Hypertriglyceridemia as a risk factor for complications of acute pancreatitis and the development of a severity prediction model.

BACKGROUND: Hypertriglyceridemia (HTG) is a major cause of acute pancreatitis (AP). We aimed to determine whether HTG is an independent risk factor for AP complications and construct a prediction model for non-mild AP. METHODS: We conducted a multi-center cohort study including 872 patients with AP and divided them into HTG-AP and non-HTG-AP groups. Multivariate logistic regression was performed, and a prediction model for non-mild HTG-AP was developed. RESULTS: HTG-AP patients had a higher risk of systemic complications, including systemic inflammatory response syndrome [odds ratio (OR): 1.718; 95% confidence interval (CI): 1.286-2.295], shock (OR: 2.103; 95%CI: 1.236-3.578), acute respiratory distress syndrome (OR: 2.231; 95%CI: 1.555-3.200), acute renal failure (OR: 1.593; 95%CI: 1.036-2.450), and local complications such as acute peripancreatic fluid collection (OR: 2.072; 95%CI: 1.550-2.771), acute necrotic collection (OR: 1.996; 95%CI: 1.394-2.856), and walled-off necrosis (OR: 2.157; 95%CI: 1.202-3.870). The area under curve of our prediction model was 0.898 (95%CI: 0.857-0.940) and 0.875 (95%CI: 0.804-0.946) in the derivation and validation datasets respectively. CONCLUSION: HTG is an independent risk factor for AP complications. We constructed a simple and accurate prediction model for progression of non-mild AP.

Interactions between genetic variants and environmental risk factors are associated with the severity of pelvic organ prolapse.

OBJECTIVE: Both environmental and genetic risk factors contribute to pelvic organ prolapse (POP). No genome-wide study has investigated the gene-environment (G × E) interactions. In this study, we aim to identify single nucleotide polymorphisms (SNPs) that may interact with the potential environmental factors, maximum birth weight, and age in Chinese women. METHODS: We recruited 576 women for phase 1 and 264 women for phase 2 with stages III and IV prolapse from six geographic regions of China. Genomic DNAs from blood samples were genotyped using Affymetrix Axiom Genome-Wide CHB1 Array of 640,674 SNPs for phase 1 and Illumina Infinium Asian Screening Array of 743,722 SNPs for phase 2. Meta-analysis was used to combine the two results. Interactions of genetic variants with maximum birth weight and age on POP severity were identified. RESULTS: In phase 1, 502,283 SNPs in 523 women passed quality control and 450 women had complete POP-quantification measurements. In phase 2, 463,351 SNPs in 257 women passed quality control with complete POP-quantification measurements. Three SNPs rs76662748 ( WDR59 , Pmeta = 2.146 × 10 -8 ), rs149541061 ( 3p26.1 , Pmeta = 9.273 × 10 -9 ), and rs34503674 ( DOCK9 , Pmeta = 1.778 × 10 -9 ) respectively interacted with maximum birth weight, and two SNPs rs74065743 ( LINC01343 , Pmeta = 4.386 × 10 -8 ) and rs322376 ( NEURL1B - DUSP1 , Pmeta = 2.263 × 10 -8 ), respectively, interacted with age. The magnitude of disease severity associated with maximum birth weight and age differed according to genetic variants. CONCLUSIONS: This study provided preliminary evidence that interactions between genetic variants and environmental risk factors are associated with POP severity, suggesting the potential use of combining epidemiologic exposure data with selected genotyping for risk assessment and patient stratification.

Age, sex and angiographic type-related phenotypic differences in inpatients with Takayasu arteritis: A 13-year retrospective study at a national referral center in China.

