Risk Stratification For Outcomes Research Articles

Improving the Assessment of Left Ventricular Diastolic Dysfunction by Including Left Atrial Strain in the Algorithm

BackgroundThe latest guidelines on echocardiographic assessment of left ventricular diastolic dysfunction (LVDD) leave a significant proportion of patients with LVDD status undetermined. We aimed to examine the implication of an alternative algorithm incorporating left atrial (LA) strain as a tiebreaker on the indeterminate LVDD category. Methods and ResultsWe included 823 patients who underwent echocardiography and cardiac magnetic resonance within 7 days. LVDD was assessed by echocardiography following contemporary guidelines and an alternative algorithm including LA reservoir strain as a tie breaker. LVDD was examined for its association with LV myocardial scar burden by cardiac magnetic resonance, and a composite outcome. There were 275 patients (33%) who had LVDD, of whom 119 had advanced grades of LVDD (grades II–III), and 117 (14%) had an indeterminate LVDD grade. When LA strain was applied at cutpoints of 18%, 24%, and 35%, patients were reclassified as normal or LVDD-dependent accordingly. Reclassification allowed a similar outcome risk stratification as the current guidelines. ConclusionsLA reservoir strain improved LVDD assessment by eliminating indeterminate status/grade while maintaining the same effective outcome stratification as the current guidelines.

Visual deterioration outcomes following optic pathway glioma treatment: a 12-year single institution retrospective study.

The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms. Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors. A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types. This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.

Abstract 348: Machine Learning Approaches for Early Outcome Risk Stratification Within 6 Hours of Cardiac Arrest

Background: Formal prognostication should be delayed at least 72 hours after cardiac arrest, but early stratification of risk severity provides important information for medical decision making, research enrollment, and precision medicine. Hypothesis: EEG-derived indices are valid biomarkers of severity of injury after cardiac arrest and contribute to early identification of risk. Aims: To assess the relative impact of early clinical data and processed EEG indices in the first 6 hours after recovery of spontaneous circulation (ROSC). Methods: Data from the first 6 hours after ROSC in the International Cardiac Arrest Registry (INTCAR) from Maine Medical Center including demographics, cardiac arrest data, admission vital signs and laboratory results and processed EEG indices at 6 hours after ROSC (bispectral index or BIS6 and suppression ratio or SR6) were extracted. Cerebral Performance Category (CPC) scores at hospital discharge and 6-month follow-up were dichotomized into good (CPC = 1-2) and poor (CPC = 3-5) outcomes. Three models were trained, one with INTCAR data, a second with EEG data, and the third combining INTCAR and BIS6-SR6. Six machine learning algorithms were applied: Catboost, random forest, Xgboost, Adaboost, support vector machine and logistic regression. Variable importance was analyzed by the decrease of impurity of random forest. Results: Among 913 included patients, median age was 59 years (95%CI 23-85), 623 (68%) were male, initial rhythm was shockable in 405 (44%) patients, and average time to ROSC was 23 (95%CI 3 - 73) minutes. Survival to hospital discharge occurred in 41% (364/893), and poor outcome occurred in 72.7% at 6-month follow-up (607/835). For CPC at discharge, area-under-the curve (AUC) was 0.85 for the combined INTCAR and EEG data, greater than INTCAR (AUC = 0.80) or EEG (AUC = 0.77). For the CPC at follow-up, the AUC was 0.88 for the combined data, greater than INTCAR (AUC = 0.83) or EEG (AUC = 0.79). Variable ranking analysis showed that BIS6 and SR6 were the two most informative features for both outcomes. Conclusions: The processed EEG variables BIS6 and SR6 significantly contribute to risk identification in the first 6 hours after ROSC, and combined with early clinical data provide reliable risk stratification.

Novel Genomic Risk Stratification Model for Primary Gastrointestinal Stromal Tumors (GIST) in the Adjuvant Therapy Era.

