Probability Of Long-term Survival Research Articles

Surgical risk scores for congenital heart surgery are useful for long-term risk prediction.

The initial and updated Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STAT and STAT 2020) and Risk Adjusted Classification for Congenital Heart Surgery-1 and Risk Adjusted Classification for Congenital Heart Surgery-2 scoring systems are validated to predict early postoperative mortality following congenital heart surgery in children; however, their ability to predict long-term mortality has not been examined. We performed a retrospective cohort study using data from the Pediatric Cardiac Care Consortium, a US-based registry of cardiac interventions in 47 participating centres between 1982 and 2011. Patients included in this cohort analysis had select congenital heart surgery representing the spectrum of severity as determined by STAT and Risk Adjusted Classification for Congenital Heart Surgery-1 and were less than 21 years of age. We applied STAT, STAT 2020, Risk Adjusted Classification for Congenital Heart Surgery-1, and Risk Adjusted Classification for Congenital Heart Surgery-2 for prediction of early mortality and long-term postoperative survival probability by surgical risk category. Long-term outcomes were obtained by matching Pediatric Cardiac Care Consortium patients with deaths reported in the National Death Index through 2021. Of 20,753 eligible patients, 18,755 survived the postoperative period and 2,058 deaths occurred over a median follow up of 24.4 years (Interquartile Range: 21-28.4). Each scoring system performed well for predicting early postoperative mortality with the following c-statistics: STAT: 0.7872, Risk Adjusted Classification for Congenital Heart Surgery-1: 0.7872, STAT 2020: 0.7724 and Risk Adjusted Classification for Congenital Heart Surgery-2: 0.7668. The predictive ability for long-term risk of death was as follows: STAT: 0.6995, Risk Adjusted Classification for Congenital Heart Surgery-1 c = 0.6741, Risk Adjusted Classification for Congenital Heart Surgery-2: 0.7156 and STAT 2020: c = 0.7156. Risk-adjusted score systems for congenital heart surgery maintain adequate but diminishing discriminative power to predict long-term mortality. Future efforts are warranted to develop a tool with improved long-term survival prediction.

The long-term conditional mortality rate in older ICU patients compared to the general population

BackgroundUnderstanding how preexisting comorbidities may interact with a critical illness is important for the assessment of long-term survival probability of older patients admitted to the ICU.Material and methodsThe mortality after a first ICU admission in patients ≥ 55 years old registered in the Swedish Intensive Care Registry was compared to age- and sex-matched individuals from the general population with a landmark after 1 year. The comparison was adjusted for age, sex, and baseline comorbidity using Cox regression.ResultsThe 7-year study period included 140 008 patients, of whom 23% were 80 years or older. Patients surviving the first year remained at an increased risk compared to the general population, but much of this difference was attenuated after adjustment for baseline comorbidity (HR, 1.03; 95% CI 1.02–1.04). Excluding cardio-thoracic ICU admissions, the increased risk remained slightly elevated (adjusted HR, 1.15; 95% CI 1.13–1.16). Also, the subgroup ≥ 75 years old surviving the first year returned to a mortality rate comparable to the general population (HR, 0.98; 95% CI 0.96–0.99). Stratified by admission diagnosis an increased mortality rate remained beyond the first year for acute-on-chronic respiratory failure (adjusted HR, 1.47; 95% CI 1.36–1.58) but not for other respiratory causes (adjusted HR, 1.03; 95% CI 0.99–1.07) or admission for septic shock (adjusted HR, 1.04; 95% CI 0.95–1.13). No substantial increased mortality rate was notable beyond the first year for other admission diagnoses.ConclusionOlder ICU patients that survive the first year after an ICU admission return to a mortality rate close to that of the general population having similar baseline comorbidity, but variability is seen depending on the ICU admission diagnosis.Trial registration ClinicalTrials.gov ID: NCT06234709, date 02/01/2024.

Transcatheter Aortic Valve Replacement in Patients With Geographic and Socioeconomic Vulnerabilities.

