Actual Patient Survival Research Articles

Comparison of Synthetic Data Generation Techniques for Control Group Survival Data in Oncology Clinical Trials: Simulation Study.

Synthetic patient data (SPD) generation for survival analysis in oncology trials holds significant potential for accelerating clinical development. Various machine learning methods, including classification and regression trees (CART), random forest (RF), Bayesian network (BN), and conditional tabular generative adversarial network (CTGAN), have been used for this purpose, but their performance in reflecting actual patient survival data remains under investigation. The aim of this study was to determine the most suitable SPD generation method for oncology trials, specifically focusing on both progression-free survival (PFS) and overall survival (OS), which are the primary evaluation end points in oncology trials. To achieve this goal, we conducted a comparative simulation of 4 generation methods, including CART, RF, BN, and the CTGAN, and the performance of each method was evaluated. Using multiple clinical trial data sets, 1000 data sets were generated by using each method for each clinical trial data set and evaluated as follows: (1) median survival time (MST) of PFS and OS; (2) hazard ratio distance (HRD), which indicates the similarity between the actual survival function and a synthetic survival function; and (3) visual analysis of Kaplan-Meier (KM) plots. Each method's ability to mimic the statistical properties of real patient data was evaluated from these multiple angles. In most simulation cases, CART demonstrated the high percentages of MSTs for synthetic data falling within the 95% CI range of the MST of the actual data. These percentages ranged from 88.8% to 98.0% for PFS and from 60.8% to 96.1% for OS. In the evaluation of HRD, CART revealed that HRD values were concentrated at approximately 0.9. Conversely, for the other methods, no consistent trend was observed for either PFS or OS. CART demonstrated better similarity than RF, in that CART caused overfitting and RF (a kind of ensemble learning approach) prevented it. In SPD generation, the statistical properties close to the actual data should be the focus, not a well-generalized prediction model. Both the BN and CTGAN methods cannot accurately reflect the statistical properties of the actual data because small data sets are not suitable. As a method for generating SPD for survival data from small data sets, such as clinical trial data, CART demonstrated to be the most effective method compared to RF, BN, and CTGAN. Additionally, it is possible to improve CART-based generation methods by incorporating feature engineering and other methods in future work.

A novel prognostic scoring system combining the revised Tokuhashi score and the New England spinal metastasis score for preoperative evaluation of spinal metastases.

Numerous scoring systems have been developed in order to determine the prognosis of spinal metastases. Predicting as accurately as possible the life expectancy of patients with spinal metastatic disease is very important, as it's the decisive factor in selecting the optimal treatment for the patient. The Revised Tokuhashi score (RTS) and the New England Spinal Metastasis score (NESMS) are popular scoring systems used to determine the optimal treatment modality. However, they sometimes provide conflicting results. We propose a novel prognostic scoring system, which combines the RTS and NESMS scores in order to predict with greater accuracy the prognosis. We retrospectively reviewed the data of 64 patients with spinal metastasis enrolled between 2012 and 2021 in the Department of Orthopedic Surgery-Spine, Hôpital Maisonneuve-Rosemont, Montréal, Que. The new score per patient was calculated as a combination of the RTS of each patient and the patient's corresponding NESMS. The new score was then compared to the actual patient survival period and divided into 3 categories: Low, Moderate and Good prognosis. We then compared the accuracy of our new score to RTS. In the Low Prognosis group, the reliability of predicting the prognosis was 51.9% in 27 patients. In the Moderate Prognosis group, the reliability of predicting the prognosis was 95.8% in 24 patients. In the Good Prognosis group, the reliability of predicting the prognosis was 100% in 13 patients. Our new score was found more accurate than RTS as the R2 parameter corresponding to the new score was significantly increased compared to the same parameter corresponding to the RTS score indicating a higher percentage of survival predictability for the new score as compared to the RTS score. This study demonstrates that a new prognostic scoring system, which would combine the RTS and the NESMS, is promising in providing an improved accuracy for predicting the actual patient survival, especially for the moderate and good prognosis patients. An appropriate prospective investigation with a larger sample size should be conducted in order to further investigate the validity of this novel scoring system and its overall predictive value.

Common hepatic artery lymph node metastasis in pancreatic ductal adenocarcinoma: an analysis of actual survival

BackgroundThe common hepatic artery lymph node represents a second-echelon node for tumors in the head of the pancreas. Although early studies suggested survival was comparable between the common hepatic artery lymph node and remote metastasis in pancreatic ductal adenocarcinoma, whether the lymph node is associated with adverse survival remains equivocal. Here, we examined a prospective cohort of patients calculating actual survival to better understand implications of this specific lymph node metastasis. MethodsWe studied 215 patients with pancreatic head pancreatic ductal adenocarcinoma, who underwent pancreaticoduodenectomies at a single institution from 2010 to 2017 wherein the common hepatic artery lymph nodes were excised. We performed actual and actuarial overall survival and disease-free survival analyses, with subsequent univariate and multivariate analyses in node-positive patients. ResultsOf this cohort, 7.3% of patients had involvement of the common hepatic artery lymph node, and all of them had metastatic spread to first echelon nodes. Actual median survival of patients with no lymph node involvement was 49 months. In patients with any nodal involvement, the survival was no different when comparing the lymph node positive and negative (13 and 20 months, respectively). Univariate and multivariate analyses likewise attached no significance to the lymph node metastasis, while demonstrating worse survival with positive margin status and poorly differentiated histology. Our disease-free survival analyses yielded similar results. ConclusionsWe found no difference in actual survival in node-positive patients regardless of the common hepatic artery lymph node involvement and recommend against its assessment in prognosticating survival or guiding surgical treatment.

