The associates of anxiety among lung cancer patients: Dehydroepiandrosterone (DHEA) as a potential biomarker.

OBJECTIVE: Anxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients. METHODS: A total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted. RESULTS: 147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (ß = 0.332, p < 0.001) and fatigue (ß = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA ß = 0.319, p = 0.004; PTSS ß = 0.396, p = 0.001; fatigue ß = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA ß = 0.346, p = 0.001; PTSS ß = 0.407, p = 0.001; fatigue ß = 0.326, p = 0.011). CONCLUSIONS: The association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.

Association of Longitudinal Changes in Cerebral Microstructure with Cognitive Functioning in Breast Cancer Survivors after Adjuvant Chemotherapy.

Background: Adjuvant chemotherapy for breast cancer might impact cognitive function and brain structure. Methods: In this study, we investigated the cerebral microstructural changes in breast cancer survivors after adjuvant chemotherapy and the correlation with cognitive function with both cross-sectional and longitudinal study designs. All participants underwent structural MRI. In total, we recruited 67 prechemotherapy patients (BB), 67 postchemotherapy patients (BA), and 77 healthy controls (BH). For the follow-up study, 28 participants in the BH and 28 in the BB groups returned for imaging and assessment (BHF, BBF). Voxel-based morphometry analysis was performed to evaluate differences in brain volume; vertex-based shape analysis was used to assess the shape alterations of subcortical regions. Moreover, multiple regression was applied to assess the association between the changes in neuropsychological assessment and brain volume. Results: The results showed brain volume reduction in the temporal and parietal gyrus in BB and BA patients. Among each group, we also found significant shape alterations in the caudate and thalamus. Volume reductions in the temporal regions and shape changes in the caudate and hippocampus were also observed in patients from time point 1 to time point 2 (postchemotherapy). An association between brain volume and cognitive performance was also found in the limbic system. Conclusions: Based on our findings, we can provide a better understanding of the cerebral structural changes in breast cancer survivors, establish a subsequent prediction model, and serve as a reference for subsequent treatment.

Longitudinal assessment of chemotherapy-induced brain connectivity changes in cerebral white matter and its correlation with cognitive functioning using the GQI.

Objective: Breast cancer was the most prevalent type of cancer and had the highest incidence rate among women worldwide. The wide use of adjuvant chemotherapy might have a detrimental effect on the human brain and result in chemotherapy-related cognitive impairment (CICI) among breast cancer patients. Furthermore, prior to chemotherapy, patients reported cancer-related cognitive impairment (CRCI), which might be due to physiological factors or mood symptoms. The present longitudinal study aimed to investigate microstructural and macroscale white matter alterations by generalized q-sampling imaging (GQI). Methods: The participants were categorized into a pre-chemotherapy group (BB) if they were diagnosed with primary breast cancer and an age-matched noncancer control group (HC). Some participants returned for follow-up assessment. In the present follow up study, 28 matched pairs of BB/BBF (follow up after chemotherapy) individuals and 28 matched pairs of HC/HCF (follow up) individuals were included. We then used GQI and graph theoretical analysis (GTA) to detect microstructural alterations in the whole brain. In addition, we evaluated the relationship between longitudinal changes in GQI indices and neuropsychological tests as well as psychiatric comorbidity. Findings: The results showed that disruption of white matter integrity occurred in the default mode network (DMN) of patients after chemotherapy, such as in the corpus callosum (CC) and middle frontal gyrus (MFG). Furthermore, weaker connections between brain regions and lower segregation ability were observed in the post-chemotherapy group. Significant correlations were observed between neuropsychological tests and white matter tracts of the CC, MFG, posterior limb of the internal capsule (PLIC) and superior longitudinal fasciculus (SLF). Conclusion: The results provided evidence of white matter alterations in breast cancer patients, and they may serve as potential imaging markers of cognitive changes. In the future, the study may be beneficial to create and evaluate strategies designed to maintain or improve cognitive function in breast cancer patients undergoing chemotherapy.

Antidepressant Use and Mortality Among Patients With Hepatocellular Carcinoma.

