Age-adjusted Research Articles

Metabolic dysfunction-associated steatotic liver disease (SLD) and alcohol-associated liver disease, but not SLD without metabolic dysfunction, are independently associated with new onset of chronic kidney disease during a 10-year follow-up period.

The new nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD). We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 or positive for urinary protein, during a 10-year period in 12138 Japanese subjects (men/women, 7984/4154; mean age, 48years) who received annual health examinations including abdominal ultrasonography. The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men/women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p=0.001) and those with ALD (1.41 [1.05-1.88], p=0.022), but not those with MetALD (1.11 [0.90-1.36], p=0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p=0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity. MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.

Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

Physical activity lower blood pressure and mortality in hypertensive patients with diabetes: data from National Health and Nutrition Examination Survey (NHANES) 1999-2018.

In prior research related to physical activity, researchers have often centered their focus on only a limited number of activities, with little regard for mortality-related outcomes and insufficient focus on outcomes among diabetes patients with hypertension. The National Health and Nutrition Examination Survey was evaluated from 1999-2018 to identify individual with both diabetes and hypertension. These individuals were classified as being physically active or inactive. Comparisons among groups were performed with appropriate statistical tests. In total, this study evaluated data from 6,163 patients with a mean age of 63.18 ± 12.80 years. A total of 50.30% of the participants were male, with 39.86% being non-Hispanic white, 57.17% with a normal body mass index, and 89.20% were insured. Physical activity was significantly negatively correlated with systolic blood pressure in the overall population (p = 0.01) and when specifically focusing on individuals undergoing antihypertensive drug treatment (p = 0.0035). This negative relationship remained intact even following adjustment for age, sex, and ethnicity (p = 0.03). Physical activity was positively correlated with diastolic blood pressure in the overall population of participants (p = 0.002) and when specifically evaluating participants undergoing antihypertensive drug treatment (p = 0.02). All-cause and hypertensive mortality risk levels were significantly higher among individuals classified as being physically inactive (p < 0.0001), and this relationship remained true even with adjustment for age, sex, and ethnicity (p < 0.0001). In conclusion, physical activity is capable of lowering systolic blood pressure and decreasing the incidence of mortality among diabetes patients with hypertension.

The association of depression and patient and resuscitation characteristics with survival after out-of-hospital cardiac arrest (OHCA): a cohort study.

Out-of-hospital cardiac arrest (OHCA) is a leading cause of death worldwide, with cardiovascular disease (CVD) being a key risk factor. This study aims to investigate disparities in patient/OHCA characteristics and survival after OHCA among patients with versus without depression. This is a retrospective cohort study using data from the AmsteRdam REsuscitation Studies (ARREST) registry from 2008-2018. History of comorbidities, including depression, was obtained from the patient's general practitioner. OHCA survival was defined as survival at 30 days post-OHCA or hospital discharge. Logistic regression models were used to obtain crude and adjusted odds ratios (ORs) for the association between depression and OHCA survival and possible effect modification by age, sex, and comorbidities. The potential mediating effects of initial heart rhythm and provision of bystander cardiopulmonary resuscitation were explored. Among 5,594 OHCA cases, 582 individuals had pre-existing depression. Patients with depression had less favourable patient and OHCA characteristics and lower odds of survival after adjustment for age, sex, and comorbidities (OR 0.65, 95% CI 0.51-0.82), with similar findings by sex and age groups. The association remained significant among the Utstein comparator group (OR 0.63, 95% CI 0.45-0.89) and patients with return of spontaneous circulation (OR 0.60, 95% CI 0.42-0.85). Initial rhythm and bystander cardiopulmonary resuscitation partially mediated the observed association (by 27% and 7%, respectively). OHCA patients with depression presented more frequently with unfavourable patient and OHCA characteristics and had reduced chances of survival. Further investigation into potential pathways is warranted.

Foreign-born 5-year-old children with cleft palate had poorer speech outcomes than their native-born peers.