Identification of telomere-associated gene signatures to predict prognosis and drug sensitivity in glioma

ObjectiveGliomas are a heterogeneous group of brain tumors with distinct biological and clinical properties, leading to significant mortality and morbidity. Emerging evidence shows telomere maintenance has implicated in glioma susceptibility and prognosis. In this study, we comprehensively analyzed gene signatures related to telomere maintenance in glioma and their predictive values for predicting the prognosis and drug sensitivity in glioma. MethodsWe initially identified telomere-related genes differentially expressed between low-grade glioma (LGG) and glioblastoma (GBM) and accordingly developed a risk model by univariate and multivariate Cox analysis to assess the expressions of telomere-related genes across the risk groups. Finally, to assess these genes in immune function the anti-tumor medications often used in the clinical treatment of glioma, we computed immune cell infiltration analysis and drug sensitivity analysis. ResultsThe consensus clustering analysis identified 20 telomere-related genes which split LGG patients into two distinct subtypes. The patient survival, the expressions of key telomere-related DEGs, and immune cell infiltration significantly differed between Cluster 1 and Cluster 2. The LASSO risk model [riskScore=(0.086)*HOXA7+(0.242)*WEE1+(0.247)*IGF2BP3+(0.052)*DUSP10] showed significant differences regarding the 1-, 3-, 5-year overall survival, immune cell infiltration, and drug sensitivity between high- and low-risk groups. The predictive nomogram constructed to quantify the survival probability of each sample at 1, 3, and 5 years was consistent with the actual patient survival. ConclusionOur comprehensive characterization of telomere-associated gene signatures in glioma reveals their possible roles in the development, tumor microenvironment, and prognosis. The study provides some suggestive relationships between four telomere-related genes (HOXA7, WEE1, IGF2BP3, and DUSP10) and glioma prognosis.

Predicting 5-year survival after kidney transplantation in Colombia using the survival benefit estimator tool.

A complex relationship between donor and recipient characteristics influences kidney transplant (KT) success. A tool developed by Bae S. et al. (Survival Benefit Estimator, SBE) helps estimate post-KT survival. We aim to evaluate the predictive performance of the SBE tool in terms of 5-year patient survival after a kidney transplant. A retrospective cohort study of all deceased-donor KT recipients between January 2009 to December 2021. A descriptive analysis of clinical and sociodemographic characteristics was performed. The SBE online tool was used to calculate the predicted patient survival (PPS) and the survival benefit at five years post-KT. Comparisons between predictive vs. actual patient survival were made using quintile subgroups. Three Cox regression models were built using PPS, EPTS, and KDPI. A total of 1145 recipients were evaluated. Mortality occurred in 157 patients. Patient survival was 86.2%. Predictive survival for patients if they remained on the waiting list was 70.6%. The PPS was 89.3%, which results in a survival benefit (SB) of 18.7% for our population. Actual survival rates were lower than the predicted ones across all the quintiles. In unadjusted analysis, PPS was a significant protective factor for mortality (HR 0.66), whereas EPTS (HR 8.9) and KDPI (HR 3.25) scores were significant risk factors. The discrimination of KDPI, PPS, and EPTS scores models were 0.59, 0.65, and 0.66, respectively. SBE score overestimated actual survival rates in our sample. The discrimination power of the score was moderate, although the utility of this tool may be limited in this specific population.

Meta-analyses of factors associated with long-term survival after resection of pancreatic ductal adenocarcinoma.

4165 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. Long-term survival (>5 years, LTS) is rarely seen even after ‘curative-intent’ resection. With improved systemic control via effective systemic therapies, LTS is now being reported more frequently. However, our understanding of LTS in PDAC remains limited. The aim of the current study was to perform a systematic review and meta-analysis to quantify the associations between various clinicopathological factors and LTS following resection of PDAC. Methods: The PubMed, Embase, Scopus, and Cochrane CENTRAL databases were systematically searched for articles reporting actual patient survival data. Two reviewers independently screened and reviewed articles, extracted relevant data, and assessed the risk of bias in included studies using the Newcastle-Ottawa scale (NOS). Data that compared patients who achieved LTS after resection with those who did not were extracted from the included studies. Meta-analyses using a random effects model were conducted to identify associations between LTS and various patient, tumor, and treatment related factors. Results: Overall, 33 studies with 46,981 patients after resection of PDAC were included. Most articles received a ‘good’ NOS assessment, indicating acceptable risk of bias. The median rate of LTS was 15.27% (IQR: 9.47-20.72). Multiple clinicopathological factors were found to be associated with LTS, including tumor grade (OR: 0.40, 95%CI: 0.31-0.52), tumor stage (OR: 0.36, 95%CI: 0.31-0.41), and margin status (OR: 0.43, 95%CI: 0.36-0.50). Factors that were not associated with LTS included patient age, tumor size, tumor location, or genetic mutations. Notably, adjuvant therapy (OR: 1.68, 95%CI: 1.24-2.28) but not neoadjuvant therapy (OR: 1.08, 95%CI: 0.62-1.87) were associated with LTS. Conclusions: This meta-analysis revealed that 15% of patients achieved LTS after resection of PDAC. Multiple clinicopathological factors are associated with LTS whereas presence of ‘traditional’ negative prognostic factors does not rule out LTS. Further studies are required to identify robust predictors of LTS in resected PDAC. [Table: see text]