Transcatheter aortic valve replacement (TAVR) is an established treatment for patients with severe aortic stenosis (AS). It remains unclear whether disparities exist in rural or socially vulnerable populations undergoing TAVR. This study assessed whether outcomes differ based on geographic location or vulnerability of patients undergoing TAVR. Patients undergoing TAVR at a single institution from August 2012 to June 2023 were studied (n = 1565). Zip codes determined Social Vulnerability Index (SVI) and measured distance to our facility. Outcomes defined by the Valve Academic Research Consortium 3 (VARC-3) included stroke, transient ischemic attack (TIA)/delirium, pacemaker implantation, new atrial fibrillation/atrial flutter, and myocardial infarction (MI). Average time between preoperative coronary angiogram (CATH)/computed tomography angiography (CTA) and TAVR was calculated. Kaplan-Meier curves estimated survival probability. The average time between CATH and TAVR in patients living furthest away was ∼9 days more than patients living closest to the implant site. The average number of days between CATH and TAVR for low and high SVI were 71 and 78 days, respectively. The average number of days between CTA and TAVR for low and high SVI were 40 and 39 days, respectively. Further distances traveled were associated with longer wait times between preoperative workup and TAVR. Patients with longer waits between CATH and TAVR had no differences in medium-term survival probability but had decreased long-term survival probability compared to patients with rapid pre-procedural evaluation. Although geographic and socioeconomic vulnerability can disadvantage patients, our study demonstrates that patients undergoing TAVR can have timely care and similar outcomes.

Perioperative anesthetic management of patients with hypoplastic left heart syndrome undergoing the comprehensive stage II surgery-A review of 148 cases.

Patients with hypoplastic left heart syndrome undergo the comprehensive stage 2 procedure as the second stage in the hybrid approach toward Fontan circulation. The complexity of comprehensive stage 2 procedure is considered a potential limitation, and limited information is available on its anesthetic management. This study aims to address this gap. A single-center retrospective cohort study analyzed 148 HLHS patients who underwent comprehensive stage 2 procedure, divided into Group A (stable condition, n = 116) and Group B (requiring preoperative intravenous inotropic therapy, n = 32). Demographic data, intraoperative hemodynamics, anesthetic management, and postoperative outcomes were collected. Etomidate (40%) was the most common induction agent, followed by esketamine (24%), midazolam (16%), and propofol (13%). Inhaled induction was rarely necessary (2%), occurring only in Group A patients. No statistical differences were found between groups for induction drug choice. Post-cardiopulmonary bypass management included moderate hypoventilation, inhaled nitric oxide (100%), and hemodynamic support with milrinone (97%) and norepinephrine (77%). Group B patients more frequently required additional levosimendan (20%) and epinephrine (18%). Extracorporeal membrane oxygenation was necessary in 8 patients (5%) with no between-group differences. Switching from fentanyl to remifentanil reduced postoperative ventilation time overall. However, Group B experienced significantly longer ventilation (6.3 vs. 3.5 h) and ICU stay (22 vs. 14 days). In-hospital mortality was 5% overall (Group A: 4%, Group B: 9%). Long-term survival analysis revealed a significant advantage for Group A. The use of short-acting opioids and adjusted ventilation modes enables optimal pulmonary blood flow and rapid transition to spontaneous breathing. Differentiated hemodynamic support with milrinone, norepinephrine, supplemented by levosimendan and epinephrine in high-risk patients, can mitigate the effects on the preoperatively volume-loaded right ventricle. However, differences in long-term survival probability were observed between groups. Local ethics committee, Medical Faculty, Justus-Liebig-University-Giessen (Trial Code Number: 216/14).

Trends in incidence, prevalence, and survival of breast cancer in the United Kingdom from 2000 to 2021

Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases. There were 5,848,436 eligible females and 5,539,681 males aged 18+ years, with ≥ one year of prior data availability in the study period. We estimated crude breast cancer incidence rates (IR), prevalence and survival probability at one-, five- and 10-years after diagnosis using the Kaplan–Meier method. Analyses were further stratified by age. Crude IR of breast cancer from 2000 to 2021 was 194.4 per 100,000 person-years for females and 1.16 for males. Crude prevalence in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in prevalence across time. Incidence increased with age for both sexes, peaking in females aged 60–69 years and males 90+ . There was a drop in incidence for females aged 70–79 years. From 2003–2019, incidence increased > twofold in younger females (aged 18–29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50–69 years; and further declined from 2015 onwards in females aged 70–89 years. Survival probability for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival probability at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000–2004 to 2015–2019 for females, particularly those aged 50–70 years. For males, there were no clear time-trends for short-term and long-term survival probability. Changes in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.

