Surrogate Marker Of Outcome Research Articles

Prediction of Neonatal Acidosis Based on the Type of Fetal Hypoxia Observed on the Cardiotocograph (CTG)

Cardiotocograph (CTG) was introduced into clinical practice to promptly recognize the features of intrapartum fetal hypoxic stress, so that timely action could be taken to avoid hypoxic-ischaemic encephalopathy (HIE) and perinatal deaths. However, the current systematic evidence suggests that the introduction of CTG into clinical practice over 50 years has not resulted in improvement in the rates of cerebral palsy or perinatal deaths. This is because most fetuses are able to withstand intrapartum hypoxic stresses without sustaining damage, and if the features of fetal compensatory responses are erroneously considered as “pathological”, “Abnormal” or “Category III” CTG tracing, it would lead to an exponential increase in unnecessary operative interventions without any improvement in perinatal outcomes. Neonatal acidosis at birth, determined by the estimation of pH in the umbilical artery has been considered as a surrogate marker of poor perinatal outcome. This is because significant intrapartum fetal hypoxic stress which leads to fetal decompensation, would lead to the onset of anaerobic metabolism and production of lactic acid in fetal tissues and organs. Entry of lactic acid into the fetal systemic circulation may cause damage to fetal central organs resulting in organ damage and death, and this lactate may lower the pH in the umbilical artery. Understanding the different types of fetal hypoxia on the CTG trace may help practicing clinicians to predict the rate of fall in fetal pH, and therefore, predict the umbilical cord pH at birth. It is important to appreciate that non-hypoxic pathways of fetal compromise such as chorioamnionitis may not be associated with low umbilical arterial pH at birth. Fetal pathophysiological approach to CTG interpretation based on deeper understanding of types of intrapartum hypoxia and features of non-hypoxic pathways of injury may help avoid the onset of neonatal metabolic acidosis and improve perinatal outcomes.

Preserved Electroencephalogram Power and Global Synchronization Predict Better Neurological Outcome in Sudden Cardiac Arrest Survivors.

Quantitative EEG (qEEG) delineates complex brain activities. Global field synchronization (GFS) is one multichannel EEG analysis that measures global functional connectivity through quantification of synchronization between signals. We hypothesized that preservation of global functional connectivity of brain activity might be a surrogate marker for good outcome in sudden cardiac arrest (SCA) survivors. In addition, we examined the relation of phase coherence and GFS in a mathematical approach. We retrospectively collected EEG data of SCA survivors in one academic medical center. We included 75 comatose patients who were resuscitated following in-hospital or out-of-hospital nontraumatic cardiac arrest between 2013 and 2017 in the intensive care unit (ICU) of National Taiwan University Hospital (NTUH). Twelve patients (16%) were defined as good outcome (GO) (CPC 1–2). The mean age in the GO group was low (51.6 ± 15.7 vs. 68.1 ± 12.9, p < 0.001). We analyzed standard EEG power, computed EEG GFS, and assessed the cerebral performance category (CPC) score 3 months after discharge. The alpha band showed the highest discrimination ability (area under curve [AUC] = 0.78) to predict GO using power. The alpha band of GFS showed the highest AUC value (0.8) to predict GO in GFS. Furthermore, by combining EEG power + GFS, the alpha band showed the best prediction value (AUC 0.86) in predicting GO. The sensitivity of EEG power + GFS was 73%, specificity was 93%, PPV was 0.67%, and NPV was 0.94%. In conclusion, by combining GFS and EEG power analysis, the neurological outcome of the nontraumatic cardiac arrest survivor can be well-predicted. Furthermore, we proved from a mathematical point of view that although both amplitude and phase contribute to obtaining GFS, the interference in phase variation drastically changes the possibility of generating a good GFS score.

Feasibility of the semi-opened method of specimen resection for a circumferential resection margin in rectal cancer surgery: a multicenter study.