Pretransplant C-peptide Levels and Pancreas Transplant Outcomes: Risk and Reward.

We read with interest the report by Parajuli et al1, chronicling the University of Wisconsin experience in simultaneous pancreas-kidney transplantation (SPKT) according to the pretransplant fasting serum C-peptide levels. The authors demonstrated that higher pretransplant C-peptide levels predicted the risk of a composite outcome (combination of pancreas graft failure according to the United Network for Organ Sharing definition and pancreas graft dysfunction defined as initiation of any antidiabetic agent) posttransplant in patients with a type 2 diabetes phenotype.1,2 Recipients were categorized into 3 groups based on pretransplant fasting serum C-peptide levels: low (≤2 ng/mL, n = 14), medium (>2–8 ng/mL, n = 47), and high (>8 ng/mL, n = 15). The uncensored composite outcome of pancreas graft failure or dysfunction occurred in 0% in the low, 23% in the medium, and 33% of patients in the high C-peptide groups, respectively, suggesting that higher levels of pretransplant C-peptide are associated with inferior posttransplant outcomes. These findings confirm our recent report based on a case-controlled, single-center, retrospective study of 46 SPKT patients with pretransplant fasting serum C-peptide levels ≥2.0 ng/mL compared with 46 control patients (C-peptide level <0.5 ng/mL) matched for recipient age, gender, race, and transplant date.3 In our study, we likewise reported inferior mid-term outcomes in the group with higher pretransplant C-peptide levels. In our overall SPKT experience, we have 205 patients with a minimum of 5-y follow-up. Using the above C-peptide categories as per the Wisconsin study, we identified 166 patients in the low, 32 patients in the medium, and 7 patients in the high C-peptide groups. Five-y actual (uncensored) patient and graft survival rates were as follows: patient (91% low versus 93.8% medium versus 85.7% high) and kidney (80.7% versus 71.9% versus 71.4%), respectively. Using the composite end point of pancreas graft failure or dysfunction, pancreas outcomes were 25.3% low versus 34.4% medium versus 71.4% high C-peptide (P = 0.10). Similar to the Wisconsin study, we are limited by the small sample size in the high pretransplant C-peptide group but the findings indicate a trend toward a greater need for supplemental antidiabetic therapy in patients with higher pretransplant C-peptide levels. Unfortunately, what is missing from these studies is a better characterization of patients with partial pancreas allograft function (dysfunction) who continue to be free from wide glycemic excursions and do not experience hypoglycemia (despite the need for antidiabetic therapy) because of preserved counterregulatory function of the pancreas allograft.4 In our experience, we identified posttransplant weight gain, insulin resistance, and rejection as potential mitigating factors to explain these inferior outcomes. Consequently, we recommend greater emphasis on weight management strategies, behavioral modification, nutritional counseling, structured physical training programs, timely adjustments in (and use of less diabetogenic) immunosuppression, more intense long-term monitoring by the transplant center, and increased use of novel antidiabetic agents such as Glucagon-like peptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors when indicated in this unique population. We congratulate the authors on this excellent study and agree that these findings should not be an impetus to limit access to pancreas transplantation but rather help guide clinical decision-making and optimize posttransplant management.

Estimation of Survival in Patients with Glioblastoma Using an Online Calculator at a Tertiary-Level Hospital in Mexico.