Importance of surgeon's experience in practicing valve-sparing aortic root replacement

BackgroundValve-sparing root replacement (VSRR) requires a unique skill set. This study aimed to examine the influence of surgeon's procedural volume on outcomes of VSRR. MethodsThis retrospective study included 1697 patients from 2 large, high-volume aortic centers who underwent aortic root replacement (ARR) between 2004 and 2021 and were potentially eligible for VSRR. Surgeons were classified as performing <5 ARRs or ≥5 ARRs annually. Multivariable logistic regression was used to examine the independent association of surgeon volume and the decision to perform VSRR. Inverse probability treatment weighting (IPTW) was used to match patients who were operated on by <5 ARR surgeons or ≥5 ARR surgeons and compare long-term survival probability. Cumulative incidence curves with mortality as a competing risk were plotted to compare the rate of aortic valve reoperation. ResultsOf 1697 patients who met the study inclusion criteria, 944 underwent composite-valve conduit ARR and 753 underwent VSRR. The median age of the cohort was 57 years (interquartile range, 45-66 years), and 268 (15.8%) were female. Aortic insufficiency was present in 1105 patients (65.1%), and 200 of the procedures (11.8%) were reoperations. The indication for surgery was aneurysm in 1496 patients (88.2%) and dissection in 201 (11.8%). Among the 743 patients who underwent VSRR, 691 (92%) were operated on by ≥ 5 ARR surgeons and 62 (8%) were operated on by <5 ARR surgeons. In multivariable logistic regression, ≥5 ARRs (odds ratio, 3.33; 95% confidence interval, 2.34-4.73; P < .001) was associated with VSRR as the procedure of choice. Following IPTW, there was no significant difference between <5 ARR and ≥5 ARR surgeons in survival probability after VSRR (P = .59) or in the rate of aortic valve reoperation (P = .60). ConclusionsIn the setting of a high-volume aortic center, patients who undergo ARR are less likely to receive VSRR if operated on by a <5 ARR surgeon; however, VSRR may be safely performed by <5 ARR surgeons.

Clinical Outcomes of Repeat Descemet Membrane Endothelial Keratoplasty After Graft Failure.

To evaluate the clinical outcomes after repeat Descemet membrane endothelial keratoplasty (DMEK) for technical failure (TF) and secondary graft failure (SGF). Retrospective analysis of 49 eyes that underwent repeat DMEK either for TF (ie, persistent graft detachment, n = 24) or for SGF (ie, late endothelial graft failure, n = 25). Surgery indications for primary DMEK were Fuchs endothelial corneal dystrophy (FECD, 80%) and bullous keratopathy (BK, 20%). Main outcome measures were best-corrected visual acuity (BCVA), endothelial cell density (ECD), corneal backscattering, pachymetry, and graft survival. Outcomes were compared with an age-matched control group of 49 primary DMEK eyes. Logarithm of the minimum angle of resolution BCVA improved from 0.92 ± 0.6 before to 0.20 ± 0.3 at 1 year after repeat DMEK with better outcomes for eyes with TF than those with SGF (P = 0.046). Donor ECD decreased from 2618 ± 171 cells/mm2 before to 1247 ± 422 cells/mm2 at 1 year postoperatively, with no difference between technical TF and SGF eyes (P > 0.05). One-year BCVA and ECD outcomes were better in the control group than in the repeat DMEK group (P < 0.05). Five-year graft survival probability after repeat DMEK was better for TF than for SGF eyes (100% vs. 75%, P = 0.010) and better for eyes with FECD than BK as primary indication for surgery (92% vs. 65%, P = 0.042). Repeat DMEK gives acceptable clinical outcomes especially when performed for TF in the early period after primary DMEK. Long-term graft survival probability after repeat DMEK is comparable to primary DMEK for FECD eyes, whereas BK eyes may show an elevated risk to develop graft failure again.

