 patients (1.8%) experienced primary graft failure and 15 (7.1%) died before achieving engraftment. Toxicity was minimal. The incidence of grade II-IV acute GVHD (aGVHD) was 27.9%, and that of grade III-IV aGVHD was 11.3%. Chronic GVHD occurred in 41.6%. 80% were free of immunosuppression at 60 months and long-term complications were seen in 8.4%. At a median of 46 months, 158 patients were alive and well, with a 5-year overall survival (OS) of 75.3 ± 3.0%. The 5-year OS was 80.6 ± 4.1% for patients age <20 years (n=93), 74.5 ± 4.6% for those age 20 to 40 years (n=91), and 59.7 ± 9.5% for those age >40 years (n=28) (P=.11). Patients classified as low risk had better OS compared with those at high risk (93.2 ± 2.9% versus 65.7 ± 4.1%; P=.000). Factors affecting OS on multivariate analysis included aGVHD (P=.02) and graft failure (P=.000). This large series using Flu/Cy for conditioning before MRD HSCT confirms good outcomes in patients with AA, with excellent outcomes in low-risk patients. Suitable modifications are needed to improve outcomes in high-risk patients.

Dual Antibiotic Prophylaxis in Primary Total Knee Arthroplasty—No Benefit for Extremely Obese Patients

We performed this study to assess the effectiveness of multimodal total knee arthroplasty prosthetic joint infection (TKA-PJI) prophylaxis including "on-time" dual-antibiotic prophylaxis, and the influence of body mass index (BMI) on prophylaxis effectiveness. After obtaining Institutional Review Board approval, we assessed 1,802 primary TKAs (1,496 patients) who received cefazolin alone or cefazolin combined with vancomycin for TKA-PJI prophylaxis. A detailed chart review was performed to determine patient demographic features (age, gender, BMI, American Society of Anesthesiologists Score), antibiotic selection, vancomycin administration timing, and 1-year PJI rates. Statistical assessment was accomplished using a two-sided Student's t-test or Fisher's exact test. Patients who received dual-antibiotic prophylaxis with "on time" vancomycin infusion (Group CVt) had significantly lower infection rates than other TKA patients (0.8 vs. 2.7%, p < 0.01). "On Time" vancomycin administration was associated with a lower TKA-PJI rate for patients with a BMI < 45 kg/m2 (0.5 vs. 2.6%, p < 0.01) with no infections in 120 TKA patients with a BMI between 40 and 44.9 kg/m2 (p < 0.01). No difference was noted for patients with a BMI ≥ 45 kg/m2 (3.3 vs. 2.6%, p = 0.71). There were no infections in 150 TKA patients with a normal BMI (18-25 kg/m2) in any PJI-prophylaxis treatment group. Adoption of a dual-antibiotic prophylaxis approach can successfully reduce TKA-PJI rates among overweight and moderately obese patients. The approach does not appear to influence outcomes for low risk patients with a normal BMI (18-25 kg/m2) or for higher risk patients with a BMI > 45 kg/m2.

The importance of clinically relevant background therapy in cardioprotective studies

Treatment of acute myocardial infarct patients (AMI) includes rapid restoration of coronary blood flow and pharmacological therapy aimed to prevent pain and maintain vessel patency. Many interventions have been investigated to offer additional protection. One such intervention is remote ischaemic conditioning (RIC) involving short-episodes of ischaemia of the arm with a blood pressure cuff, followed by reperfusion to protect the heart organs from subsequent severe ischaemia. However, the recent CONDI2-ERIC-PPCI multicentre study of RIC in STEMI showed no benefit in clinical outcome in low risk patients. It could also be argued that these patients were already in a partially protected state, highlighting the disconnect between animal- and clinical-based outcome studies. To improve potential translatability, we developed an animal model using pharmacological agents similar to those given to patients presenting with an AMI, prior to PPCI. Rats underwent MI on a combined background of an opioid agonist, heparin and a platelet-inhibitor thereby allowing us to assess whether additional cardioprotective strategies had any effect over and above this “cocktail”. We demonstrated that the “background drugs” were protective in their own right, reducing MI from 57.5 ± 3.7% to 37.3 ± 2.9% (n = 11, p < 0.001). On this background of drugs, RIC did not add any further protection (38.0 ± 3.4%). However, using a caspase inhibitor, which acts via a different mechanistic pathway to RIC, we were able to demonstrate additional protection (20.6 ± 3.3%). This concept provides initial evidence to develop models which can be used to evaluate future animal-to-clinical translation in cardioprotective studies.

External validation of the Canadian Syncope Risk Score for patients presenting with undifferentiated syncope to the emergency department.