Speech difficulties are common in children with cleft palate, but research on foreign-born children is limited. This study aimed to compare speech outcomes, surgery and speech intervention in 5-year-old foreign-born and Swedish-born children with cleft palate with or without cleft lip. This retrospective study analysed data from the Swedish cleft lip and palate registry for children born between 2009 and 2016 using Pearson's Chi-squared test and binary logistic regression. Among 160 foreign-born (106 boys, 54 girls) and 847 Swedish-born (479 boys, 368 girls) 5-year-olds, foreign-born children had significantly lower rates of sufficient velopharyngeal competence (77% vs. 86%), age-appropriate consonant production (28% vs. 60%), and speech without non-oral speech errors (70% vs. 86%). Differences remained after adjustment for cleft type, gender and additional diagnosed conditions. After further adjustments for age at completed primary palatal surgery, differences in age-appropriate consonant production and speech without non-oral speech errors remained significant. Foreign-born children underwent completed primary palatal surgery at older ages and received more secondary palatal surgery and speech intervention than Swedish-born peers. Foreign-born children showed poorer speech outcomes than Swedish-born peers, despite more secondary palatal surgery and speech intervention. Age at completed primary palatal surgery could partly explain these differences.

Distinct patterns of hippocampal subfieldvolumes predict coping strategies, emotion regulation, and impulsivity in healthy adults.

Recent studies have suggested that the hippocampus (HC) is involved in cognitive and behavioral functions beyond memory.We aimed to investigate how the volume of each subfield of the HC is associated with distinct patterns of coping strategies, emotion regulation, and impulsivity in a healthy population. We studied a total of 218 healthy subjects using the Leipzig mind-brain-body dataset. Participants were assessed for coping strategies, emotion regulation, and impulsivity using the Cognitive Emotion Regulation Questionnaire(CERQ), Coping Orientations to Problems Experienced (COPE), Impulsive Behavior Scale (UPPS), and Behavioral Activation and Inhibition System (BAS/BIS). The associations between HC subfield volumes including CA1, CA2/3, CA4/DG, SR-SL-SM, and subiculum, and behavioral scores were examined using multiple linear regression models adjusted for possible confounders, including age, sex, years of education, handedness, total intracranial volume (ICV), and HC volume. The use of emotional support, venting, and positive reframing coping strategies were significantly and positively correlated with total, total right, and total left HC volumes. Venting was significantly associated with CA1 after adjusting for age, sex, handedness, and education (P=0.001, B = 0.265, P-FDR = 0.005).No significant association was observed between CERQ subscales and HC subfieldvolumesafter controlling for confounders and multiple analyses. However,sensation-seeking subscale of the UPPS-P was positively correlated with total and right CA2-CA3 volumes after adjustments for age, sex, handedness, ICV, and HC volumes(P=0.002, B = 0.266, P-FDR = 0.035).BAS and BIS subscales did not showsignificant relationshipwith HC subfield volumes. Patterns ofHC subfieldsvolumes are associated with copingstrategies, impulsivity, and emotion regulation.In particular, using emotional support, positive reframing, venting, and sensation seeking aresignificantly associated with certain HC subfield volumes.These findings suggest that the hippocampus may play a crucial role in modulating emotional responses and behavioral adaptations, offering potential targets for therapeutic interventions.

Are Neighborhood Greenspaces Associated with Leisure-time Physical Activity? Results from ELSA-Brasil Eight-year Follow-up.