Backgrounds: We aimed to investigate the demographic characteristics, vascular involvement, angiographic patterns, complications, and associations of these variables in a large sample of TAK patients at a national referral center in China. Methods: The medical records of TAK patients discharged from 2008 to 2020 were retrieved from the hospital discharge database using ICD-10 codes. Demographic data, vascular lesions, Numano classifications and complications were collected and analyzed. Results: The median age at onset was 25 years in 852 TAK patients (670 female, 182 male). Compared with the females, the male patients were more likely to have type IV and were more likely to have iliac (24.7% vs. 10.0%) and renal artery (62.7% vs. 53.9%) involvement. They also had a higher prevalence of systemic hypertension (62.1% vs. 42.4%), renal dysfunction (12.6% vs. 7.8%) and aortic aneurysm (AA) (8.2% vs. 3.6%). The childhood-onset group was more likely to have involvement of the abdominal aorta (68.4% vs. 52.1%), renal artery (69.0% vs. 51.8%) and superior mesenteric artery (41.5% vs. 28.5%), and they were more likely to have type IV, V and hypertension than the adult-onset group. After adjusting for sex and age at onset, the patients with type II were associated with an increased risk of cardiac dysfunction (II vs. I: OR = 5.42; II vs. IV: OR = 2.63) and pulmonary hypertension (II vs. I: OR = 4.78; II vs. IV: OR = 3.95) compared with those with types I and IV. Valvular abnormalities (61.0%) were observed to be most prevalent in patients with type IIa. The patients with Type III were associated with a higher risk of aortic aneurysm (23.3%) than the patients with types IV (OR = 11.00) and V (OR = 5.98). The patients with types III and IV were more commonly complicated with systemic hypertension than the patients with types I, II and V. P < 0.05 in all of the above comparisons. Conclusion: Sex, adult/childhood presentation and Numano angiographic type were significantly associated with differences in phenotypic manifestations, especially cardiopulmonary abnormalities, systemic hypertension, renal dysfunction and aortic aneurysm.

Safety of Withholding Perioperative Hydrocortisone for Patients With Pituitary Adenomas With an Intact Hypothalamus-Pituitary-Adrenal Axis: A Randomized Clinical Trial.

Importance: Pituitary adenoma is the second most common primary brain tumor. Perioperative hydrocortisone has been used for decades to avoid postoperative adrenal insufficiency. Recent studies suggest that withholding perioperative hydrocortisone may be safe for patients with an intact hypothalamus-pituitary-adrenal (HPA) axis. Objective: To assess the safety of withholding hydrocortisone during the perioperative period of pituitary adenoma surgery for patients with an intact HPA axis. Design, Setting, and Participants: A parallel-group, triple-masked, noninferiority randomized clinical trial was conducted at Peking Union Medical College Hospital from November 1, 2020, to January 31, 2022, among 436 patients aged 18 to 70 years with an intact HPA axis undergoing surgery for pituitary adenomas. Interventions: Hydrocortisone supplementation protocol (intravenous and subsequent oral hydrocortisone, using a taper program) or no-hydrocortisone protocol. Main Outcomes and Measures: The primary outcome was the incidence of new-onset adrenal insufficiency (morning cortisol level, <5 µg/dL with adrenal insufficiency-related symptoms) during the perioperative period (on the day of operation and the following 2 days). The secondary outcome was the incidence of adrenal insufficiency in postoperative month 3. Analysis was on an intention-to-treat basis. Results: Of the 436 eligible patients, 218 were randomly assigned to the hydrocortisone group (136 women [62.4%]; mean [SD] age, 45.4 [13.0] years) and 218 to the no-hydrocortisone group (128 women [58.7%]; mean [SD] age, 44.5 [13.8] years). All patients completed 3-month postoperative follow-up. The incidence of new-onset adrenal insufficiency during the perioperative period was 11.0% (24 of 218; 95% CI, 6.9%-15.2%) in the no-hydrocortisone group and 6.4% (14 of 218; 95% CI, 3.2%-9.7%) in the hydrocortisone group, with a difference of 4.6% (95% CI, -0.7% to 9.9%), meeting the prespecified noninferiority margin of 10 percentage points. The incidence of adrenal insufficiency at the 3-month follow-up was 3.7% (8 of 218) in the no-hydrocortisone group and 3.2% (7 of 218) in the hydrocortisone group (difference, 0.5%; 95% CI, -3.0% to 3.9%). Incidences of new-onset diabetes mellitus (1 of 218 [0.5%] vs 9 of 218 [4.1%]), hypernatremia (9 of 218 [4.1%] vs 21 of 218 [9.6%]), hypokalemia (23 of 218 [10.6%] vs 34 of 218 [15.6%]), and hypocalcemia (6 of 218 [2.8%] vs 19 of 218 [8.7%]) were lower in the no-hydrocortisone group than in the hydrocortisone group. Lower preoperative morning cortisol levels were associated with higher risks of the primary event (<9.3 µg/dL; odds ratio, 3.0; 95% CI, 1.5-5.9) and the secondary event (<8.8 µg/dL; odds ratio, 7.8; 95% CI, 2.6-23.4) events. Conclusions and Relevance: This study found that withholding hydrocortisone was safe and demonstrated noninferiority to the conventional hydrocortisone supplementation regimen regarding the incidence of new-onset adrenal insufficiency among patients with an intact HPA axis undergoing pituitary adenomectomy. Trial Registration: ClinicalTrials.gov Identifier: NCT04621565.