Importance: Liver cancer, primarily hepatocellular carcinoma (HCC), is the third leading cause of cancer deaths worldwide. Although some studies have proposed that antidepressants may have apoptotic effects on cancer, no study has examined the association between antidepressant use and HCC prognosis. Objective: To investigate the association between antidepressant use and mortality risk in patients with HCC. Design, Setting, and Participants: This population-based cohort study analyzed Taiwan's National Health Insurance Research Database, which covers 99% of Taiwan's population and includes comprehensive medical information. Patients with a new diagnosis of HCC between 1999 and 2017 were identified. Analysis took place in June 2023. Main Outcomes and Measures: All patients with HCC were followed up until 2018 to measure overall and cancer-specific mortality. To examine whether the timing of antidepressant use influenced the association with mortality, antidepressant use was examined before and after HCC diagnosis. Cox proportional hazards regression was performed to estimate hazard ratios (HRs) and the 95% CIs for the association between antidepressant use and overall mortality and cancer-specific mortality. Results: The study cohort comprised 308 938 participants, primarily consisting of older individuals (131 991 [42.7%] were aged ≥65 years) with a higher proportion of male individuals (202 589 [65.6%]). Antidepressant use before the diagnosis of HCC was not associated with lower risks of overall mortality (adjusted HR, 1.10; 95% CI, 1.08-1.12) and cancer-specific mortality (adjusted HR, 1.06; 95% CI, 0.96-1.17). However, antidepressant use after a diagnosis of HCC was associated with a lower risk of overall mortality (adjusted HR, 0.69; 95% CI, 0.68-0.70) and cancer-specific mortality (adjusted HR, 0.63; 95% CI, 0.59-0.68). The observed associations were consistent across subgroups with different antidepressant classes and comorbidities, including hepatitis B virus or hepatitis C virus infection, liver cirrhosis, and alcohol use disorders. Conclusions and Relevance: Based on this nationwide cohort study, postdiagnosis antidepressant use may be associated with lower mortality in patients with HCC. Further randomized clinical trial evaluation should be considered.

Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis.

Liver cancer is one of the most lethal malignant cancers worldwide. However, the therapeutic options for advanced liver cancers are limited and reveal scant efficacy. The current study investigated the effects of nivolumab (Niv) and escitalopram oxalate (Esc) in combination on proliferation of liver cancer cells both in vitro and in vivo. Significantly decreased viability of HepG2 cells that were treated with Esc or Niv was observed in a dose-dependent manner at 24 h, 48 h, and 72 h. Administration of Esc (50 µM) + Niv (20 µM), Esc (75 µM) + Niv (5 µM), and Esc (75 µM) + Niv (20 µM) over 24 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Additionally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) over 48 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Finally, treatment with Esc (50 µM) + Niv (1 µM), Esc (50 µM) + Niv (20 µM), and Esc (75 µM) + Niv (20 µM) for 72 h exhibited synergistic effects, inhibiting HepG2 survival. Com-pared with controls, HepG2 cells treated with Esc (50 µM) + Niv (20 µM) exhibited significantly increased sub-G1 portion and annexin-V signals. In a xenograft animal study, Niv (6.66 mg/kg) + Esc (2.5 mg/kg) significantly suppressed the growth of xenograft HepG2 tumors in nude mice. This study reports for the first time the synergistic effects of combined administration of Niv and Esc for inhibiting HepG2 cell proliferation, which may provide an alternative option for liver cancer treatment.

Detecting microstructural alterations of cerebral white matter associated with breast cancer and chemotherapy revealed by generalized q-sampling MRI.

Objective: Previous studies have discussed the impact of chemotherapy on the brain microstructure. There is no evidence of the impact regarding cancer-related psychiatric comorbidity on cancer survivors. We aimed to evaluate the impact of both chemotherapy and mental health problem on brain microstructural alterations and consequent cognitive dysfunction in breast cancer survivors. Methods: In this cross-sectional study conducted in a tertiary center, data from 125 female breast cancer survivors who had not received chemotherapy (BB = 65; 49.86 ± 8.23 years) and had received chemotherapy (BA = 60; 49.82 ± 7.89 years) as well as from 71 age-matched healthy controls (47.18 ± 8.08 years) was collected. Chemotherapeutic agents used were docetaxel and epirubicin. We used neuropsychological testing and questionnaire to evaluate psychiatric comorbidity, cognitive dysfunction as well as generalized sampling imaging (GQI) and graph theoretical analysis (GTA) to detect microstructural alterations in the brain. Findings: Cross-comparison between groups revealed that neurotoxicity caused by chemotherapy and cancer-related psychiatric comorbidity may affect the corpus callosum and middle frontal gyrus. In addition, GQI indices were correlated with the testing scores of cognitive function, quality of life, anxiety, and depression. Furthermore, weaker connections between brain regions and lower segregated ability were found in the post-treatment group. Conclusion: This study suggests that chemotherapy and cancer-related mental health problem both play an important role in the development of white matter alterations and cognitive dysfunction.