We investigated whether neighborhood greenspaces were associated with physical activity in adulthood over 3 cohort visits after considering perceived safety and neighborhood contextual factors. We also evaluated whether the association with greenspace varied by neighborhood socioeconomic status. Participants (N = 4,800) from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) residing in two Brazilian state capitals were evaluated in Visits 1 (2008-2010), 2 (2012-2014) and 3 (2017-2019). Greenspaces were categorized by quintiles of positive Normalized Difference Vegetation Index (NDVI) scores. Physical activity frequency was given by the number of visits at which participants reported moderate/vigorous physical activity (none, 1 or 2, and 3 visits). We used multinomial logistic regression. After adjustment for age, sex, education, research center, residence in slums, individuals in the 4th and 5th NDVI quintiles showed 73% higher odds of physical activity over 3 visits than those in the 1st quintile (4th quintile: 95%CI = 1.24-2.43; 5th quintile: 95%CI = 1.24-2.41). The strength of the association was attenuated after adjustment for perceived safety. After adjustment for contextual factors quantity of sidewalks and streetlights, the OR for the 4th and 5th NDVI quintiles decreased to 1.66 (95%CI = 1.18-2.33) and 1.62 (95%CI = 1.16-2.28), respectively. Finally, after including average household income per capita, the OR for physical activity in 3 visits for the 4th and 5th NDVI quintiles decreased to 1.48 (95%CI = 1.04-2.12) and 1.43 (95%CI = 1.00-2.04; p = 0.053), respectively. Greater greenspace contributed to sustained physical activity during the eight years of follow-up, indicating the potential contribution of public greenspaces to reducing health-related inequalities.

Sarcopenia definitions and their association with injurious falls in older Swedish women from the Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone fractures (SUPERB) study.

To investigate the association between three commonly used sarcopenia definitions and the risk of injurious falls in a population of older Swedish women. A total of 2,883 75-80-year-old women with complete data on relevant sarcopenia definitions from the Swedish SUPERB cohort were studied. Sarcopenia was defined based on the Sarcopenia Definitions and Outcomes Consortium (SDOC: low handgrip strength and gait speed), revised European Working Group on Sarcopenia in Older People (EWGSOP2: low appendicular lean mass index (ALMI, dual-energy X-ray absorptiometry (DXA)-derived), appendicular lean mass (kg)/height (m2), hand grip strength (kg), or low chair stand time (s)), and Asian Working Group for Sarcopenia (AWGS: low ALMI and hand grip strength (kg) or low gait speed (m/s)). Questionnaires captured the occurrence of falls in the past 12months. Incident injurious falls were identified using national registers. Cox regression (hazard ratios (HR) and 95% confidence intervals (CI)) analyses were performed without adjustment and after adjustment for age, body mass index, previous falls, and the Charlson comorbidity index. During a median (IQR) follow-up time of 7.06 (6.2-7.9) years, there were 491 injurious falls without fracture and 962 injurious falls when also including falls resulting in a fracture. Sarcopenia according to EWGSOP2 and AWGS was not associated with an increased risk of injurious falls. Individuals with sarcopenia defined by SDOC had a higher risk of injurious falls with and without fracture (HR 2.11; 95% CI, 1.63-2.73 and HR, 2.16; 95% CI, 1.55-3.02, respectively). Sarcopenia definitions confined to muscle function and strength such as SDOC, rather than including DXA-determined ALMI (EWGSOP2 and AWGS), are associated with incident injurious falls with and without fractures in older women.

Pre-Stroke Frailty and Outcomes Following Percutaneous Endoscopic Gastrostomy Tube Insertion

Background: Frailty is common in stroke, where it exerts disease- and treatment-modifying effects. However, there has been little work evaluating how frailty influences outcomes after percutaneous endoscopic gastrostomy (PEG) tube insertion. This study investigates the relationship between pre-stroke frailty and one-year mortality following PEG insertion. Methods: A pre-stroke frailty index (FI) was calculated for individuals with post-stroke dysphagia who underwent PEG insertion between March 2019 and February 2021. Mortality was recorded at one year, as well as instances of post-PEG pneumonia and discharge destination. Results: Twenty-nine individuals underwent PEG insertion, eleven (37.9%) of whom died in the subsequent year. The mean (SD) FI for those who survived was 0.10 (0.09), compared to 0.27 (0.19) for those who died (p = 0.02). This remained significant after adjustment for age and sex, with each 0.1 increase in the FI independently associated with an increased odds of one-year mortality (aOR 1.39, 95% CI 1.17–1.67). There was no association between frailty and post-PEG pneumonia (0.12 (0.21) in those who aspirated versus 0.11 (0.18) in those who did not, p = 0.75). Conclusions: Pre-stroke frailty is associated with increased one-year mortality after PEG, a finding that may help inform shared clinical decision-making in complex decisions regarding PEG feeding.