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasm and derivation of a prognostic model: An international multicenter study (ADENO-IPMN study)

Predictors of long-term survival after resection of adenocarcinoma arising from intraductal papillary mucinous neoplasms are unknown. This study determines predictors of long-term (>5 years) disease-free survival and recurrence in adenocarcinoma arising from intraductal papillary mucinous neoplasms and derives a prognostic model for disease-free survival. Consecutive patients who underwent pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms in 18 academic pancreatic centers in Europe and Asia between 2010 to 2017 with at least 5-year follow-up were identified. Factors associated with disease-free survival were determined using Cox proportional hazards model. Internal validation was performed, and discrimination and calibration indices were assessed. In the study, 288 patients (median age, 70 years; 52% male) were identified; 140 (48%) patients developed recurrence after a median follow-up of 98 months (interquartile range, 78.4-123), 57 patients (19.8%) developed locoregional recurrence, and 109 patients (37.8%) systemic recurrence. At 5 years after resection, the overall and disease-free survival was 46.5% (134/288) and 35.0% (101/288), respectively. On Cox proportional hazards model analysis, multivisceral resection (hazard ratio, 2.20; 95% confidence interval, 1.06-4.60), pancreatic tail location (hazard ratio, 2.34; 95% confidence interval, 1.22-4.50), poor tumor differentiation (hazard ratio, 2.48; 95% confidence interval, 1.10-5.30), lymphovascular invasion (hazard ratio, 1.74; 95% confidence interval, 1.06-2.88), and perineural invasion (hazard ratio, 1.83; 95% confidence interval, 1.09-3.10) were negatively associated with long-term disease-free survival. The final predictive model incorporated 8 predictors and demonstrated good predictive ability for disease-free survival (C-index, 0.74; calibration, slope 1.00). A third of patients achieve long-term disease-free survival (>5 years) after pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasms. The predictive model developed in the current study can be used to estimate the probability of long-term disease-free survival.

Longevity of different abutments placed on narrow diameter implants: Assessment of structural damage and loosening

ObjectivesTo evaluate structural damage and loosening of abutments placed on narrow diameter implants after cyclic fatigue. MethodsSixty Morse taper narrow diameter implants (Neodent, Brazil) received two types of abutments (1PA- one-piece abutment or 2PA- two-piece abutment), which were randomly divided into 3 fatigue experiments (n = 10). The implants were placed into a customized supporting holder and a software-assisted digital torque wrench secured the manufacturer recommended torque for each abutment. Cone beam computed tomography (CBCT) scans were acquired, before and after fatigue, and post-processed (software e-Vol DX) to assess damage and abutment displacement. The boundary fatigue method was adapted to use 2 × 106 cycles, 2 Hz of frequency and constant peak load of 80 N (first experiment) that varied according to the failure rate of previous specimens (second and third experiments). Failure was evaluated using CBCT scans and removal torque values. Data were used to estimate long-term torque degradation, probability of failure and Weibull modulus (software ALTA PRO9). ResultsAll 2PA specimens became loosen independently of the applied fatigue load, and structural bending was observed in 14 abutments. Eight 1PA got loosen during the fatigue experiment. The Weibull analysis showed a lower modulus (m = 1.0; 0.7, 1.4) for 1PA than for 2PA (m = 2.6; 2, 3.4) resulting in longer predicted lifetimes and slower torque degradation for 1PA than for 2PA specimens. Significance1PA showed greater long-term survival probability than 2PA. Predicting the lifetime and mechanical behavior of implant-abutment systems are useful information to clinicians during the decision-making process of oral rehabilitations.

Cross-sectional and longitudinal associations between PG-SGA criteria with survival of cancer patients.