Traditional risk stratification schemes in gastrointestinal stromal tumors (GIST) were defined in the pre-imatinib era and rely solely on clinicopathologic metrics. We hypothesize that genomic-based risk stratification is prognostically relevant in the current era of tyrosine kinase inhibitor (TKI) therapeutics. Comprehensive mutational and copy-number profiling using MSK-IMPACT was performed. We integrated clinicopathologic and genomic parameters and utilized an elastic-net penalized Cox proportional hazards machine learning model for outcome risk stratification. A 3-tier genomic risk stratification model for recurrence-free survival (RFS) in 152 primary localized gastric and 80 small bowel GISTs was proposed. Gastric GISTs were classified as high risk if chr1p deletion or SDHB loss was present, and intermediate risk if chr14q deletion was present or KIT exon 11 mutation was absent. Small bowel GISTs were classified as high risk if MAX/MGA/MYC, CDKN2A, or RB1 alterations were present, and intermediate risk if chr1p deletion or chr5q amplification was present. Compared with conventional risk stratification, genomic risk stratification both upgrades and downgrades, suggesting that conventional risk stratification may underestimate or overtreat some high-risk and low-risk patients, respectively. Longitudinal sequencing detected most KIT-independent genomic alterations at baseline. Subanalysis in 26 SDH-deficient GISTs revealed that presence of TP53 mutations or chr1q amplifications portends worse RFS and disease-free survival. We developed a novel, next-generation genomic risk stratification model for primary gastric and small bowel GISTs, complementing traditional clinicopathologic models. Future independent validation of our model in external cohorts is essential.

567 Drivers of 30-day Readmission, Drivers of 30-day Readmission, Reoperation, and Length of Stay Following Clipping Surgery of Unruptured Aneurysms in Elderly: A National Surgical Quality Improvement Program (NSQIP) Study

INTRODUCTION: Elderly population is increasing worldwide with a consistent increase in the incidence of aneurysms. There are limited data evaluating the rate and predictors of reoperation and readmission after microsurgical clipping of unruptured aneurysms in elderly. METHODS: Data on elderly patients (≥65 years) who underwent surgical clipping of an unruptured aneurysm between 2016 and 2020 were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP). Multivariable logistic regression evaluated the independent predictors of nonroutine hospital discharge, length of stay (LOS), 30-day reoperation, and readmission. Shapley additive explanations (SHAP) were calculated for feature importance using the best-performing model. RESULTS: A total of 367 elderly patients underwent surgical clipping for both ruptured (N = 142) and unruptured aneurysms (N = 225). Among the 225 unruptured cases, 11.6% (N=26) were readmitted and 6.2% (N = 14) were reoperated after 30 days. The mean LOS is 6.53 days (± 7.15). Most patients were discharged home (N = 160; 71.1%). Morbidity and morbidity probabilities were 2.15% and 3.8%, respectively. Male sex; preoperative BUN; preoperative creatinine and preoperative platelet count (p &lt; 0.05) are more likely to predict 30-day readmission. Male sex, history of cancer , and history of COPD (p &lt; 0.05) are more likely to predict reoperation. LOS was predicted with simple aneurysm , history of sepsis; history of COPD; elective surgery; operative time and days till the operation (p &lt; 0.05). Machine learning using SHAP showed that BUN, platelet count, and sex had the highest impact on readmission; WBC, hematocrit, and sodium levels had the highest impact on reoperation; while operative time and history of sepsis had the highest impact on LOS. CONCLUSIONS: Our predictive model validates risk stratification of outcomes of patients undergoing microsurgical clipping of unruptured cerebral aneurysms in the elderly.

Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare cause of end-stage kidney disease and associated with poor outcomes after kidney transplantation from early disease recurrence. Prophylactic eculizumab treatment at the time of transplantation is used in selected patients with aHUS. We report a retrospective case note review describing transplant outcomes in patients with aHUS transplanted between 1978 and 2017, including those patients treated with eculizumab. The National Renal Complement Therapeutics Centre database identified 118 kidney transplants in 86 recipients who had a confirmed diagnosis of aHUS. Thirty-eight kidney transplants were performed in 38 recipients who received prophylactic eculizumab. The cohort not treated with eculizumab comprised 80 transplants in 60 recipients and was refined to produce a comparable cohort of 33 transplants in 32 medium and high-risk recipients implanted since 2002. Complement pathway genetic screening was performed. Graft survival was censored for graft function at last follow-up or patient death. Graft survival without eculizumab treatment is described by complement defect status and by Kidney Disease: Improving Global Outcomes risk stratification. Prophylactic eculizumab treatment improved renal allograft survival ( P = 0.006) in medium and high-risk recipients with 1-y survival of 97% versus 64% in untreated patients. Our data supports the risk stratification advised by Kidney Disease: Improving Global Outcomes. Prophylactic eculizumab treatment dramatically improves graft survival making transplantation a viable therapeutic option in aHUS.

