Lu Tian

• Stanford University

Importance Aspirin (acetylsalicylic acid) and intravenous immunoglobulin (IVIG) are standard treatments for Kawasaki disease (KD) to reduce coronary artery lesions (CALs). However, the optimal duration and dosage of aspirin remain inconsistent across hospitals. The absence of large-scale, multicenter randomized clinical trials hinders a clear under...

Given the limitations of using the Cox hazard ratio to summarize the magnitude of the treatment effect, alternative measures that do not have these limitations are gaining attention. One of the recently proposed alternative methods uses the average hazard with survival weight (AH). This population quantity can be interpreted as the average intensit...

A surrogate marker is a biological measurement in a clinical trial that aims to replace the primary outcome in evaluating the treatment effect, and can be measured earlier, with less cost, or with less patient burden. In theory, once a surrogate is validated, future studies can evaluate treatment efficacy using only the surrogate. While there are m...

Meta-analysis aggregates information across related studies to provide more reliable statistical inference and has been a vital tool for assessing the safety and efficacy of many high-profile pharmaceutical products. A key challenge in conducting a meta-analysis is that the number of related studies is typically small. Applying classical methods th...

Clinical trials or studies oftentimes require long-term and/or costly follow-up of participants to evaluate a novel treatment/drug/vaccine. There has been increasing interest in the past few decades in using short-term surrogate outcomes as a replacement of the primary outcome i.e., in using the surrogate outcome, which can potentially be observed...

As standards of care advance, patients are living longer and once-fatal diseases are becoming manageable. Clinical trials increasingly focus on reducing disease burden, which can be quantified by the timing and occurrence of multiple non-fatal clinical events. Most existing methods for the analysis of multiple event-time data require stringent mode...

Purpose The purpose of this article is to report a case of acute superior mesenteric artery embolism due to infective endocarditis treated with endovascular therapy. Case Report A patient with infective endocarditis was admitted to the hospital with abdominal pain, and abdominal enhanced computer tomography showed acute superior mesenteric artery...

Background Preterm birth (PTB) is a serious health problem. PTB complications is the main cause of death in infants under five years of age worldwide. The ability to accurately predict risk for PTB during early pregnancy would allow early monitoring and interventions to provide personalized care, and hence improve outcomes for the mother and infant...

Background: The LITE randomized clinical trial evaluated the effect of high-intensity vs low-intensity walking exercise on walking ability for peripheral artery disease (PAD). In post-hoc analyses, this study evaluated whether people with PAD who walked more exercise minutes per week had greater six-minute walk (6MW) improvement, compared to those...

Introduction: Lower income is associated with a higher prevalence of peripheral artery disease (PAD). However, whether lower income is associated with faster rates of mobility loss among people with PAD is unknown. This study describes associations of income with mobility loss in people with PAD. Methods: Data from four longitudinal studies of part...

Background Mitochondrial abnormalities exist in lower-extremity peripheral artery disease (PAD), yet the association of the ankle–brachial index (ABI) with mitochondrial respiration in gastrocnemius muscle is unknown. The association of gastrocnemius mitochondrial respiration with 6-minute walk distance in PAD is unknown. This objective of this stu...

Duration of response is an important endpoint used in drug development. Prolonged duration for response is often viewed as an early indication of treatment efficacy. However, there are numerous difficulties in studying the distribution of duration of response based on observed data subject to right censoring in practice. The most important obstacle...

Background: Though Aspirin and intravenous immunoglobulin (IVIG) remain the standard treatments for Kawasaki Disease (KD) to minimize coronary artery damage, the duration and dosage of aspirin are inconsistent across hospitals. However, the lack of multi-center randomized trials prevents definitive answers to the impact of high-dose aspirin. Method...

People with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, t...

Determining whether a surrogate marker can be used to replace a primary outcome in a clinical study is complex. While many statistical methods have been developed to formally evaluate a surrogate marker, they generally do not provide a way to examine heterogeneity in the utility of a surrogate marker. Similar to treatment effect heterogeneity, wher...

Limitations of using the traditional Cox’s hazard ratio for summarizing the magnitude of the treatment effect on time-to-event outcomes have been widely discussed, and alternative measures that do not have such limitations are gaining attention. One of the alternative methods recently proposed, in a simple 2-sample comparison setting, uses the aver...

Differential censoring, which refers to censoring imbalance between treatment arms, may bias the interpretation of survival outcomes in clinical trials. In 146 phase III oncology trials with statistically significant time-to-event surrogate primary endpoints, we evaluated the association between differential censoring in the surrogate primary endpo...