e23277 Background: Malnutrition is prevalent in cancer patients and is associated with treatment efficacy and clinical outcomes. Whether the available malnutrition assessment tools contain optimal survival prediction value for cancer patients, especially from developing countries, remains unclear. Methods: In this retrospective cohort study, cancer patients were selected from our center between Nov 2019 and Sep 2023. According to the PG-SGA criteria, PG-SGA scores &lt; 4 referred to well-nourished, ≥ 4 PG-SGA scores &lt; 9 referred to malnutrition, and ≥ 9 referred to severe malnutrition. Kaplan-Meier (KM) curves were used to estimate the survival patterns of cancer patients with varied levels of PG-SGA scores. The Cox proportional hazard model was used to evaluate the association between baseline and longitudinal changes of PG-SGA scores with the all-cause mortality of cancer patients. Subgroup analysis with interaction tests was used to determine the high-risk subgroups. A series of sensitive analyses were performed to validate the findings we determined. Results: There were 1,415 cancer patients included in our study, with a mean age of 46 years old. The mean PG-SGA score was 2.42 in non-malnourished patients, 10.10 in malnourished patients, and 12.65 in severely malnourished patients, respectively. The KM curves showed that cancer patients with severe malnourished status (PG-SGA ≥9) presented the lowest short- and long-term survival probability, compared with the other two subgroups. A linear trend was observed between the PG-SGA scores and cancer mortality (p for overall test &lt; 0.001). The Cox regression analysis showed that baseline malnourished status was significantly associated with the survival of cancer patients [≥4 PG-SGA &lt; 9: hazard ratio (HR): 1.46, 95% confidence interval (CI): 1.09 – 1.96, p = 0.012; PG-SGA ≥9: HR = 1.78, 95%CI: 1.34 – 2.37, p &lt; 0.001]. Cancer patients with longitudinal increased PG-SGA scores ( &gt; 2 points) were observed to have a high risk for mortality (HR = 1.69, 95%CI: 1.04 – 2.74, p = 0.033). Compared with longitudinal changes in PG-SGA scores, the baseline PG-SGA scores showed significantly higher predictive power in identifying the risk subgroup (concordance index: 0.646 vs. 0.586, p &lt; 0.001). PG-SGA scores showed more pronounced predicting value among subgroups with features of younger age, normal and underweight body mass index, late cancer stage, without history of diabetes, smoking, radiotherapy, and immunotherapy. A series of sensitive analyses determined consistent correlations. . Conclusions: Our study validates the clinical value of baseline, as well as longitudinal changes of PG-SGA, scored status for predicting the survival of cancer patients. Our findings provide new insights into the identification and prevention strategies for malnourished conditions in cancer patients, resulting in improved cancer-related nursing in resource-limited regions.

Enhancing long-term survival prediction with two short-term events: Landmarking with a flexible varying coefficient model.

Patients with cardiovascular diseases who experience disease-related short-term events, such as hospitalizations, often exhibit diverse long-term survival outcomes compared to others. In this study, we aim to improve the prediction of long-term survival probability by incorporating two short-term events using a flexible varying coefficient landmark model. Our objective is to predict the long-term survival among patients who survived up to a pre-specified landmark time since the initial admission. Inverse probability weighting estimation equations are formed based on the information of the short-term outcomes before the landmark time. The kernel smoothing method with the use of cross-validation for bandwidth selection is employed to estimate the time-varying coefficients. The predictive performance of the proposed model is evaluated and compared using predictive measures: area under the receiver operating characteristic curve and Brier score. Simulation studies confirm that parameters under the landmark models can be estimated accurately and the predictive performance of the proposed method consistently outperforms existing methods that either do not incorporate or only partially incorporate information from two short-term events. We demonstrate the practical application of our model using a community-based cohort from the Atherosclerosis Risk in Communities (ARIC) study.

Relationship between 24 h blood pressure variability and mortality in acute myocardial infarction patients.

In recent years, the mortality of patients with AMI has not declined significantly. The relationship between blood pressure variability (BPV) and acute myocardial infarction (AMI) is unclear. We explored the relationship between 24-h BPV and mortality in patients with AMI. The mortality of patients with AMI is related to BPV. We hope to provide therapeutic ideas for reducing the risk of death in patients with AMI. This is a retrospective cohort study. We extracted and analyzed data from the MIMIC-IV 2.0, which was established in 1999 under the auspices of the National Institutes of Health (America). The average real variability (ARV) was calculated for the first 24-h blood pressure measurement after patients with AMI were admitted to the intensive care unit (ICU). Patients were divided into four groups according to ARV quartiles. The outcomes were 30-day, 1-year, and 3-year all-cause mortalities. Data were analyzed using Cox regression, Kaplan-Meier curves, and restricted cubic spline (RCS) curves. We enrolled 1291 patients with AMI, including 475 female. The patients were divided into four groups according to the qualities of diastolic blood pressure (DBP)-ARV. There were significant differences in the 30-day, 1-year and 3-year mortality among the four groups (p = .02, p < .001, p < .001, respectively). After adjustment for confounding factors, systolic blood pressure (SBP)-ARV could not predict AMI patient mortality (p > .05), while the highest DBP-ARV was associated strongly with increased 30-day mortality (HR: 2.291, 95% CI 1.260-4.168), 1-year mortality (HR: 1.933, 95% CI 1.316-2.840) and 3-year mortality (HR: 1.743, 95% CI 1.235-2.461). Kaplan-Meier curves demonstrated that, regardless of SBP or DBP, the long-term survival probabilities of patients in the highest ARV group were significantly lower than that of those in other groups. RCS curves showed that the death risk of patients with AMI first decreased and then increased with the increase in ARV when DBP-ARV < 8.04. The 30-day death risk first increased and then decreased, and the 1-year and 3-year death risks increased and then stabilized with ARV increase when DBP-ARV > 8.04. This study showed that patients with AMI may have an increased risk of short- and long-term death if their DBP-ARV is higher or lower during the first 24-h in ICU.

