Association between gastrectomy and the risk of type 2 diabetes in gastric cancer survivors: a nationwide cohort study.

AIM: Postprandial glycemic fluctuations after gastrectomy are seen in patients with gastric cancer but, no studies have investigated the association between gastrectomy and type 2 diabetes mellitus (T2DM) in gastric cancer survivors. This study aimed to elucidate the relationship between gastrectomy (total or subtotal) and incident T2DM. In addition, we explored whether vitamin B12 supplementation modulates this risk among patients who have undergone total gastrectomy. METHODS: In this large nationwide population-based retrospective cohort study using the National Health Insurance Service database of South Korea, we identified patients aged >20 years who underwent gastrectomy from 2008 to 2015 (n=150,074) and age- and sex-matched controls without gastrectomy (n=301,508). A Cox proportional hazards model was used. RESULTS: During the median follow-up duration of 4.4 years after the 2-year time lag after gastrectomy, of the 78,006 subjects, 4,597 (5.9%) developed T2DM. Compared with matched controls, the adjusted hazard ratio (AHR[95% confidence interval]) for T2DM of patients with total gastrectomy was 1.34[1.23;1.47]. The corresponding AHR after subtotal gastrectomy was 0.81[0.76;0.86]. Among the patients with total gastrectomy, the risk of T2DM was significantly increased in those who did not receive any vitamin B12 supplementation (AHR=1.60[1.33;1.92]), whereas the risk of T2DM was lower (close to being statistically significant) in those who received continuous vitamin B12 supplementation after gastrectomy (AHR=0.70[0.49;1.01]). CONCLUSION: These results show a significantly reduced risk of T2DM in gastric cancer patients undergoing subtotal gastrectomy and a significantly increased risk of T2DM in gastric cancer patients undergoing total gastrectomy, which is mitigated by continuous vitamin B12 supplementation.

Multimodal pulmonary clearance kinetics of carbon black nanoparticles deposited in the lungs of rats: the role of alveolar macrophages.

BACKGROUND: Alveolar macrophages (AMs) have been predicted to affect the pulmonary clearance of nanomaterials; however, their qualitative and quantitative roles are poorly understood. In this study, carbon black nanoparticles (CBNPs) were instilled into the lungs of Wistar rats at 30, 100, and 300 µg/rat. The concentrations of particles in organs, including the lung, lung-associated lymph nodes (LALN), liver, spleen, and kidney, were evaluated at days 0 (immediately after instillation), 1, 7, 28, 60, and 90 post-instillation. RESULTS: The results indicated a multimodal pulmonary clearance pattern for CBNPs: slow clearance until day 28, fast clearance from days 28 to 60, and slow clearance from days 60 to 90. To determine the mechanism of this unique clearance pattern, CBNPs were instilled into AM-depleted rats using clodronate liposomes (CLO). At 28 days after instillation, the CBNP levels in the lungs treated with CLO showed about 31% higher reduction than in normal rats. In addition, the concentration of CBNPs in LALN treated with CLO significantly increased on day 28, whereas in normal rats, no detectable levels were observed. CONCLUSIONS: This result highlights that the prolonged retention of poorly soluble NPs in the lung until day 28 is mediated by the phagocytosis of AMs, and the fast clearance between days 28-60 is due to the turnover time of AMs, estimated around 1-2 months after birth. Similarly, new generations of AMs mediate the slow phase between days 60 and 90. However, further studies are needed to understand the multimodal clearance mechanism and the modulation of pulmonary clearance of poorly soluble NPs.

Methylglyoxal-derived hydroimidazolone-1/RAGE axis induces renal oxidative stress and renal fibrosis in vitro and in vivo.

Advanced glycation end products (AGEs) are important contributors to the progression of chronic kidney diseases (CKD), including renal fibrosis. Although the relationship between AGEs and renal fibrosis has been well studied, the mechanisms of individual AGE-induced renal injury remain poorly understood. This study investigated the adverse effect of methylglyoxal-derived hydroimidazolone-1 (MG-H1), a methylglyoxal (MG)-derived AGE generated by the glycation of MG and arginine residues, on kidney damage. We aimed to elucidate the molecular mechanisms of MG-H1-mediated renal injury and fibrosis, focusing on the receptor for AGEs (RAGE) signaling and its effects on the Wnt/ß-catenin pathway, MAPK pathway, and inflammatory responses. Our results suggest that the MG-H1/RAGE axis plays a significant role in the pathogenesis of CKD and its downstream events involving MAPK kinase-related factors and inflammatory factors. MG-H1 treatment modulated the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) and MAPK proteins (ERK1/2, JNK, and p38).