RETROSPECTIVE REVIEW OF ORAL FOOD CHALLENGE OUTCOMES IN A MILITARY MEDICAL CENTER

<h3>Introduction</h3> Oral food challenges (OFCs) are the gold standard for diagnosis of food allergies. Limited data exists comparing OFCs across adult and pediatric subgroups in the military's health care system. The purpose of this study is to identify clinical and laboratory predictors of negative OFCs in one military medical center. <h3>Methods</h3> A retrospective chart review was performed on all open OFCs between June 2014 and June 2021 at a military tertiary center allergy clinic. <h3>Results</h3> 652 patients who underwent 1,112 OFCs were included with 910 negative total OFCs (81.8%). A total of 615 pediatric (82.0%) and 294 of adult (81.4%) passed their OFCs. Successful OFCs were highest among almond (94.4%), shrimp (94.2%), crab (91.9%), and egg (88.9%) and lowest among cashew (62.0%), walnut (63.5%), pistachio (69.7%), and pecan (71.2%). There was statistical significance in outcomes when analyzing sIgE (P <0.001), SPT wheal size (P <0.001), and history of a prior failed challenge (p=0.042). Walnut OFCs demonstrated an outcome difference between age groups (P= 0.008) – pediatrics subgroup with a higher pass rate (74.4%) compared to adults (40.0%). Higher levels of Ara h2 were also associated with a greater number of failed challenges (p= 0.045). <h3>Conclusion</h3> For OFCs performed in a military medical center which can influence career decisions, sIgE is a reliable lab marker in risk stratification of outcomes. Higher Ara h 2 was associated with failed OFCs. A significant difference in pass rate was noted between pediatric and adult populations for certain foods.

Clinical phenotypes for risk stratification in small‐for‐gestational‐age fetuses

To evaluate whether clinical phenotypes of small-for-gestational-age (SGA) fetuses can be identified and used for adverse perinatal outcome risk stratification to facilitate clinical decision-making. This was a multicenter observational cohort study conducted in two tertiary care university hospitals. SGA fetuses were classified according to maternal, fetal and placental conditions using a two-step cluster algorithm, in which fetuses with more than one condition were assigned to the cluster associated with the highest mortality risk. Delivery and perinatal outcomes were compared using chi-square test among SGA clusters, and the associations between outcomes and each cluster were evaluated by calculating odds ratios (OR), adjusted for gestational age. The study included 17 631 consecutive singleton pregnancies, of which 1274 (7.2%) were defined as SGA at birth according to INTERGROWTH-21st standards. Nine SGA clinical phenotypes were identified using a predefined conceptual framework. All delivery and perinatal outcomes analyzed were significantly different among the nine phenotypes. The whole SGA cohort had a three-times higher risk of perinatal mortality compared with non-SGA fetuses (1.4% vs 0.4%; P < 0.001). SGA clinical phenotypes exhibited three patterns of perinatal mortality risk: the highest risk was associated with congenital anomaly (8.3%; OR, 17.17 (95% CI, 2.17-136.12)) and second- or third-trimester hemorrhage (8.3%; OR, 9.94 (95% CI, 1.23-80.02)) clusters; medium risk was associated with gestational diabetes (3.8%; OR, 9.59 (95% CI, 1.27-72.57)), preterm birth (3.2%; OR, 4.65 (95% CI, 0.62-35.01)) and intrauterine growth restriction (3.1%; OR, 5.93 (95% CI, 3.21-10.95)) clusters; and the lowest risk was associated with the remaining clusters. Perinatal mortality rate did not differ between SGA fetuses without other clinical conditions (54.1% of SGA fetuses) and appropriate-for-gestational-age fetuses (0.1% vs 0.4%; OR, 0.41 (95% CI, 0.06-2.94); P = 0.27). SGA combined with other obstetric pathologies increased significantly the risk of perinatal mortality, as demonstrated by the increased odds of perinatal death in SGA cases with gestational diabetes compared to non-SGA cases with the same condition (OR, 24.40 (95% CI, 1.31-453.91)). We identified nine SGA clinical phenotypes associated with different patterns of risk for adverse perinatal outcome. Our findings suggest that considering clinical characteristics in addition to ultrasound findings could improve risk stratification and decision-making for management of SGA fetuses. Future clinical trials investigating management of fetuses with SGA should take into account clinical information in addition to Doppler parameters and estimated fetal weight. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Perioperative Inflammatory Status Predicts Mid-Term Outcomes in Patients Undergoing Femoropopliteal Paclitaxel-Coated Balloon Angioplasty