CCL17 acts as a novel therapeutic target in pathological cardiac hypertrophy and heart failure.

Circulating proteomic signatures of age are closely associated with aging and age-related diseases; however, the utility of changes in secreted proteins in identifying therapeutic targets for diseases remains unclear. Serum proteomic profiling of an age-stratified healthy population and further community-based cohort together with heart failure patients study demonstrated that circulating C-C motif chemokine ligand 17 (CCL17) level increased with age and correlated with cardiac dysfunction. Subsequent animal experiments further revealed that Ccll7-KO significantly repressed aging and angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis, accompanied by the plasticity and differentiation of T cell subsets. Furthermore, the therapeutic administration of an anti-CCL17 neutralizing antibody inhibited Ang II-induced pathological cardiac remodeling. Our findings reveal that chemokine CCL17 is identifiable as a novel therapeutic target in age-related and Ang II-induced pathological cardiac hypertrophy and heart failure.

Remission and Transition of Female Urinary Incontinence and Its Subtypes and the Impact of Body Mass Index on This Progression: A Nationwide Population-Based 4-Year Longitudinal Study in China.

PURPOSE: We estimated the remission and transition rate between urinary incontinence (UI) subtypes in women with UI and evaluated the impact of body mass index (BMI) on this process. MATERIALS AND METHODS: A Chinese population-based longitudinal study was conducted. Women aged ≥20 years were included using a multistage, stratified, cluster sampling method. Self-reported data on demographics, medical history, and physiological and anthropometric information were collected. UI was identified using 2 questions about any leaking symptom of stress UI (SUI) and urgency UI (UUI) in the past 6 months. Predicted probabilities of UI subtypes were calculated using multinomial logistic regression. RESULTS: Analyses included 5,189 women (mean age 52.6 years, mean BMI 23.8 kg/m2), of whom 98.5% were parous. The median followup time was 4.0 years. Overall, the annual remission rate of UI was 12.7% among adult women. Regarding UI subtypes, the remission rates for UUI and SUI were similar, but higher than that for mixed urinary incontinence (MUI; p <0.05). In total, 7.6% of SUI patients and 16.4% of UUI patients developed MUI, and 35.3% of MUI patients continued to report MUI after 4 years. For women aged ≥60 years with a BMI ≥24 kg/m2 and MUI at onset, the predicted remission rate (95% CI) was only 0.32 (0.29-0.35), but the predicted probability of the MUI remaining reached 0.50 (0.46-0.54). CONCLUSIONS: The annual remission rate of UI was 12.7% among adult women. Women with a higher BMI had less remission and a higher predicted probability of MUI 4 years later.

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis.

Background: Carotid artery stenosis (CAS) is caused by the formation of atherosclerotic plaques inside the arterial wall and accounts for 20-30% of all strokes. The development of an early, noninvasive diagnostic method and the identification of high-risk patients for ischemic stroke is essential to the management of CAS in clinical practice. Methods: We used the data-independent acquisition (DIA) technique to conduct a urinary proteomic study in patients with CAS and healthy controls. We identified the potential diagnosis and risk stratification biomarkers of CAS. And Ingenuity pathway analysis was used for functional annotation of differentially expressed proteins (DEPs). Furthermore, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic values of DEPs. Results: A total of 194 DEPs were identified between CAS patients and healthy controls by DIA quantification. The bioinformatics analysis showed that these DEPs were correlated with the pathogenesis of CAS. We further identified 32 DEPs in symptomatic CAS compared to asymptomatic CAS, and biological function analysis revealed that these proteins are mainly related to immune/inflammatory pathways. Finally, a biomarker panel of six proteins (ACP2, PLD3, HLA-C, GGH, CALML3, and IL2RB) exhibited potential diagnostic value in CAS and good discriminative power for differentiating symptomatic and asymptomatic CAS with high sensitivity and specificity. Conclusions: Our study identified novel potential urinary biomarkers for noninvasive early screening and risk stratification of CAS.