Association between weight loss and cardiovascular outcomes and mortality in Korea: A nationwide cohort study.

AIMS: While the benefit of weight loss in reducing the incidence of cardiovascular disease (CVD) is recognized, its association with CVD mortality remains controversial. This study investigates the association between weight loss and the incidence of CVD outcomes. METHODS: This was a 7.2-year retrospective cohort study of 1,020,533 adults aged 40-80 years who underwent at least two general health checkups within a 2-year interval in Korea. Weight was measured by trained examiners at certified hospitals. We used Cox proportional hazards models to examine the association between weight loss and the incidence of CVD outcomes. RESULTS: Weight loss of more than 3 % was associated with an increased risk of combined CVD events (hazard ratio [HR] for moderate weight loss: 1.24, 95 % confidence interval [CI]: 1.21-1.28; HR for severe weight loss: 1.45, 95 % CI: 1.33-1.57). Weight loss was significantly associated with an increased risk of both nonfatal CVD events and CVD mortality, but regular exercise mitigated the adverse effects on CVD mortality. CONCLUSIONS: Weight loss of more than 3% is associated with an increased risk of a combined CVD events, consistent across most risk factors. However, regular exercise may reduce the adverse effects on CVD mortality, suggesting a potential protective role of physical activity.

Different modifiable risk factors for the development of non-advanced adenoma, advanced adenomatous lesion, and sessile serrated lesions, on screening colonoscopy.

The development of premalignant colorectal polyps is significantly influenced by various lifestyle and modifiable risk factors. In our study, we used a large cohort of 9025 patients, who underwent screening colonoscopies at a university hospital, to assess the risk factors associated with the development of three different colorectal cancer precursor lesions: non-advanced adenomas (NAs), advanced adenomatous lesions (ADLs), and sessile serrated lesions (SSLs). Among the participants, 3641 had NAs, 836 had ADLs, and 533 had SSLs. We identified obesity, current smoking, and appendicular skeletal muscle mass as modifiable lifestyle risk factors that increase the development of NAs and ADLs (all P < 0.05). Furthermore, we found a positive correlation between the degree of obesity and an increased risk of developing NAs and ADLs (all P for trend < 0.001), while non-smoking was associated with a decreased risk (P for trend < 0.001 and 0.003, respectively). Smoking was the only modifiable risk factor for developing SSLs (adjusted odds ratio [aOR] 1.58; 95% confidence interval [CI] 1.20-2.07), and the risk was even higher in patients with metabolic syndrome (aOR 1.71; 95% CI 1.05-2.77). Addressing modifiable lifestyle factors such as smoking and obesity could play an important role in reducing the risk of both non-advanced and advanced adenomatous lesions. Smoking cessation is especially important as it is a significant modifiable risk factor for sessile serrated lesions.

The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.

AIMS/HYPOTHESIS: Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. METHODS: In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. RESULTS: A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. CONCLUSIONS/INTERPRETATION: The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.

Advancing Fab-Compatible Color-Selective Organic Photodiodes: Tailored Molecular Design and Nanointerlayers.

High-performance organic photodiodes (OPDs) and OPD-based image sensors are primarily realized using solution processes based on various additives and coating methods. However, vacuum-processed OPDs, which are more compatible with large-scale production, have received little attention, thereby hindering their integration into advanced systems. This study introduces innovations in the material and device structures to prepare superior vacuum-processed OPDs for commercial applications. A series of vacuum-processable, low-cost p-type semiconductors is developed by introducing an electron-rich cyclopentadithiophene core containing various electron-accepting moieties to fine-tune the energy levels without any significant structural or molecular weight changes. An additional nanointerlayer strategy is used to control the crystalline orientation of the upper-deposited photoactive layer, compensating for device performance reduction in inverted, top-illuminated OPDs. These approaches yielded an external quantum efficiency of 70% and a specific detectivity of 2.0 × 1012 Jones in the inverted structures, which are vital for commercial applications. These OPDs enabled visible-light communications with extremely low bit error rates and successful X-ray image capture.

Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function with chronic kidney disease.

PURPOSE: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function. METHODS: An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-ß and p-cresyl sulfate were administered with butyrate. RESULTS: In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study. CONCLUSIONS: This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.

A randomized controlled trial of an app-based intervention on physical activity and glycemic control in people with type 2 diabetes.

BACKGROUND: We investigated the effects of a physical activity encouragement intervention based on a smartphone personal health record (PHR) application (app) on step count increases, glycemic control, and body weight in patients with type 2 diabetes (T2D). METHODS: In this 12-week, single-center, randomized controlled, 12-week extension study, patients with T2D who were overweight or obese were randomized using ratio 1:2 to a group using a smartphone PHR app (control group) or group using the app and received individualized motivational text messages (intervention group) for 12 weeks. During the extension period, the sending of the encouraging text messages to the intervention group was discontinued. The primary outcome was a change in daily step count after 12 weeks and analyzed by independent t-test. The secondary outcomes included HbA1c, fasting glucose, and body weight analyzed by paired or independent t-test. RESULTS: Of 200 participants, 62 (93.9%) and 118 (88.1%) in the control and intervention group, respectively, completed the 12-week main study. The change in daily step count from baseline to week 12 was not significantly different between the two groups (P = 0.365). Among participants with baseline step counts < 7,500 steps per day, the change in the mean daily step count at week 12 in the intervention group (1,319 ± 3,020) was significantly larger than that in control group (-139 ± 2,309) (P = 0.009). At week 12, HbA1c in the intervention group (6.7 ± 0.5%) was significantly lower than that in control group (6.9 ± 0.6%, P = 0.041) and at week 24, changes in HbA1c from baseline were significant in both groups but, comparable between groups. Decrease in HbA1c from baseline to week 12 of intervention group was greater in participants with baseline HbA1c ≥ 7.5% (-0.81 ± 0.84%) compared with those with baseline HbA1c < 7.5% (-0.22 ± 0.39%) (P for interaction = 0.014). A significant reduction in body weight from baseline to week 24 was observed in both groups without significant between-group differences (P = 0.370). CONCLUSIONS: App-based individualized motivational intervention for physical activity did not increase daily step count from baseline to week 12, and the changes in HbA1c levels from baseline to week 12 were comparable. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03407222).

Disruption of early embryonic development in mice by polymethylmethacrylate nanoplastics in an oxidative stress mechanism.

Polymethylmethacrylate (PMMA) has been used in many products, such as acrylic glass, and is estimated to reach 5.7 million tons of production per year by 2028. Thus, nano-sized PMMA particles in the environment are highly likely due to the weathering process. However, information on the hazards of nanoplastics, including PMMA in mammals, especially reproductive toxicity and action mechanism, is scarce. Herein, we investigated the effect of PMMA nanoplastics on the female reproductive system of mice embryos during pre-implantation. The treated plastic particles in embryos (10, 100, and 1000 µg/mL) were endocytosed into the cytoplasm within 30 min, and the blastocyst development and indices of embryo quality were significantly decreased from at 100 µg/mL. Likewise, the transfer of nanoplastic-treated embryos at 100 µg/mL decreased the morula implantation rate on the oviduct of pseudopregnant mice by 70%, calculated by the pregnant individual, and 31.8% by the number of implanted embryos. The PMMA nanoplastics at 100 µg/mL significantly increased the cellular levels of reactive oxygen species in embryos, which was not related to the intrinsic oxidative potential of nanoplastics. This study highlights that the nanoplastics that enter systemic circulation can affect the early stage of embryos. Thus, suitable action mechanisms can be designed to address nanoplastic occurrence.

Metabolic dysfunction-associated fatty liver disease and heavy alcohol consumption increase mortality:A nationwide study.

