Psychosocial adjustment changes and related factors in young and middle-aged patients with first-episode acute myocardial infarction: a longitudinal study.

AIMS: This study aimed to explore the change trend and group heterogeneity of psychosocial adjustment level and to determine its influencing factors among young and middle-aged patients with first-episode acute myocardial infarction (AMI). METHODS AND RESULTS: The Psychosocial Adjustment Scale of Illness was used to assess the psychosocial adjustment level of the patients at 1, 3, and 6 months after discharge, respectively. Data were analyzed using Pearson correlation analysis, generalized estimating equations, and growth mixed models. A total of 233 patients were included, and their psychosocial adjustment scores at the three-time points were 57.18 ± 15.50, 36.17 ± 15.02, and 24.22 ± 12.98, respectively. The trajectories of changes in patients' psychosocial adjustment levels were divided into three latent categories: moderate adjustment improvement group (72.5%), low adjustment improvement group (16.3%), and persistent maladjustment group (11.2%). Among them, predictors of the persistent maladjustment group included no spouse, low monthly family income per capita, normal body mass index, never smoking, never exercising, combined with hyperlipidemia, low social support, submission coping, and high perceived stress. CONCLUSIONS: The psychosocial adjustment level of young and middle-aged patients with first-episode AMI showed an upward trend within 6 months after discharge, and there was group heterogeneity in the change trajectory of psychosocial adjustment level. It is suggested that a multi-center, large-sample longitudinal study should be carried out in the future, and the time of follow-up investigation should be extended to further clarify the change trajectory and influencing factors of psychosocial adjustment of patients with different subtypes, to provide the theoretical basis for formulating targeted intervention programs.

Financial hardship and neighborhood socioeconomic disadvantage in long-term childhood cancer survivors.

BACKGROUND: Long-term survivors of childhood cancer face elevated risk for financial hardship. We evaluate whether childhood cancer survivors live in areas of greater deprivation and the association with self-reported financial hardships. METHODS: We performed a cross-sectional analysis of data from the Childhood Cancer Survivor Study between 1970 and 1999 and self-reported financial information from 2017 to 2019. We measured neighborhood deprivation with the Area Deprivation Index (ADI) based on current zip code. Financial hardship was measured with validated surveys that captured behavioral, material and financial sacrifice, and psychological hardship. Bivariate analyses described neighborhood differences between survivors and siblings. Generalized linear models estimated effect sizes between ADI and financial hardship adjusting for clinical factors and personal socioeconomic status. RESULTS: Analysis was restricted to 3475 long-term childhood cancer survivors and 923 sibling controls. Median ages at time of evaluation was 39 years (interquartile range [IQR] = 33-46 years and 47 years (IQR = 39-59 years), respectively. Survivors resided in areas with greater deprivation (ADI ≥ 50: 38.7% survivors vs 31.8% siblings; P < .001). One quintile increases in deprivation were associated with small increases in behavioral (second quintile, P = .017) and psychological financial hardship (second quintile, P = .009; third quintile, P = .014). Lower psychological financial hardship was associated with individual factors including greater household income (≥$60 000 income, P < .001) and being single (P = .048). CONCLUSIONS: Childhood cancer survivors were more likely to live in areas with socioeconomic deprivation. Neighborhood-level disadvantage and personal socioeconomic circumstances should be evaluated when trying to assist childhood cancer survivors with financial hardships.

Hierarchical MOF@AuNP/Hairpin Nanotheranostic for Enhanced Photodynamic Therapy via O2 Self-Supply and Cancer-Related MicroRNA Imaging In Vivo.