Establishing a Risk Prediction Model for Atherosclerosis in Systemic Lupus Erythematosus.

Background and aims: Patients with systemic lupus erythematosus (SLE) have a significantly higher incidence of atherosclerosis than the general population. Studies on atherosclerosis prediction models specific for SLE patients are very limited. This study aimed to build a risk prediction model for atherosclerosis in SLE. Methods: RNA sequencing was performed on 67 SLE patients. Subsequently, differential expression analysis was carried out on 19 pairs of age-matched SLE patients with (AT group) or without (Non-AT group) atherosclerosis using peripheral venous blood. We used logistic least absolute shrinkage and selection operator regression to select variables among differentially expressed (DE) genes and clinical features and utilized backward stepwise logistic regression to build an atherosclerosis risk prediction model with all 67 patients. The performance of the prediction model was evaluated by area under the curve (AUC), calibration curve, and decision curve analyses. Results: The 67 patients had a median age of 42.7 (Q1-Q3: 36.6-51.2) years, and 20 (29.9%) had atherosclerosis. A total of 106 DE genes were identified between the age-matched AT and Non-AT groups. Pathway analyses revealed that the AT group had upregulated atherosclerosis signaling, oxidative phosphorylation, and interleukin (IL)-17-related pathways but downregulated T cell and B cell receptor signaling. Keratin 10, age, and hyperlipidemia were selected as variables for the risk prediction model. The AUC and Hosmer-Lemeshow test p-value of the model were 0.922 and 0.666, respectively, suggesting a relatively high discrimination and calibration performance. The prediction model had a higher net benefit in the decision curve analysis than that when predicting with age or hyperlipidemia only. Conclusions: We built an atherosclerotic risk prediction model with one gene and two clinical factors. This model may greatly assist clinicians to identify SLE patients with atherosclerosis, especially asymptomatic atherosclerosis.

Reduction in SLEDAI is associated with improved arterial stiffness in systemic lupus erythematosus.

Lipid abnormalities are an important cause of premature atherosclerosis in patients with systemic lupus erythematosus (SLE). This longitudinal study investigates the changes in lipid profile and arterial stiffness with SLE disease activity index (SLEDAI) reduction.Fifty one female SLE patients with baseline SLEDAI ≥ 6 and SLEDAI reduction >3 at 1-year follow-up were included. Neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and mean brachial-ankle pulse wave velocity (baPWV) were measured and compared between baseline and 1-year follow-up. Correlations between inflammation biomarkers, SLEDAI, mean baPWV and lipid profile were assessed.We observed significant decreases in ESR, mean baPWV, TG and TC to HDL-C ratio compared with baseline at 1-year follow up, while HDL-C, hsCRP, and NLR were not significantly changed. Significant correlations were found between the reductions in ESR and TG, and SLEDAI and mean baPWV, with adjustment to age, disease duration, blood pressure, and medications (prednisone, immunosuppressants and ARB/ACEI).SLE patients experiencing SLEDAI reductions showed improvements in arterial stiffness. This finding may provide insight into the beneficial effects of reducing SLEDAI on atherosclerosis risk in SLE.

Clinical characteristics and survival analysis in critical and non-critical patients with COVID-19 in Wuhan, China: a single-center retrospective case control study.