Cognitive function and breast cancer molecular subtype before and after chemotherapy.

Chemotherapy-related cognitive impairment has been reported in patients with breast cancer and received growing attention due to increased survival rate. However, cognitive outcome according to pathological tumor features, especially human epidermal growth factor receptor (HER2) status, has not been clearly elucidated. Despite its potential link with cognitive status through neuroinflammatory response, existing research is sparse and limited to cross-sectional studies. In this observational cohort study, 52 breast cancer patients received a series of neuropsychological examinations before and after chemotherapy. Patients' performances were compared with normative data, and analyzed with Reliable Change Indices and mixed-model analysis of covariance. Results showed that there was a higher percentage of HER2+ patients than HER2- patients who showed defective attention and processing speed before chemotherapy, and that there were more patients with HER2+ status showing cognitive decline on tests of attention and executive functions following chemotherapy. Group-wise analyses confirmed the foregoing pattern and further revealed that patients with HER2+ status also tended to deteriorate more in verbal memory after chemotherapy. These findings indicate that HER2 overexpression may serve as prognostic factors that help explain the heterogeneous cognitive outcome in breast cancer survivors. Further studies are needed to replicate this finding and delineate the underlying mechanisms.

Synergistic Effects of the Combinational Use of Escitalopram Oxalate and 5-Fluorouracil on the Inhibition of Gastric Cancer SNU-1 Cells.

Owing to its high recurrence rate, gastric cancer (GC) is the leading cause of tumor-related deaths worldwide. Besides surgical treatment, chemotherapy is the most commonly used treatment against GC. However, the adverse events associated with chemotherapy use limit its effectiveness in GC treatment. In this study, we investigated the effects of using combinations of low-dose 5-fluorouracil (5-FU; 0.001 and 0.01 mM) with different concentrations of escitalopram oxalate (0.01, 0.02, 0.06, and 0.2 mM) to evaluate whether the assessed combination would have synergistic effects on SNU-1 cell survival. 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.06 mM) administered over 24 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Moreover, 5-FU (0.001 mM) + escitalopram oxalate (0.02 or 0.06 mM) and 5-FU (0.01 mM) + escitalopram oxalate (0.02, 0.06, or 0.2 mM) administered over 48 h showed synergistic effects on the inhibition of SNU-1 cell proliferation. Compared with controls, SNU-1 cells treated with 5-FU (0.01 mM) + escitalopram oxalate (0.02 mM) exhibited significantly increased levels of annexin V staining, reactive oxygen species, cleaved poly (ADP-ribose) polymerase, and caspase-3 proteins. Furthermore, 5-FU (12 mg/kg) + escitalopram oxalate (12.5 mg/kg) significantly attenuated xenograft SNU-1 cell proliferation in nude mice. Our study is the first to report the synergistic effects of the combinational use of low-dose 5-FU and escitalopram oxalate on inhibiting SNU-1 cell proliferation. These findings may be indicative of an alternative option for GC treatment.

Quality of life and symptom distress after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/ HIPEC) for peritoneal surface malignancy can effectively control the disease, however it is also associated with adverse effects which may affect quality of life (QoL). AIM: To investigate early perioperative QoL after CRS/HIPEC, which has not been discussed in Taiwan. METHODS: This single institution, observational cohort study enrolled patients who received CRS/HIPEC. We assessed QoL using the Taiwanese version of the MD Anderson Symptom Inventory (MDASI-T) and European Organization Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Participants completed the questionnaires before CRS/HIPEC (S1), at the first outpatient follow-up (S2), and 3 mo after CRS/HIPEC (S3). RESULTS: Fifty-eight patients were analyzed. There was no significant perioperative difference in global health status. Significant changes in physical and role functioning scores decreased at S2, and fatigue and pain scores increased at S2 but returned to baseline at S3. Multiple regression analysis showed that age and performance status were significantly correlated with QoL. In the MDASI-T questionnaire, distress/feeling upset and lack of appetite had the highest scores at S1, compared to fatigue and distress/feeling upset at S2, and fatigue and lack of appetite at S3. The leading interference items were working at S1 and S2 and activity at S3. MDASI-T scores were significantly negatively correlated with the EORTC QLQ-C30 results. CONCLUSION: QoL and symptom severity improved or returned to baseline in most categories within 3 mo after CRS/HIPEC. Our findings can help with preoperative consultation and perioperative care.

