Effects of ambient air pollution on brain cortical thickness and subcortical volume: A longitudinal neuroimaging study.

INTRODUCTION: Long-term exposure to air pollutants is associated with an increased risk of Alzheimer's disease and mild cognitive impairment. Therefore, we investigated the association between long-term air pollution exposure and changes in neuroimaging markers. METHODS: In this longitudinal study, we studied a prospective cohort of 361 adults residing in four cities in the Republic of Korea. Long-term concentrations of particulate matter with aerodynamic diameters of ≤10 µm (PM10) and ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2) at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images at baseline (August 2014 to March 2017) and at the 3-year follow-up (until September 2020). Linear mixed-effects models were used, adjusting for covariates. RESULTS: A 10-µg/m3 increase in PM10 was associated with reduced whole-brain mean (ß= -0.45, standard error (SE)= 0.10, P< 0.001), frontal (ß= -0.53, SE= 0.11; P< 0.001) and temporal thicknesses (ß= -0.37, SE= 0.12; P= 0.002). A 10-ppb increase in NO2 was associated with a decline in the whole brain mean cortical thickness (ß= -0.23, SE= 0.05; P< 0.001), frontal (ß= -0.25, SE= 0.05; P< 0.001), parietal (ß= -0.12, SE= 0.05; P= 0.025), and temporal thicknesses (ß= -0.19, SE= 0.06; P= 0.001). Subcortical structures associated with air pollutants include the thalamus volume. CONCLUSIONS: Long-term exposure to PM10 and NO2 may lead to cortical thinning in adults.

Association between exposure to heavy metals in atmospheric particulate matter and sleep quality: A nationwide data linkage study.

BACKGROUND: Recent studies have demonstrated that long-term exposure to particulate matter (PM) is associated with poor sleep quality. However, no studies have linked PM constituents, particularly heavy metals, to sleep quality. OBJECTIVE: This study investigated the association between exposure to heavy metals in PM and sleep quality. METHODS: We obtained nationwide data from the Korean Community Health Survey conducted in 2018 among adults aged 19-80 years. Sleep quality was evaluated using Pittsburgh Sleep Quality Index (PSQI). Poor sleep quality was defined as PSQI ≥5. One-year and three-month average concentrations of heavy metals (lead, manganese, cadmium, and aluminum) in PM with diameter ≤10 µm were obtained from nationwide air quality monitoring data and linked to the survey data based on individual district-level residential addresses. Logistic regression analyses were performed after adjusting for age, gender, education level, marital status, smoking status, alcohol consumption, history of hypertension, and history of diabetes mellitus. RESULTS: Of 32,050 participants, 17,082 (53.3%) reported poor sleep quality. Increases in log-transformed one-year average lead (odds ratio, 1.14; 95% confidence interval, 1.08-1.20), manganese (1.31; 1.25-1.37), cadmium (1.03; 1.00-1.05), and aluminum concentrations (1.17; 1.10-1.25) were associated with poor sleep quality. Increases in log-transformed three-month average manganese (odds ratio, 1.13; 95% confidence interval, 1.09-1.17) and aluminum concentrations (1.28; 1.21-1.35) were associated with poor sleep quality. CONCLUSION: We showed for the first time that exposure to airborne lead, manganese, cadmium, and aluminum were associated with poor sleep quality. This study may be limited by self-reported sleep quality and district-level exposure data.

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis.

AIMS/HYPOTHESIS: The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS: All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS: A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION: At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.

Remnant cholesterol, but not low-density lipoprotein cholesterol, is associated with intra-pancreatic fat deposition.

AIM: To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD). METHODS: All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition. RESULTS: A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD. CONCLUSION: Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.

Associations of Particulate Matter Exposures With Brain Gray Matter Thickness and White Matter Hyperintensities: Effect Modification by Low-Grade Chronic Inflammation.

BACKGROUND: Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). METHODS: We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant's home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. RESULTS: Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 µg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07-2.97) and periventricular WMH (2.00; 1.20-3.33). A 1 µg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08-2.56). These associations did not significantly differ by the level of high sensitivity CRP. CONCLUSION: Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.

All-Cause and Cause-Specific Mortality Attributable to Seasonal Influenza: A Nationwide Matched Cohort Study.

BACKGROUND: Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. METHODS: Individuals with influenza during four consecutive influenza seasons (2013-2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. RESULTS: Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63-4.48), and 5.6% (95% CI, 4.5-6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40-17.55) and PAF (20.7%; 95% CI, 13.2-27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6-10.7%) for liver disease, 5.8% (95% CI, 2.9-8.5%) for respiratory disease, and 3.8% (95% CI, 1.4-6.1%) for cancer. CONCLUSION: Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.