A circumferential resection margin (CRM) > 1mm is a surrogate marker of oncologic outcomes in rectal cancer patients. In Japan, because the mesentery is removed from the rectum, the CRM cannot be measured. This multicenter prospective study evaluates the feasibility of a resected specimen processing method that allows CRM measurement. Fifty patients with rectal cancer were enrolled. Resected specimens were processed as previously reported. The primary outcomes were CRM measurement and the rate of CRM positivity. The secondary outcomes were the quality of total mesorectal excision, the possibility to visualize and sample the tumor, the number of harvested lymph nodes, and comparison between the pathological CRM and preoperative mesorectal fascia (MRF) involvement. This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry under identification number UMIN000031735. The CRM was measurable in all patients and found to be positive in three (6%). We confirmed tumor localization, sampled the tumor, and measured the distal margin in all patients. A median of 20 lymph nodes were harvested. The concordance rate between preoperative MRF involvement and pathological CRM status was 90%. A semi-opened rectal specimen with transverse slicing is a feasible method for measuring the CRM.

The changing landscape of general surgery in the elderly - trends over a decade in a tertiary centre in Singapore.

We take stock of our local experience in a high volume tertiary centre in Singapore, Tan Tock Seng Hospital by reviewing the number of surgical procedures performed for elderly patients (65 years old and above) across a decade and reviewing their post-operative outcomes. This retrospective cohort study included elderly patients (>= aged 65) who underwent surgical procedures under general anaesthesia from January 2008 to December 2019. Demographic data, nature of operation, preoperative American Society of Anaesthesiologists (ASA) status of patients and surrogate markers of outcome including average length of stay (ALOS), 30 and 90-day mortality were retrospectively analysed. Across a 12-year period, we observed a nearly overall two-fold increase in the number of surgical procedures for elderly patients from 1,129 cases in 2008 to 2,118 cases in 2019. The ALOS for elderly surgical patients trended downwards from an average of 12.3 days in 2008 to 9.0 days in 2019. All cause 30-day mortality rate of elderly patients dropped from 5.8% in 2008 to 2.7% in 2019. The landscape for general surgery in the elderly is changing in the context of advances in health care and a paradigm shift in treatment beliefs and perspectives. Ultimately, informed decision making, patient engagement and empowerment by the surgeon are keys to better outcomes and improved patient experience.

Relationship of NT-proBNP to All-Cause Death and Heart Transplant in Children with Ventricular Dysfunction and Compared to Adults with Heart Failure

<h3>Purpose</h3> Plasma NT-proBNP concentration is a widely used diagnostic biomarker for heart failure (HF) in adults and children. We sought to determine whether NT-proBNP concentrations predicted the risk of heart transplantation or death in pediatric HF patients. <h3>Methods</h3> We studied medical records from 109 children with HF in the IBM Watson Explorys database and from 150 children in the Cardiac Biomarkers in Pediatric Cardiomyopathy (PCMR) study. Nonlinear regression with an Emax function was used to model the relationship between NT-proBNP concentrations and the number of events in the two cohorts and with adult patients from Explorys. <h3>Results</h3> All children in the PCMR cohort had dilated cardiomyopathy, whereas the Explorys cohort also included children with congenital heart diseases (Table). Mean age at diagnosis was 3 years in the Explorys cohort and 1.4 years in the PCMR cohort; median NT-proBNP concentrations were 1250 pg/mL and 183.5 pg/mL, respectively. The percentage of deaths and transplantations was higher in the Explorys cohort (7% and 22%, respectively, over 2 years) than in the PCMR cohort (3% and 16%, respectively, over 5 years). Mean estimates of NT-proBNP concentration indicative of half-maximum risk for events (EC50 values) at 2 and 5 years were 3730 pg/mL and 4199 pg/mL, values both close to the mean of 3880 pg/mL established for adults with HF (Figure). <h3>Conclusion</h3> NT-proBNP concentration is suitable for estimating the risk of mortality and morbidity in children with HF, independent of age, and is a candidate surrogate marker for clinical outcome both in adults and children with HF.