Protective Effect of Escitalopram on Hepatocellular Carcinoma by Inducing Autophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with poor prognosis. Although recent research has indicated that selective serotonin reuptake inhibitors (SSRIs), including escitalopram, have anticancer effects, little is known about the effects of escitalopram on HCC. METHODS: Both in vitro and in vivo studies were conducted to verify the potentials of escitalopram on HCC treatment. To explore whether the effects of escitalopram are clinically consistent with laboratory findings, a nationwide population-based cohort study was also adopted to examine the association between escitalopram and HCC risk. RESULTS: As compared with THLE-3 cells, escitalopram significantly inhibited the proliferation of HepG2 and Huh-7 cells. Specifically, escitalopram significantly induced autophagy in HepG2 and Huh-7 cells by increasing the LC3-II/LC3-I ratio and the expression of ATG-3, ATG-5, ATG-7, and Beclin-1 proteins. Moreover, escitalopram significantly inhibited the growth of xenografted Huh-7 cells in SCID mice that were treated with 12.5 mg/kg escitalopram. Accordingly, the risk of HCC was negatively correlated with escitalopram use. CONCLUSIONS: These findings provided evidence supporting the therapeutic potential of escitalopram for HCC. Both laboratory and nationwide population-based cohort evidence demonstrated the attenuated effects of escitalopram on HCC.

Association of Risperidone With Gastric Cancer: Triangulation Method From Cell Study, Animal Study, and Cohort Study.

Purpose: To examine the effects of risperidone, an atypical antipsychotic agent, on gastric cancer. Methods: A triangulation method comprising bench studies, including cell and animal experiments, and a retrospective cohort study, was subsequently performed. Results: The bench study indicated that risperidone exerted more prominent tumor inhibition effects than other atypical antipsychotics on the proliferation of KATO-III cells, a human gastric cancer cell line. Significant and dose-dependent cell viability was observed in Hs27 cells (control cells) in the presence of risperidone compared with in KATO-III cells. Both in vivo and in vitro results indicated that risperidone significantly inhibited the proliferation of KATO-III cells by inducing ROS and apoptosis, and that it suppressed the growth of xenografted KATO-III tumors in nude mice. In addition, the population-based cohort study found that risperidone users had reduced risks of gastric cancer compared with non-users, with lowered adjusted hazard ratios (HRs) for two induction periods (HR = 0.75; 95% confidence interval [CI] 0.68-0.83 for the one-year induction period, and HR = 0.68; 95% CI 0.61-0.75 for the two-year induction period). Conclusion: The findings are consistent with anticancer effects associated with risperidone, but further research and evaluations are warranted.

Asthma and early smoking associated with high risk of panic disorder in adolescents and young adults.

PURPOSE: Studies have reported a strong link between asthma and panic disorder. We conducted a 17-year community-based large cohort study to examine the relationship between asthma, early smoking initiation, and panic disorder during adolescence and early adulthood. METHODS: A total of 162,766 participants aged 11-16 years were categorized into asthma and nonasthma groups at baseline and compared within the observation period. Covariates during late childhood or adolescence included parental education, cigarette smoking by family members of participants, and participant's gender, age, alcohol consumption, smoking, and exercise habits. Data for urbanicity, prednisone use, allergic comorbidity, and Charlson comorbidity index were acquired from the National Health Insurance Research Database. The Cox proportional-hazards model was used to evaluate the association between asthma and panic disorder. RESULTS: Our findings revealed that asthma increased the risk of panic disorder after adjustment for key confounders in the Cox proportional hazard regression model (adjusted HR: 1.70, 95% CI 1.28-2.26). Hospitalizations or visits to the emergency department for asthma exhibited a dose-response effect on the panic disorder (adjusted HR: 2.07, 95% CI 1.30-3.29). Patients with asthma with onset before 20 years of age who smoked during late childhood or adolescence had the greatest risk for panic disorder (adjusted HR: 4.95, 95% CI 1.23-19.90). CONCLUSIONS: Patients newly diagnosed with asthma had a 1.7-times higher risk of developing panic disorder. Smoking during late childhood or adolescence increased the risk for developing the panic disorder in patients with asthma.