To evaluate the association of perioperative inflammatory status, as determined using the neutrophil-to-lymphocyte ratio (NLR) and high-sensitivity C-reactive protein (hs-CRP) level, with the efficacy of femoropopliteal paclitaxel-coated balloon (PCB) angioplasty. The data of 122 patients (138 limbs) were retrospectively analyzed (median follow-up time, 21months). The pre- and postoperative NLRs and hs-CRP levels were evaluated to determine their predictive value for mid-term primary patency and clinically driven target lesion revascularization (CD-TLR) during follow-up. Cox regression and Kaplan-Meier survival analyses were performed to investigate the predictive value of the inflammatory parameters and clinical risk factors. The study population had a median age of 67.2±9.2years, and 85.2±3% of them were men. Approximately, 18.0±3% of the cases were classified under Rutherford grade II; 52.5±4%, grade III; 24.6±3%, grade IV; 4.1±1%, grade V; and 0.8±0.7%, grade VI. The 12- and 24-month cumulative patency rates were 81.2±27.0% and 60.4±30.1%, respectively, and the freedom from CD-TLR rates were 90.8±19.1% and 82.5±28.3%, respectively. Severe lesion calcification was identified as an independent risk factor for CD-TLR (hazard ratio [HR]=1.51, 95% confidence interval [CI]=1.05-3.01), while hypertension was found as a protective factor for primary patency (HR=0.54, 95% CI=0.30-0.93). The patients with Trans-Atlantic Inter-Society Consensus (TASC) C/D lesions had more than a 2-fold increased adjusted risk of both primary patency loss and CD-TLR compared with those with TASC A/B lesions (HR=2.44 for primary patency loss; HR=2.51 for CD-TLR). The perioperative NLRs and hs-CRP levels were stratified into three grades. The patients with a higher preoperative hs-CRP level (>9.2 vs. 0.6-9.2 vs. <0.6mg/L by each tertile) had a 2.4-fold increased adjusted risk of primary patency loss compared with those with a lower preoperative hs-CRP level. The patients with a higher hs-CRP level on the first postoperative day (>13.0 vs. 7.7-13.0 vs. <7.7mg/L by each tertile) had a 1.8-fold increased adjusted risk of primary patency loss compared with those with a lower hs-CRP level. In contrast, the patients with a higher NLR at 4-6hr postoperatively (>3.6 vs. 2.5-3.6 vs. <2.5 by each tertile) showed better primary patency (adjusted HR=0.57) than did those with a lower NLR. A higher hs-CRP level on the first postoperative day was the only inflammatory marker associated with a high risk of CD-TLR (adjusted HR=2.37). Perioperative inflammatory status serves as a valuable prognostic parameter for assessing the potential risk stratification of outcomes after paclitaxel-coated balloon (PCB) angioplasty.

Use of the Progression of Adapted Diabetes Complications Severity Index to Predict Acute Coronary Syndrome, Ischemic Stroke, and Mortality in Asian Patients with Type 2 Diabetes Mellitus: A Nationwide Cohort Investigation

BackgroundWe report on a retrospective population study aimed at identifying and validating the progression of adapted Diabetes Complications Severity Index (DCSI) for acute coronary syndrome (ACS), ischemic stroke, and mortality in Asian people with type 2 diabetes mellitus (DM). MethodsUtilizing a Taiwanese national dataset, we included 84 450 type 2 diabetic individuals between 2000 and 2011. The area under the receiver operating characteristic curve (C statistics of logistic model) and the C statistics of the Cox model were used to evaluate whether the progression of diabetic complication status could be a predictor of ACS, ischemic stroke, and death. The optimum threshold for adverse outcomes risk stratification were obtained using Youden's J statistic as the cutoff that gives the highest threshold. ResultsAmong the study patients, the C statistics of the logistic model of the progression of the score predictive of ACS, ischemic stroke, and death were 0.72 (95% confidence interval [CI]: 0.71-0.73), 0.84 (95% CI: 0.84-0.85), and 0.66 (95% CI: 0.65-0.67), respectively. The progression of adapted DCSI had moderate discrimination for ACS, ischemic stroke, and death (C statistics = 0.71, 0.72, and 0.75, respectively) based on Cox regression analysis (Harrell C). The optimum threshold of the progression of the score for ACS, ischemic stroke, and death in type 2 DM patients were 0.30, 0.36, and 0.39, respectively. Conclusions: The acceptable discriminative power of the progression of adapted DCSI for Asian people affected by type 2 DM was demonstrated in a large cohort in Taiwan.