Background The mean survival duration of patients with glioblastoma after diagnosis is 15 months (14-21 months), while progression-free survival is 10 months (+/- one month). Although there are well-defined overall survival statistics for glioblastoma, individual survival prediction remains a challenge. Therefore, there is a need to validate an accessible and cost-effective prognostic toolto provide valuable data for decision-making. This study aims to calculate the mean survival of patients with glioblastoma at a tertiary-level hospital in Mexico using the online glioblastoma survival calculator developed by researchers at Harvard Medical School & Brigham and Women's Hospital and compare it with the actual mean survival. Methodology We conducted a retrospective observational study of patients who received a histopathological diagnosis of glioblastoma from the National Institute of Neurology and Neurosurgery "Manuel Velasco Suárez" between 2015 and 2021. We included 50 patients aged 20-83 years, with a tumor size of 15-79 mm, and who had died 30 days after surgery. Patient survival was estimated using the online calculator developed at Harvard Medical School & Brigham and Women's Hospital. The estimated mean survival was then compared with the actual mean survival of the patient. Atwo-tailed equivalence test for paired samples was performed to conduct this comparison. A value of p < 0.05 was considered significant. Results The mean age of the sample was 55.5 years (confidence interval (CI) 95%, 52.61-58.71). The mean tumor size in our sample was 49.12 mm (±14.9mm). We identified a difference between the mean estimated survival and the mean actual survival of -1.37 months (CI 95%; range of -3.7 to +0.9). After setting the inferior (IL) and superior limits (SL) at -3.8 and +3.8 months, respectively, we found that the difference between the mean estimated survival and the actual mean survival is within the equivalence interval (IL: p = 0.0453; SL: p = 0.0002). Conclusions The actual survival of patients diagnosed with glioblastoma at the National Institute of Neurology and Neurosurgery was equivalent to the estimated survival calculated by the online prediction calculator developed at Harvard Medical School & Brigham and Women's Hospital. This study validates a practical, cost-effective, and accessible tool for predicting patient survival, contributing to significant support for medical and personal decision-making for glioblastoma management.

Treating Type 1 Diabetes by Pancreas Transplant Alone: A Cohort Study on Actual Long-term (10 Years) Efficacy and Safety.

Physiologically regulated insulin secretion and euglycemia are achievable in type 1 diabetes (T1D) by islet or pancreas transplantation. However, pancreas transplant alone (PTA) remains a debated approach, with uncertainties on its relative benefits and risks. We determined the actual long-term (10 y) efficacy and safety of PTA in carefully characterized T1D subjects. This is a single-center, cohort study in 66 consecutive T1D subjects who received a PTA between April 2001 and December 2007, and were then all followed until 10 y since transplant. Main features evaluated were patient survival, pancreas graft function, C-peptide levels, glycemic parameters, and the function of the native kidneys. Ten-year actual patient survival was 92.4%. Optimal (insulin independence) or good (minimal insulin requirement) graft function was observed in 57.4% and 3.2% of patients, respectively. Six (9.0%) patients developed stage 5 or 4 chronic kidney disease. In the remaining individuals bearing a successful PTA, estimated glomerular filtration rate (eGFR) decline per year was -2.29 ± 2.69 mL/min/1.73 m2. Reduction of eGFR at 1 y post-PTA was higher in those with pre-PTA hyperfiltration and higher HbA1c concentrations; eGFR changes afterward significantly correlated with diabetes duration. In recipients with normoglycemia at 10 y, 74% of normoalbuminuric or microalbuminuric subjects pre-PTA remained stable, and 26% progressed toward a worse stage; conversely, in 62.5% of the macroalbuminuric individuals albuminuria severity regressed. These long-term effects of PTA on patient survival, graft function, and the native kidneys support PTA as a suitable approach to treat diabetes in selected T1D patients.

Do pretransplant C-peptide levels predict outcomes following simultaneous pancreas-kidney transplantation? A matched case-control study.

Following simultaneous pancreas-kidney transplantation (SPKT), survival outcomes are reported as equivalent in patients with detectable pretransplant C-peptide levels (Cp+) and a "type 2″ diabetes mellitus (DM) phenotype compared to type 1 (Cp negative [Cp-]) DM. We retrospectively compared 46 Cp+ patients pretransplant (≥2.0ng/mL, mean 5.4ng/mL) to 46 Cp- (level<0.5ng/mL) case controls matched for recipient age, gender, race, and transplant date. Early outcomes were comparable. Actual 5-year patient survival (91% versus 94%), kidney graft survival (69% versus 86%, p=.15), and pancreas graft survival (60% versus 86%, p=.03) rates were lower in Cp+ versus Cp- patients, respectively. The Cp+ group had more pancreas graft failures due to insulin resistance (13% Cp+ versus 0% Cp-, p=.026) or rejection (17% Cp+ versus 6.5% Cp-, p=.2). Post-transplant weight gain>5kg occurred in 72% of Cp+ versus 26% of Cp- patients (p=.0001). In patients with functioning grafts, mean one-year post-transplant HbA1c levels (5.0 Cp+ versus 5.2% Cp-) were comparable, whereas Cp levels were higher in Cp+ patients (5.0 Cp+ versus 2.6ng/mL Cp-). In this matched case-control study, outcomes were inferior in Cp+ compared to Cp- patients following SPKT, with post-transplant weight gain, insulin resistance, and rejection as potential mitigating factors.