Reduced brain subcortical volumes in patients with glaucoma: a pilot neuroimaging study using the region-of-interest-based approach.

BACKGROUND: While numerous neuroimaging studies have demonstrated that glaucoma is associated with smaller volumes of the visual cortices in the brain, only a few studies have linked glaucoma with brain structures beyond the visual cortices. Therefore, the objective of this study was to compare brain imaging markers and neuropsychological performance between individuals with and without glaucoma. METHODS: We identified 64 individuals with glaucoma and randomly selected 128 age-, sex-, and education level-matched individuals without glaucoma from a community-based cohort. The study participants underwent 3 T brain magnetic resonance imaging and neuropsychological assessment battery. Regional cortical thickness and subcortical volume were estimated from the brain images of the participants. We used a linear mixed model after adjusting for potential confounding variables. RESULTS: Cortical thickness in the occipital lobe was significantly smaller in individuals with glaucoma than in the matched individuals (ß = - 0.04 mm, P = 0.014). This did not remain significant after adjusting for cardiovascular risk factors (ß = - 0.02 mm, P = 0.67). Individuals with glaucoma had smaller volumes of the thalamus (ß = - 212.8 mm3, P = 0.028), caudate (ß = - 170.0 mm3, P = 0.029), putamen (ß = - 151.4 mm3, P = 0.051), pallidum (ß = - 103.6 mm3, P = 0.007), hippocampus (ß = - 141.4 mm3, P = 0.026), and amygdala (ß = - 87.9 mm3, P = 0.018) compared with those without glaucoma. Among neuropsychological battery tests, only the Stroop color reading test  score was significantly lower in individuals with glaucoma compared with those without glaucoma (ß = - 0.44, P = 0.038). CONCLUSIONS: We found that glaucoma was associated with smaller volumes of the thalamus, caudate, putamen, pallidum, amygdala, and hippocampus.

Acute Nutritional Ketosis and Its Implications for Plasma Glucose and Glucoregulatory Peptides in Adults with Prediabetes: A Crossover Placebo-Controlled Randomized Trial.

BACKGROUND: The potential of a ketone monoester (ß-hydroxybutyrate; KEßHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEßHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown. OBJECTIVES: The primary objective was to investigate the effect of KEßHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides. METHODS: This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of ß-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEßHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [ß-hydroxybutyrate (ßHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time. RESULTS: Blood ßHB concentrations increased to 3.5 mmol/L within 30 minutes after KEßHB supplementation. Plasma glucose AUC was significantly lower after KEßHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEßHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1. CONCLUSIONS: Ingestion of the KEßHB-supplemented drink acutely increased the blood ßHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEßHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.

Dietary carbohydrate intake and insulin traits in individuals after acute pancreatitis: Effect modification by intra-pancreatic fat deposition.

OBJECTIVES: Current knowledge of the link between dietary carbohydrate intake and insulin regulation in individuals after an attack of pancreatitis is limited. We aimed to investigate the associations between dietary carbohydrate intake and insulin traits in post-pancreatitis versus healthy individuals, taking into account intrapancreatic fat deposition (IPFD). METHODS: All participants underwent magnetic resonance imaging (using the same protocol and 3T scanner) to quantify IPFD. Dietary carbohydrate intake was assessed using a validated 131-item food frequency questionnaire. Insulin, HOMA-IR, HOMA-ß were determined in the fasted state. Linear regression and effect modification analyses were conducted in unadjusted and adjusted models (accounting for age, sex, body mass index, daily energy intake, use of anti-diabetic medications, and recurrence of acute pancreatitis). RESULTS: The study included 111 post-pancreatitis individuals (categorized into low IPFD (n = 33), moderate IPFD (n = 40), high IPFD (n = 38)) and 47 healthy controls. In the high IPFD group, starch intake was negatively associated with fasting insulin and HOMA-ß in both the unadjusted (p < 0.001 both) and fully adjusted models (p < 0.001 both); and with HOMA-IR in the fully adjusted model (p < 0.001) only. Total sugar intake was positively associated with fasting insulin (p = 0.015) and HOMA-ß (p = 0.007) in the fully adjusted model but not associated with HOMA-IR. None of the above associations was statistically significant in the low IPFD, moderate IPFD, and healthy controls groups. The studied associations were more pronounced in the high IPFD group but not in the moderate IPFD or low IPFD groups (when compared with the healthy controls group). CONCLUSIONS: Dietary carbohydrate intake is differentially associated with insulin traits in individuals after an attack of pancreatitis and the associations are modified by IPFD. These findings will be helpful for the development of dietary guidelines specifically for individuals after an attack of pancreatitis.