Emergency General Surgery (EGS) Risk Stratification Scores

Risk stratification is an important metric for a mature surgical system. It not only is the development of comparative outcome data but serves as an important tool for is a tool for goal concordant care discussions with patients. As we move to an Emergency General Surgery (EGS) regional system that mirrors the existing trauma system risk stratification will allow for triage of high-risk patients to receive appropriate preoperative and postoperative care. Evidence has shown that the EGS population has unique physiology with markedly different outcomes than their elective counterparts. The tools we use to measure the outcomes in this challenging population are still evolving. An ideal risk stratification system will provide accurate prediction from readily obtainable objective data in all populations and can be used easily in clinical practice. There are many different types of risk stratification systems which use a combination of patient comorbidity, physiology, and disease mechanism to predict outcomes, with varying levels of accuracy. An ideal tool would incorporate variables from all these non-modifiable factors yet still be easy enough to use in real time by the clinician. Currently there is no idealized EGS risk stratification system. An ideal model may combine comorbidity factors, physiologic factors, and emergent pathology factors to clarify the degree of severity based more on a mechanistic model. Here in, we review the existing literature on the above factors and propose the direction EGS risk stratification may take in the future. There are many different scoring systems providing stratification of risk in EGS patients created over the previous 80 years. Accuracy of outcome prediction varies based on the system chosen and the components the system uses. As prediction models become more accurate, the complexity typically increases. Recent literature suggests that linear regression for prediction of outcomes may not be the most accurate risk stratification technique. Further research is necessary to determine which outcomes bear the most clinical significance. Benchmarking EGS systems by risk stratification of outcomes also requires further analysis. Each risk stratification system has advantages and disadvantages to use. Pathology in EGS patients suggests outcomes are dependent on the mechanism of disease, physiology of patients on presentation, as well as current comorbidities. An idealized EGS risk stratification system will provide accurate prediction from readily obtainable objective data in all EGS populations and can be used easily in clinical practice. Further research is necessary to provide integration of these factors into a user-friendly and easily applicable interface.

Novel Blood Cytokine-Based Model for Predicting Severe Acute Kidney Injury and Poor Outcomes After Cardiac Surgery.

BackgroundAlterations in serum creatinine levels delay the identification of severe cardiac surgery‐associated acute kidney injury. To provide timely diagnosis, novel predictive tools should be investigated.Methods and ResultsThis prospective observational study consists of a screening cohort (n=204) and a validation cohort (n=198) from 2 centers from our hospital. Thirty‐two inflammatory cytokines were measured via a multiplex cytokine assay. Least absolute shrinkage and selection operator regression was conducted to select the cytokine signatures of severe cardiac surgery‐associated acute kidney injury. Afterwards, the significant candidates including interferon‐γ, interleukin‐16, and MIP‐1α (macrophage inflammatory protein‐1 alpha) were integrated into the logistic regression model to construct a predictive model. The predictive accuracy of the model was evaluated in these 2 cohorts. The cytokine‐based model yielded decent performance in both the screening (C‐statistic: 0.87, Brier 0.10) and validation cohorts (C‐statistic: 0.86, Brier 0.11). Decision curve analysis revealed that the cytokine‐based model had a superior net benefit over both the clinical factor‐based model and the established plasma biomarker‐based model for predicting severe acute kidney injury. In addition, elevated concentrations of each cytokine were associated with longer mechanical ventilation times, intensive care unit stays, and hospital stays. They strongly predicted the risk of composite events (defined as treatment with renal replacement therapy and/or in‐hospital death) (OR of the fourth versus the first quartile [95% CI]: interferon‐γ, 27.78 [3.61–213.84], interleukin‐16, 38.07 [4.98–291.07], and MIP‐1α, 9.13 [2.84–29.33]).ConclusionsOur study developed and validated a promising blood cytokine‐based model for predicting severe acute kidney injury after cardiac surgery and identified prognostic biomarkers for assisting in outcome risk stratification.