23 Pre-surgical visceral adipose tissue may be a novel pre-surgical risk factor for acute kidney injury among clear cell renal cell cancer patients undergoing radical nephrectomy

Abstract Background Patients with renal cancer undergoing partial (PN) or radical nephrectomy (RN) are at risk for acute kidney injury (AKI). Established risk factor for AKI include baseline comorbidities (e.g., obesity, hypertension), normal renal parenchymal loss, and ischemia-reperfusion injury. Pre-surgical body composition may be an overlooked modifiable patient characteristic that influences risk of AKI. We hypothesized that patients with higher visceral adipose tissue quantity or lower skeletal muscle quantity would have a higher risk of AKI. Methods The RESOLVE study at Memorial Sloan Kettering Cancer Center is a retrospective study of 1239 patients with stage I-III clear cell renal cell carcinoma (ccRCC) undergoing PN or RN from 2000 to 2020. We excluded from analysis patients with solitary kidney, those without preoperative serum creatinine (sCr) measurements, and those without a sCr measurement within seven days following nephrectomy, yielding a study population of 1,200 ccRCC patients with longitudinal sCr assessment (n=754 PN; n=446 PN). AKI was defined as a binary variable using the Kidney Disease – Improving Global Outcomes (KDIGO) criteria, based on a threshold of either a 1.5x relative or 0.3 mg/dl absolute increase in sCr within seven days. The cross-sectional areas and radiodensities of visceral adipose and skeletal muscle tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. We used generalized linear models with a binomial family and identity link to estimate seven-day risk differences (RD) and 95% confidence intervals in subgroups defined by surgery type. Results AKI was more frequent among patients undergoing RN (66% vs 26% among PN). Male patients, those with higher eGFR prior to surgery, those with lower stage/smaller tumors, and those with a history of hyperlipidemia more frequently experienced AKI in the post-operative period. No associations were observed with other reported comorbidities (diabetes, hypertension). While no association was observed between BMI and risk of AKI, visceral adipose and skeletal muscle variables were significantly associated with risk of AKI in univariate models. After adjustment for age, sex, comorbidities, and other body composition variables, only higher visceral adipose tissue quantity remained significantly associated with increased risk of AKI [RD per 40 unit increase (95% CI): 5.2 (1.3, 9.2)]. Muscle characteristics were not associated with AKI in multivariable models. Among patients undergoing PN, we observed a higher frequency of AKI among male patients, those with higher stage/larger tumors, and those with longer ischemia times. No significant associations were observed with comorbidity histories. In univariate models, visceral adipose tissue quantity and quality as well as skeletal muscle quantity were associated with AKI risk; however, after adjustment for age, sex, comorbidities, and other body composition variables, we observed no significant associations between any body composition feature and AKI in patients undergoing PN. Conclusions Associations between pre-surgical body composition and risk of AKI vary by surgery type. Visceral adipose tissue quantity was associated with risk of AKI among patients undergoing RN, but not PN. This finding may be relevant for patient counseling, consideration for nephron-sparing surgery, and development of interventions to lower visceral adipose tissue quantity. Future studies should evaluate the impact of both pre-surgical and post-surgical change in body composition in relation on chronic kidney disease after nephrectomy.

Effect of dual tobacco smoking of hookah and cigarettes on semen parameters of infertile men.