Survival of Chronic Myeloid Leukemia Patients in Comparison to General Population in the Tyrosine Kinase Inhibitors Era: A US Population Based Study

Background:Chronic myelogenous leukemia (CML) is a myeloproliferative neoplasm characterized by the presence of the BCR-ABL fusion gene resulting in activation of the ABL tyrosine kinase. Treatment of CML has been revolutionized by the introduction of ABL tyrosine kinase inhibitors (TKI) since 2001, leading many patients to reach deep remissions. Recent reports based on clinical trial series and international registries suggest that a substantial subset of CML patients treated with TKIs may have similar survival to that of the general population, but those studies are somewhat limited by the small sample size, possible selection bias or less diverse population. We intend to compare the survival of US patients with CML with the general population.Methods:We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to select adult patients diagnosed with BCR-ABL positive CML between 2001 (introduction of TKIs) and 2014 (most recent year with follow up available). Cases with unknown age or survival data and those informed only by autopsy or death certificate were excluded. For different subsets of patients we described relative survival (RS), the ratio between actual survival of CML patients and the survival expected in a population, with same age, sex, race/ethnicity characteristics. We subsequently performed sensitive analysis to identify a time landmark beyond which CML patients are expected to have survival more closely resembling the survival of the general population. These analyses were performed for different sex, age, race/ethnicity and insurance-status subsets. Analysis per insurance-status was partially limited by unavailability of this information for cases diagnosed before 2007. The analysis was performed using the survival function in SEER*Stat v 8.3.4.Results:There were 3,946 patients included in the analysis with a median follow up of 72 months. Of these, 2,253 (57.1%) were males and 1,693 (42.9%) were females; 1,738 patients (44.0%) were younger than 50 years of age, 1,204 (30.5%) were between ages 50 and 64, and 1,004(25.4%) were 65 or older. There were 2,514 (63.7%) Non-Hispanic Whites (NHW), 602 (15.2%) Hispanics and 426 (10.8%) Non-Hispanic Blacks (NHB). Relative survival for the different subsets is displayed in the Figure, panel A. Ten year RS for male patients was 71.1% (95% C.I. 66.8%-74.9%) vs 74.7% (95% C.I. 70.2%-78.7%) for female patients (P=0.118). Ten year RS for patients 65 or older was 46.9% (95% C.I. 37.3%-55.9%), inferior to RS of patients younger than 50 (80.5%, 95% C.I. 77.1%-83.4%, P<0.001) and to RS of patients 50-64 (77.0%, 95% C.I. 71.2%-81.8%, P<0.001). There was no significant difference in RS at 10 years according to race/ethnicity, reaching 73.7% (95% C.I. 69.8%-77.2%) for NWH, 68.0% (95% C.I. 60.0-74.7%, P=0.09 for comparison with NHW) for Hispanics and 64.8%(95% C.I. 53.8%-73.8%, P=0.05 for comparison with NHW) for NHB. RS at 6 years from diagnosis was 88.4% (95% C.I. 85.4%-90.8%) for insured patients vs. 85.7% (95% C.I. 77.0%-91.3%, P=0.237 for comparison with insured) for uninsured patients and 70.6% (95%, C.I. 61.3%-78.2%, P<0.001 for comparison with insured) for Medicaid beneficiaries. Sensitive analysis identified 7 years from diagnosis as the time landmark that best identifies patients with subsequent survival resembling the general population (Figure, panel B). Seven-year survivors of CML have 12-year RS that approaches 100% for most subsets, except males and patients 65 and older.Conclusion:RS of CML patients in US is not similar to the general population possibly influenced by outcomes disparities by age and insurance status. For 7-year survivors of CML, subsequent survival approaches the general population for younger and female patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

External validation of multimodal termination of resuscitation rules for out-of-hospital cardiac arrest patients in the COVID-19 era

BackgroundFutile resuscitation for out-of-hospital cardiac arrest (OHCA) patients in the coronavirus disease (COVID)-19 era can lead to risk of disease transmission and unnecessary transport. Various existing basic or advanced life support (BLS or ALS, respectively) rules for the termination of resuscitation (TOR) have been derived and validated in North America and Asian countries. This study aimed to evaluate the external validation of these rules in predicting the survival outcomes of OHCA patients in the COVID-19 era.MethodsThis was a multicenter observational study using the WinCOVID-19 Daegu registry data collected during February 18–March 31, 2020. The subjects were patients who showed cardiac arrest of presumed cardiac etiology. The outcomes of each rule were compared to the actual patient survival outcomes. The sensitivity, specificity, false positive value (FPV), and positive predictive value (PPV) of each TOR rule were evaluated.ResultsIn total, 170 of the 184 OHCA patients were eligible and evaluated. TOR was recommended for 122 patients based on the international basic life support termination of resuscitation (BLS-TOR) rule, which showed 85% specificity, 74% sensitivity, 0.8% FPV, and 99% PPV for predicting unfavorable survival outcomes. When the traditional BLS-TOR rules and KoCARC TOR rule II were applied to our registry, one patient met the TOR criteria but survived at hospital discharge. With regard to the FPV (upper limit of 95% confidence interval < 5%), specificity (100%), and PPV (> 99%) criteria, only the KoCARC TOR rule I, which included a combination of three factors including not being witnessed by emergency medical technicians, presenting with an asystole at the scene, and not experiencing prehospital shock delivery or return of spontaneous circulation, was found to be superior to all other TOR rules.ConclusionAmong the previous nine BLS and ALS TOR rules, KoCARC TOR rule I was most suitable for predicting poor survival outcomes and showed improved diagnostic performance. Further research on variations in resources and treatment protocols among facilities, regions, and cultures will be useful in determining the feasibility of TOR rules for COVID-19 patients worldwide.