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study

To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients.

Maximizing the survival probability in a cash flow inventory problem with a joint service level constraint

This paper investigates a multi-period stochastic cash flow inventory problem with the aim of maximizing the long-term survival probability, which may be the objective of some retailers especially in periods of economic distress. Demand in each period is stochastic and can be non-stationary. In order to avoid too many lost sales under this objective, we introduce a joint chance constraint requiring the probability of no stockouts during the planning horizon to be higher than a specified service level. We develop a scenario-based model and a sample average approximation (SAA) model to solve the problem. A statistical upper bound on the survival probability based on SAA is provided and we discuss upper and lower bounds for the problem based on stochastic dynamic programming. We also propose a rolling horizon approach with service rate updating to test the out-of-sample performance of the two stochastic models and solve problems with long planning horizons. We test the two methods in large numerical tests and find that the rolling horizon approach together with the stochastic models can solve realistically sized problems in reasonable time.

Prognostic significance of socioeconomic deprivation in patients with colorectal liver metastasis undergoing liver resection: a retrospective cohort study.

To evaluate the effect of socioeconomic deprivation on overall survival (OS) in patients undergoing liver resection for colorectal liver metastasis (CRLM). The STROCSS guideline for observational studies was followed to conduct a single-centre retrospective cohort study. All consecutive patients undergoing resection of CRLM between 2013 and 2021 were considered eligible for inclusion. The Welsh Index of Multiple Deprivation (WIMD) rank was used to determine socioeconomic deprivation status of each patient. Prognostic significance of socioeconomic deprivation was determined by Kaplan-Meier survival statistics and stepwise Cox proportional-hazards regression model. A total of 455 patients were eligible for inclusion; 237 patients were classed as least socioeconomically deprived and 218 patients as most socioeconomically deprived. Kaplan-Meier survival statistics showed that socioeconomic deprivation was associated with significantly lower probability of overall survival (HR: 1.55, 95% CI 1.23-1.95; logrank test: P = 0.0001). The stepwise Cox proportional-hazards regression analysis identified socioeconomic deprivation as predictor of OS (HR: 1.56, P = 0.0003) alongside the following variables: ASA status 1 (HR: 0.43, P = 0.0349), presence of extrahepatic disease (HR: 1.51, P = 0.0075), number of tumours (HR: 1.07, P = 0.0221), size of largest tumour (HR: 1.01, P = 0.0003), extended hemihepatectomy (HR: 3.24, P = 0.0018) and absence of recurrence (HR: 0.55, P < 0.0001). Socioeconomic deprivation reduces the probability of long-term overall survival following liver resection in patients with CRLM. This should be taken into account at different levels of health care planning for management of patients with CRLM including preoperative risk assessment, health care need assessment and allocation of resources.

Naples Prognostic Score: A Novel Predictor of Survival in Patients with Triple-Negative Breast Cancer.