Hepatitis C Donors Are Not Associated with Higher Rates of Rejection After Cardiac Transplantation

<h3>Purpose</h3> Utilization of Hepatitis C (HCV) donors has led to a rapid expansion of the heart donor pool. Short term safety as measured by one year mortality has been published, however data on morbidity is lacking. We leveraged the multi-center SHORE registry to compare surrogate markers for outcomes in recipients of HCV+ vs HCV- donors. <h3>Methods</h3> The SHORE registry was queried for all heart transplant recipients with known donor status of HCV. Baseline characteristics were compared between recipients of HCV+ and HCV- donors. Since the registry does not differentiate between HCV viremic and non-viremic, the HCV+ donor group was inclusive of both. Outcomes of interest were rejection defined as ISHLT ≥ 2R and/or AMR ≥ 1 and average AlloSure levels during the first year. We also compared a composite outcome of de novo DSA, rejection, decline in LVEF, and/or development of CAV at one year. <h3>Results</h3> There were 1372 recipients of HCV- and 140 HCV+ donors. Baseline characteristics including age, sex, race and pre-transplant PRA were well matched. Over the first year, incidence of rejection was similar between groups 6.9% vs 4.3% (p=0.32). AlloSure levels over the first year were similar in the HCV- group and HCV+ groups (0.05 (0.0,8.36) vs 0.05 (0.0, 6.4)). Finally, the cumulative incidence of the composite outcome was not different between groups (Fig 1). <h3>Conclusion</h3> In this large analysis of recipients of HCV+ donor hearts, we did not find differences in the rates of rejection or clinically significant differences in levels of AlloSure in the first year. Similarly, the incidence of a composite outcome at one year was not different. These findings should reassure the community on short term safety of HCV+ donors.

Real World Responses to Neoadjuvant Chemotherapy for Early Breast Cancer

Purpose: Neoadjuvant chemotherapy (NACT) for early breast cancer (EBC) is indicated for downstaging tumours to allow for breast conserving surgery (BCS). Furthermore, pCR is a surrogate marker for outcome which allows for tailoring of adjuvant treatment to optimise outcomes, especially for Her2(+) and triple negative. This retrospective review aims to provide real world data, regarding downstaging rates, pCR rates and correlation between pCR rates and post-NACT MRI.

Intracoronary Application of Super-Saturated Oxygen to Reduce Infarct Size Following Myocardial Infarction.

Optimal medical therapy for secondary prevention following acute myocardial infarction reduces non-fatal ischaemic events. Intensive antithrombotic or lipid-lowering approaches have failed to significantly lower mortality. In the past, reduction of infarct size in patients undergoing primary percutaneous revascularisation for acute myocardial infarction had been considered as a surrogate outcome marker. However, infarct size measured by magnetic resonance imaging or SPECT is strongly associated with all-cause mortality and hospitalization for heart failure within the first year after an acute myocardial infarction. Intracoronary administration of super-saturated oxygen (SSO2) immediately after revascularisation is an approach that can be used to reduce infarct size and, therefore, improve cardiovascular outcome in patients with acute myocardial infarction. In this article, we describe the modulation of pathophysiology by SSO2, review the existing trial data and present our first impressions with the technique in real clinical practice.

Vitamin K Supplementation for Prevention of Vascular Calcification in Chronic Kidney Disease Patients: Are We There Yet?

Chronic Kidney Disease (CKD) patients are at high risk of presenting with arterial calcification or stiffness, which confers increased cardiovascular mortality and morbidity. In recent years, it has become evident that VC is an active process regulated by various molecules that may act as inhibitors of vessel mineralization. Matrix Gla Protein (MGP), one the most powerful naturally occurring inhibitors of arterial calcification, requires vitamin K as a co-factor in order to undergo post-translational γ-carboxylation and phosphrorylation and become biologically active. The inactive form of MGP (dephosphorylated, uncarboxylated dp-ucMGP) reflects vitamin K deficiency and has been repeatedly associated with surrogate markers of VC, stiffness, and cardiovascular outcomes in CKD populations. As CKD is a state of progressive vitamin K depletion and VC, research has focused on clinical trials aiming to investigate the possible beneficial effects of vitamin K in CKD and dialysis patients. In this study, we aim to review the current evidence regarding vitamin K supplementation in uremic patients.