The research regarding the effect of hookah smoking on health is still deficient, even though it has been proven to jeopardize human health by raising the hazard of different types of cancers, infections, and cardiovascular disease. We aimed to study the effect of dual tobacco smoking (hookah and cigarettes) on semen parameters of infertile men. In this cross-sectional study, we studied the effect of different types of smoking patterns on human semen parameters among men who visited IVF laboratories to do a seminal fluid analysis (SFA). A total number of 761 participants were included, divided into the following: 108 dual smokers, 219 hookah smokers, 222 cigarette smokers, and 212 non-smokers. To analyze the effect of dual smoking on normal morphology, an interaction term between the cigarette index and hookah index was used. Multivariable regression analysis after adjustment for age, BMI, education level, children, chronic diseases, varicocele, testicular surgery history, infertility duration, and cause revealed no significant difference in the sperm concentration and the percentage of progressive motility between non-smokers, cigarette smokers, or hookah smokers. However, there was a significant difference in the log of normal morphology percentage between the three groups. Cigarette and hookah smoking were significantly associated with having lower percentages of normal morphology. There was a significant difference in the log-normal morphology %, where light and heavy dual smokers had the least exponential beta of log-normal morphology %, 0.43 (95% CI: 0.33-0.55) and 0.36 (95% CI: 0.24-0.53), respectively. Dual tobacco smoking can adversely affect sperm morphology.

A systematic review and meta-analysis of loss-of-control eating in relation to cardiometabolic health components and inflammatory markers.

Loss-of-control (LOC) eating, or the subjective experience of being unable to stop eating, is a hallmark feature of binge-eating episodes, which are also characterized by consuming an unusually large amount of food. However, regardless of the size of eating episode, LOC-eating may be a risk factor for adverse health outcomes. This systematic review and meta-analysis comprehensively examine the relationship of LOC-eating with cardiometabolic health components and inflammatory markers. Search procedures were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines in six electronic databases. Studies of adult or youth samples published in English from the year 2000 onward were included. Given heterogeneity in age groups and adjustment for body mass index across studies, these factors were included as meta-regression moderators. Fifty-eight studies were identified through the literature search. Among individuals with (versus without) LOC-eating, relative risk ratios provided evidence of a greater relative risk for metabolic syndrome, hypertension, and dyslipidemia; standardized mean differences also provided evidence of higher waist circumference and impaired levels of fasting plasma glucose, high-density lipoprotein (HDL)-cholesterol, and triglycerides, but not blood pressure. Age group did not impact cardiometabolic health components. Body mass index differences moderated the effect on waist circumference. A narrative review of inflammatory markers revealed mixed findings linking inflammatory markers to LOC-eating. Overall, evidence for the relationship between LOC-eating and impaired cardiometabolic health underscores LOC-eating as an important early intervention target for prevention of serious adverse health outcomes.

Earlier vs. later time period of COVID-19 infection and emergent autoimmune signs, symptoms, and serologies

ObjectiveAutoantibodies and autoimmune diseases after SARS-CoV-2 infection are widely reported. Given evolving variants, milder infections, and increasing population vaccination, we hypothesized that SARS-CoV-2 infection earlier in the pandemic would be associated with more autoimmune connective tissue disease (CTD) symptoms and immunologic abnormalities. MethodsPatients ≥18 years old with COVID-19 3/1/2020-8/15/2022 completed the CTD Screening Questionnaire and were tested for 27 autoimmune serologies, SARS-CoV-2 serologies, cell-bound complement activation products (CB-CAPs), and T and B lymphocyte immunophenotypes by flow cytometry. We assessed relationships between symptoms, serologies, and immunophenotypes in earlier (3/1/2020-1/31/2021) vs. later (2/1/2021-8/15/2022) periods, with different predominating SARS-CoV-2 viruses. Results57 subjects had earlier and 23 had later pandemic COVID-19. 35 % of earlier vs. 17 % of later pandemic patients had CTD symptoms (p 0.18). More patients were antinuclear antibody (ANA) positive (44 % vs. 13 %, p 0.01) and had lupus anticoagulant (11 % vs. 4 %, p 0.67). After adjustment for age, race, and sex, earlier (vs. later) COVID-19 was associated with increased ANA positivity (OR 4.60, 95%CI 1.17, 18.15). No subjects had positive CB-CAPs. T and B cell immunophenotypes and SARS-CoV-2 serologies did not differ by group. In heatmap analyses, higher autoantibody variety was seen among those with infection in the early pandemic. ConclusionIn this sample, having COVID-19 infection in the earlier (pre-2/1/2021) vs. later pandemic was associated with more CTD symptoms, ANA positivity, and autoantibody reactivities. Earlier SARS-CoV-2 variants circulating in a less vaccinated population with less natural immunity may have been more immunogenic.