Associations between ambient air pollution and medical care visits for atopic dermatitis.

BACKGROUND: Previous studies have reported numerous environmental factors for atopic dermatitis (AD), such as allergens and chemical stimulants. However, few studies have addressed the relationship between ambient air pollution and AD at a population level. OBJECTIVE: To evaluate the effect of air pollutants on medical care visits for AD and to identify susceptible populations. METHODS: In this time-series study conducted on 513,870 medical care visits for AD from 2012 to 2015 identified by reviewing national health insurance claim data in Incheon, Republic of Korea. Treating daily number of medical care visits for AD as a dependent variable, generalized additive models with Poisson distributions were constructed, which included air pollutant levels, ambient temperature, relative humidity, day of the week, national holiday, and season. Risks were expressed as relative risks (RR) with 95% confidence intervals (95% CIs) per interquartile range increase of each air pollutant. RESULTS: Higher levels of particulate matter of diameter ≤10 µm (PM10) (RR, 1.009; 95% CI, 1.007-1.012), ozone (1.028; 1.023-1.033), and sulfur dioxide (1.033; 1.030-1.037) were significantly associated with increased risk of medical care visits for AD on same days. In all age and sex groups, ozone was associated with a significantly higher risk of medical care visits, with the greatest risk among 13- to 18-year-old males (RR, 1.127; 95% CI, 1.095-1.159). CONCLUSION: This study suggests relationships of ambient PM10, ozone, and sulfur dioxide levels with medical care visits for AD.

The influence of cholecystectomy and recurrent biliary events on the risk of post-pancreatitis diabetes mellitus: a nationwide cohort study in patients with first attack of acute pancreatitis.

BACKGROUND: It is unknown whether cholecystectomy for acute pancreatitis (AP) affects the risk of post-pancreatitis diabetes mellitus (PPDM). We aimed to investigate the associations between cholecystectomy, recurrent biliary events prior to cholecystectomy, and the risk of PPDM in patients with AP. METHODS: Using New Zealand nationwide data from 2007 to 2016, patients with first admission for AP were identified (n = 10,870). Cholecystectomy was considered as a time-dependent exposure. Timing of cholecystectomy was categorized as same-admission, readmission, and delayed cholecystectomy. Recurrent biliary events prior to cholecystectomy were identified. Multivariable Cox regression analyses were conducted. RESULTS: Among 2147 patients who underwent cholecystectomy, 141 (6.6%) developed PPDM. Overall, cholecystectomy was not significantly associated with the risk of PPDM (adjusted hazard ratio, 1.14; 95% confidence interval, 0.94-1.38). Delayed cholecystectomy was significantly associated with an increased risk of PPDM (adjusted hazard ratio, 1.36; 95% confidence interval, 1.01-1.83). Patients who had 2 or ≥3 recurrent biliary events prior to cholecystectomy were at a significantly increased risk of PPDM. CONCLUSION: Cholecystectomy in general was not associated with the risk of PPDM in patients with AP. Two or more repeated attacks of AP (or other biliary events) were associated with a significantly increased risk of PPDM.

Relationship of pancreas volume to tobacco smoking and alcohol consumption following pancreatitis.

BACKGROUND: Tobacco smoking and alcohol consumption are established risk factors for diseases of the pancreas. With the recent advances in imaging modalities (such as magnetic resonance (MR) imaging), opportunities have arisen to study pancreas size, in both health and disease. Studies investigating the relationship between tobacco smoking, alcohol consumption, and total pancreas volume (TPV) - a holistic measure of pancreatic exocrine reserve - are lacking. The aim of the present study was to investigate the associations between MR-derived TPV and tobacco smoking/alcohol consumption. METHODS: This cross-sectional study recruited individuals with a history of pancreatitis and healthy controls. A validated questionnaire was used to ascertain current and lifetime tobacco smoking and alcohol consumption. TPV was quantified using MR images by two independent raters. Generalized additive models and linear regression analyses were conducted and adjusted for demographic, metabolic, and pancreatitis-related factors. RESULTS: A total of 107 individuals following pancreatitis and 38 healthy controls were included. There was no statistically significant difference in TPV between any of the tobacco smoking/alcohol consumption categories of individuals following pancreatitis and healthy controls, in both unadjusted and adjusted analyses. In individuals following pancreatitis, multivariate linear regression found no association between TPV and 7 smoking- and alcohol-related variables. Sensitivity analyses constrained to individuals who did not abstain from either smoking or drinking following their first attack of pancreatitis did not yield statistical significance with TPV. In post-hoc analysis, age was significantly inversely associated with TPV in the most adjusted model (p = 0.016). CONCLUSIONS: This is the first study to investigate the association between tobacco smoking, alcohol consumption, and MR-derived TPV following pancreatitis. It appears that age, but not tobacco smoking or alcohol consumption, is associated with a significantly reduced TPV.