Abstract P5-18-08: The relative risk of various endocrinopathies associated with neoadjuvant chemoimmunotherapy use in early-stage triple-negative breast cancer: A systematic review and meta-analysis

Abstract Background: Immune checkpoint inhibitors (ICIs) are known to cause various irreversible endocrinopathies. Lately, multiple clinical trials have demonstrated that the addition of ICI to the standard neoadjuvant chemotherapy improves pathological complete response (pCR) rate in high-risk early-stage triple-negative breast cancer (TNBC). The pCR has long been regarded as a surrogate marker of favorable outcomes in early-stage TNBC. This systematic review and meta-analysis attempt to determine the risks of various endocrinopathies associated with neoadjuvant chemoimmunotherapy use in early-stage TNBC. Methods: We conducted a systematic search in the PUBMED, MEDLINE, EMBASE, American Society of Clinical Oncology, and San Antonio Breast Cancer Symposium meeting abstracts as per PRISMA guidelines from inception through May 30th, 2021. Published phase 2 and 3 randomized control trials (RCTs) using neoadjuvant ICI plus chemotherapy (ICI+C) in the intervention arm for early-stage TNBC and reporting the number of events for various endocrinopathies were included in the analyses. We used the Mantel-Haenszel method and random-effects model to calculate the estimated pooled risk ratio (RR) with a 95% confidence interval (CI). Heterogeneity was tested with the I2 value and Cochran’s Q-test. Results: Two phase 3 RCTs (IMpassion031 and KEYNOTE-522) and Two phase 2 RCTs (GeparNuevo and I-SPY2) were included in the final analysis. These RCTs randomized 1,106 patients in the ICI+C arm and 819 patients in the placebo plus chemotherapy (P+C) arm. Some essential characteristics of these trials are included in table 1. The incidence of any grade hypothyroidism was 12.84% in the ICI+C arm versus 3.17% in the P+C arm. The pooled RR of any grade hypothyroidism was 3.63 (95% CI: 1.78-7.43, p = 0.0004, I2 = 28%), which was statistically significant. The incidence of any grade hyperthyroidism was 5.24% in the ICI+C arm versus 0.98% in the P+C arm. The pooled RR of any grade hyperthyroidism was 4.08 (95% CI: 1.94-8.59, p = 0.0002, I2 = 3%), which was statistically significant. The incidence of any grade adrenal insufficiency was 2.66% in the ICI+C arm versus 0.14% in the P+C arm. The pooled RR of any grade adrenal insufficiency was 6.84 (95% CI: 0.43-108.95, p = 0.17, I2 = 62%), which was not significant. The incidence of any grade hypophysitis was 1.45% in the ICI+C arm versus 0.16% in the P+C arm. The pooled RR of any grade hypophysitis was 5.29 (95% CI: 0.96-29.25, p = 0.06, I2 = 0%), which was not significant. The incidence of any grade diabetes mellitus was 0.42% in the ICI+C arm versus 0.18% in the P+C arm. The pooled RR of any grade diabetes mellitus 1.81 (95% CI: 0.24-13.63, p = 0.57, I2 = 0%), which was not statistically significant. Conclusions: The addition of immune checkpoint inhibitors (ICIs) to the standard neoadjuvant chemotherapy significantly increases the risk of any grade hypothyroidism and hyperthyroidism. Although the incidences of adrenal insufficiency, hypophysitis, and diabetes mellitus were numerically higher in the ICI+C arm than the P+C arm, they have not achieved statistical significance, possibly due to the rarity of these events. Careful endocrine functions monitoring and appropriate early interventions are crucial in reducing endocrine-related morbidities and mortalities in these patients. Table 1.Characteristics of the studies included in the meta-analysisStudyPhaseICI usedC usedNo. of patients (ICI+C)No. of patients (P+C)GaperNuevo2DurvalumabNab-paclitaxel + EC9282I-SPY22PembrolizumabPaclitaxel + AC69181IMpassion0313AtezolizumabNab-paclitaxel + AC164167KEYNOTE-5223PembrolizumabPaclitaxel + carboplatin + AC/EC781389AC: doxorubicin + cyclophosphamide; C: chemotherapy; EC: epirubicin + cyclophosphamide; ICI: immune checkpoint inhibitor; P: placebo Citation Format: Nusrat Jahan, Shabnam Rehman, Lukman Tijani. The relative risk of various endocrinopathies associated with neoadjuvant chemoimmunotherapy use in early-stage triple-negative breast cancer: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-18-08.