Relation of Frailty to Outcomes After Catheter Ablation of Atrial Fibrillation

Catheter ablation for atrial fibrillation (AF) improves outcomes compared with medical treatment alone. Risk stratification for outcomes following AF ablation remains an important area of uncertainty. This analysis evaluated the association between frailty and outcomes following AF ablation. We evaluated US inpatients receiving AF ablation between January 1, 2016 and December 1, 2016 using Medicare fee-for-service billing codes. Diagnosis codes were used to calculate patients' Hospital Frailty Risk Score, with the cohort divided according to established cut-points of low (<5), intermediate (5 to 15), and high (>15) risk for frailty. The primary outcome was survival. Among 5,070 in patients treated with catheter ablation (mean age 74.9 ± 6.8 years, 51.1% female), 38.6% were defined as frail with a Hospital Frailty Risk Score >5, including 8.3% at high risk. Mortality rates (up to 630 days) were 5.8% in the low-risk group, 23.4% in the intermediate-risk group, and 42.2% in the high-risk group (log-rank p values <0.001 for comparison between categories). In restricted cubic spline regression analysis, the adjusted hazard ratios for long-term mortality monotonically increased with increasing values of the Hospital Frailty Risk Score (adjusted hazard ratio 1.065, 95% confidence interval 1.054 to 1.077). In secondary end points, frailty was independently associated with length of stay, postprocedure 30-day mortality, 30-day readmission and postdischarge 30-day mortality rates. In conclusion, frailty as assessed by a claims-based score is common in inpatient recipients of AF ablation, and provides risk stratification for mortality and other key clinical outcomes.

Dynamic of end-tidal carbon dioxide pressure during cardiopulmonary exercise testing before and after heart transplantation

Aim: to assess the dynamic and prognostic significance of the end-tidal carbon dioxide pressure (PetCO 2 ) during cardiopulmonary exercise testing in recipients before and after heart transplantation (HT). Materials and methods. The study included 55 patients with severe chronic heart failure (CHF) from the HT waiting list. All patients underwent cardiopulmonary exercise testing before and in the long-term follow-up after TS, including determination of PetCO 2 at rest and during exercise. Results. Physical capacity, the efficiency of pulmonary ventilation and gas exchange in the long-term after the HT significantly improved compared with the preoperative data. Peak oxygen consumption before and after HT was 10.8 (9.4-11.7) ml/min/kg and 18.9 (18.2-21.0) ml/in/kg (p = 0.020), respectively, the value of the VE/VCO 2 slope decreased from 38 (34-45) to 32 (30-36), p = 0.017. PetCO 2 at rest before the HT was below the norm, amounted to 30 (28-32) mm Hg, increased to the anaerobic threshold by an average of 3.6 (0.2-5.2)%. After the HT, the level of PetCO 2 at rest did not change significantly, but the increase during exercise was 7.6 (3.2-9.4)% (p = 0.001). It was shown that a low baseline PetCO2 value and the absence of its increase during cardiopulmonary exercise test significantly increase the risk of adverse outcome in patients with severe CHF before and after HT (OR 0.62 (0.35-0.87), p = 0.035 and, 16 (0.10-0.24), p = 0.002, respectively). Conclusion. Heart transplantation in patients with severe CHF leads to a significant improvement in the efficiency of pulmonary ventilation and gas exchange in the long-term follow-up. Estimation of the PetCO 2 level at rest and during exercise is a promising predictor of adverse outcomes risk stratification in patients with severe CHF before and after HT.

Inflammatory Markers and Severity of Intracerebral Hemorrhage.