Psoas muscle size as a magnetic resonance imaging biomarker of progression of pancreatitis.

OBJECTIVE: Pancreatitis often represents a continuous inflammatory process, from the first episode of acute pancreatitis (FAP) to recurrent acute pancreatitis (RAP) to chronic pancreatitis (CP). Psoas muscle size is a validated surrogate for global skeletal mass, changes in which are associated with inflammation. The objective was to investigate psoas muscle size in individuals following FAP, RAP, and CP, as well as its associations with pro-inflammatory cytokines. METHODS: Individuals following pancreatitis and healthy individuals were recruited. All participants underwent magnetic resonance imaging, from which psoas muscle volume was derived independently by two raters in a blinded fashion. Circulating levels of four major cytokines (interleukin-6, tumour necrosis factor-α, C-C motif chemokine ligand 2, and leptin) were measured. Five linear regression additive models were built to adjust for possible confounders (age, sex, body composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and endocrine and exocrine pancreatic functions). RESULTS: A total of 145 participants were enrolled. A significant downward trend in psoas muscle volume was observed between healthy controls and individuals following FAP, RAP, and CP in all adjusted models (p = 0.047, 0.005, 0.004, and < 0.001). Leptin was significantly associated with psoas muscle volume in all models (ß = - 0.16, p = 0.030 in the most adjusted model). The other studied cytokines were not significantly associated with psoas muscle volume. CONCLUSIONS: Psoas muscle size is significantly reduced along the continuum from FAP to RAP to CP. Leptin appears to be one of the factors implicated in this. Further studies are warranted to investigate the relationship between skeletal muscle and inflammation of the pancreas. KEY POINTS: • First acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis were associated with progressively reduced psoas muscle size. • The findings were independent of age, sex, body fat composition, physical activity, tobacco smoking, alcohol consumption, comorbidities, and exocrine and endocrine functions of the pancreas. • The mechanism underlying the observed findings may involve hyperleptinaemia.

Risk of Mortality and Hospitalization After Post-Pancreatitis Diabetes Mellitus vs Type 2 Diabetes Mellitus: A Population-Based Matched Cohort Study.

OBJECTIVES: To investigate the risk of mortality and hospitalization in individuals with post-pancreatitis diabetes mellitus (PPDM) compared with those with type 2 diabetes mellitus (T2DM). METHODS: Using nationwide hospital discharge data on pancreatitis and diabetes in New Zealand (n = 231,943), a total of 959 individuals with PPDM were identified. For each individual with PPDM, 10 age- and sex-matched individuals with T2DM were randomly selected. Multivariable Cox regression analysis was conducted, and the risk was expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3,867 deaths occurred among 10,549 study individuals. Individuals with PPDM had all-cause mortality rate at 80.5 (95% CI, 70.3-90.6) per 1,000 person-years, which was higher compared with T2DM individuals (adjusted HR, 1.13 (95% CI, 1.00-1.29); absolute excess risk, 14.8 (95% CI, 4.5-25.2) per 1,000 person-years). Compared with T2DM, PPDM was associated with higher risks of mortality from cancer (adjusted HR, 1.44; 95% CI, 1.13-1.83), infectious disease (adjusted HR, 2.52; 95% CI, 1.69-3.77), and gastrointestinal disease (adjusted HR, 2.56; 95% CI, 1.64-4.01). Individuals with PPDM vs T2DM were also at significantly higher risks of hospitalization for chronic pulmonary disease, moderate to severe renal disease, and infectious disease. CONCLUSIONS: Individuals with PPDM have higher risk of mortality and hospitalization compared with individuals with T2DM. Guidelines for management of PPDM need to be developed with a view to preventing excess deaths and hospitalizations in individuals with PPDM.