Developing a nanotheranostic with a high sensing performance and efficient therapy was significant in cancer diagnosis and treatment. Herein, a Au nanoparticle and hairpin-loaded photosensitive metal-organic framework (PMOF@AuNP/hairpin) nanotheranostic was constructed by growing AuNPs on PMOF in situ and then attaching hairpins. On the one hand, the PMOF@AuNP/hairpin nanotheranostic could effectively transfer O2 into ROS, facilitating efficient PDT. Additionally, the nanotheranostic possessed catalase-like activity, which could effectively catalyze H2O2 to generate O2, thus achieving O2-evolving PDT and significantly enhancing the antitumor effect of PDT in vivo. On the other hand, the nanotheranostic showed a high loading efficiency of hairpins and achieved the sensitive and selective detection of miR-21 both in living cells and in vivo. Moreover, the nanotheranostic could dynamically monitor the miR-21 level. Due to the excellent imaging performance, the nanotheranostic could recognize cancer cells and might provide important information on cancer progression for PDT. The developed PMOF@AuNP/hairpin nanotheranostic provided a useful tool for tumor diagnosis and antitumor therapy.

Genetic risk score enhances the risk prediction of severe obesity in adult survivors of childhood cancer.

Adult survivors of childhood cancer have high rates of obesity, which, in combination with the cardiotoxic effects of specific cancer therapies, places them at high risk for cardiovascular morbidity. Here we show the contribution of genetic risk scores (GRSs) to increase prediction of those survivors of childhood cancer who are at risk for severe obesity (body mass index ≥40 kg m-2) as an adult. Among 2,548 individuals of European ancestry from the St. Jude Lifetime Cohort Study who were 5-year survivors of childhood cancer, the GRS was found to be associated with 53-fold-higher odds of severe obesity. Addition of GRSs to risk prediction models based on cancer treatment exposures and lifestyle factors significantly improved model prediction (area under the curve increased from 0.68 to 0.75, resulting in the identification of 4.3-times more high-risk survivors), which was independently validated in 6,064 individuals from the Childhood Cancer Survivor Study. Genetic predictors improve identification of patients who could benefit from heightened surveillance and interventions to mitigate the risk of severe obesity and associated cardio-metabolic complications.

A Novel Locus on 6p21.2 for Cancer Treatment-Induced Cardiac Dysfunction Among Childhood Cancer Survivors.

BACKGROUND: Adult survivors of childhood cancer are at increased risk of cardiac late effects. METHODS: Using whole-genome sequencing data from 1870 survivors of European ancestry in the St. Jude Lifetime Cohort (SJLIFE) study, genetic variants were examined for association with ejection fraction (EF) and clinically assessed cancer therapy-induced cardiac dysfunction (CCD). Statistically significant findings were validated in 301 SJLIFE survivors of African ancestry and 4020 survivors of European ancestry from the Childhood Cancer Survivor Study. All statistical tests were 2-sided. RESULTS: A variant near KCNK17 showed genome-wide significant association with EF (rs2815063-A: EF reduction = 1.6%; P = 2.1 × 10-8) in SJLIFE survivors of European ancestry, which replicated in SJLIFE survivors of African ancestry (EF reduction = 1.5%; P = .004). The rs2815063-A also showed a 1.80-fold (P = .008) risk of severe or disabling or life-threatening CCD and replicated in 4020 Childhood Cancer Survivor Study survivors of European ancestry (odds ratio = 1.40; P = .04). Notably, rs2815063-A was specifically associated among survivors exposed to doxorubicin only, with a stronger effect on EF (3.3% EF reduction) and CCD (2.97-fold). Whole blood DNA methylation data in 1651 SJLIFE survivors of European ancestry showed statistically significant correlation of rs2815063-A with dysregulation of KCNK17 enhancers (false discovery rate <5%), which replicated in 263 survivors of African ancestry. Consistently, the rs2815063-A was associated with KCNK17 downregulation based on RNA sequencing of 75 survivors. CONCLUSIONS: Leveraging the 2 largest cohorts of childhood cancer survivors in North America and survivor-specific polygenomic functional data, we identified a novel risk locus for CCD, which showed specificity with doxorubicin-induced cardiac dysfunction and highlighted dysregulation of KCNK17 as the likely molecular mechanism underlying this genetic association.