Background: Markers of aging hold promise in the context of colorectal cancer (CRC) care. Utilizing high-resolution metabolomic profiling, we can unveil distinctive age-related patterns that have the potential to predict early CRC development. Our study aims to unearth a panel of aging markers and delve into the metabolomic alterations associated w...

In clinical studies of chronic diseases, the effectiveness of an intervention is often assessed using "high cost" outcomes that require long-term patient follow-up and/or are invasive to obtain. While much progress has been made in the development of statistical methods to identify surrogate markers, that is, measurements that could replace such co...

Background There is tremendous interest in evaluating surrogate markers given their potential to decrease study time, costs, and patient burden. Objectives The purpose of this statistical workshop article is to describe and illustrate how to evaluate a surrogate marker of interest using the proportion of treatment effect (PTE) explained as a measu...

Congenital heart disease (CHD) represents a significant contributor to both morbidity and mortality in neonates and children. There’s currently no analogous dried blood spot (DBS) screening for CHD immediately after birth. This study was set to assess the feasibility of using DBS to identify reliable metabolite biomarkers with clinical relevance, w...

Background: Home-based walking exercise improves walking performance in people with lower extremity peripheral artery disease (PAD). However, whether clinical and sociodemographic factors, such as age, sex, race, comorbidities, and income, are associated with response to exercise or rates of serious adverse events (SAEs) during a home-based walking...

Introduction: In people with lower extremity peripheral artery disease (PAD), rates of participation in supervised exercise therapy are lower in women and Black Americans, compared to men and White Americans, respectively. This study used data from randomized clinical trials in participants with PAD to assess whether walking exercise improved walki...

Importance Few people with lower extremity peripheral artery disease (PAD) participate in supervised treadmill exercise covered by the Center for Medicare and Medicaid Services. In people with PAD, the benefits of home-based walking exercise, relative to supervised exercise, remain unclear. Objective To study whether home-based walking exercise im...

Motivation: Ovarian cancer (OC) is a highly lethal gynecological malignancy. Extensive research has shown that OC cells undergo significant metabolic alterations during tumorigenesis. In this study, we aim to leverage these metabolic changes as potential biomarkers for assessing ovarian cancer. Methods: A functional module-based approach was uti...

Background Congenital heart disease (CHD) represents a significant contributor to both morbidity and mortality in neonates and children. The prompt recognition of CHD can facilitate timely and appropriate intervention, reducing the probability of complications and enhancing the prognosis for impacted newborns. However, unlike other rare conditions...

Meta-analysis aggregates information across related studies to provide more reliable statistical inference and has been a vital tool for assessing the safety and efficacy of many high profile pharmaceutical products. A key challenge in conducting a meta-analysis is that the number of related studies is typically small. Applying classical methods th...

This cohort study demonstrates how to use cumulative event count curves to create a clinically meaningful end point by simultaneously considering recurrence, progression, and survival times from the individual patient.

Preeclampsia (PE) is a condition that poses a significant risk of maternal mortality and multiple organ failure during pregnancy. Early prediction of PE can enable timely surveillance and interventions, such as low-dose aspirin administration. In this study, conducted at Stanford Health Care, we examined a cohort of 60 pregnant women and collected...

Objective: To report demographics and clinical, laboratory, and imaging features of acute renal infarction (ARI) due to symptomatic isolated spontaneous renal artery dissection (SISRAD) and to analyze outcomes after the initial therapy for SISRAD. Methods: Thirteen patients with ARI due to SISRAD between January 2016 and March 2021 were enrolled...

This cohort study assesses the relative stability of median and mean survival time estimates reported in cancer clinical trials.

Objective To present our experience of preserving the isolated left vertebral artery (ILVA) with physician-modified fenestration (PM-F) or in situ fenestration (ISF) during thoracic endovascular aortic repair (TEVAR) for aortic pathologies involving aortic arch. Methods This is a single-center, retrospective, observational cohort study. Between Ju...

Background Mitochondrial abnormalities exist in gastrocnemius muscle of people with peripheral artery disease (PAD). Whether abnormalities in mitochondrial biogenesis and autophagy are associated with greater ischemia or walking impairment in PAD is unknown. Methods and Results Protein markers of mitochondrial biogenesis and autophagy and the abun...

Background: Supervised or home-based walking exercise therapy (ET) are guideline recommended to improve walking performance in people with peripheral artery disease (PAD). This study compared serious adverse event (SAE) rates associated with home-based compared to supervised exercise in people randomized into clinical trials of ET for PAD. Methods:...