Background and purposeThe pathogenesis of brain injury after intracerebral hemorrhage is thought to be due to mechanical damage followed by ischemic, cytotoxic, and inflammatory changes in the underlying and surrounding tissue.In recent years, there has been a greater research interest into the various inflammatory biomarkers and growth factors that are secreted during intracerebral hemorrhage. The biomarkers investigated in this study are tumor necrosis factor alpha (TNF alpha), C-reactive protein (CRP), homocysteine (Hcy), and vascular endothelial growth factor (VEGF). The aim of this study was to further investigate the effects of these biomarkers in predicting the acute severity outcome of intracerebral hemorrhage (ICH).MethodsWe conducted a retrospective chart review of patients with spontaneous ICH with TNF alpha, CRP, VEGF, and Hcy levels drawn on admission. Forty-two patients with spontaneous ICH with at least one of the above labs were included in the study. Primary outcomes included death, Glasgow Coma Scale (GCS) on admission, early neurologic decline (END), and hemorrhage size. Secondary outcomes included GCS on discharge, ICH score, functional outcome risk stratification scale of intracerebral hemorrhage (FUNC score), change in hemorrhage size, need for surgical intervention, and length of intensive care unit (ICU) stay.ResultsForty-two patients with spontaneous intracerebral hemorrhage (ICH) were analyzed, 12 patients (28.5%) required surgical intervention, and four patients (9.5%) died. Only low VEGF serum values were found to predict mortality. TNF alpha, CRP, Hcy, and VEGF levels in our patients with ICH were not found to predict early neurologic decline and were not correlated with GCS on admission, initial hemorrhage size, change in hemorrhage size, need for surgical intervention, ICH score, FUNC score, midline shift, and length of ICU stay. CRP and Hcy were elevated in 58% and 31% of patients tested, respectively. GCS on admission and ICH score were significantly associated with mortality.ConclusionAfter careful statistical review of the data obtained from this patient population, only low VEGF values were found to be a significant predictor of mortality. However, elevated CRP and Hcy levels were associated with a non-significant trend in hemorrhage size and mortality suggesting that CRP and Hcy-lowering therapies may decrease hemorrhagic stroke risk and severity.

Use of the progression of adapted Diabetes Complications Severity Index to predict acute coronary syndrome, ischemic stroke, and mortality in Asian patients with type 2 diabetes mellitus: A nationwide cohort investigation.

We report on a retrospective population study aimed at identifying and validating the progression of adapted Diabetes Complications Severity Index (DCSI) for acute coronary syndrome (ACS), ischemic stroke, and mortality in Asian people with type 2 diabetes mellitus (DM). Utilizing a Taiwanese national dataset, we included 84 450 type 2 diabetic individuals between 2000 and 2011. The area under the receiver operating characteristic curve (C statistics of logistic model) and the C statistics of the Cox model were used to evaluate whether the progression of diabetic complication status could be a predictor of ACS, ischemic stroke, and death. The optimum threshold for adverse outcomes risk stratification were obtained using Youden's J statistic as the cutoff that gives the highest threshold. Among the study patients, the C statistics of the logistic model of the progression of the score predictive of ACS, ischemic stroke, and death were 0.72 (95% confidence interval [CI]: 0.71-0.73), 0.84 (95% CI: 0.84-0.85), and 0.66 (95% CI: 0.65-0.67), respectively. The progression of adapted DCSI had moderate discrimination for ACS, ischemic stroke, and death (C statistics = 0.71, 0.72, and 0.75, respectively) based on Cox regression analysis (Harrell C). The optimum threshold of the progression of the score for ACS, ischemic stroke, and death in type 2 DM patients were 0.30, 0.36, and 0.39, respectively. The acceptable discriminative power of the progression of adapted DCSI for Asian people affected by type 2 DM was demonstrated in a large cohort in Taiwan.

Risk Factors Associated With Circumferential Resection Margin Positivity in Rectal Cancer: A Binational Registry Study.

Rectal cancer outcomes have improved with the adoption of a multidisciplinary model of care. However, there is a spectrum of quality when viewed from a national perspective, as highlighted by the Consortium for Optimizing the Treatment of Rectal Cancer data on rectal cancer care in the United States. The aim of this study was to assess and identify predictors of circumferential resection margin involvement for rectal cancer across Australasia. A retrospective study from a prospectively maintained binational colorectal cancer database was interrogated. This study is based on a binational colorectal cancer audit database. Clinical information on all consecutive resected rectal cancer cases recorded in the registry from 2007 to 2016 was retrieved, collated, and analyzed. The primary outcome measure was positive circumferential resection margin, measured as a resection margin ≤1 mm. A total of 3367 patients were included, with 261 (7.5%) having a positive circumferential resection margin. After adjusting for hospital and surgeon volume, hierarchical logistic regression analysis identified a 6-variable model encompassing the independent predictors, including urgent operation, abdominoperineal resection, open technique, low rectal cancer, T3 to T4, and N1 to N2. The accuracy of the model was 92.3%, with an receiver operating characteristic of 0.783 (p < 0.0001). The quantitative risk associated with circumferential resection margin positivity ranged from <1% (no risk factors) to 43% (6 risk factors). This study was limited by the lack of recorded long-term outcomes associated with circumferential resection margin positivity. The rate of circumferential resection margin involvement in patients undergoing rectal cancer resection in Australasia is low and is influenced by a number of factors. Risk stratification of outcome is important with the increasing demand for publicly accessible quality data. See Video Abstract at http://links.lww.com/DCR/A512.