Sex-Specific Associations Between Chemotherapy, Chronic Conditions, and Neurocognitive Impairment in Acute Lymphoblastic Leukemia Survivors: A Report From the Childhood Cancer Survivor Study.

BACKGROUND: The purpose was to examine associations between treatment and chronic health conditions with neurocognitive impairment survivors of acute lymphoblastic leukemia (ALL) treated with chemotherapy only. METHODS: This cross-sectional study included 1207 ALL survivors (54.0% female; mean age 30.6 years) and 2273 siblings (56.9% female; mean age 47.6 years), who completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire. Multivariable logistic regression compared prevalence of neurocognitive impairment between survivors and siblings by sex. Associations between neurocognitive impairment with treatment exposures and chronic conditions (graded according to Common Terminology Criteria for Adverse Events) were also examined. Statistical tests were 2-sided. RESULTS: Relative to same-sex siblings, male and female ALL survivors reported increased prevalence of impaired task efficiency (males: 11.7% vs 16.9%; adjusted odds ratio [OR] = 1.89, 95% confidence interval [CI] = 1.31 to 2.74; females: 12.5% vs 17.6%; OR = 1.50, 95% CI = 1.07 to 2.14), as well as impaired memory (males: 11.6% vs 19.9%, OR = 1.89, CI = 1.31 to 2.74; females: 14.78% vs 25.4%, OR = 1.96, 95% CI = 1.43 to 2.70, respectively). Among male survivors, impaired task efficiency was associated with 2-4 neurologic conditions (OR = 4.33, 95% CI = 1.76 to 10.68) and with pulmonary conditions (OR = 4.99, 95% CI = 1.51 to 16.50), and impaired memory was associated with increased cumulative dose of intrathecal methotrexate (OR = 1.68, 95% CI = 1.16 to 2.46) and with exposure to dexamethasone (OR = 2.44, 95% CI = 1.19 to 5.01). In female survivors, grade 2-4 endocrine conditions were associated with higher risk of impaired task efficiency (OR = 2.19, 95% CI = 1.20 to 3.97) and memory (OR = 2.26, 95% CI = 1.31 to 3.92). CONCLUSION: Neurocognitive impairment is associated with methotrexate, dexamethasone, and chronic health conditions in a sex-specific manner, highlighting the need to investigate physiological mechanisms and monitor impact through survivorship.

Generalizability of "GWAS Hits" in Clinical Populations: Lessons from Childhood Cancer Survivors.

With mounting interest in translating genome-wide association study (GWAS) hits from large meta-analyses (meta-GWAS) in diverse clinical settings, evaluating their generalizability in target populations is crucial. Here, we consider long-term survivors of childhood cancers from the St. Jude Lifetime Cohort Study, and we show the limited generalizability of 1,376 robust SNP associations reported in the general population across 12 complex anthropometric and cardiometabolic phenotypes (n = 2,231; observed-to-expected replication ratio = 0.70, p = 6.2 × 10-8). An examination of five comparable phenotypes in a second independent cohort of survivors from the Childhood Cancer Survivor Study corroborated the overall limited generalizability of meta-GWAS hits to survivors (n = 4,212; observed-to-expected replication ratio = 0.55, p = 5.6 × 10-15). Finally, in direct comparisons of survivor samples against independent equivalently powered general population samples from the UK Biobank, we consistently observed lower meta-GWAS hit replication rates and poorer polygenic risk score predictive performance in survivor samples for multiple phenotypes. As a possible explanation, we found that meta-GWAS hits were less likely to be replicated in survivors who had been exposed to cancer therapies that are associated with phenotype risk. Examination of complementary DNA methylation data in a subset of survivors revealed that treatment-related methylation patterns at genomic sites linked to meta-GWAS hits may disrupt established genetic signals in survivors.

The analysis of the lipid levels in patients with coronary artery disease after percutaneous coronary intervention: a one-year follow-up observational study.