Associations between intra-pancreatic fat deposition and circulating levels of cytokines.

While a plethora of studies have been conducted to investigate the associations between pro-inflammatory cytokines and obesity, the inter-relationship between pro-inflammatory cytokines and intra-pancreatic fat deposition (IPFD) has been poorly investigated. In the present study, circulating levels of C-C motif chemokine ligand 2 (CCL2), interleukin-6 (IL-6), leptin, and tumor necrosis factor-alpha (TNFα) were measured in 90 individuals after acute pancreatitis (AP) as well as 21 healthy non-obese individuals. Magnetic resonance imaging was used to quantify IPFD and visceral-to-subcutaneous fat volume ratio by two independent raters. Linear regression analyses were performed to investigate the associations between IPFD and each cytokine, adjusting for demographic, metabolic, and pancreatitis-related factors, as well as abdominal fat distribution. In healthy non-obese individuals, IPFD was not significantly associated with any of the studied cytokines in both the unadjusted and adjusted models. In individuals after AP, IPFD was significantly associated with leptin in the models adjusted for age and sex (ß = 0.063 [95% confidence interval: 0.007, 0.119], P = 0.026); age, sex, visceral-to-subcutaneous fat volume ratio, glycated hemoglobin, and pancreatitis-related factors (ß = 0.056 [95% confidence interval: 0.000, 0.111], P = 0.049). Also, IPFD was significantly associated with TNFα in the unadjusted model (ß = 0.102 [95% confidence interval: 0.002, 0.202], P = 0.045) and the model adjusted for age, sex, visceral-to-subcutaneous fat volume ratio, glycated hemoglobin, and pancreatitis-related factors (ß = 0.128 [95% confidence interval: 0.034, 0.223], P = 0.008). The associations between IPFD and IL-6, CCL2 were not statistically significant, in both the unadjusted and adjusted models. These findings indicate that leptin and TNFα are associated with IPFD independent of abdominal fat distribution and other covariates in individuals after AP. The role of IPFD in low-grade inflammation warrants further investigations.

Pancreas shrinkage following recurrent acute pancreatitis: an MRI study.

OBJECTIVE: Transition from the first attack of acute pancreatitis (AP) to chronic pancreatitis (CP) via recurrent AP is common. Total pancreas volume (TPV) and pancreas diameters are often reduced in advanced CP but have never been studied after AP. The objective of this study was to investigate pancreas size after clinical resolution of AP and its association with the number of AP attacks. METHODS: Individuals with a history of AP were grouped based on the number of attacks (1, 2, ≥ 3 attacks). Healthy individuals were also recruited. All participants underwent magnetic resonance imaging, from which TPV and pancreas diameters (across the head, body, and tail) were measured independently by two raters in a blinded fashion. Generalised additive models (including age, sex, body mass index, and glycated haemoglobin levels) were used. RESULTS: A total of 123 participants were studied. Total pancreas volume and tail diameter were significantly reduced in both unadjusted (TPV (p = 0.036), tail diameter (p = 0.009)) and adjusted (TPV (p = 0.026), tail diameter (p = 0.034)) models in individuals with ≥ 3 attacks, but not with 1 or 2 attacks, compared with healthy individuals. Head and body diameters did not differ significantly. CONCLUSIONS: Reduced TPV and tail diameter characterise individuals after ≥ 3 attacks of AP and may represent one of the earliest irreversible morphological changes in individuals after AP. A high-risk population for transition to CP might include individuals with at least 3 attacks of AP whereas those with less than 3 attacks might be at a low risk. KEY POINTS: • A significant reduction in total pancreas volume was demonstrated in individuals after 3 or more attacks of acute pancreatitis (without conventional signs of chronic pancreatitis). • Pancreas tail diameter, but not head or body diameter, was reduced in individuals after 3 or more attacks of acute pancreatitis (without conventional signs of chronic pancreatitis). • The above findings were independent of age, sex, body mass index, and glycated haemoglobin levels.

Serum lipid profile as a biomarker of intra-pancreatic fat deposition: A nested cross-sectional study.