To validate the accuracy and safety of the Canadian Syncope Risk Score (CSRS) for patients presenting with syncope. Single centre prospective observational study in Brisbane, Australia. Adults presenting to the ED with syncope within the last 24 h were recruited after applying exclusion criteria. Study was conducted over 1 year, from March 2018 to March 2019. Thirty-day serious adverse events (SAE) were reported based on the original derivation study and standardised outcome reporting for syncope. Individual patient CSRS was calculated and correlated with 30-day SAE and disposition status from ED. Two hundred and eighty-three patients were recruited to the study. Average age was 55.6 years (SD 22.7 years), 37.1% being male with a 39.9% admission rate. Thirty-day SAE occurred in seven patients (2.5%) and no recorded deaths. The CSRS performed with a sensitivity of 71.4% (95% confidence interval [CI] 30.3-94.9%), specificity 72.8% (95% CI 67.1-77.9%) for a threshold score of 1 or higher. Syncope patients in our study were predominantly very low to low risk (72%). The prevalence of 30-day SAE was low, majority occurring following hospital discharge. Sensitivity estimates for CSRS was lower than the derivation study but lacked robustness with wide CIs because of a small sample size and number of events observed. However, the CSRS did not miss any clinically relevant outcomes in low risk patients making it potentially useful in aiding their disposition. Larger validation studies in Australia are encouraged to further test the diagnostic accuracy of the CSRS.

Influence of surgical volume on outcomes in low-risk patients undergoing isolated surgical aortic valve replacement

BackgroundIntermediate- and high-risk patients undergoing isolated surgical aortic valve replacement have superior outcomes at higher-volume compared with lower-volume hospitals. This study examines the impact of hospital volume on outcomes in low-risk patients undergoing aortic valve replacement. MethodsUsing data from our 29 North Texas hospital collaborative, we examined 2066 low-risk cases (Society of Thoracic Surgeons Predicted Risk of Mortality of ≤3%) undergoing aortic valve replacement surgery between January 1, 2012, and December 31, 2017. Cases from 3 high-volume hospitals (≥200 aortic valve replacement cases total) and 26 low-volume hospitals (<200 cases total) were examined. ResultsSome 53.5% of the cases were at high-volume hospitals. No statistical differences were seen in the Predicted Risk of Mortality or pertinent demographics between the high-volume and low-volume hospitals. Significant differences in outcomes were seen between the 2 groups in operative mortality (2.28% vs 1.19%, P = .007), renal failure (2.14% vs 1.00%, P = .003), and readmission within 30 days (9.72% vs 6.25%, P < .001) when comparing low-volume with high-volume hospitals. In patients undergoing aortic valve replacement, undergoing the procedure in a low-volume hospital was an independent predictor for operative mortality (odds ratio, 1.95; 95% confidence interval, 1.20-3.20; P = .008) and renal failure (odds ratio, 2.25; 95% confidence interval, 1.33-3.81; P = .003). ConclusionsOperative mortality in low-risk patients undergoing aortic valve replacement is higher in low-volume compared with high-volume hospitals. The probability of a major complication, such as renal failure, is also greater in low-volume hospitals. The relationship between volume and outcomes in low-risk patients will require more research to understand the causes and design appropriate interventions.

Robotic iliopubic tract (r-IPT) repair: technique and preliminary outcomes of a minimally invasive tissue repair for inguinal hernia.

The iliopubic tract repair was first introduced by Nyhus in 1959, as an open non-mesh posterior preperitoneal repair for inguinal hernia. We have adapted this repair using a robotic approach to offer a minimally invasive (MIS) non-mesh inguinal hernia repair, termed the robotic iliopubic tract (r-IPT) repair. The aim of this pilot study is to evaluate the safety and effectiveness of this new technique. Starting in 2015, patients were enrolled in a Phase I trial of r-IPT repair. Inclusion criteria included low-risk patients with small inguinal hernias. Using a robotic TAPP approach, the direct and/or indirect defects were repaired by approximating the transversalis arch to the iliopubic tract. This trial was then expanded in Phase II to include a wider range of patients. Outcomes were collected prospectively. Twenty-four inguinal hernias were repaired in 13 patients via r-IPT as outpatients. Patients were followed for a mean of 24.9months (range 2.7-55.3, median 24). There were no surgical site occurrences and no recurrences. One (7.7%) patient had acute post-operative genital branch neuralgia, which self-resolved. One (7.7%) patient has chronic pain. The Nyhus-inspired robotic iliopubic tract (r-IPT) repair is an MIS approach to provide a non-mesh repair in inguinal hernia. The repair is safe with acceptable preliminary outcomes in low-risk patients. We propose the r-IPT repair to be a MIS option for non-mesh inguinal hernia repair in low-risk patients.

