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.

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.

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.

C-reactive protein for predicting cardiovascular and all-cause mortality in type 2 diabetic patients: A meta-analysis.

AIMS: There is interest in using blood C-reactive protein (CRP) to predict adverse prognosis outcomes patients with type 2 diabetes. This meta-analysis aimed to investigate the association between elevated baseline CRP level and unfavorable outcomes in type 2 diabetes patients. MATERIALS/METHODS: PubMed and Embase databases were systematically searched for studies on the association of elevated baseline CRP level with cardiovascular mortality and all-cause mortality from their inception to July 2018. Pooled risk ratio (RR) with 95% confidence intervals (CI) was calculated for the highest versus the lowest CRP level. RESULTS: Six prospective cohort studies and two post hoc analyses of randomized controlled trials involving 22,322 type 2 diabetes patients were included. Meta-analysis indicated that type 2 diabetes patients with the highest CRP level had a greater risk of all-cause mortality (RR 2.03; 95% CI 1.49-2.75) and cardiovascular mortality (RR 1.76; 95% CI 1.46-2.13). Subgroups analysis indicated that the increased cardiovascular and all-cause mortality risk was consistently found in different study design, follow-up duration or patients with or without cardiovascular risk/established cardiovascular disease subgroups. CONCLUSIONS: This meta-analysis indicates that elevated baseline serum CRP level is independently associated with future cardiovascular and all-cause mortality in type 2 diabetes patients.

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.

The prognostic impact of primary tumor resection in pancreatic neuroendocrine tumors with synchronous multifocal liver metastases.

BACKGROUND: Whether primary tumor resection benefits patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors remains controversial. We investigated whether primary tumor resection significantly affects survival in this study. METHODS: A retrospective study of patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors between 1998 and 2016 was performed. Patient demographics, operation details, adjuvant treatment, and pathological and survival information were collected, and relevant clinical-pathological parameters were assessed in univariate and multivariate survival analyses. RESULTS: Sixty-three patients were included in this study, including 35 who underwent primary tumor resection. The median survival time and 5-year survival rate of this cohort were 50 months and 44.5%, respectively. Median survival time in the resected group was significantly longer at 72 months than that of 32 months in the nonresected group (p = 0.010). Multivariate analysis showed that primary tumor surgery was a significant independent prognostic factor (HR 0.312, 95% CI: 0.128-0.762, p = 0.011). CONCLUSIONS: Primary tumor resection significantly benefits patients with synchronous multifocal liver metastases from pancreatic neuroendocrine tumors.

Surgery in overweight patients with insulinoma: effects on weight loss.

OBJECTIVE: Weight loss induced by the complete resection of insulinoma is controversial in overweight patients. The study sought to explore postoperative weight loss and metabolic changes in overweight insulinoma patients. METHODS: A retrospective study was conducted to review the follow-up data of insulinoma patients with a BMI ≥25kg/m2 who underwent complete lesion resection between May 2010 and May 2015. Body mass index (BMI), weight loss (WL) and percentage weight loss (%WL) were main outcomes. RESULTS: Fifty-one patients were included with a median follow-up of 28 months. The BMI at 3 months, 1 year, 2 years and 3 years postoperatively were significantly lower than the preoperative BMI values (p < .01). The WL% was 12.9% at 3 months postoperatively without significant changes throughout the 3-year follow-up. WL and the %WL were significantly higher in the high BMI group (BMI≥ 27.5 kg/m2). Multivariate analysis indicated that higher initial BMI was associated with increased weight loss (p = .001). 63.8% of patients with hypertension recovered and improved sleep quality was evident in all patients with obstructive sleep apnea syndrome within 1 year postoperatively. CONCLUSIONS: Weight significantly decreased postoperatively in overweight insulinoma patients, which was more evident in patients with higher BMI and metabolic comorbidities were largely improved.

Association Between a CCL17 Genetic Variant and Risk of Coronary Artery Disease in a Chinese Han Population.

BACKGROUND: In the present study we investigated the effects of genetic variations in the C-C motif chemokine ligand 17 (CCL17) gene on serum CCL17 levels and risk of coronary artery disease (CAD).Methods and Results:A case-control study was conducted to determine causal inferences amongCCL17single-nucleotide polymorphisms (SNPs), serum CCL17 levels, and risk of CAD. Luciferase assays, electrophoretic mobility shift assays (EMSA), and allele-specific quantitative chromatin immunoprecipitation (ChIP) assays were used to assess the function of the SNPs. In all, 947 participants (794 with CAD, 153 without CAD) were included in the study. The T allele in rs223828, located in intron of theCCL17gene, was associated with increased serum CCL17 levels as well as increased CAD risk. A causal inference test using mediation analysis suggested that rs223828 had a significant indirect casual effect on the increased risk of CAD mediated via serum CCL17 levels. Luciferase assays confirmed that the rs223828T allele enhancesCCL17promoter activity. Protein-DNA binding studies using EMSA and allele-specific quantitative ChIP assays indicated preferential activator protein-1 (AP-1) complex formation and recruitment with the rs223828 T allele compared with the C allele. CONCLUSIONS: We propose that theCCL17SNP rs223828 is associated with increased risk of CAD, and that this site may be a potential AP-1 binding site.