BACKGROUND: Coronary heart disease (CHD) is one of the leading causes of death worldwide. Percutaneous coronary intervention (PCI) has been an important technology for the treatment of CHD. Blood lipid management is critical for PCI patients because not only should local vascular pathological changes be considered but the whole atherosclerotic process should be considered as well. METHODS: A total of 522 patients diagnosed with CHD (including acute myocardial infarction and unstable angina) successfully underwent stent implantation in acute or elective PCI in the cardiology department of one general hospital in Guangzhou from June 2015 to December 2017. The 2016 Chinese Guideline for the Management of dyslipidaemia in Adults and the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report (NCEP-ATP III) were used to classify total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) levels. RESULTS: A total of 522 patients were recruited for the study. The mean values of TC, TG, LDL-C, and HDL-C at baseline were 4.76, 1.80, 2.93 and 1.03 mmol/L, respectively. After 1 year of follow-up, the mean values of TC, TG, LDL-C, and HDL-C were 3.94, 1.62, 2.26 and 1.01 mmol/L, respectively. The prevalence of high TC, high TG, high LDL-C and low HDL-C at baseline was 12.05, 21.80, 10.90 and 56.79%, respectively, and the prevalence at follow-up was 4.59, 15.68, 3.25 and 59.85%, respectively. Logistic regression revealed that gender was risk factor for high TC (≥ 6.22 mmol/L), low HDL-C (< 1.04 mmol/L) and high LDL-C (≥ 4.14 mmol/L) at follow-up. Age was the factor associated with high TG (≥ 2.26 mmol/L) and low HDL-C (< 1.04 mmol/L) at follow-up. Besides, smoking and diet control were risk factors for low HDL-C (< 1.04 mmol/L) and high LDL-C (≥ 4.14 mmol/L) at follow-up, respectively. CONCLUSION: The patients with PCI at follow-up experienced lower mean values of lipids and prevalence of dyslipidaemia than those at baseline. Gender, age, smoking and diet control were the risk factors associated with elevated lipids. Improvement in lipid management at follow up demonstrated that such intervention can be effective.

Total flavonoids from Semen Cuscutae target MMP9 and promote invasion of EVT cells via Notch/AKT/MAPK signaling pathways.

Miscarriage is a common condition during pregnancy and its mechanisms remain largely unknown. Extravillous trophoblast (EVT) cell invasion is required to maintain normal pregnancy and its malfunction has been proposed as a major cause for miscarriage. Homeostasis of matrix metalloproteinase 9 (MMP9) is a key to regulate EVT cell invasion. Total flavonoids from Semen Cuscutae (TFSC) have been applied clinically used for preventing or treating miscarriage in the past. Given its potential clinical benefit on preventing miscarriage, this study aims at examining the therapeutic effect of TFSC in the prevention of premature birth by upregulating MMP9 and promote EVT cell invasion. HTR-8 cells migration and invasion functions were analyzed using wound healing and transwell assays. The regulatory effect of TFSC on MMP9 expression and relevant signaling pathways were analyzed by Western Blot. The results show compared to control group, TFSC significantly promoted the migration of EVT cells in a dose and time-dependent manner. The migration and invasion of EVT cells were maximized at the highest dosage of 5 µg/ml of TFSC. The expression of MMP9 in EVT cells was significantly increased after TFSC treatment. Furthermore, cells treated with TFSC significantly upregulated protein expressions in Notch, AKT and p38/MAPK signaling pathways. We believe TFSC can promote the migration and invasion of EVT cells by increasing MMP9 expression, and prevent miscarriage by activating Notch, AKT, and MAPK signaling pathways.

Effect of Total Flavones from Cuscuta Chinensis on Anti-Abortion via the MAPK Signaling Pathway.