This study investigated the correlation between the Naples prognostic score (NPS), clinicopathological traits, and the postoperative prognoses of patients with triple-negative breast cancer (TNBC). Based on NPS, a predictive nomogram was developed to estimate the long-term survival probabilities of patients with TNBC post-surgery. We retrospectively examined the clinical records of 223 women with TNBC treated at Ningbo Medical Center, Lihuili Hospital between January 1, 2016 and December 31, 2020. Blood tests and biochemical analyses were conducted before surgery. The prognostic nutritional index (PNI), controlling nutritional status (CONUT), neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and NPS were determined based on blood-related markers. A Kaplan-Meier survival analysis assessed the association between NPS, PNI, CONUT score, overall survival (OS), and breast cancer-specific survival (BCSS). Predictive accuracy was evaluated using the area under the receiver operating characteristic curve (AUC) and C index. The patients were randomly divided into the training and the validation group (6:4 ratio). A nomogram prediction model was developed and evaluated using the R Software for Statistical Computing (RMS) package. NPS outperformed other scores in predicting inflammation outcomes. Patients with an elevated NPS had a poorer prognosis (P<0.001). Lymph node ratio (LNR), surgical method, postoperative chemotherapy, and NPS independently predicted OS, whereas M stage, LNR, and NPS independently predicted BCSS outcome. The OS and BCSS predicted by the nomogram model aligned well with the actual OS and BCSS. The decision curve analysis showed significant clinical utility for the nomogram model. In this study, NPS was an important prognostic indicator for patients with TNBC. The nomogram prognostic model based on NPS outperformed other prognostic scores for predicting patient prognosis. The model demonstrated a clear stratification ability for patient prognosis, which emphasized the potential benefits of early intervention for high-risk patients.

Incidence of Second Primary Malignancies in Patients with AL Amyloidosis and the Impact of Disease Stage and Therapies

AL amyloidosis is a clonal disease, characterized by the production of light chains from a usually small or modest in size plasma or B-cell clone. Early mortality due to severe organ involvement is the most ominous complication, long term sequalae, associated with organ involvement resulting in end stage dysfunction occurs but other long-term complications due to therapy or immunosuppression are often neglected. The treatment of AL amyloidosis is based on the elimination of the clone with the use of chemotherapy (including high dose melphalan) or immunochemotherapy. Among patients (pts) with myeloma or other B-cell malignancies the development of 2 nd primary cancers is a well described complication, associated with longer survival, exposure to multiple drugs and long-standing immunosuppression. However, data on the incidence and risk factors for second malignancies are not available for pts with AL amyloidosis. Thus, the aim of our study was to describe the incidence and risk factors for the development of 2nd malignancies among consecutive pts with AL amyloidosis. The analysis included 417 consecutive pts, treated and followed in the Department of Clinical Therapeutics, Athens. The analysis accounted for death due to AL amyloidosis and diagnosis of 2 nd malignancy as competing events (competing risks analysis). The median age of the cohort was 65 years, 56% were females; heart, renal and liver involvement were present in 76%, 65% and 19% respectively. Per Mayo staging, 16%, 44% and 40 were stage -1, -2 and -3. Treatment, across all lines, included alkylators in 75% (mostly cyclophosphamide, melphalan was given in 21%, of which 5% as high dose), lenalidomide in 36% and daratumumab 31% while 95% had received bortezomib. The median follow up of the cohort was 56 months and the estimated median overall survival of all pts was 57 months. A second primary malignancy, after the diagnosis of AL amyloidosis, was diagnosed in 26 (6.2%) pts; these included breast (4 pts), renal (4 pts), colon (3 pts), lung (3 pts), gastric (2 pts), MDS (2 pts) and one case each from AML, ovarian, pancreatic, urothelial, sarcoma, head&amp; neck cancers while two pts had multiple 2 nd cancers. The median age of the affected pts was 66 years and 13 (50%) were males; 29% had Mayo stage-1 disease, 52% had stage -2 and 19% stage 3 disease at initial diagnosis of AL amyloidosis. Accounting for death due to amyloidosis as a competing event, the cumulative incidence of 2nd primary malignancy was 0.7% at 2 years, 2% at 3 years, 4.5% at 4 years, 5.4% at 5 years, 7% at 6 years, 8.7% at 7 years and 10.25% at 10 years (figure 1). We then performed competing event univariate analysis to evaluate the potential association of several clinical, laboratory and treatment characteristics with the probability of developing a 2 nd malignancy. Notably, there was no increased risk of a 2 nd malignancy associated with the use of alkylators (either cyclophosphamide or melphalan), or melphalan (standard or high dose), lenalidomide or daratumumab. Since 95% of ptshad been exposed to bortezomib we could not make a meaningful analysis for this drug. Among baseline clinical characteristics, the presence of purpura or liver involvement (and with a trend for heart involvement) was associated with lower probability of diagnosis of a 2 nd malignancy, in the competing risk analysis. However, when analyzing the cumulative incidence of a 2 nd malignancy in ptswith different stages per Mayo system (1 vs 2 vs 3), the 5-year cumulative probability of death among pts with stage 1 disease per Mayo 2004, was 10.5% and the 5-year cumulative probability of 2 nd malignancy was 8.9% (the respective 5-year probabilities for Mayo stage 2 were 50.2% and 5.4% and for Mayo stage 3 were 69.7% and 3.7%). Thus, 2 nd cancers seem to affect mainly those with Mayo stage 1 discase, which also have the highest probability of long term survival. The 2 nd cancer was the cause of death in 10/26 (38%) of the affected pts. In conclusion, second primary malignancies occur in 6% of pts with AL amyloidosis, affecting mostly pts without or with early cardiac involvement who have also the longest survival probability, with a 5-year cumulative risk of 9%. Second hematologic malignancies are uncommon (0.7%). We did not find a significant correlation with the use of alkylators of other specific agents. This data emphasizes the need for screening for the most common malignancies among pts with AL amyloidosis as new therapies improve the long-term survival.