Percentage grade 4 tumour predicts outcome for prostate adenocarcinoma in needle biopsies from patients with advanced disease: 10-year data from the TROG 03.04 RADAR trial.

Previous reports have shown that quantification of high tumour grade is of prognostic significance for patients with prostate cancer. In particular, percent Gleason pattern 4 (GP4) has been shown to predict outcome in several studies, although conflicting results have also been reported. A major issue with these studies is that they rely on surrogate markers of outcome rather than patient survival. We have investigated the prognostic predictive value of quantifying GP4 in a series of prostatic biopsies containing Gleason score 3+4=7 and 4+3=7 tumours. It was found that the length of GP4 tumour determined from the measurement of all biopsy cores from a single patient, percent GP4 present and absolute GP4 were all significantly associated with distant progression of tumour, all-cause mortality and cancer-specific mortality over a 10-year follow-up period. Assessment of the relative prognostic significance showed that these parameters outperformed division of cases according to Gleason score (3+4=7 versus 4+3=7). International Society of Urological Pathology (ISUP) Grade Groups currently divide these tumours, according to Gleason grading guidelines, into grade 2 (3+4=7) and grade 3 (4+3=7). Our results indicate that this simple classification results in the loss of important prognostic information. In view of this we would recommend that ISUP Grade Groups 2 and 3 be amalgamated as grade 2 tumour with the percentage of GP4 carcinoma being appended to the final grade, e.g., 3+4=7 carcinoma with 40% pattern 4 tumour would be classified as ISUP Grade Group 2 (40%).

Letter to the Editor: ‘Euthyroid sick syndrome as an early surrogate marker of poor outcome in mild SARS‑CoV‑2 disease’—prognostic significance of non-thyroidal illness syndrome across the whole spectrum of COVID-19 severity

Letter to the Editor: ‘Euthyroid sick syndrome as an early surrogate marker of poor outcome in mild SARS‑CoV‑2 disease’—prognostic significance of non-thyroidal illness syndrome across the whole spectrum of COVID-19 severity

Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer

Degree of expression of programmed death-ligand 1 (PD-L1) is related with Immune check point inhibitors (ICIs) response but it needs sufficient tumor tissue. There is unmet need for easily accessible and prognostic peripheral blood (PB) biomarkers. We investigated the application of serum peripheral lymphocyte count (PLC) as a predictive PB biomarker for ICI response in patients with NSCLC. We conducted a retrospective study and reviewed the patients with NSCLC who were treated with ICIs from April 1, 2016, to March 31, 2019. The PLC before and after 1 month of immunotherapy was collected. We evaluated the association between PLC and progression-free survival (PFS), overall survival (OS) and adverse events. A total of 231 patients were treated with ICIs for NSCLC. The median follow-up period was 4.7 months and the disease progressed in 138 patients (59.7%). Compared with the lowest quartile (Q1: the lowest 25%), the highest quartile (Q4: the highest 25%) of post-treatment PLC showed a significantly higher PFS (HR 0.28, 95% CI 0.16–0.52) and OS (HR 0.35, 95% CI 0.19–0.65) in the adjusted model. An association between adverse events and PLC was not observed. We revealed that an increased pre- and post-treatment PLC was associated with favorable PFS and OS with NSCLC patients treated with ICIs. PLC could be a helpful for ICI responses in NSCLC.

Euthyroid sick syndrome as anearly surrogate marker of poor outcome in mild SARS-CoV-2 disease.