Associations between circulating levels of FABP4 and TNF receptors are more evident in patients with type 2 diabetes mellitus than in patients with type 1 diabetes mellitus.

Fatty acid-binding protein 4 (FABP4) is an adipokine that plays significant roles in the development of insulin resistance and atherosclerosis. High levels of soluble tumor necrosis factor receptors (TNFRs) including TNFR1 and TNFR2 are associated with renal dysfunction and increased mortality in patients with diabetes mellitus (DM). However, the association between circulating levels of FABP4 and TNFRs remains unclear. We investigated the associations of FABP4 with TNFRs and metabolic markers in Japanese patients with type 1 DM (T1DM, n=76, men/women: 31/45) and type 2 DM (T2DM, n=575, men/women: 312/263). FABP4 concentration was positively correlated with levels of TNFR1 and TNFR2 in both patients with T1DM and those with T2DM. Multivariable regression analyses showed that there were independent associations of FABP4 concentration with body mass index (BMI) and estimated glomerular filtration rate (eGFR) after adjustment of age and sex in both patients with T1DM and those with T2DM. FABP4 concentration was independently associated with circulating levels of TNFR1 and TNFR2 after adjustment of the confounders in patients with T2DM but not in those with T1DM. Similarly, levels of TNFR1 and TNFR2 were independently associated with FABP4 concentration after adjustment of age, sex, systolic blood pressure, duration of DM and levels of eGFR, high-density lipoprotein cholesterol and C-reactive protein in patients with T2DM but not in those with T1DM. FABP4 concentration is independently associated with levels of TNFRs in patients with DM, but the association is more evident in patients with T2DM than in those with T1DM.

Cardiac biomarkers for screening and prognostication of cardiac dysfunction in critically ill patients.

This study aimed to assess the use of high-sensitivity troponin T (hsTNT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in screening for cardiac dysfunction [left ventricular (LV) systolic or diastolic dysfunction or right ventricular (RV) dysfunction] in mixed intensive care unit (ICU) patients and establish whether these biomarkers are independently associated with an increased risk of death. We performed a secondary analysis of a single-centre prospective observational study in which consecutive ICU patients were examined with transthoracic echocardiography (TTE) and cardiac biomarkers. Patients with systolic or diastolic LV dysfunction, RV dysfunction or a combination of these were compared with patients with normal cardiac function. Sensitivity and specificity for different cut-off levels were calculated using receiver operating characteristic curves. Regression models were used to evaluate the associations between cardiac biomarkers, sepsis, renal failure and mortality. A total of 276 patients were included. Most of the patients had cardiac dysfunction on TTE (64%). Combined cardiac dysfunction was most prevalent (71 patients, 26%), followed by isolated diastolic LV dysfunction (40 patients, 15%). Levels of hsTNT and NT-proBNP were higher in all types of cardiac dysfunction versus patients with normal cardiac function. The area under the curve (AUC) for hsTNT to detect any cardiac dysfunction was 0.75. An optimal cut-off at 30.5ng/L rendered a positive predictive value (PPV) of 80% and a negative predictive value (NPV) of 58%. The AUC for NT-proBNP to detect any cardiac dysfunction was 0.788. Using an optimal cut-off at 1145ng/L rendered a PPV of 86% and an NPV of 58%. Using a clinically relevant 90% sensitivity for detecting cardiac dysfunction put the cut-offs at 14.1ng/L for hsTNT and 247ng/L for NT-proBNP, resulting in a specificity of 48% and 46%, respectively. Levels of NT-proBNP were associated with sepsis and renal failure (P<0.001), while levels of hsTNT were associated with renal failure only (P<0.001) after adjustment for cardiac dysfunction. Levels of biomarkers were associated with an increased risk of 90day mortality after adjustments for age, Simplified Acute Physiology Score 3, cardiac dysfunction and factors independently associated with biomarker increase (sepsis and renal failure) (P=0.048 for hsTNT and P<0.006 for NT-proBNP). Cardiac biomarkers, hsTNT and NT-proBNP, are strongly correlated to cardiac dysfunction in ICU patients and have a robust association with increased mortality. However, the relatively low NPV and the low specificity at relevant sensitivity levels of the biomarkers make them unsuitable for use in screening for cardiac dysfunction.