Association Between Oxidative Stress and Peripheral Leukocyte Telomere Length in Patients with Premature Coronary Artery Disease.

BACKGROUND Leukocyte telomere length (LTL) is regarded as a potential marker of biological aging. Oxidative stress plays a major role in the rate of telomeric DNA loss. The aim of this study was to explore whether the LTL was shorter in Chinese patients with premature coronary artery disease (PCAD) than in non-CAD controls and to determine the relationship between oxidative stress and LTL shortening in this population. MATERIAL AND METHODS Patients for coronary angiography were recruited. In total, 128 patients with PCAD and 128 non-CAD controls were enrolled. Samples of circulating leukocytes and plasma were collected. The mean LTL was measured using a polymerase chain reaction-based assay and expressed as the ratio of telomere repeat copies to single-copy gene (SCG) copies (T/S ratio). Reactive oxygen species (ROS) levels and total antioxidant capacity (T-AOC) were determined in plasma. RESULTS Both the T/S ratio (0.88±0.86 vs. 1.10±0.57, P=0.015) and telomere base pairs (4.97±1.37 kb vs. 5.32±0.91 kb, P=0.015) were significantly shorter in the PCAD group than in non-CAD controls. The T-AOC levels of the PCAD group were significantly lower than those of the non-CAD controls (0.482 mM [0.279, 0.603 mM]) vs. 0.778 mM [0.421, 0.924 mM], P=0.000). The ratio of T-AOC to ROS in the PCAD patients was significantly decreased compared to that of the non-CAD controls (0.1026±0. 1587 [Mm*ml/ng] vs. 0.1435±0.1946 [Mm*ml/ng], P=0.013). CONCLUSIONS The results point to a potential link between reduced LTLs in patients with PCAD and early onset of atherosclerosis. The decline in antioxidant capacity may play an important role in accelerating the attrition of telomeres in PCAD patients.

Accelerated Age-Related Arterial Stiffness in Systemic Lupus Erythematosus Patients.

BACKGROUND: An increased prevalence of arterial stiffness in systemic lupus erythematosus (SLE) patients has been established, but the mechanisms of progression of arterial stiffness with increasing age have not been fully explored. OBJECTIVES: To investigate age-related progression of arterial stiffness among SLE patients relative to healthy controls. METHODS: A total of 161 female SLE patients who were enrolled in the Chinese SLE Treatment and Research group (CSTAR) registry and 135 age-matched healthy control subjects participated in this cross-sectional investigation. Traditional cardiovascular risk factors and SLE-related parameters were assessed on the day that brachial-ankle pulse wave velocity (baPWV) was examined. SAS 9.3 was used to perform all statistical analyses in this study. Linear regression and curvilinear regression models were utilized to analyze the association between age and arterial stiffness. RESULTS: Arterial stiffness based on baPWV significantly differed between the SLE patients and controls in the different age groups, and within the SLE group. The baPWV increments for each age group (<25, 25-34, 35-45, and >45) were 30 cm/s, 52 cm/s, and 121 cm/s for the controls and 61 cm/s, 132 cm/s, and 155 cm/s for the SLE patients, respectively. Curvilinear regression and linear regression revealed various trends of increased arterial stiffness among the SLE patients compared with the healthy controls. The correlation coefficients between age and arterial stiffness significantly differed among the SLE patients relative to the healthy controls (correlation coefficients of 0.46478 and 0.52612, respectively; t = 2.05; P = 0.0409). Multivariate analysis revealed that age, mean blood pressure (BP) (P < 0.0001), erythrocyte sedimentation rate (ESR) (P = 0.0073), prednisone course (P = 0.0144), and SLE disease activity (P = 0.0405) were associated with arterial stiffness among the SLE patients. Further, these patients exhibited earlier exposure to and higher frequencies of several risk factors compared with the controls in each age group (<25 years: OR = 6.3253; 25-34 years: OR = 3.1043; 35-45 years: OR = 3.1316; >45 years: OR = 3.6020). CONCLUSIONS: The mechanisms of the age-related progression of arterial stiffness differed among the SLE patients relative to the healthy controls. Furthermore, accelerated arterial stiffness was observed among the SLE patients relative to the healthy controls with advancing age.

Effects of active, passive, and combined smoking on cervical cancer mortality: a nationwide proportional mortality study in Chinese urban women.