Classification and Visualization of Chemotherapy-Induced Cognitive Impairment in Volumetric Convolutional Neural Networks.

Breast cancer is the most common female cancer worldwide, and breast cancer accounts for 30% of female cancers. Of all the treatment modalities, breast cancer survivors who have undergone chemotherapy might complain about cognitive impairment during and after cancer treatment. This phenomenon, chemo-brain, is used to describe the alterations in cognitive functions after receiving systemic chemotherapy. Few reports detect the chemotherapy-induced cognitive impairment (CICI) by performing functional MRI (fMRI) and a deep learning analysis. In this study, we recruited 55 postchemotherapy breast cancer survivors (C+ group) and 65 healthy controls (HC group) and extracted mean fractional amplitudes of low-frequency fluctuations (mfALFF) from resting-state fMRI as our input feature. Two state-of-the-art deep learning architectures, ResNet-50 and DenseNet-121, were transformed to 3D, embedded with squeeze and excitation (SE) blocks and then trained to differentiate cerebral alterations based on the effect of chemotherapy. An integrated gradient was applied to visualize the pattern that was recognized by our model. The average performance of SE-ResNet-50 models was an accuracy of 80%, precision of 78% and recall of 70%; on the other hand, the SE-DenseNet-121 model reached identical results with an average of 80% accuracy, 86% precision and 80% recall. The regions with the greatest contributions highlighted by the integrated gradients algorithm for differentiating chemo-brain were the frontal, temporal, parietal and occipital lobe. These regions were consistent with other studies and strongly associated with the default mode and dorsal attention networks. We constructed two volumetric state-of-the-art models and visualized the patterns that are critical for identifying chemo-brains from normal brains. We hope that these results will be helpful in clinically tracking chemo-brain in the future.

Association of Prenatal Maternal Anemia with Tics and Tourette's Syndrome in Offspring.

Iron deficiency anemia (IDA) accounts for most of the anemia in pregnancy, and iron is essential for neurodevelopment. Tics and Tourette's syndrome (TS) are neurodevelopmental disorders that manifest in childhood. A few studies reported an inconclusive association between iron deficiency and tics in children. No study has investigated the relationship between prenatal maternal anemia and tics in children. We aimed to assess the relationship between prenatal anemia exposure and the incidence of tics or TS in offspring. We linked the Taiwan National Health Insurance Research Database to the Maternal and Child Health Database for the analysis and identified 153,854 children with prenatal anemia exposure and 2,014,619 children without prenatal anemia exposure from 2004 to 2016 and followed them through 2017. Cox regression models were applied to compare the risk of tics or TS between the exposed and nonexposed groups. Among the exposed group, 37,832 were exposed at ≤12 weeks of gestational age (GA) and 116,022 at >12 weeks of GA. We observed an increased risk of tics and TS in those exposed at ≤12 weeks compared with the nonexposed group (adjusted hazard ratio (aHR) = 1.23, 95% confidence interval (CI): 1.12-1.34). The result remained consistent after adjusting for birth year, sex, birth order, maternal age, low-income levels, gestational age, birth weight, and alcohol use and smoking during pregnancy (aHR = 1.16, CI: 1.04-1.28). Fetuses exposed to maternal anemia at ≤12 weeks of GA are at high risk of tics or TS. However, this effect was attenuated to insignificance in the sibling comparison. Our study highlights the importance of detection of anemia during pregnancy and proper timing of iron supplementation.

Statins and the risks of decompensated liver cirrhosis and hepatocellular carcinoma determined in patients with alcohol use disorder.

BACKGROUND: Alcohol-related liver disease (ALD) is the most common cause of liver disease. No medication can improve ALD and abstinence from alcohol is the sole effective strategy. Statin use has been demonstrated to have protective effects against liver cirrhosis and hepatocellular carcinoma (HCC) in patients with virus-related liver diseases. Whether statin use has a similar association among patients with alcohol use disorder (AUD) that can lead to ALD, is unknown. METHOD: We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database from 1997 to 2013 to compare risks of decompensated liver cirrhosis and hepatocellular carcinoma (HCC) between the statin exposed and unexposed groups in the patients with AUD. The incidence rates of decompensated liver cirrhosis and HCC were calculated between patients exposed and unexposed to statins with 1:4 propensity score matching. Cox proportional hazard regressions were performed to evaluate hazard ratios (HRs). RESULTS: The incidence rates of decompensated liver cirrhosis and HCC in the statin-exposed group differed from those in the unexposed group (decompensated cirrhosis: 269.9 vs. 628.9 cases per 100,000 person-years; HCC: 116.7 vs. 318.3 cases per 100,000 person-years). The HRs for decompensated liver cirrhosis and HCC were 0.43 (95% CI, 0.37-0.51) and 0.40 (95% CI, 0.31-0.51), respectively, after adjustment. CONCLUSIONS: Statin use was associated with reduced risk of decompensated liver cirrhosis and HCC among AUD patients in a cumulative dose effect manner. Statins might have some potential effects on mitigating ALD progression beside abstinence from alcohol. Further research is needed.