BACKGROUND AND AIMS: The relationship between intra-pancreatic fat deposition (IPFD) and lipid profile has been investigated in individuals with obesity and/or type 2 diabetes, but not in healthy non-obese individuals and those after acute pancreatitis. The aim of the study was to investigate the association between serum lipid profile and IPFD in the latter individuals and to determine the effect of abdominal fat distribution and other covariates. METHODS AND RESULTS: A total of 90 individuals with a history of acute pancreatitis as well as 23 healthy non-obese individuals participated in the study. Magnetic resonance imaging was used to quantify IPFD and visceral-to-subcutaneous fat volume ratio, followed by fasting state measurement of high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TC/HDL-C ratio, and triglycerides. In healthy non-obese individuals, IPFD was not significantly associated with any of the studied markers. In individuals after acute pancreatitis, IPFD was significantly associated with triglycerides in both unadjusted (ß = 0.360; 95% CI, 0.090-0.629; p = 0.009) and adjusted models, with a ß-coefficient of 0.280 [(95% CI, 0.016-0.545); p = 0.038] in the most adjusted model. Also, IPFD was significantly associated with TC/HDL-C ratio in both unadjusted (ß = 0.336; 95% CI, 0.045-0.626; p = 0.024) and adjusted models, with a ß-coefficient of 0.375 [(95% CI, 0.090-0.660); p = 0.010] in the most adjusted model. Multiple regression yielded triglycerides, but not TC/HDL-C ratio, as a significant marker of IPFD in individuals after acute pancreatitis. CONCLUSIONS: Serum lipid profile is not associated with IPFD in healthy non-obese. Triglycerides, but not other components of lipid profile, is a promising biomarker for IPFD in individuals following acute pancreatitis.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and ß-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for ß-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

Suicide loss, changes in medical care utilization, and hospitalization for cardiovascular disease and diabetes mellitus.

AIMS: The impact of suicide loss on family members' cardiometabolic health has little been evaluated in middle-aged and elderly people. We investigated the effect of suicide loss on risks for cardiovascular disease (CVD) and diabetes mellitus (DM) in suicide completers' family members using a national representative comparison group. METHODS AND RESULTS: The study subjects were 4253 family members of suicide completers and 9467 non-bereaved family members of individuals who were age and gender matched with the suicide completers in the Republic of Korea. National health insurance data were used to identify medical care utilization during the year before and after a suicide loss. A recurrent-events survival analysis was performed to estimate the hazard ratios (HRs) of hospitalizations for CVD, DM, or psychiatric disorders, after adjusting for age, residence, and socioeconomic status. Among subjects without a past history of CVD, DM, or psychiatric disorders, the increased risks of recurrent hospitalizations were observed for CVD [HR 1.343, 95% confidence interval (CI) 1.001-1.800 in men; HR 1.240, 95% CI 1.025-1.500 in women] and DM (HR 2.238, 95% CI 1.379-3.362 in men; HR 1.786, 95% CI 1.263-2.527 in women). In subjects with a past history of CVD, DM, or psychiatric disorders, the number of medical care visits decreased after a suicide loss, and suicide completers' family members showed lower rates of hospitalization for CVD and DM than the comparison group. CONCLUSION: Compared with non-bereaved family members, suicide completers' family members without a past history of CVD, DM, or psychiatric disorder showed a high risk of hospitalization for those conditions.

Decreased blood pressure associated with in-vehicle exposure to carbon monoxide in Korean volunteers.

BACKGROUND: Carbon monoxide (CO) is one of the primary components of emissions from light-duty vehicles, and reportedly comprises 77% of all pollutants emitted in terms of concentration. Exposure to CO aggravates cardiovascular disease and causes other health disorders. The study was aimed to assess the negative effects by injecting different amounts of CO concentration directly to human volunteers boarding in the car. METHODS: Human volunteers were exposed to CO concentrations of 0, 33.2, and 72.4 ppm, respectively during the first test and 0, 30.3, and 48.8 ppm respectively during the second test while seated in the car. The volunteers were exposed to each concentration for approximately 45 min. After exposure, blood pressure measurement, blood collection (carboxyhemoglobin [COHb] analysis), medical interview, echocardiography test, and cognitive reaction test were performed. RESULT: In patients who were exposed to a mean concentration of CO for 72.4 ± 1.4 ppm during the first exposure test and 48.8 ± 3.7 ppm during the second exposure test, the COHb level exceeded 2%. Moreover, the diastolic blood pressure was decreased while increasing in CO concentration after exposure. The medical interview findings showed that the degree of fatigue was increased and the degree of concentration was reduced when the exposed concentration of CO was increased. CONCLUSION: Although the study had a limited sample size, we found that even a low concentration of CO flowing into a car could have a negative influence on human health, such as change of blood pressure and degree of fatigue.