Since the outbreak of COVID-19 in China at the end of 2019, the world has experienced a large-scale epidemic caused by the SARS-CoV-2. The epidemiological and clinical course of COVID-19 patients has been reported, but there have been few analyses about the characteristics, predictive risk factors, and outcomes of critical patients. In this single-center retrospective case-control study, 90 adult inpatients hospitalized at Tongji Hospital (Wuhan, China) were included. Demographic, clinical, laboratory tests, and treatment data were obtained and compared between critical and non-critical patients. We found that compared with non-critical patients, the critical patients had higher SOFA score and qSOFA scores. Critical patients had lower lymphocyte and platelet count, elevated D-dimer, decreased fibrinogen, and elevated high-sensitivity C-reactive protein (hsCRP), and interleukin-6(IL-6). More critical patients received treatment including antibiotics, anticoagulation, corticosteroid, and oxygen therapy than non-critical ones. Multivariable regression showed higher qSOFA score and elevation of IL-6 were related to critical patients. Antibiotic usage and anticoagulation were associated with decreased in-hospital mortality. And critical grouping contributed greatly to in-hospital death. Critical COVID-19 patients have a more severe clinical course. qSOFA score and elevation of IL-6 are risk factors for critical condition. Non-critical grouping, positive antibiotic application, and anticoagulation may be beneficial for patient survival.

Clinical Characteristics, Treatment, and Outcomes in Patients with Idiopathic Inflammatory Myopathy Concomitant with Heart Failure.

This study sought to evaluate clinical features, treatment patterns, and outcomes of patients with idiopathic inflammatory myopathy (IIM) complicated by heart failure (HF). Thirty-two patients with IIM-HF admitted to the Peking Union Medical College Hospital between January 1999 and January 2018 were retrospectively reviewed, including 14 patients with polymyositis, 11 with dermatomyositis, and 7 with overlap syndrome. Survivors and no-survivors were compared on clinical characteristics and treatment. Although systemic symptoms were variable, all patients presented with elevated troponin I. Rapid atrial arrhythmia was the most frequent arrhythmia. Systolic dysfunction and restrictive diastolic dysfunction were typical presentations in echocardiography. Twenty-nine patients were followed up for a median of 2.8 years (0.1 month to 11 years). We recorded 13 deaths of cardiogenic cause, 1 of serious IIM, and 3 of infective complications. The median survival time from diagnosis of IIM-HF to all-cause mortality was 8.4 months (range from 1 month to 5 years). Both all-cause deaths and cardiogenic deaths were more reported in the methotrexate-alone group than in the combination therapy group (6/7 versus 3/10, P = 0.050; 5/6 versus 2/9, P = 0.041). Combination therapy including methotrexate (HR = 0.188, 95%CI 0.040-0.871, P = 0.033) and taking ß-receptor blockers (HR = 0.249, 95%CI 0.086-0.719, P = 0.010) was associated with reduced risk of all-cause deaths. In conclusion, elevated troponin I, atrial arrhythmia, and systolic and restrictive diastolic dysfunction are typical characteristics of IIM-HF. Combined immunosuppression that includes methotrexate and ß-receptor blockers seems to be important to improve survival.

Health status of middle-aged and older cancer survivors: a nationwide cross-sectional study from the China Health and Retirement Longitudinal Study (CHARLS).

BACKGROUND: The number of Chinese cancer survivors has increased bolstered by the combined trends of an aging population and improved cancer survival; however, related research on cancer survivorship remains limited. Therefore, this study aimed to provide an overview of the health status of middle-aged and older cancer survivors in China. METHODS: We used the cross-sectional self-reported survey data from wave 4 in the China Health and Retirement Longitudinal Study (CHARLS). A total of 354 cancer survivors and 16,664 participants without cancer were identified from CHARLS. Physical and mental health, health behavior, and health care information collected by questionnaire were compared between these two groups. RESULTS: Compared with the general middle-aged and older population, cancer survivors had more concomitant chronic diseases (2.75 vs. 2.00, P<0.001). In addition, cancer survivors were found to be more statistically likely to have difficulties with activity (3.53 vs. 2.39, P<0.001) and have depressive symptoms (10.07 vs. 8.01, P<0.001) compared with participants without cancer. Also, cancer survivors were less likely to drink compared to those without a cancer diagnosis (OR 0.49; 95% CI, 0.36-0.66, P<0.001), but smoking behavior and physical activity did not show a significant difference. Coexisting chronic diseases and smoking harmed the physical and mental health of middle-aged and older people. We also found that cancer survivors had higher medical care expenses when compared with participants without cancer. CONCLUSIONS: Cancer survivors older than 45 years in China have poorer outcomes in comorbidities and physical and mental health than their age-matched individual counterparts without cancer. Therefore, a higher quality and more cost-effective supportive care for these individuals is needed.

Factors associated with health-related quality of life in community-dwelling elderly people in China.