BACKGROUND: The effects of excessive alcohol consumption on the prognosis of metabolic dysfunction-associated fatty liver disease (MAFLD) remain unclear. We investigated all-cause and cause-specific mortality according to the amount of alcohol consumed by Asian individuals with MAFLD. METHODS: This nationwide retrospective study included 996,508 adults aged 40-79 years who underwent health check-ups between 2009 and 2012. Participants were categorized by the alcohol consumption-non-alcohol, moderate alcohol, and heavy alcohol group (≥ 30 g/day for men, ≥ 20 g/day for women) and by the combination of the presence or absence of MAFLD. Hepatic steatosis was defined as the fatty liver index ≥ 30. Cox analyses were used to analyze the association between alcohol consumption and MAFLD and all-cause and cause-specific mortality. RESULTS: MAFLD significantly increased all-cause, liver-, and cancer-related mortality. Individuals with both MAFLD and heavy alcohol consumption expressed the highest mortality risk in liver-related mortality compared to non-MAFLD and non-alcohol group (adjusted hazard ratio (HR), 9.8; 95% confidence interval (CI), 8.20-12.29). Regardless of MAFLD, heavy alcohol consumption increased the risk of liver- and cancer-related mortality. CONCLUSIONS: MAFLD and heavy alcohol consumption increased all-cause, liver-, and cancer-related mortality. Heavy alcohol consumption and MAFLD synergistically increase liver-related mortality.

Association between nonalcoholic fatty liver disease and left ventricular diastolic dysfunction: A 7-year retrospective cohort study of 3,380 adults using serial echocardiography.

AIM: Left ventricular diastolic dysfunction (LVDD) has been observed in people with nonalcoholic fatty liver disease (NAFLD) in cross-sectional studies but the causal relationship is unclear. This study aimed to investigate the impact of NAFLD and the fibrotic progression of the disease on the development of LVDD, assessed by serial echocardiography, in a large population over a 7-year longitudinal setting. METHODS: This retrospective cohort study included the data of 3,380 subjects from a medical health check-up program. We defined subjects having NAFLD by abdominal ultrasonography and assessed significant liver fibrosis by the aspartate transaminase (AST) to platelet ratio index (APRI), the NAFLD fibrosis score (NFS), and the fibrosis-4 (FIB-4) index. LVDD was defined using serial echocardiography. A parametric Cox proportional hazards model was used. RESULTS: During 11,327 person-years of follow-up, there were 560 (16.0 %) incident cases of LVDD. After adjustment for multiple risk factors, subjects with NAFLD showed an increased adjusted hazard ratio (aHR) of 1.21 (95 % confidence interval [CI]=1.02-1.43) for incident LVDD compared to those without. The risk of LV diastolic dysfunction increased progressively with increasing degree of hepatic steatosis (P< 0.001). Compared to subjects without NAFLD, the multivariable-aHR (95 % CI) for LVDD in subjects with APRI < 0.5 and APRI ≥ 0.5 were 1.20 (1.01-1.42) and 1.36 (0.90-2.06), respectively (P= 0.036), while other fibrosis prediction models (NFS and FIB-4 index) showed insignificant results. CONCLUSIONS: This study demonstrated that NAFLD was associated with an increased risk of LVDD in a large cohort. More severe forms of hepatic steatosis and/or significant liver fibrosis may increase the risk of developing LVDD.

Clinical Characteristics, Diagnosis, and Treatment of Thyroid Stimulating Hormone-Secreting Pituitary Neuroendocrine Tumor (TSH PitNET): A Single-Center Experience.