Validation of Online Prognostication Model that Predicts Survival for Women with Early Breast Cancer in Egypt

&#x0D; Introduction: Breast Cancer is estimated to be the most common female cancer in Egypt. The decision on adjuvant therapy in early breast cancer is complex and requires many considerations. PREDICT is an online prognostication tool for early breast cancer. It was first revealed in 2011 and it has been widely used. This study aimed to illustrate the applicability of this model on Egyptian patients. Methods: This study included 128 female patients treated for early breast cancer with surgery and adjuvant therapy in Alexandria, Egypt in 2005 to validate the efficacy of PREDICT as an online prognostication model to estimate survival in those patients. Patients’ data were obtained from the archives of the Department of Clinical Oncology, Faculty of Medicine, and the Department of Cancer Management and Research, Medical Research Institute, University of Alexandria, Egypt. Patients’ data were manually entered into the prognostication model and the predicted survival results obtained were compared to the actual survival of study patients. Results: The predicted number of survivors after 5 years in the entire cohort was 125 (97.7%) compared to 123 (96.1%) actual survivors. The difference was 1.6% which was not significant (p= 0.625). The predicted number of survivors after 10 years in the entire cohort was 77 (60.2%) compared to 81 (63.3%) actual survivors. The difference was -3.1% which was not significant (p= 0.671). Conclusion: PREDICT accurately predicts 5-year and 10-year OS in the entire study population. This validates the use of this online model to aid in the decision as regard systemic therapy.

LIVER TRANSPLANTATION IN THE UNITED ARAB EMIRATES: INITIAL TWO-YEAR EXPERIENCE

Background: Passage of the landmark brain death law in the United Arab Emirates (UAE) in May 2017 enabled the establishment of solid organ transplantation, including liver transplant (LT). The shortage of deceased donor (DD) organs mandated the development of living donor LT (LDLT) as well. We report our initial experience following the formal establishment of LT in the UAE. Materials and Methods: The first DDLT and LDLT in the UAE were performed on Feb 1 and July 29, 2018 respectively.Since inception, a total of 11 DDLTs and 12 LDLTs have been performed – 8 left-lobe and 4 right-lobe LDLTs. Five (22%) recipients were expatriates (four of whom underwent DDLT), while the remainder were UAE nationals. Primary indication for LT was NAFLD (48%). All four (17%) recipients with HCC had cirrhosis from NAFLD. Two recipients (9%) each underwent LT for PSC, Wilson’s disease, HBV and AIH. Two emergent LTs were performed - one for fulminant Wilson’s disease (left lobe LDLT), and the other for early graft dysfunction following LDLT. Mean graft to recipient weight ratio (GRWR) for LDLTs was 0.92 (range: 0.64 – 1.30). GRWR for left and right lobe grafts were 0.83 and 1.1 respectively. All but one of the left lobe recipients underwent splenectomy. All recipients underwent duct to duct biliary reconstruction. Results: All living donors recovered uneventfully with a median duration of hospitalization of 6.5 days (6 and 8 days respectively for left and right lobe donors). Two recipients underwent unplanned re-operation within 30 days of LT. Four (17%) recipients developed acute cellular rejection. All episodes were mild-moderate and responded to either escalation of immunotherapy or pulse steroids, with the exception of one severe episode due to non-compliance. CMV viremia was noted in 11, with invasive disease (retinitis) occurring only in one recipient. Four DDLT and 6 LDLT recipients developed biliary strictures, all of which were anastomotic in nature and responded promptly to endoscopic therapy, with the exception of four post-LDLT strictures that required more than 3 ERCPs. 14 recipients have completed at least a year of follow up, with one-year actual graft and patient survival of 100% and 100% respectively. The overall patient and graft survival for the 22 patients and 23 grafts were 100% and 96% respectively. The solitary graft loss occurred due to portal vein steal syndrome via coronary vein shunt following left lobe LDLT causing graft dysfunction, necessitating emergent DDLT. Conclusions: We report the successful establishment of LT from living and deceased donors in the UAE and our results after the first two years. Ongoing efforts to overcome shortage of deceased donor organs include creation of a national digital donor registry, regional organ sharing agreements for critically ill patients and establishment of donation after circulatory death. These initiatives will enable us to build on our early success and meet the anticipated increase in demand for LT related to the growing burden of NAFLD in the region.

Survival prediction for oral tongue cancer patients via probabilistic genetic algorithm optimized neural network models.