PURPOSE: To determine whether smoking, in any form, is a risk factor in the development of cervical cancer (CC) among urban Chinese women. METHODS: We ascertained retrospectively the smoking habits of 1,865 women (aged 35+) who had died from CC (cases) and 48,781 who had died from causes unrelated to smoking (controls) in 24 cities using data from a large national survey of smoking and mortality in 1989-1991. We assessed the risk of smoking on CC mortality with and without considering passive smoke exposure from a spouse using a proportional mortality study design. RESULTS: Overall, there was a 51.0 % excess risk of death from CC among smokers. When the spouse's exposure was further considered, the RR (95 % CI) for exposed versus unexposed women was 1.28 (1.04-1.57) for passive smokers, 1.49 (1.02-2.20) for active smokers, and 1.69 (1.27-2.26) for women with both exposures (all p < 0.001). Significant dose-response associations were observed between smoking and CC for all categories of exposure. For example, individuals with both smoking exposure had the highest risk of CC mortality with moderate [RR = 1.67 (1.18-2.38)] and high [RR = 1.88 (1.04-3.41)] daily cigarette consumption, and they also had the highest risk with ≤15 years exposure [RR = 1.73 (1.19-2.52)] and >15 years exposure [RR = 1.95 (1.15-3.32)], compared with the active and passive groups (p for trend <0.001). CONCLUSIONS: Younger trend of CC death and the rapid increase in smoking among young women may have a profound impact on future incidence of CC. Our findings emphasize the need for preventive efforts among both women and men in China.

Interarm Blood Pressure Difference in Patients With Systemic Lupus Erythematosus.

OBJECTIVES: This study was performed to determine the relationship between systemic lupus erythematosus (SLE) and the interarm blood pressure difference (IAD) and to elucidate the role of the IAD as a surrogate marker for early detection of peripheral artery disease (PAD) in patients with SLE. METHODS: In total, 135 patients with SLE and 135 age- and gender-matched subjects were enrolled. The IAD and risk of an abnormal IAD were compared between the SLE and control groups, and logistic regression analysis was performed to determine the relationship between SLE and an abnormal IAD. The specificity and sensitivity of an IAD of 10 mm Hg or greater for diagnosis of PAD (ankle brachial index of <0.90) were calculated. RESULTS: Both the systolic and diastolic IADs were significantly higher in the SLE group than in the control group (P < 0.001). After adjustment for confounding factors, SLE remained significantly associated with an abnormal IAD (P = 0.039). Both the systolic and diastolic IADs were negatively associated with the ankle brachial index. Using a systolic IAD of 10 mm Hg or greater as the cutoff point, the specificity and sensitivity for PAD were 90% and 41%, respectively. A diastolic IAD of 10 mm Hg or greater exhibited higher specificity (92%), but lower sensitivity (30%). CONCLUSIONS: Systemic lupus erythematosus is independently associated with an abnormal IAD, and an IAD of 10 mm Hg or greater predicts PAD with high specificity but low sensitivity. Blood pressure should be measured at least once in both arms in patients with SLE for early detection of asymptomatic PAD.

Contributions of major smoking-related diseases to reduction in life expectancy associated with smoking in Chinese adults: a cross-sectional study.

BACKGROUND: Cigarette smoking is a prominent risk factor for a wide range of diseases. The current study aimed to evaluate the impact of smoking on deaths from major smoking-related diseases (neoplasms, vascular diseases and respiratory diseases) in Chinese adults by estimating the potential gains in life expectancy (LE) that would accrue from eliminating deaths from these diseases, and to determine the contribution of each disease to the reduction in LE associated with smoking. METHODS: Two cohorts of Chinese smokers and non-smokers were constructed from a retrospective national mortality survey that had been conducted in 1989-1991 and included one million all-cause deaths among adults during 1986-1988 in 103 geographical regions. For each cohort, potential gains in LE by eliminating deaths from each major smoking-related disease were estimated. The contributions of each disease to smoking-associated reduction in LE were assessed using the LE decomposition approach. RESULTS: Among the major smoking-related diseases, it was estimated that elimination of vascular diseases would provide the greatest potential gain in LE (years), regardless of smoking status. The gains for smokers versus non-smokers in populations of urban men, urban women, rural men and rural women aged 35 years were 3.5 vs. 4.3, 3.8 vs. 4.1, 2.4 vs. 3.0, and 2.6 vs. 2.9 years, respectively. Respiratory diseases contributed most to smoking-associated LE reductions in urban women, rural men and rural women of 43.6%, 46.4%, and 62.9%, respectively. In urban men, neoplasms contributed most to smoking-associated LE reduction, their contribution being estimated as 45.8%. CONCLUSIONS: Respiratory disease has the greatest influence on the LE reduction associated with smoking. Thus, smoking prevention could significantly reduce deaths from respiratory disease and improve LE.

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.

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.

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.

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.