AIM: Few studies have comprehensively evaluated the factors associated with health-related quality of life (HRQOL) in the elderly. The purpose of the study is to identify the factors associated with HRQOL using a comprehensive geriatric assessment of community-dwelling elderly people in Beijing, China. METHODS: A cross-sectional survey of 896 community-dwelling elderly people in Beijing was conducted through face-to-face interviews. Data regarding sociodemographic factors, chronic disease (assessed by the Cumulative Illness Rating Scale for Geriatrics, CIRS-G), common geriatric syndromes and HRQOL (assessed by the EuroQol 5-Dimension questionnaire, EQ-5D) were collected using a structured questionnaire. Binary logistic regression analysis was used to identify the factors related to HRQOL. RESULTS: The CIRS-G comorbidity index was negatively related to the EQ-5D index and EQ-Visual Analog Scale (VAS) (P < 0.05). Geriatric syndromes such as chronic pain and non-optimal nutrition were negatively related to HRQOL (P < 0.05), and the negative influence of geriatric syndromes on the EQ-5D index was stronger than that of the cumulative comorbidities. Functional status in daily living activities was positively related to HRQOL (P < 0.05). Receiving care from children was positively related to EQ-VAS (P < 0.05). CONCLUSIONS: Besides cumulative comorbidities and geriatric syndromes, in particular nutritional problems and chronic pain exert a substantial negative impact on the HRQOL of elderly people in China, whereas family support is an important protective factor. Geriatr Gerontol Int 2020; 20: 422-429.

Usefulness of Myocardial Strain and Twist for Early Detection of Myocardial Dysfunction in Patients With Autoimmune Diseases.

Cardiac involvement in autoimmune diseases (AD) is common but underdiagnosed due to a lack of sensitive imaging methods. We aim to evaluate the characteristics of left ventricular (LV) systolic dysfunction in patients with AD using deformational parameters from 2-dimensional speckle-tracking echocardiography (STE). We retrospectively enrolled 86 AD patients and 71 healthy controls. All subjects underwent transthoracic echocardiography and STE to analyze LV strain and twist. A twist-radial displacement loop was constructed to investigate the relation between LV contractility and dimension. In AD patients, 68 had preserved LV ejection fraction (EF ≥ 50%), and 18 had reduced LVEF (EF < 50%). The patients with preserved LVEF exhibited significantly lower values of global longitudinal, circumferential, and radial strain than controls (-19.11 ± 4.18 vs -21.49 ± 2.53%, -25.17 ± 5.04% vs -27.37 ± 2.87%, 17.68 ± 5.69% vs 21.17 ± 6.44%, respectively; all p <0.01) and a marked attenuation in peak twist (14.24 ± 5.57 vs 18.10 ± 5.97, p <0.01) attributed to impaired apical rotation (9.03 ± 5.17 vs 12.79 ± 5.99, p <0.01). AD patients were more likely to present with abnormal loop types with flat ascending slope and delayed peak twist time. In conclusion, abnormal strain and twist precede deterioration in LVEF, suggesting early myocardial involvement in AD. STE can be used as a good alternative for early detection of myocardial dysfunction in AD patients.

Risk factors for progression of carotid intima-media thickness in patients with systemic lupus erythematosus: protocol for an observational cohort study in China.

INTRODUCTION: Accelerated atherosclerosis is a major complication of systemic lupus erythematosus (SLE), and it leads to increased cardiovascular morbidity and mortality in patients with SLE. This study aimed to investigate the natural progression of carotid intima-media thickness (CIMT), and to examine the risk factors for progression of CIMT and atherosclerotic plaques based on a Chinese SLE cohort. METHODS AND ANALYSIS: Participants were continuously enrolled as outpatients of the Department of Rheumatology in Peking Union Medical College Hospital (PUMCH) from October 2013 to December 2016. Inclusion criteria were as follows: (1) age ≥18 years, (2) fulfilment of clinical classification criteria of SLE and (3) provision of signed written informed consent. Patients with clinically overt coronary artery disease, a history of cardiovascular disease (previous stroke, heart failure, myocardial infarction, angina or symptomatic peripheral artery disease) and malignancy, and pregnant/lactating women were excluded. The primary outcome is progression of CIMT from baseline. A total of 440 patients with SLE will be enrolled. Participants will receive follow-up surveys ~5 years after their baseline visit. A standard structural survey form, including demographic data, medical history, clinical and laboratory assessments and CIMT measurement, is planned for data collection at baseline and follow-up. The risk prediction model for progression of CIMT will be created by using a mixed effect model. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review board of PUMCH (S-599). Informed consent was obtained from all participants according to the Declaration of Helsinki on Biomedical Research Involving Human Studies. All data will be managed confidentially according to guidelines and legislation. Dissemination will include publication of scientific papers and/or presentations of the study findings at international conferences.