BackgroundThe new coronavirus 19 disease (COVID-19) represents the current worldwide emergency. According to past evidence, a simple biomarker, such as low free triiodothyronine (fT3) levels, within the framework of euthyroid sick syndrome (ESS), might help to identify patients with unfavourable outcomes.ObjectiveEvaluation of ESS significance in hospitalized mild COVID-19 patients.DesignProspective study, from 1 April 2020 to 31 May 2021.ParticipantsCOVID-19 patients with mild disease at hospital admission.Main measuresAt hospital admission, eligible patients underwent a complete thyroid function evaluation. Subjects with previous thyroid disease or with thyroid-interfering medications were excluded. Levels of fT3 were correlated to biochemical markers and to patient outcome, the latter considered as favourable in the event of infection recovery and unfavourable in the event of death or transfer to an intensive care unit (ICU).Key resultsOf 600 screened patients, 506 were eligible for this study. Of those, 94 (19%) died during hospitalization and 80 (18%) required a transfer to ICU. The most frequent thyroid disorder was ESS (57%). Admission levels of fT3 were significantly lower within the unfavourable outcome subgroup (p < 0.001) and were negatively associated with several poor prognostic markers, including IL-6 (p < 0.001). In Kaplan–Meier and Cox regression analyses, fT3 was independently associated with poor outcome and death (p = 0.005 and p = 0.037, respectively). A critical fT3 threshold for levels < 2.7 pmol/l (sensitivity 69%, specificity 61%) was associated with a 3.5-fold increased risk of negative outcome (95%CI 2.34–5.34).ConclusionLow fT3 levels, in the framework of ESS, resulted as being a valid predictor of unfavourable outcomes in a very early stage population of COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40618-021-01714-1.

Effect of Sacubitril/Valsartan vs Standard Medical Therapies on Plasma NT-proBNP Concentration and Submaximal Exercise Capacity in Patients With Heart Failure and Preserved Ejection Fraction

There is limited evidence on the benefits of sacubitril/valsartan vs broader renin angiotensin system inhibitor background therapy on surrogate outcome markers, 6-minute walk distance, and quality of life in patients with heart failure and mildly reduced or preserved left ventricular ejection fraction (LVEF >40%). To evaluate the effect of sacubitril/valsartan on N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, 6-minute walk distance, and quality of life vs background medication-based individualized comparators in patients with chronic heart failure and LVEF of more than 40%. A 24-week, randomized, double-blind, parallel group clinical trial (August 2017-October 2019). Of 4632 patients screened at 396 centers in 32 countries, 2572 patients with heart failure, LVEF of more than 40%, elevated NT-proBNP levels, structural heart disease, and reduced quality of life were enrolled (last follow-up, October 28, 2019). Patients were randomized 1:1 either to sacubitril/valsartan (n = 1286) or to background medication-based individualized comparator (n = 1286), ie, enalapril, valsartan, or placebo stratified by prior use of a renin angiotensin system inhibitor. Primary end points were change from baseline in plasma NT-proBNP level at week 12 and in the 6-minute walk distance at week 24. Secondary end points were change from baseline in quality of life measures and New York Heart Association (NYHA) class at 24 weeks. Among 2572 randomized patients (mean age, 72.6 years [SD, 8.5 years]; 1301 women [50.7%]), 2240 (87.1%) completed the trial. At baseline, the median NT-proBNP levels were 786 pg/mL in the sacubitril/valsartan group and 760 pg/mL in the comparator group. After 12 weeks, patients in the sacubitril/valsartan group (adjusted geometric mean ratio to baseline, 0.82 pg/mL) had a significantly greater reduction in NT-proBNP levels than did those in the comparator group (adjusted geometric mean ratio to baseline, 0.98 pg/mL) with an adjusted geometric mean ratio of 0.84 (95% CI, 0.80 to 0.88; P < .001). At week 24, there was no significant between-group difference in median change from baseline in the 6-minute walk distance with an increase of 9.7 m vs 12.2 m (adjusted mean difference, -2.5 m; 95% CI, -8.5 to 3.5; P = .42). There was no significant between-group difference in the mean change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (12.3 vs 11.8; mean difference, 0.52; 95% CI, -0.93 to 1.97) or improvement in NYHA class (23.6% vs 24.0% of patients; adjusted odds ratio, 0.98; 95% CI, 0.81 to 1.18). The most frequent adverse events in the sacubitril/valsartan group vs the comparator group were hypotension (14.1% vs 5.5%), albuminuria (12.3% vs 7.6%), and hyperkalemia (11.6% vs 10.9%). Among patients with heart failure and left ventricular ejection factor of higher than 40%, sacubitril/valsartan treatment compared with standard renin angiotensin system inhibitor treatment or placebo resulted in a significantly greater decrease in plasma N-terminal pro-brain natriuretic peptide levels at 12 weeks but did not significantly improve 6-minute walk distance at 24 weeks. Further research is warranted to evaluate potential clinical benefits of sacubitril/valsartan in these patients. ClinicalTrials.gov Identifier: NCT03066804.