High throughput pre-treatment imaging features may predict radiation treatment outcome and guide individualized treatment in radiotherapy (RT). Given relatively small patient sample (as compared with high dimensional imaging features), identifying potential prognostic imaging biomarkers is typically challenging. We aimed to develop robust machine learning methods for patient survival prediction using pre-treatment quantitative CT image features for a subgroup of head-and-neck cancer patients. Three neural network models, including back propagation (BP), Genetic Algorithm-Back Propagation (GA-BP), and Probabilistic Genetic Algorithm-Back Propagation (PGA-BP) neural networks were trained to simulate association between patient survival and radiomics data in radiotherapy. To evaluate the models, a subgroup of 59 head-and-neck patients with primary cancers in oral tongue area were utilized. Quantitative image features were extracted from planning CT images, a novel t-Distributed Stochastic Neighbor Embedding (t-SNE) method was used to remove irrelevant and redundant image features before fed into the network models. 80% patients were used to train the models, and remaining 20% were used for evaluation. Of the three supervised machine-learning methods studied, PGA-BP yielded the best predictive performance. The reported actual patient survival interval of 30.5 ± 21.3 months, the predicted survival times were 47.3 ± 38.8, 38.5 ± 13.5 and 29.9 ± 15.3 months using the traditional PCA. Combining with the novel t-SNE dimensionality reduction algorithm, the predicted survival intervals are 35.8 ± 15.2, 32.3 ± 13.1 and 31.6 ± 15.8 months for the BP, GA-BP and PGA-BP neural network models, respectively. The work demonstrated that the proposed probabilistic genetic algorithm optimized neural network models, integrating with the t-SNE dimensionality reduction algorithm, achieved accurate prediction of patient survival. The proposed PGA-BP neural network, integrating with an advanced dimensionality reduction algorithm (t-SNE), improved patient survival prediction accuracy using pre-treatment quantitative CT image features of head-and-neck cancer patients.

Atypical Hemolytic Uremic Syndrome After Kidney Transplantation: Lessons Learned From the Good, the Bad, and the Ugly. A Case Series With Literature Review

Atypical hemolytic uremic syndrome (aHUS) after kidney transplantation is rare and carries a grave outcome. We present a single-center experience of all aHUS cases since the program’s inception. Six patients were diagnosed with aHUS, all after kidney transplants, except for 1 patient. All had nonreactive crossmatches. Delayed graft function (DGF) occurred in 2 patients. Five patients developed aHUS after transplant; 4 (80%) of these patients manifested aHUS ≤ 14 days. All were confirmed by allograft biopsy. Genetic testing was abnormal in all patients except for 1 patient. Actual patient and graft survival during the first year was 100% and 83.3%, respectively. A single graft was lost early in the study secondary to aHUS (eculizumab was not used in the treatment process). Prophylactic and therapeutic use of eculizumab salvaged all other cases. At 1 year, mean creatinine level was 1.9 mg/dL (range, 1.3-2.5). After 6 months of eculizumab treatment (halted in 2 cases) 1 patient had recurrence 2 months later and eculizumab was restarted. However, graft function continued to worsen, and the graft was ultimately lost at 20 months after kidney transplantation. High index of suspicion, prompt diagnosis, and utilization of eculizumab are key to successful salvage of allografts in cases of aHUS after kidney transplantation. aHUS can be prevented by prophylactic use of eculizumab. It still needs to be determined when and if eculizumab therapy can be safely discontinued.

Pacemaker therapy in very elderly patients: survival and prognostic parameters of single center experience.

BackgroundPermanent pacing is the therapy of choice for treating severe and/or symptomatic bradyarrhythmias. The number of very elderly patients receiving pacemakers is increasing and little is known about survival in this specific subgroup. This study is aimed at assessing the actual survival of patients requiring pacing therapy at age > 85 years and investigating variables associated with death.MethodsBetween 2010 and 2017, 572 patients aged ≥ 85 years underwent pacemaker implantation for conventional bradycardia indications in Department of Cardiology, S. Chiara Hospital, Italy.ResultsThirty percent of patients were ≥ 90-year-old and comorbidities were frequent. Fifty-seven percent of patients required pacing for prognostic reasons (acquired atrioventricular block), and the remaining for relief of bradycardia symptoms. A dual-chamber pacemaker was implanted in 34% of patients. The 5-year survival was 45% (standard error: 3%), and the 8-year survival was 26% (standard error: 4%). The risk of death was similar in patients who received pacemaker for symptom relief and for prognostic reasons in the overall population (HR = 1.19, 95% CI: 0.93–1.52, P = 0.156), as well as in the ≥ 90-year-old group (HR = 1.39, 95% CI: 0.92–2.11, P = 0.102). At multivariate analysis, following variables were associated with death: higher age, lower ejection fraction, dementia/dysautonomia and diagnosis of cancer. The pacing indication and the implantation of a single chamber pacemaker were not associated with worse prognosis.ConclusionsThis study showed a good life expectancy in patients aged ≥ 85 years who received a pacemaker. Strong risk factors for all-cause death were non-cardiac. Pacemaker therapy seems a clinically effective therapeutic option to improve survival and to control bradyarrhythmia-related symptoms in very elderly patients.

Management of Biliary Atresia in France 1986 to 2015: Long-term Results.