Early detection of cognitive impairment in patients with insulinoma.

PURPOSE: Long-standing hypoglycemia can cause cognitive impairment, and whether recurrent severe hypoglycemia impacts cognitive function in patients with insulinoma has not been studied. This study focused on exploring the cognitive function in patients with insulinoma. METHODS: A prospective study was conducted to assess cognitive function in patients with insulinoma by administering the Montreal Cognitive Assessment (MoCA) questionnaire between January 2016 and July 2017, and patients with cognitive impairment were followed up to undergo the MoCA test 1 year after surgery. The MoCA scores after surgery were compared with the scores before surgery, and the associations between cognitive impairment and relevant factors were further evaluated by multiple linear regression analysis. RESULTS: Eighteen out of thirty-four patients (53%) with insulinoma were screened positive for cognitive impairment as defined by a MoCA score <26. Performance in certain cognitive domains, including visuospatial and executive functions, delayed memory, attention, language, and abstraction, was significantly worse in patients with cognitive impairment. Multivariate analysis indicated that MoCA scores correlated significantly with tumor grade and years of education. Eight patients with cognitive impairment were lost to follow-up. The remaining ten patients with cognitive impairment showed improvements 1 year postoperatively, and seven patients recovered to normal cognitive function. CONCLUSIONS: Cognitive impairment was found in patients with insulinoma and was reversible in some patients 1 year after surgery. More studies are needed to explore the underlying mechanisms of the existence and reversibility of cognitive impairment in patients with insulinoma.

Validity of discharge ICD-10 codes in detecting the etiologies of endogenous Cushing's syndrome.

OBJECTIVE: To investigate the validity of discharge ICD-10 codes in detecting the etiology of endogenous Cushing's syndrome (CS) in hospitalized patients. METHODS: We evaluated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CS etiology-related ICD-10 codes or code combinations by comparing hospital discharge administrative data (DAD) with established diagnoses from medical records. RESULTS: Coding for patients with adrenocortical adenoma (ACA) and those with bilateral macronodular adrenal hyperplasia (BMAH) demonstrated disappointingly low sensitivity at 78.8% (95% CI: 70.1-85.6%) and 83.9% (95% CI: 65.5-93.9%), respectively. BMAH had the lowest PPV of 74.3% (95% CI: 56.4-86.9%). In confirmed ACA patients, the sensitivity for ACA code combinations was higher in patients initially admitted to the Department of Endocrinology before surgery than that in patients directly admitted to the Department of Urology (90.0 vs 73.1%, P = 0.033). The same phenomenon was observed in the PPV for the BMAH code (100.0 vs 60.9%, P = 0.012). Misinterpreted or confusing situations caused by coders (68.1%) and by the omission or denormalized documentation of symptomatic diagnosis by clinicians (26.1%) accounted for the main source of coding errors. CONCLUSIONS: Hospital DAD is an effective data source for evaluating the etiology of CS but not ACA and BMAH. Improving surgeons' documentation, especially in the delineation of symptomatic and locative diagnoses in discharge abstracts; department- or disease-specific training for coders and more multidisciplinary collaboration are ways to enhance the applicability of administrative data for CS etiologies.

Plasma levels of receptor interacting protein kinase-3 correlated with coronary artery disease.