For centuries, the Chinese herb Cuscuta chinensis has been applied clinically for abortion prevention in traditional Chinese medicine (TCM). Total flavones extracted from Cuscuta chinensis (TFCC) are one of the active components in the herb and also display anti-abortion effect similar to the unprocessed material. However, how TFCC exerts the anti-abortion effect remains largely unknown. In this study, we aim at characterizing the anti-abortion effects of TFCC and its underlying molecular mechanism in vitro and in vivo using human primary decidua cells and a mifepristone-induced abortion model in rat, respectively. The damage to the decidua caused by mifepristone in vivo was reversed by TFCC treatment in a dosage-dependent manner. High dosage of TFCC significantly upregulated the expression of estrogen receptor (ER), progesterone receptor (PR), and prolactin receptor (PRLR) in decidua tissue but downregulated the expression of p-ERK. Furthermore, we detected higher level of p-ERK and p-p38 in primary decidua cells from spontaneous abortion while treatment by TFCC downregulated their expression. Our results suggest TFCC mediates its anti-abortion effect by interfering with MAPK signaling pathway.

Differences in Short- and Long-Term Mortality Associated With BMI Following Coronary Revascularization.

BACKGROUND: The association between obesity and mortality risks following coronary revascularization is not clear. We examined the associations of BMI (kg/m2) with short-, intermediate-, and long-term mortality following coronary artery bypass graft surgery (CABG) and percutaneous coronary intervention (PCI) in patients with different coronary anatomy risks and diabetes mellitus status. METHODS AND RESULTS: Data from the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry were analyzed. Using normal BMI (18.5-24.9) as a reference, multivariable-adjusted hazard ratios for all-cause mortality within 6 months, 1 year, 5 years, and 10 years were individually calculated for CABG and PCI with 4 prespecified BMI categories: overweight (25.0-29.9), obese class I (30.0-34.9), obese class II (35.0-39.9), and obese class III (≥40.0). The analyses were repeated after stratifying for coronary risks and diabetes mellitus status. The cohorts included 7560 and 30 258 patients for CABG and PCI, respectively. Following PCI, overall mortality was lower in patients with overweight and obese class I compared to those with normal BMI; however, 5- and 10-year mortality rates were significantly higher in patients with obese class III with high-risk coronary anatomy, which was primarily driven by higher mortality rates in patients without diabetes mellitus (5-year adjusted hazard ratio, 1.78 [95% CI, 1.11-2.85] and 10-year adjusted hazard ratio, 1.57 [95% CI, 1.02-2.43]). Following CABG, overweight was associated with lower mortality risks compared with normal BMI. CONCLUSIONS: Overweight was associated with lower mortality following CABG and PCI. Greater long-term mortality in patients with obese class III following PCI, especially in those with high-risk coronary anatomy without diabetes mellitus, warrants further investigation.

Severe Obesity Is Associated With Increased Risk of Early Complications and Extended Length of Stay Following Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Better understanding of the relationship between obesity and postsurgical adverse outcomes is needed to provide quality and efficient care. We examined the relationship of obesity with the incidence of early adverse outcomes and in-hospital length of stay following coronary artery bypass grafting surgery. METHODS AND RESULTS: We analyzed data from 7560 patients who underwent coronary artery bypass grafting. Using body mass index (BMI; in kg/m(2)) of 18.5 to 24.9 as a reference, the associations of 4 BMI categories (25.0-29.9, 30.0-34.9, 35.0-39.9, and ≥40.0) with rates of operative mortality, overall early complications, subgroups of early complications (ie, infection, renal and pulmonary complications), and length of stay were assessed while adjusting for clinical covariates. There was no difference in operative mortality; however, higher risks of overall complications were observed for patients with BMI 35.0 to 39.9 (adjusted odds ratio 1.35, 95% CI 1.11-1.63) and ≥40.0 (adjusted odds ratio 1.56, 95% CI 1.21-2.01). Subgroup analyses identified obesity as an independent risk factor for infection (BMI 30.0-34.9: adjusted odds ratio 1.60, 95% CI 1.24-2.05; BMI 35.0-39.9: adjusted odds ratio 2.34, 95% CI 1.73-3.17; BMI ≥40.0: adjusted odds ratio 3.29, 95% CI 2.30-4.71). Median length of stay was longer with BMI ≥40.0 than with BMI 18.5 to 24.9 (median 7.0 days [interquartile range 5 to 10] versus 6.0 days [interquartile range 5 to 9], P=0.026). CONCLUSIONS: BMI ≥40.0 was an independent risk factor for longer length of stay, and infection was a potentially modifiable risk factor. Greater perioperative attention and intervention to control the risks associated with infection and length of stay in patients with BMI ≥40.0 may improve patient care quality and efficiency.