Comparison of functional dorsal attention network alterations in breast cancer survivors before and after chemotherapy.

ABSTRACT: Breast cancer is the leading type of cancer among women worldwide, and a high number of breast cancer patients are suffering from psychological and cognitive disorders. This cross-sectional study used resting-state functional magnetic resonance imaging (rs-fMRI) and clinical neuropsychological tests to evaluate the possible underlying mechanisms.We enrolled 32 breast cancer patients without chemotherapy (BC), 32 breast cancer patients within 6 to 12 months after the completion of chemotherapy (BC_CTx) and 46 healthy controls. Participants underwent neuropsychological tests and rs-fMRI with mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity analyses. Between groups whole-brain voxel-wise rs-fMRI comparisons were calculated using two-sample t test. rs-fMRI and neuropsychological tests correlation analyses were calculated using multiple regression. Age and years of education were used as covariates. A false discovery rate-corrected P-value of less than .05 was considered statistically significant.We found significantly alteration of mean fractional amplitude of low-frequency fluctuation and mean regional homogeneity in the frontoparietal lobe and occipital lobe in the BC group compared with the other 2 groups, indicating alteration of functional dorsal attention network (DAN). Furthermore, we found the DAN alteration was correlated with neuropsychological impairment.The majority of potential underlying mechanisms of DAN alteration in BC patients may due to insufficient frontoparietal lobe neural activity to drive DAN and may be related to the effects of neuropsychological distress. Further longitudinal studies with comprehensive images and neuropsychological tests correlations are recommended.

Antidepressants use is associated with overall survival improvement of patients with gastric cancer after surgery and adjuvant chemotherapy in Taiwan: A large population-based cohort study.

ABSTRACT: To determine whether exposure to antidepressants (ATDs) results in improved overall survival (OS) of patients with gastric cancer (GC) after surgery, we conducted a large cohort study and considered confounding factors that might affect the research outcomes.Patients who received a new diagnosis of GC and received surgery and chemotherapy between 1999 and 2008 were recruited and were classified into different groups based on the ATD level used. The association between the OS of patients with GC after surgery with different levels of ATD use, and the hazard ratio with comorbidities at different ATD use levels were compared.According to Kaplan-Meier method, the more of an ATD was taken, the longer the OS and a dose-dependent relationship was discovered in the OS curve; the adjusted HRs were 0.76 (95% confidence interval [CI] = 0.68-0.84) and 0.48 (95% CI = 0.41-0.57) for ATD users taking a cumulative defined daily dose (cDDD) of 28-167 and ≧168, respectively. Sensitivity analyzes were performed to investigate the effect of various comorbidities on OS with different degrees of ATD use and the results remained consistent among the varying models. Additionally, the effect of ATD use still exhibited a dose-dependent relationship in distinct stratifications for sex and age.The OS for patients with GC after surgery and chemotherapy improved with ATD use, and a dose-dependent relationship was discovered in this study. Further studies on the association between OS of GC and ATD use are required.

Added burden of major depressive disorder on cardiovascular morbidity and mortality among patients with cardiovascular disease and the modifying effects of antidepressants: A national retrospective cohort study.