BACKGROUND: Necroptosis plays an important role in human atherosclerosis and atheroma development. Since receptor interacting protein kinase-3 (RIP3) acts as a key mediator of necroptosis, this study aimed to explore its relationship between plasma RIP3 levels and coronary artery disease (CAD) and discover a potential new biomarker for screening CAD subtypes and severity. METHODS: A total of 318 patients with CAD who had coronary angiography and 166 controls in Peking Union Medical College Hospital from September 2017 to January 2018 were enrolled in this study. Patients with CAD were divided into three subgroups: patients with stable coronary artery disease (SCAD), patients with unstable angina (UA), and patients with myocardial infarction (MI). The severity of atherosclerosis was determined by Gensini score (GSS). Logistic regression was used to determine the relationship between plasma RIP3 levels and CAD. The correlation between plasma RIP3 and GSS was calculated using multiple linear regression models. RESULTS: Overall, plasma RIP3 levels were significantly higher than serum RIP3 levels. Plasma RIP3 levels in patients with CAD were significantly higher than those in controls. Plasma RIP3 levels were strongly associated with CAD (odds ratio: 6.00, 95% confidence interval 3.04-11.81; P < 0.001). Plasma RIP3 levels increased linearly from controls to patients with SCAD, then patients with UA, and finally to patients with MI. We found a significantly positive correlation between proportion of cases of acute coronary syndrome in subjects and their plasma RIP3 level quartile. Plasma RIP3 levels were also associated with GSS (B 0.027; standard error 0.012; P < 0.05). CONCLUSIONS: Plasma RIP3 levels were independently associated with CAD. Plasma RIP3 levels could potentially supplement clinical assessment to screen CAD and determine CAD severity.

Is exposure to tobacco associated with extrahepatic cholangiocarcinoma epidemics? A retrospective proportional mortality study in China.

BACKGROUND: Extrahepatic cholangiocarcinoma (ECC) has become one of the most rapidly increasing malignancies in China during recent decades. The relationship between tobacco exposure and ECC epidemics is unclear; this study aimed to explore this relationship. METHODS: We included 55,806 participants aged 30 years or older from the National Mortality and Smoking Survey of China. Smoking in participants and spouses was defined as 1 cigarette or more per day for up to 1 year. Spouses' smoking was taken as a measure of exposure to passive smoking. Smoking information in 1980 was ascertained and outcomes were defined as ECC mortality during 1986-1988. RESULTS: We found that either passive or active smoking increased the risk of death from ECC by 20% (risk ratio [RR], 1.20; 95% confidence interval [CI], 0.99-1.47), compared with no exposure to any tobacco. This risk was a notable 98% (RR, 1.98; 95% CI, 1.49-2.64) for individuals exposed to passive plus active smoking. These findings were highly consistent among men and women. Pathology-based analyses showed dose-response relationships of ECC with pack-years for all types of smoking exposure (Ps for trend < 0.05); the RR reached 2.75 (95% CI, 1.20-6.30) in individuals exposed to combined smoking with the highest exposure dose. The findings were similar for non-pathology-based analysis. CONCLUSIONS: This study indicates that tobacco exposure increases ECC risk. Given the dramatic increase of exposure to secondhand smoke and patients with ECC, an inadequate provision of smoke-free environments could be contributing to ECC epidemics and could further challenge public health and medical services, based on the current disease spectrum.

Alterations in the gut microbiome and metabolism with coronary artery disease severity.

BACKGROUND: Coronary artery disease (CAD) is associated with gut microbiota alterations in different populations. Gut microbe-derived metabolites have been proposed as markers of major adverse cardiac events. However, the relationship between the gut microbiome and the different stages of CAD pathophysiology remains to be established by a systematic study. RESULTS: Based on multi-omic analyses (sequencing of the V3-V4 regions of the 16S rRNA gene and metabolomics) of 161 CAD patients and 40 healthy controls, we found that the composition of both the gut microbiota and metabolites changed significantly with CAD severity. We identified 29 metabolite modules that were separately classified as being positively or negatively correlated with CAD phenotypes, and the bacterial co-abundance group (CAG) with characteristic changes at different stages of CAD was represented by Roseburia, Klebsiella, Clostridium IV and Ruminococcaceae. The result revealed that certain bacteria might affect atherosclerosis by modulating the metabolic pathways of the host, such as taurine, sphingolipid and ceramide, and benzene metabolism. Moreover, a disease classifier based on differential levels of microbes and metabolites was constructed to discriminate cases from controls and was even able to distinguish stable coronary artery disease from acute coronary syndrome accurately. CONCLUSION: Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified the relationships between the features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host-gut microbiota interplay in atherosclerotic pathogenesis.