Diabetic Foot Disease, Self-Care and Clinical Monitoring in Adults with Type 2 Diabetes: The Alberta's Caring for Diabetes (ABCD) Cohort Study.

OBJECTIVE: To examine the prevalence and predictors of foot disease, self-care and clinical monitoring in adults with type 2 diabetes in Alberta, Canada. METHOD: Baseline data from a prospective cohort of adults with type 2 diabetes were used. Assessment of foot disease included self-reported peripheral neuropathy, peripheral vasculopathy, foot or leg ulcer/infection or gangrene/amputation. Foot self-care was assessed using the Summary of Diabetes Self-Care Activities, and clinical monitoring using patients' reports of having feet checked for lesions or sensory loss. RESULTS: The mean age of respondents (N=2040) was 64 (SD 10.7) years; 45% were female, and 91% were Caucasian. Peripheral neuropathy was reported by 18% of the respondents, peripheral vasculopathy by 28%, ulcer/infection by 6% and gangrene/amputation by 1.4%. Only 14% of respondents performed foot self-care behaviours ≥6 days per week, and only 41% and 34% had their feet clinically checked for lesions or sensory loss, respectively. Predictors of foot disease included longer duration of diabetes, smoking, depressive symptoms, low self-efficacy and a history of cardiovascular diseases. Predictors of good self-care included older age, female sex, longer duration of diabetes and no report of hyperlipidemia. Predictors of clinical monitoring included female sex, current smoking, residing in urban areas, longer duration of diabetes, and histories of heart disease or hyperlipidemia. CONCLUSIONS: Peripheral neuropathy and vasculopathy were the most common reported foot problems in this population. Foot self-care is generally infrequent, and clinical monitoring is performed for less than half of these patients, with significant variations by patient demographics and clinical presentation.

Collaborative care versus screening and follow-up for patients with diabetes and depressive symptoms: results of a primary care-based comparative effectiveness trial.

OBJECTIVE: Depressive symptoms are common and, when coexisting with diabetes, worsen outcomes and increase health care costs. We evaluated a nurse case-manager-based collaborative primary care team model to improve depressive symptoms in diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a controlled implementation trial in four nonmetropolitan primary care networks. Eligible patients had type 2 diabetes and screened positive for depressive symptoms, based on a Patient Health Questionnaire (PHQ) score of ≥10. Patients were allocated using an "on-off" monthly time series. Intervention consisted of case-managers working 1:1 with patients to deliver individualized care. The main outcome was improvement in PHQ scores at 12 months. A concurrent cohort of 71 comparable patients was used as nonscreened usual care control subjects. RESULTS: Of 1,924 patients screened, 476 (25%) had a PHQ score >10. Of these, 95 were allocated to intervention and 62 to active control. There were no baseline differences between groups: mean age was 57.8 years, 55% were women, and the mean PHQ score was 14.5 (SD 3.7). Intervention patients had greater 12-month improvements in PHQ (7.3 [SD 5.6]) compared with active-control subjects (5.2 [SD 5.7], P = 0.015). Recovery of depressive symptoms (i.e., PHQ reduced by 50%) was greater among intervention patients (61% vs. 44%, P = 0.03). Compared with trial patients, nonscreened control subjects had significantly less improvement at 12 months in the PHQ score (3.2 [SD 4.9]) and lower rates of recovery (24%, P < 0.05 for both). CONCLUSIONS: In patients with type 2 diabetes who screened positive for depressive symptoms, collaborative care improved depressive symptoms, but physician notification and follow-up was also a clinically effective initial strategy compared with usual care.