Insulin resistance-related differences in the relationship between left ventricular hypertrophy and cardiorespiratory fitness in asymptomatic newly diagnosed hypertensive Black sub-Saharan Africans

Abstract Background Left ventricular hypertrophy (LVH) is associated with impaired cardiorespiratory fitness (CRF), a surrogate marker of poor outcome. Insulin resistance (IR) plays a central role in all stages of cardiovascular disease continuum. Purpose This study evaluates IR-related differences in the relationship between left ventricular mass (LVM) and CRF in asymptomatic newly diagnosed hypertensive patients. Methods In this cross-sectional observational study, 126 asymptomatic newly diagnosed hypertensive participants (50.5±9.5 years) underwent comprehensive resting transthoracic echocardiographic examination and maximal incremental cardiopulmonary exercise test (CPET). CRF was estimated in peak oxygen uptake (VO2 peak). CPET results were compared between participants with and without LVH. Multivariate analysis examined the influence of IR on the observed differences. Results Those with LVH had lower VO2 peak (15.7±5.5 mL min–1 kg–1 vs. 18.4±3.7 mL min–1 kg–1; p=0.001) than those without LVH. In patients with IR, LVM (r=−0.261, p=0.012), LVM indexed to body surface area (LVMIbsa; r=−0.229, p=0.027), and LVM indexed to height to an allometric power of 2.7 (LVMIh2.7; r=−0.351, p=0.001), and VO2 peak were negatively correlated. In hypertensive patients without IR, these same parameters and VO2 peak have no significant correlation. Body mass index (BMI), LVM, and LVMIbsa emerged as independent determinants of VO2 peak, explaining 46.9% of its variability (overall p=0.001) in IR participants, a relationship not found in participants without IR. Conclusions IR may participate in the deterioration of CRF associated with LVH. Targeting IR in hypertensive patients with LVH could improve prognosis. Funding Acknowledgement Type of funding sources: None.

Body Adiposity Index Is Predictive of Weight Loss after Roux-en-Y Gastric Bypass

Background/Aims: Roux-en-Y gastric bypass (RYGB) is one of the most effective therapies for morbid obesity, yet some patients who have taken the surgery still undergo insufficient weight loss. Visceral adiposity index (VAI), lipid accumulation product (LAP), body adiposity index (BAI), and cardiometabolic index (CMI) have been regarded as clinical indicators of adiposity phenotypes that associated closely with obesity-related metabolic diseases. However, no studies have evaluated the relationship between these indexes and weight loss after bariatric surgery. In this prospective study, we aimed to evaluate whether VAI, LAP, BAI, and CMI would predict postoperative weight loss outcomes after RYGB. Methods: This study included 38 men and 67 women who have undergone RYGB between January 2017 and May 2018 and recorded their %TWL (percent of total weight loss), %EBMIL (percent of excess body mass index loss), %EWL (percent of excess weight loss), anthropometric indices, and biochemical parameters before and 12 months after the surgery. In addition, VAI, LAP, BAI, and CMI were measured with anthropometric measures or lipid profiles using related equations and analyzed with metabolic characteristics. Results: Subjects with lower BAI (<32.54 in men and 37.39 in women) displayed higher %EBMIL and %EWL 12 months after surgery. BAI was independently associated with %EWL 12 months after surgery in both men and women (both p < 0.05). The area under the receiver operating characteristic curve for BAI was significantly higher (0.773 in men and 0.818 in women) than VAI, LAP, and CMI. Conclusions: BAI serves as a reliable surrogate marker of the weight loss outcome after RYGB. The predictivity of adiposity indexes in beneficial outcomes after weight loss therapies is of important referential value for the implementation and optimization of individualized and refined weight loss treatments for obese patients.

Effect of estimating equations for glomerular filtration rate on novel surrogate markers for renal outcome.