BACKGRUOUND: Thyroid-stimulating hormone (TSH)-secreting pituitary neuroendocrine tumor (TSH PitNET) is a rare subtype of PitNET. We investigated the comprehensive characteristics and outcomes of TSH PitNET cases from a single medical center. Also, we compared diagnostic methods to determine which showed superior sensitivity. METHODS: A total of 17 patients diagnosed with TSH PitNET after surgery between 2002 and 2022 in Samsung Medical Center was retrospectively reviewed. Data on comprehensive characteristics and treatment outcomes were collected. The sensitivities of diagnostic methods were compared. RESULTS: Seven were male (41%), and the median age at diagnosis was 42 years (range, 21 to 65); the median follow-up duration was 37.4 months. The most common (59%) initial presentation was hyperthyroidism-related symptoms. Hormonal co-secretion was present in four (23%) patients. Elevated serum alpha-subunit (α-SU) showed the greatest diagnostic sensitivity (91%), followed by blunted response at thyrotropin-releasing hormone (TRH) stimulation (80%) and elevated sex hormone binding globulin (63%). Fourteen (82%) patients had macroadenoma, and a specimen of one patient with heavy calcification was negative for TSH. Among 15 patients who were followed up for more than 6 months, 10 (67%) achieved hormonal and structural remission within 6 months postoperatively. A case of growth hormone (GH)/TSH/prolactin (PRL) co-secreting mixed gangliocytoma-pituitary adenoma (MGPA) was discovered. CONCLUSION: The majority of the TSH PitNET cases was macroadenoma, and 23% showed hormone co-secretion. A rare case of GH/TSH/PRL co-secreting MGPA was discovered. Serum α-SU and TRH stimulation tests showed great diagnostic sensitivity. Careful consideration is needed in diagnosing TSH PitNET. Achieving remission requires complete tumor resection. In case of nonremission, radiotherapy or medical therapy can improve the long-term remission rate.

Association between depression, antidepressant use, and the incidence of atherosclerotic cardiovascular diseases.

OBJECTIVE: To examine the association between depression, the use of antidepressants, and atherosclerotic cardiovascular disease (ASCVD). METHODS: The South Korean national claims data was used. Among a nationally representative population, 273,656 subjects who had been diagnosed with depression and prescribed antidepressants ("DEP with antidepressants") and 78,851 subjects who had been diagnosed with depression but not prescribed antidepressants ("DEP without antidepressants") were identified to be eligible. Healthy controls (HCs) were 1:1 matched with DEP with antidepressants group for age and sex. We followed up on the occurrence of ASCVD including ischemic heart diseases and ischemic stroke. RESULTS: The risk of ASCVD was increased in the DEP with antidepressants group and decreased in the DEP without antidepressants group compared to HCs. Among those under antidepressants, tricyclic antidepressant users showed the highest risk of ASCVD compared to HCs. Among young adults, the risk of ASCVD was increased in both groups. CONCLUSION: The risk of ASCVD increased in depression patients taking antidepressants, while it decreased in depression patients not taking antidepressants. However, the relationship showed differences according to drug class and age group.

Petabase-Scale Homology Search for Structure Prediction.

The recent CASP15 competition highlighted the critical role of multiple sequence alignments (MSAs) in protein structure prediction, as demonstrated by the success of the top AlphaFold2-based prediction methods. To push the boundaries of MSA utilization, we conducted a petabase-scale search of the Sequence Read Archive (SRA), resulting in gigabytes of aligned homologs for CASP15 targets. These were merged with default MSAs produced by ColabFold-search and provided to ColabFold-predict. By using SRA data, we achieved highly accurate predictions (GDT_TS > 70) for 66% of the non-easy targets, whereas using ColabFold-search default MSAs scored highly in only 52%. Next, we tested the effect of deep homology search and ColabFold's advanced features, such as more recycles, on prediction accuracy. While SRA homologs were most significant for improving ColabFold's CASP15 ranking from 11th to 3rd place, other strategies contributed too. We analyze these in the context of existing strategies to improve prediction.

Psychotic Disorders and the Risk of Type 2 Diabetes Mellitus, Atherosclerotic Cardiovascular Diseases, and All-Cause Mortality: A Population-Based Matched Cohort Study.