Importance: For personalized or stratified medicine, it is critical to establish a reliable and efficient prediction model for a clinical outcome of interest. The goal is to develop a parsimonious model with fewer predictors for broad future application without compromising predictability. A general approach is to construct various empirical model...

The pattern of the difference between two survival curves we often observe in randomized clinical trials for evaluating immunotherapy is not proportional hazards; the treatment effect typically appears several months after the initiation of the treatment (ie, delayed difference pattern). The commonly used logrank test and hazard ratio estimation ap...

Background This study evaluated the association of smoking with mitochondrial function in gastrocnemius muscle of people with peripheral artery disease (PAD). Methods Participants were enrolled from Chicago, Illinois and consented to gastrocnemius biopsy. Mitochondrial oxidative capacity was measured in muscle with respirometry. Abundance of volta...

Background Supervised exercise therapy (SET) is the first‐line therapy for walking impairment in peripheral artery disease (PAD). This study evaluated the association between attendance at SET and improved walking performance, compared with a control group, in PAD. Methods and Results Data from 2 randomized clinical trials of SET for PAD were comb...

The primary benefit of identifying a valid surrogate marker is the ability to use it in a future trial to test for a treatment effect with shorter follow‐up time or less cost. However, previous work has demonstrated potential heterogeneity in the utility of a surrogate marker. When such heterogeneity exists, existing methods that use the surrogate...

Introduction: In humans without peripheral artery disease (PAD) and animal models, exposure to cigarette smoke is associated with reduced mitochondrial respiratory function. Many people with PAD smoke cigarettes, but the association of smoking with mitochondrial function in lower extremity skeletal muscle of people with PAD is unknown. Methods: Fro...

Background: Home-based exercise is recommended by guidelines for people with lower extremity peripheral artery disease (PAD) to improve walking performance. This post-hoc analysis of three randomized clinical trials studied the association of home-based exercise, compared to control, on rates of serious adverse events in people with PAD. Methods Da...

Introduction: Benefits of home-based exercise (HBE) interventions in lower extremity peripheral artery disease (PAD) are variable. This post-hoc analysis of the HONOR randomized trial studied characteristics of a home-based exercise intervention associated with greater 6-minute walk improvement in PAD. Methods: HONOR was a multi-centered randomized...

BACKGROUND. People with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan, an angiotensin receptor blocker (ARB), has properties that reverse these abnormalities. This randomized clinical trial tested whether telmisarta...

Background: Walking exercise is first line therapy for lower extremity peripheral artery disease (PAD); however, hospitalizations during therapy are common. In post-hoc analyses, we evaluated the effect of hospitalizations on benefits from the exercise interventions in the LITE trial. Methods: In the LITE randomized clinical trial, participants wit...

Background Peripheral artery disease (PAD) is associated with gastrocnemius muscle abnormalities. However, the biological pathways associated with gastrocnemius muscle dysfunction and their associations with progression of PAD are largely unknown. This study characterized differential gene and microRNA (miRNA) expression in gastrocnemius biopsies f...

Importance Patients with lower extremity peripheral artery disease (PAD) have reduced lower extremity perfusion, impaired lower extremity skeletal muscle function, and poor walking performance. Telmisartan (an angiotensin receptor blocker) has properties that reverse these abnormalities. Objective To determine whether telmisartan improves 6-minute...

Motivated by increasing pressure for decision makers to shorten the time required to evaluate the efficacy of a treatment such that treatments deemed safe and effective can be made publicly available, there has been substantial recent interest in using an earlier or easier to measure surrogate marker, $S$, in place of the primary outcome, $Y$. To v...

The primary benefit of identifying a valid surrogate marker is the ability to use it in a future trial to test for a treatment effect with shorter follow-up time or less cost. However, previous work has demonstrated potential heterogeneity in the utility of a surrogate marker. When such heterogeneity exists, existing methods that use the surrogate...

Background: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) occurs when a tear in the inner layer of the superior mesenteric artery (SMA) allows blood to flow between the layers of the SMA, forcing the layers apart, and creating two lumens. Abdominal pain is the most prevalent clinical manifestation. Other people may hav...

Objective This study identified barriers to participation in supervised exercise therapy covered by the Centers for Medicare and Medicaid Services (CMS), reported by people with lower extremity peripheral artery disease (PAD). Methods People with PAD participating in research studies of walking impairment due to PAD in the Chicagoland area were as...

This decision analytical model study examines premature treatment discontinuation in clinical trials for patients with advanced renal cell carcinoma.