Correlation of CD123 Expression Level with Disease Characteristics and Outcomes in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group

Introduction: Despite maximally intensified chemotherapy, cure rates remain suboptimal for children and young adults with acute myeloid leukemia (AML). As CD123 (IL3RA) is expressed on the majority of AML cells, it is a promising immunotherapeutic target. Increased CD123 expression has been linked to high-risk disease characteristics in adult AML, but clinical implications for childhood AML are less well-defined. Methods: The Children's Oncology Group AAML1031 phase 3 trial (NCT01371981) tested the efficacy of the addition of bortezomib to standard chemotherapy in a randomized fashion. A total of 1400 children and young adults were enrolled on study. All diagnostic specimens were centrally and prospectively evaluated for the expression of CD123 by multi-dimensional flow cytometry (MDF) at Hematologics, Inc. Patients were stratified to either a low-risk (LR) or high-risk (HR) arm of the therapy based on cytogenetic and molecular alterations and end-of-induction (EOI) minimal residual disease (MRD) measured by MDF. LR patients received four cycles of chemotherapy, while HR patients received 3 courses of chemotherapy followed by best allogeneic hematopoietic stem cell transplantation (HSCT). Patients with high allelic ratio FLT3-ITD enrolled on arm C received sorafenib in combination with standard chemotherapy followed by HSCT. Here we provide data on expression of CD123 across all patients and correlate this expression with disease characteristics and clinical outcomes. Results: Surface CD123 expression on AML cells was available for 1040 patients, and expression level varied significantly across the study population with a median CD123 molecules per cell of 1300 (range 120-13,100 molecules per cell). For analysis, the study population was divided into quartiles (n=260 each) based on CD123 expression levels. Significant variation in cytogenetic/molecular characteristics was observed across the four quartiles, where those with highest CD123 expression had a lower prevalence of t(8;21), inv(16), and CEBPA mutations (p&amp;lt;0.001 for all) and higher prevalence of KMT2A rearrangements and FLT3-ITD mutations (p&amp;lt;0.001 for both) (Figure 1A). CD123 expression quartile was not significantly different among those in morphological complete remission (CR) (p=0.278) or MRD negative (bone marrow &amp;lt; 0.1%) (p=0.182) at EOI. Evaluation of outcome parameters across the four quartiles demonstrated that those in lower CD123 expression quartiles 1, 2 and 3 (Q1-3) had similar relapse risk (RR), event-free and overall survival (EFS and OS). However, those with the highest CD123 expression (Q4) had a significantly higher RR (53% vs. 39%, p&amp;lt;0.001), lower EFS (49% vs. 69%, p&amp;lt;0.001), and lower OS (32% vs 50%, p&amp;lt;0.001) (Figure 1B) in comparison to Q1-3. These differences were maintained within the protocol-defined LR cohort, as those with LR disease but high CD123 expression (Q4) had worse RR, EFS, and OS versus those in Q1-3 (p&amp;lt;0.001 for all) (Figure 1C). Given the observed association of CD123 expression with known risk groups, we performed a multivariable Cox regression analysis of all prognostic factors, including cytogenetic/molecular risk group, age, MRD status, and FLT3-ITD status, which demonstrated that high CD123 expression was independently associated with worse OS (HR 1.54, 95% CI 1.21-1.96, p&amp;lt;0.001) (Figure 1D). Conclusions: CD123 expression is strongly associated with disease-relevant cytogenetic and molecular alterations in childhood AML. Patients with highest CD123 surface expression are more likely to have HR genetic alterations and a paucity of LR features. Further, despite similar induction remission rates, those with high CD123 expression had inferior clinical outcomes compared to patients with lower CD123 expression. However, despite an association with HR features, expression of CD123 appears to be independently associated with therapeutic response given that outcome differences were maintained in multivariate regression analysis. This suggests that CD123 expression may provide additional prognostic information, as highlighted by the inferior outcomes in LR patients that had high CD123 expression. In pediatric and young adult patients with the highest risk disease, the higher CD123 expression represents a valuable therapeutic target in the development of immunotherapies for childhood AML. Disclosures Eidenschink Brodersen: Hematologics, Inc: Employment. Pardo:Hematologics, Inc: Employment. Tasian:Gilead Sciences: Research Funding; Aleta Biotherapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte Corportation: Research Funding. Loken:Hematologics, Inc: Employment, Equity Ownership.

Long-term biochemical progression-free survival following brachytherapy for prostate cancer: Further insight into the role of short-term androgen deprivation and intermediate risk group subclassification.