BACKGRUOUND: The effects of psychotic disorders on cardiometabolic diseases and premature death need to be determined in Asian populations. METHODS: In this population-based matched cohort study, the Korean National Health Insurance Service database (2002 to 2018) was used. The risk of type 2 diabetes mellitus (T2DM), acute myocardial infarction (AMI), ischemic stroke, composite of all cardiometabolic diseases, and all-cause death during follow-up was compared between individuals with psychotic disorders treated with antipsychotics (n=48,162) and 1:1 matched controls without psychiatric disorders among adults without cardiometabolic diseases before or within 3 months after baseline. RESULTS: In this cohort, 53,683 composite cases of all cardiometabolic diseases (during median 7.38 years), 899 AMI, and 1,216 ischemic stroke cases (during median 14.14 years), 7,686 T2DM cases (during median 13.26 years), and 7,092 deaths (during median 14.23 years) occurred. The risk of all outcomes was higher in subjects with psychotic disorders than matched controls (adjusted hazard ratios [95% confidence intervals]: 1.522 [1.446 to 1.602] for T2DM; 1.455 [1.251 to 1.693] for AMI; 1.568 [1.373 to 1.790] for ischemic stroke; 1.595 [1.565 to 1.626] for composite of all cardiometabolic diseases; and 2.747 [2.599 to 2.904] for all-cause mortality) during follow-up. Similar patterns of associations were maintained in subgroup analyses but more prominent in younger individuals (P for interaction <0.0001) when categorized as those aged 18-39, 40-64, or ≥65 years. CONCLUSION: Patients with psychotic disorders treated with antipsychotics were associated with increased risk of premature allcause mortality and cardiometabolic outcomes in an Asian population. This relationship was more pronounced in younger individuals, especially aged 18 to 39 years.

Risk of Depression according to Cumulative Exposure to a Low-Household Income Status in Individuals with Type 2 Diabetes Mellitus: A Nationwide Population- Based Study.

BACKGRUOUND: We aimed to identify the risk of incident depression according to cumulative exposure to a low-household income status in individuals with type 2 diabetes mellitus (T2DM). METHODS: For this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2002 to 2018. Risk of depression was assessed according to cumulative exposure to low-household income status (defined as Medical Aid registration) during the previous 5 years among adults (aged ≥20 years) with T2DM and without baseline depression who underwent health examinations from 2009 to 2012 (n=2,027,317). RESULTS: During an average 6.23 years of follow-up, 401,175 incident depression cases occurred. Advance in cumulative number of years registered for medical aid during the previous 5 years from baseline was associated with an increased risk of depression in a dose-dependent manner (hazard ratio [HR], 1.44 [95% confidence interval (CI), 1.38 to 1.50]; HR, 1.40 [95% CI, 1.35 to 1.46]; HR, 1.42, [95% CI, 1.37 to 1.48]; HR, 1.46, [95% CI, 1.40 to 1.53]; HR, 1.69, [95% CI, 1.63 to 1.74] in groups with 1 to 5 exposed years, respectively). Insulin users exposed for 5 years to a low-household income state had the highest risk of depression among groups categorized by insulin use and duration of low-household income status. CONCLUSION: Cumulative duration of low-household income status, defined as medical aid registration, was associated with an increased risk of depression in a dose-response manner in individuals with T2DM.

Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer.

We aimed to determine the association between cholesterol values and the risk of all-cause mortality in newly diagnosed patients with cancer in a large-scale longitudinal cohort. Newly diagnosed patients with cancer were reviewed retrospectively. Cox proportional hazards regression models determined the association between baseline levels of total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and the risk of all-cause mortality. A restricted cubic spline curve was used to identify the association between total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol with the risk of death on a continuous scale and to present the lowest values of lipid measurements associated with death. The median follow-up duration of the study was 5.77 years. Of the 59,217 patients with cancer, 12,624 patients were expired. The multivariable adjusted hazard ratio (aHR) for all-cause mortality in patients with cancer with 1st-5th (≤ 97 mg/dL) and 96th-100th (> 233 mg/dL) in TC levels was 1.54 (95% CI 1.43-1.66) and 1.28 (95% CI 1.16-1.41), respectively, compared to 61st-80th (172-196 mg/dL). The TC level associated with the lowest mortality risk in the multivariable model was 181 mg/dL. In comparison with LDL-C levels in the 61st-80th (115-136 mg/dL), the multivariable aHR for all-cause mortality in cancer patients with LDL-C levels in the 1st-5th (≤ 57 mg/dL) and 96th-100th (> 167 mg/dL) was 1.38 (95% CI 1.14-1.68) and 0.94 (95% CI 0.69-1.28), respectively. The 142 mg/dL of LDL cholesterol showed the lowest mortality risk. We demonstrated a U-shaped relationship between TC levels at baseline and risk of mortality in newly diagnosed patients with cancer. Low LDL levels corresponded to an increased risk of all-cause death.