Purpose: To report the early experience and mid-term outcomes of physician-modified fenestrated or branched endovascular repair (PM-F/BEVAR) for patients with post-dissection thoracoabdominal aortic aneurysm (PD-TAAA). Methods: PD-TAAA patients treated with PM-F/BEVAR between December 2014 and September 2020 in our institution were retrospective...

Background: Data on the occurrence times of multiple outcomes, reflecting the temporal profile of disease burden/progression, have been used to estimate treatment effects in various recent randomized trials. Most procedures for analyzing these data require specific model assumptions. When the assumptions are not met, the results may be misleading....

Objectives Coarctation of the aorta with poststenotic aneurysms is rare and complex. Here we report a relatively large group of endovascular treatments for the disease. Materials and Methods 15 patients from two centers between 2006 and 2019 were included in the study. The patients were retrospectively divided into two groups. Patients in the comp...

Objectives: Leiomyosarcoma of the inferior vena cava (IVC) is rare. The study reviewed patients with IVC leiomyosarcoma in our hospital in the past ten years. Methods: Twenty patients diagnosed with IVC leiomyosarcoma between October 2010 and October 2020 were enrolled. Their clinical manifestations, treatments, and follow-up results were analyz...

Background: Pregnancy triggers longitudinal metabolic alterations in women to allow precisely-programmed fetal growth. Comprehensive characterization of such a “metabolic clock” of pregnancy may provide a molecular reference in relation to studies of adverse pregnancy outcomes. However, a high-resolution temporal profile of metabolites along a heal...

Purpose To evaluate the safety and efficacy of covered stents for visceral artery aneurysms (VAA). Methods This multicenter retrospective study included patients with VAAs that were treated with covered stents between January 2015 and December 2020. A total of 65 patients (mean age, 58 years [range, 27-89]) with 70 VAAs (60 true aneurysms [86%], 1...

206 Background: Human serum metabolome profiles have been analyzed to explore the molecular changes that occur with aging. We hypothesized that deep metabolic profiling of sera with different ages would allow the identification of distinct metabolic chronologic patterns as a normal biological baseline to study personal aging. We further hypothesize...

Background In people with peripheral artery disease, post hoc analyses of the LITE (Low Intensity Exercise Intervention in Peripheral Artery Disease) randomized trial were conducted to evaluate the effects of walking exercise at a pace inducing ischemic leg symptoms on walking velocity and the Short Physical Performance Battery, compared with walki...

Background Associations of 1‐year change in functional performance measures with subsequent mobility loss and mortality in people with lower extremity peripheral artery disease are unknown. Methods and Results Six‐minute walk and 4‐meter walking velocity (usual and fastest pace) were measured at baseline and 1 year later in 612 people with periphe...

In studies that require long-term and/or costly follow-up of participants to evaluate a treatment, there is often interest in identifying and using a surrogate marker to evaluate the treatment effect. While several statistical methods have been proposed to evaluate potential surrogate markers, available methods generally do not account for or addre...

Importance In a comparative trial, the time to a clinical event is often a key end point. However, the occurrence of a terminal event, such as death or premature study discontinuation, may preclude observation of this outcome. Although various methods for handling competing risks are available, no specific recommendations have been made for scenari...

Objective: In a randomized clinical trial of people with lower extremity peripheral artery disease (PAD), to test whether walking exercise conducted at a pace without ischemic leg symptoms improved physical activity more than walking exercise conducted at a pace that induced ischemic leg symptoms and more than an attention control group. Methods &...

Introduction: Recent evidence showed that among people with peripheral artery disease (PAD), walking exercise conducted at a pace inducing ischemic leg symptoms improved six-minute walk distance (6MW), while walking exercise conducted at a pace without ischemic leg symptoms had no effect on 6MW. This report describes associations of walking exercis...

Introduction: The LITE randomized trial recently demonstrated that home-based pain free walking exercise did not improve 6-minute walk distance, compared to home-based ischemic pain inducing walking exercise, and compared to an attention control group, among people with lower extremity peripheral artery disease (PAD). This study examined effects of...

Introduction: Among patients with peripheral artery disease (PAD), there is an inverse association between the ABI and the risk of functional decline. Whether the association is consistent for adults with vs without diabetes is unknown. Methods: Adults with PAD (ABI<0.90) were identified from vascular labs and outpatient clinics from 4 Chicago-area...

Introduction: Supervised exercise therapy (SET) is first line therapy for improving walking ability in people with peripheral artery disease (PAD), but adherence to SET is poor. The association of SET adherence with change in six-minute walk distance in PAD is unclear. Methods: Data were combined from two randomized clinical trials of SET for PAD....