IntroductionBrachytherapy is a well-established treatment of localized prostate cancer. Few studies have documented long-term results, specifically biochemical progression-free survival (bPFS) in men with brachytherapy alone, with or without short-term androgen deprivation therapy (ADT), or in combination with external beam radiotherapy (EBRT). Our aim was to analyze long-term bPFS of brachytherapy treated patients.Materials and methodsRetrospective analysis of 1457 patients with low and intermediate risk prostate cancer treated with brachytherapy alone (1255) or combined with EBRT (202). Six-months ADT was administrated for all EBRT combined patients and for prostate volume downsizing when >55 cc (328). Failure was by the Phoenix definition. Kaplan-Meier analysis and multivariate Cox regression estimated and compared 10-yr and 15-yr rates of bPFS.ResultsMedian follow-up was 6.1 yr. Ten and 15-yr bPFS rates of the entire cohort were 93.2% and 89.2%, respectively. On multivariate analysis, PSA density (PSAD), ADT and clinical stage were significantly associated with failure. The most powerful independent factor was PSAD with a HR of 3.5 (95% CI, 1.7–7.4) for PSAD above 0.15. No significant difference was found between low and intermediate risks patients regardless of treatment regimen. However, comparison of two intermediate risk groups, Gleason score (GS) 7, PSA<20 ng/ml versus GS≤6 and PSA = 10–20 ng/ml, revealed 10- and 15-yr bPFS rates of 94.2% and 94.2% compared to 88.2% and 79.9%, (P = 0.022), respectively. ADT improved bPFS rates in low risk patients. The ten and 15-yr bPFS rates were 97.6% and 94.6% compared to 92.3% and 88.2%, (P = 0.020), respectively.ConclusionsOur retrospective large scale study suggests that brachytherapy provides excellent long-term bPFS rates in low and intermediate risk disease. Combination of brachytherapy with EBRT yields favorable outcomes in GS 7 intermediate risk patients and short-term ADT has a positive effect on outcomes in low risk patients.Further prospective studies are warranted to discriminate the role of adding either EBRT and/or ADT to brachytherapy protocols.

P5602Impact of preprocedural TIMI flow on clinical outcome in low-risk patients with ST-elevation myocardial infarction: results from the ATLANTIC study

P5602Impact of preprocedural TIMI flow on clinical outcome in low-risk patients with ST-elevation myocardial infarction: results from the ATLANTIC study

Abstract 339: Predictors of Periopertive Neurologic Outcomes Following CEA

Objective: The prospective registry study intended to identify risk factors of periinterventional neurologic outcomes after carotid endarteriectomy (CEA) to improve patient selection. Neurologic outcome predicition differs from the endpoint MACCE as previously shown. Methods: Patient characteristics and procedural factors were prospectively acquired and analysed using Cox regression to determine predictors for stroke and death within 30-days of CEA. Results: The analysis included 748 operations, 262 (35%) asymptomatic, 208 (28%) with previous strokes, and 278 (37%) with transient ischemic attacks (TIA). The overall 30-day stroke rate was 5.5%, 3.1% in asymptomatic and 6.8% in symptomatic patients and for stroke and death 5.6%, 3.1% and 7.0% respectively. Independent predictors of stroke and death were contralateral occlusion (HR=3.826, p=0.006, CI 1.483 - 9.867), symptomatic status (HR=3.626, p=0.004, CI 1.51 - 8.706), First-degree atrioventricular block (HR=2.209, p=0.041, CI 1.034 - 4.722), resection (HR=2.448, p=0.027, CI 1.106 - 5.416) and myocardial infarction (HR=2.03, p=0.04, CI 1.032 - 3.994) compared to all patients. Similar effect estimates were found for stroke alone. Compared to lower risk patients, SHR and SEC criteria predicted stroke and death after adjustment for symptomatic status (HR=2.29, p=0.02, CI 1.142 - 4.592) and (HR=2.286, p=0.028, CI 1.094 - 4.778). Outcome in low risk patients were not related to the symptomatic status for stroke and death (HR=2.484, p=0.148, CI 0.724 - 8.524), correspondingly for stroke. Conclusions: This is the first report identifying preprocedural myocardial infarction, first degree AV-block, SHR and SEC as predictors of stroke and stroke and death at 30 days postoperatively.

Relationship Between Labor and Delivery Unit Management Practices and Maternal Outcomes

(Obstet Gynecol. 2017;130(2):358–365) The specific management practices of labor and delivery units and their sensitivity to operational pressures have not been well assessed in the context of improved patient outcomes. In the present review, the authors assessed whether or not labor and delivery unit management practices that proactively mitigated unit challenges were independently associated with lower risk of primary cesarean delivery, prolonged length of stay, and adverse maternal outcomes in low-risk patients.