This study analyses the prognosis of biliary atresia (BA) in France since 1986, when both Kasai operation (KOp) and liver transplantation (LT) became widely available. The charts of all patients diagnosed with BA born between 1986 and 2015 and living in France were reviewed. A total of 1428 patients were included; 1340 (94%) underwent KOp. Total clearance of jaundice (total bilirubin ≤20 μmol/L) was documented in 516 patients (39%). Age at KOp (median 59 days, range 6-199) was stable over time. Survival with native liver after KOp was 41%, 35%, 26%, and 22% at 5, 10, 20, and 30 years, stable in the 4 cohorts. 25-year survival with native liver was 38%, 27%, 22%, and 19% in patients operated in the first, second, third month of life or later, respectively (P = 0.0001). Center caseloads had a significant impact on results in the 1986 to 1996 cohort only. 16%, 7%, 7%, and 8% of patients died without LT in the 4 cohorts (P = 0.0001). A total of 753 patients (55%) underwent LT. Patient survival after LT was 79% at 28 years. Five-year patient survival after LT was 76%, 91%, 88%, and 92% in cohorts 1 to 4, respectively (P < 0.0001). Actual BA patient survival (from diagnosis) was 81%. Five-year BA patient survival was 72%, 88%, 87%, and 87% in cohorts 1986 to 1996, 1997 to 2002, 2003 to 2009, and 2010 to 2015, respectively (P < 0.0001). In France, 87% of patients with BA survive nowadays and 22% reach the age of 30 years without transplantation. Improvement of BA prognosis is mainly due to reduced mortality before LT and better outcomes after LT.

Prediction of survival after surgical management of femoral metastatic bone disease – A comparison of prognostic models

BackgroundOperative fixation for femoral metastatic bone disease is based on the principles of reducing pain and restoring function. Recent literature has proposed a number of prognostic models for appendicular metastatic bone disease. The aim of this study was to compare the accuracy of proposed soring systems in the setting of femoral metastatic bone disease in order to provide surgeons with information to determine the most appropriate scoring system in this setting. MethodsA retrospective cohort analysis of patients who underwent surgical management of femoral metastatic bone disease at a single institution were included. A pre-operative predicted survival for all 114 patients was retrospectively calculated utilising the revised Katagiri model, PathFx model, SSG score, Janssen nomogram, OPTModel and SPRING 13 nomogram. Univariate and multivariate Cox regression proportional hazard models were constructed to assess the role of prognostic variables in the patient group. Area under the receiver characteristics and Brier scores were calculated for each prognostic model from comparison of predicted survival and actual survival of patients to quantify the accuracy of each model. ResultsFor the femoral metastatic bone disease patients treated with surgical fixation, multivariate analysis demonstrated a number of pre-operative factors associated with survival in femoral metastatic bone disease, consistent with established literature. The OPTIModel demonstrated the highest accuracy at predicting 12-month (Area Under the Curve [AUC] = 0.79) and 24-month (AUC = 0.77) survival after surgical management. PathFx model was the most accurate at predicting 3-month survival (AUC = 0.70) and 6-month (AUC = 0.70) survival. The PathFx model was successfully externally validated in the femoral patient dataset for all time periods. ConclusionsAmong six prognostic models assessed in the setting of femoral metastatic bone disease, the present study observed the most accurate model for 3-month, 6-month, 12-month and 24-month survival. The results of this study may be utilised by the treating surgical team to determine the most accurate model for the required time period and therefore improve decision-making in the care of patients with femoral metastatic bone disease.

Dual Kidney Transplantation from Donors at the Extremes of Age

The study purpose was to analyze outcomes in recipients of pediatric dual en bloc (PEB) kidneys from small pediatric donors (SPDs, age ≤ 3 years) and dual kidney transplants (KTs) from adult marginal deceased donors (DDs) in the context of the Kidney Donor Profile Index (KDPI). This was a single center retrospective review. Recipient selection included primary transplant, low BMI, low immunologic risk, and informed consent. All patients received antibody induction with FK/MPA/± prednisone. From 2002 to 2015, we performed 34 PEB and 73 adult dual KTs. Mean donor ages were 17months for the PEB and 59 years for the dual KTs; mean KDPIs were 73% for PEB and 83% for dual KT, and mean cold ischemia times were 21.0 hours for PEB and 26.5 hours for dual KT. Adult dual KT recipients were older (mean age 38 years for PEB and 60 years for dual KT) and had shorter waiting times (mean 25 months for PEB and 12 months for dual KT). With a mean follow-up of 7.6 years, actual patient survival (88% for PEB and 62% for dual KT) and graft survival (71% for PEB and 44% for dual KT) rates were higher in PEB compared with dual KT. Death-censored kidney graft survival rates were 77% for PEB and 58% for dual KT. Delayed graft function (DGF) rates were 15% for PEB and 23% for dual KT; incidences of DGF in single kidney transplantations from SPDs and adult nonmarginal DDs were 20% and 32%, respectively. Based on actual 5-year graft survival rates, the adjusted KDPIs for dual PEB and dual KTs were 3% and 60%, respectively. Acceptable mid-term outcomes are associated with PEB and adult dual KTs, which may expand the donor pool and prevent kidney discard. The KDPI is inaccurate for predicting outcomes from either PEB from SPDs or dual KT from adult marginal DDs, which may prevent acceptance of these organs.