To the Editor Jabbour and colleagues¹ conducted an important, exploratory nonrandomized clinical trial to evaluate treatment outcomes and safety of pembrolizumab plus concurrent chemoradiation therapy for patients with non–small cell lung cancer in 2 cohorts: A (squamous/nonsquamous) and B (nonsquamous). One of the primary end points was the object...

Introduction An individual’s understanding of disease risk factors and outcomes is important for the ability to make healthy lifestyle choices and decisions about disease treatment. Peripheral artery disease (PAD) is a condition with increasing global prevalence and high risk of adverse patient outcomes. This study seeks to understand the adequacy...

In a comparative oncology study with progression-free or overall survival as the endpoint, the primary or key secondary analysis is routinely stratified by patients’ baseline characteristics when evaluating the treatment difference. The validity of a conventional strategy such as a stratified HR analysis depends on stringent model assumptions that...

Background Hospitalized preterm infants with compromised skin barrier function treated topically with sunflower seed oil (SSO) have shown reductions in sepsis and neonatal mortality rate (NMR). Mustard oil and products commonly used in high-mortality settings may possibly harm skin barrier integrity and enhance risk of infection and mortality in ne...

The potential benefit of using a surrogate marker in place of a long‐term primary outcome is very attractive in terms of the impact on study length and cost. Many available methods for quantifying the effectiveness of a surrogate endpoint either rely on strict parametric modeling assumptions or require that the primary outcome and surrogate marker...

Background: Leiomyosarcoma of the inferior vena cava (IVC) is rare. The study reviewed patients with IVC leiomyosarcoma in our hospital in the past ten years. Methods: 20 patients diagnosed with IVC leiomyosarcoma between October 2010 and October 2020 were enrolled. Their clinical manifestations, treatments and follow-up results were analyzed. Resu...

Statement of Retraction We, the Editors and Publisher of the journal Cell Cycle, have retracted the following article: Qian-Qian Zhu, Xi-Bin Pu, Tian-Chi Chen, Chen-Yang Qiu, Zi-Heng Wu, Lu Tian, Yang-Yan He, Xiao-Hui Wang, Tao Shang, Xun Wang, Yi-Lang Xiang, Dong-Lin Li, and Hong-Kun Zhang. Hsa_circ_0008360 sponges miR-186-5p to target CCND2 to mo...

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effects of endovascular therapy versus medical treatment for people with spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Numerous studies have revealed that hyperglycemia is a pivotal driver of diabetic vascular complications. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspec...

Background In people with lower‐extremity peripheral artery disease, the effects of exercise on patient‐reported outcomes remain unclear. Methods and Results Four hundred four people with peripheral artery disease in 3 clinical trials were randomized to exercise (N=205) or a control group (N=199) and completed the 6‐minute walk and the Walking Imp...

Objective Supervised exercise therapy (SET) improves walking ability in people with peripheral artery disease (PAD). However, the effects of SET on cardiovascular health in PAD remains unclear. Using data from a randomized clinical trial, this post-hoc study investigated the effects of a 6-month SET intervention, compared to a control group, on cha...

Introduction: Peripheral artery disease (PAD) affects 10-15% of people age 65 and older, and the prevalence is expected to rise as the population ages. People with PAD have greater functional impairment and faster decline in walking performance than people without PAD. Objectives: To determine the association between 1-year change in walking perfor...

Background: Pathogenesis of cardiovascular diseases begins with endothelial dysfunction. Our previous study has shown that advanced glycation end products (AGE) could inhibit the expression of homeobox A9 (Hoxa9), thereby inducing endothelial dysfunction. Leucine-rich repeat flightless-interacting protein 1 (LRRFIP1) has been found to participate...

To the Editor The RELAx study examined whether lower positive end-expiratory pressure (PEEP) was noninferior to higher PEEP among intensive care unit (ICU) patients without acute respiratory distress syndrome.¹ The study’s primary outcome was the number of days that patients were alive and free of invasive mechanical ventilation at 28 days of follo...

This study investigated cross-sectional associations of peripheral artery disease (PAD) severity (defined by the ankle–brachial index (ABI)) and amounts of daily sustained physical activity (PA) (defined as > 100 activity counts per minute lasting 5 consecutive minutes or more). This study also investigated associations of amounts of daily sustaine...

Importance Supervised high-intensity walking exercise that induces ischemic leg symptoms is the first-line therapy for people with lower-extremity peripheral artery disease (PAD), but adherence is poor. Objective To determine whether low-intensity home-based walking exercise at a comfortable pace significantly improves walking ability in people wi...

Objective Numerous evidence indicates that hyperglycemia is a pivotal driver of the vascular complications of diabetes. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia fr...