THU491 GRHL2 Overexpression In Breast Cancer Progression

Abstract Disclosure: C. Zheng: None. K.O. Allen: None. R. Reese: None. N.M. Solodin: None. J. Vera: None. S. Mcilwain: None. T. Liu: None. E.T. Alarid: None. Metastasis constitutes the permissive migration and growth of cancerous cells from the primary tumor to a distant location in the body. Epithelial to mesenchymal transition (EMT) is implicated in metastasis as it allows for cells to abandon an epithelial identity, adopt a mesenchymal phenotype, become migratory, and promote tumor progression. Grainyhead-like protein 2 (GRHL2) is a nuclear transcription factor responsible for driving epithelial cell fate. By regulating epithelial differentiation and integrity in estrogen receptor (ER) positive breast cancer, GRHL2 suppresses EMT, and as such, it was long thought to act primarily as a tumor suppressor. However, clinical evidence contradicts its tumor suppressive role in that patients expressing high levels of GRHL2 have a significantly lower probability of long-term recurrence free survival compared to low levels of GRHL2, and high levels of GRHL2 are also associated with high grade tumors. To better understand this discrepancy, a tetracycline (tet) inducible GRHL2 overexpression model in the ER-positive breast cancer MCF7 cell line was developed to assess cancer associated phenotypes and the transition between epithelial and mesenchymal states. Dose response and time course studies were performed to determine optimal GRHL2 induction in our tet-inducible model using immunofluorescent microscopy and Western blot analysis. Gene expression analyses was performed to assess representative genes associated with epithelial and mesenchymal states, and the intermediates between them known as hybrid or partial EMT. Interestingly, immunocytochemistry identified that the overexpression of GRHL2 induces the late EMT marker, vimentin, despite the inhibition of migration in the epithelial dominant MCF7 cell line. Together, these data indicates that GRHL2 overexpression leads to a complex phenotype that cannot be defined by a binary epithelial or mesenchymal state. Further analyses are aimed at understanding the pleiotropic roles GRHL2 plays in ER+ tumor progression. Presentation: Thursday, June 15, 2023

A commentary on 'Nomogram of conditional survival probability of long-term survival for metastatic colorectal cancer: a real-world data retrospective cohort study from SEER database'.

A commentary on 'Nomogram of conditional survival probability of long-term survival for metastatic colorectal cancer: a real-world data retrospective cohort study from SEER database'.

Thrombectomy for proximal intracranial occlusion beyond 24 hours after time last seen normal: A narrative review

Endovascular thrombectomy (EVT) revolutionized the treatment for acute ischemic stroke due to large vessel occlusion (LVO). Current guidelines published by multiple academic societies recommend EVT for eligible patients who present within 24 hours of the time last seen well. However, more recent data suggests that extending this window past 24 hours produces more favorable outcomes in specific patients presenting with anterior circulation LVO. More specifically, recent observational data indicates a higher probability of functional independence, functional improvement, and long-term survival with EVT when compared to best medical management. Based on the available data, there is unclear equipoise in randomizing all patients with acute ischemic stroke due to LVO to EVT or medical management. However, for those patients with large established infarction, distal occlusions, or well beyond the 24-hour window, randomized clinical trials are called upon to determine whether there is benefit of EVT in these patient groups. In this narrative review, we will summarize the most recent data on EVT in the ultra extended window (&gt;24 hours after time last seen normal) and discuss further considerations of this treatment.