Numeracy and Interpretation of Prognostic Estimates in Intracerebral Hemorrhage Among Surrogate Decision Makers in the Neurologic ICU.

Clinicians caring for patients with intracerebral hemorrhage must often discuss prognosis and goals of care with their patients' surrogate decision makers, and may make numeric estimates of likelihood of survival and functional independence, informed by validated prediction models. Surrogates' prognostic estimates are often discordant with physicians', suggesting that physicians' numeric statements may not be accurately interpreted. We sought to assess the relationship between numeracy and interpretation of prognostic estimates in intracerebral hemorrhage among surrogate decision makers. We also assessed surrogates' application of prognostic estimates to decisions regarding goals of care. Single-center, survey-based, cross-sectional study. Twenty-two-bed neurologic ICU at an urban, academic hospital. Surrogate decision makers for patients admitted to the neurologic ICU. Participants completed a survey containing five clinical vignettes describing patients with nontraumatic intracerebral hemorrhage. For each patient, numerical estimates of survival and functional independence were explicitly provided, based on the validated outcome risk stratification scale (intracerebral hemorrhage score) and the Prediction of Functional Outcome in Patients with Primary Intracerebral Hemorrhage score. Participants were asked to make their own prognostic estimates, as well as to describe their preferred goals of care for each hypothetical patient. Respondent demographics were collected, and numeracy was assessed using a modified Lipkus 11-item scale. Poor numeracy was common (42 of 96 total subjects) in this relatively highly educated population. Most prognostic estimates (55%) made by surrogates were discordant with the provided estimates. High numeracy correlated with better concordance (odds ratio, 23.9 [5.57-97.64]; p < 0.001), independent of several factors, including level of education and religion. Numeracy also affected goals-of-care decisions made by surrogates. Poor numeracy is common among surrogate decision makers in an intensive care setting and poses a barrier to communication between surrogates and clinicians regarding prognosis and goals of care.

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non-Small Cell Lung Cancer and Serum DNA.

Purpose: To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC).Experimental Design: Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples.Results: A methylation panel of 6 genes (CDO1, HOXA9, AJAP1, PTGDR, UNCX, and MARCH11) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of CDO1, HOXA9, PTGDR, and AJAP1 refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with HOXA9 methylation, showed poor outcomes.Conclusions: Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. Clin Cancer Res; 23(22); 7141-52. ©2017 AACR.

The Medication Level Variability Index (MLVI) Predicts Poor Liver Transplant Outcomes: A Prospective Multi-Site Study.

Nonadherence to immunosuppressant medications is a leading cause of poor long-term outcomes in transplant recipients. The Medication Level Variability Index (MLVI) provides a vehicle for transplant outcome risk-stratification through continuous assessment of adherence. The MALT (Medication Adherence in children who had a Liver Transplant) prospective multi-site study evaluated whether MLVI predicts late acute rejection (LAR). Four hundred pediatric (1-17-year-old) liver transplant recipients were enrolled and followed for 2 years. The a-priori hypothesis was that a higher MLVI predicts LAR. Predefined secondary analyses evaluated other outcomes such as liver enzyme levels, and sensitivity analyses compared adolescents to pre-adolescents. In the primary analysis sample of 379 participants, a higher prerejection MLVI predicted LAR (mean prerejection MLVI with LAR: 2.4 [3.6 standard deviation] versus without LAR, 1.6 [1.1]; p = 0.026). Fifty-three percent of the adolescents with MLVI>2 in year 1 had LAR by the end of year 2, as compared with 6% of those with year 1 MLVI≤2. A higher MLVI was significantly associated with all secondary outcomes. MLVI, a marker of medication adherence that uses clinically derived information, predicts LAR in pediatric liver transplant recipients.