BackgroundsRecently, alternative surrogate endpoints such as a 30% or 40% decline in estimated glomerular filtration rate (eGFR) or eGFR slope over 2 to 3 years have been proposed for predicting renal outcomes. However, the impact of GFR estimation methods on the accuracy and effectiveness of surrogate markers is unknown.MethodsWe retrospectively enrolled participants in health screening programs at three hospitals from 1995 to 2009. We defined two different participant groups as YR1 and YR3, which had available 1-year or 3-year eGFR values along with their baseline eGFR levels. We compared the effectiveness of eGFR percentage change or slope to estimate end-stage renal disease (ESRD) risk according to two estimating equations (modified Modification of Diet in Renal Disease equation [eGFRm] and Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation [eGFRc]) for GFR.ResultsIn the YR1 and YR3 groups, 9,971 and 10,171 candidates were enrolled and ESRD incidence during follow-up was 0.26% and 0.19%, respectively. The eGFR percentage change was more effective than eGFR slope in estimating ESRD risk, regardless of the method of estimation. A 40% of decline in eGFR was better than 30%, and a 3-year baseline period was better than a 1-year period for prediction accuracy. Although some diagnostic indices from the CKD-EPI equation were better, we found no significant differences in the discriminative ability and hazard ratios for incident ESRD between eGFRc and eGFRm in either eGFR percentage change or eGFR slope. Conclusion There were no significant differences in the prediction accuracy of GFR percentage change or eGFR slope between eGFRc and eGFRm in the general population.

Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer

Peripheral lymphocyte count as a surrogate marker of immune checkpoint inhibitor therapy outcomes in patients with non-small-cell lung cancer

Chemotherapy response score: Validation of a three-tier system to quantify histopathologic response to neoadjuvant chemotherapy in ovarian carcinoma.

e17539 Background: Neoadjuvant chemotherapy (NACT) with interval debulking surgery is considered for patients with advanced-stage ovarian carcinoma (OC) who are not ideal candidates for primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have disease unlikely to be optimally resected. Moreover, response to NACT may be a suitable surrogate end point for long-term clinical outcome in ovarian cancer. The aim of the present study is to evaluate the utility of a three-tier Chemotherapy Response Score (CRS) and validate whether residual disease or evidence of regression following NACT may provide prognostic information in ovarian cancer. Methods: We conducted a retrospective single-institution study of patients who received NACT with carboplatin and paclitaxel for FIGO stage III/IV ovarian cancer. Response to NACT was graded as no or minimal tumor response (CRS1); appreciable tumor response amid readily identifiable viable tumor (CRS2); or complete/near-complete response with no residual tumor or minimal scattered tumor foci (CRS3) as described previously (Böhm S, et al. J Clin Oncol 33:2457-2463). Multivariate progression free survival (PFS) and overall survival (OS) analyses were performed accounting for age, FIGO stage and BRCA status. Results: Of the 86 patients accrued to date, median age was 65 years, 62% had stage IV disease and 16% had a somatic/germline BRCA mutation. CRS scores 1, 2 and 3 were found in 26 (30%), 43 (50%) and 17 (20%) of cases, respectively, and were associated with PFS (log rank p = 0.002). A high CRS score predicted improved PFS and OS (CRS 2/3 vs 1; median PFS 17.3 vs. 11.8 mo, adjusted hazard ratio (HR), 0.33; 95%CI 0.17-0.62; p &lt; 0.001; median OS 47.9 vs. 38.3 mo, adjusted HR 0.36, 95%CI 0.15-0.88, p = 0.026). Similarly, when comparing CRS 3 with 1/2, the high score predicted improved outcome for PFS but not OS (median PFS 17.3 vs. 14.7 mo, adjusted HR, 0.42; 95%CI 0.19-0.95; p = 0.037; median OS 48.6 vs. 46.5 mo, adjusted HR 0.43, 95%CI 0.14-1.35, p = 0.149). Conclusions: In this study, we validate a simple three-tier chemotherapy response scoring system for assessing histopathologic response of OC to NACT. Residual disease and evidence of complete/near complete regression following NACT provides prognostic information in OC. CRS may serve as a potential surrogate marker for long-term outcome and be a useful alternative intermediate end point in future clinical trials.