BACKGROUND: To evaluate the likelihood of a future cardiovascular event (i.e., in-hospital mortality or cardiovascular disease [CVD] complications/interventions) among patients with CVD and major depressive disorder (MDD) compared to those without MDD, and the antidepressant use on future cardiovascular events between the two groups. METHODS: This is a retrospective cohort with propensity score matching with 8941 patients with CVD and MDD, and 8941 non-MDD patients using data from the Longitudinal Health Insurance Database from 1999 to 2013 in Taiwan. The outcome was in-hospital mortality and the incidence of revascularization (i.e., percutaneous transluminal coronary angioplasty [PTCA] and coronary artery bypass graft surgery [CABG]). RESULTS: Patients with CVD and MDD were more likely to need revascularization (an adjusted hazard ratio [aHR]: 1.26 and 95% CI: 1.12-1.43) than those without MDD, regardless of whether PTCA (aHR: 1.23 and 95% CI: 1.07-1.40) or CABG (aHR: 1.60 and 95% CI: 1.16-2.21) had occurred. Antidepressant use was associated with a tendency of reduced risk of mortality (aHR: 0.92 and 95% CI: 0.84-1.00). Although the magnitude of aHR ranged from 0.92 to 0.95 with revascularization, they did not reach significant levels. LIMITATIONS: Some covariates could not be controlled because they were not included in the national register dataset, and the causality is limited in an observational study. CONCLUSIONS: Patients with CVD with MDD are more likely to experience a cardiovascular complication requiring intervention than CVD patients without MDD. Antidepressant use is associated with reduced in-hospital mortality.

Sleep Quality and Related Factors in Patients with Breast Cancer: A Cross-Sectional Study in Taiwan.

BACKGROUND: Sleep disturbances are common and symptomatic burden in patients with breast cancer, but they are poorly documented and managed in routine clinical practice. This descriptive and cross-sectional study evaluated factors associated with post-treatment sleep disturbances in patients with breast cancer. PATIENTS AND METHODS: Patients with breast cancer who underwent standard treatment were enrolled and surveyed for their basic demographic data and precancerous and cancer treatment-related factors; they were also administered self-report questionnaires including the Family Adaptation, Partnership, Growth, Affection, Resolve questionnaire; Impact of Event Scale; Center for Epidemiologic Studies Depression Scale; and Maudsley Personality Inventory. Their sleep disturbances were evaluated using the Pittsburgh sleep quality index (PSQI). Independent sample t test and chi-square tests were used to compare the variables between patients with or without sleep disturbance, and multivariate logistic regression analyses were conducted to detect the independent factors. RESULTS: In total, 448 patients, including 145 with PSQI ≤ 5 and 303 with PSQI > 5, completed the investigation. Multiple logistic regression analysis revealed that significantly more patients with sleep disturbances demonstrated psychological distress, severe pain, depression, and impact of stress events than patients without sleep disturbances (adjusted odds ratios [95% confidence intervals]: 2.83 [1.135-7.067], P = 0.026; 1.14 [1.023-1.280], P = 0.018; 1.08 [1.036-1.133], P < 0.001; and 1.03 [1.002-1.051], P = 0.037, respectively). CONCLUSION: Patients with breast cancer showed 67.6% prevalence of sleep disturbances after treatment. The patients with sleep disturbances were more likely to have previously experienced psychological disturbances, severe pain, depression within 5 years after diagnosis. After diagnosis for more than 5 years, higher distress caused by traumatic events still associated with sleep disturbances.

Effects of Cancer, Chemotherapy, and Cytokines on Subjective and Objective Cognitive Functioning Among Patients with Breast Cancer.

BACKGROUND: We aimed to investigate the associations of breast cancer (BC) and cancer-related chemotherapies with cytokine levels, and cognitive function. METHODS: We evaluated subjective and objective cognitive function in BC patients before chemotherapy and 3~9 months after the completion of chemotherapy. Healthy volunteers without cancer were also compared as control group. Interleukins (IL) 2, 4, 5, 6, 10, 12p70, 13, 17A, 1ß, IFNγ, and TNFα were measured. Associations of cancer status, chemotherapy and cytokine levels with subjective and objective cognitive impairments were analyzed using a regression model, adjusting for covariates, including IQ and psychological distress. RESULTS: After adjustment, poorer performance in semantic verbal fluency was found in the post-chemotherapy subgroup compared to controls (p = 0.011, η2 = 0.070); whereas pre-chemotherapy patients scored higher in subjective cognitive perception. Higher IL-13 was associated with lower semantic verbal fluency in the post-chemotherapy subgroup. Higher IL-10 was associated with better perceived cognitive abilities in the pre-chemotherapy and control groups; while IL-5 and IL-13 were associated with lower perceived cognitive abilities in pre-chemotherapy and control groups. Our findings from mediation analysis further suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. CONCLUSIONS: Our findings suggest that verbal fluency might be affected by cancer status, although mediated by anxiety. Different cytokines and their interactions may have different roles of neuroinflammation or neuroprotection that need further research.