Arterial stiffness and cardiovascular risk in patients with nephrolithiasis: a 10-year prospective study.

Nephrolithiasis is frequently associated with cardiovascular diseases. These conditions present common risk factors: systemic inflammation that promotes oxidative stress leading to arterial wall stiffening may also play a role in plaque formation predisposing to nephrolithiasis. The aim of this study was to evaluate arterial stiffness indices at baseline and after a 10-year follow-up, in patients with nephrolithiasis compared with patients without. A total of 82 patients (37 men; mean age 45 ± 13 years) were enrolled at the Geriatrics and Nephrology Outpatient Clinic: 66 were diagnosed with nephrolithiasis, whereas the control group consisted of 16 individuals. At baseline and after 10 years, they underwent clinical evaluation and arterial stiffness measurement, such as carotid-femoral pulse wave velocity (CF-PWV), by arterial applanation tonometry. At baseline, when compared with the control group, patients with nephrolithiasis showed higher SBP and CF-PWV. After 10 years, patients with nephrolithiasis, but not those without, showed a significant raise in CF-PWV, even after adjustment for age and sex. In a stepwise regression model, with CF-PWV changes during the follow-up as the dependent variable, and age, sex, follow-up years, Δ mean arterial pressure, BMI, hypertension and nephrolithiasis as independent variables, nephrolithiasis was proved to be the only significant predictor of ΔCF-PWV, accounting for 6% of the variance. Our study shows higher baseline CF-PWV and greater increase in ΔCF-PWV within 10 years in individuals with nephrolithiasis than in those without, demonstrating an increased cardiovascular risk for nephrolithiasis patients.

The relationship between bone health and type of intracranial internal carotid calcifications in patients with ischemic stroke

IntroductionVascular calcifications, primarily in the aorta and its proximal branches, are commonly observed among subjects with impaired bone health. In this study, we sought to determine if a comparable association holds true for the calcifications in the intracranial internal carotid arteries (IICA), in general and also for particular calcification patterns. MethodsA consecutive series of ischemic stroke patients were prospectively enrolled into the study, where computed tomography angiography source images were used to determine the presence and type of IICA calcifications, and dual-energy X-ray absorptiometry was used to determine the bone mineral density in the left femoral neck region. IICA calcifications were categorized as none, intimal, medial, and mixed types based on previously validated classification schemes. Their relationships with femoral bone T-scores were evaluated by bivariate and multivariate analyses. ResultsFemoral neck T-score was highest among patients without any vascular calcifications (n=65), when compared to the bone density measures among patients with any type of calcification (n=185) (p<0.001). After adjustment for age, gender, vascular risk factors, and serum biomarkers related to bone health, the T-score remained significantly associated only with the pattern of intimal calcification [OR 0.63 (0.42 – 0.95), p=0.028]. ConclusionsOur findings suggest that the intracranial vasculature, in particular the internal carotid arteries, is not immune to the interplay between suboptimal bone health and vascular calcifications. This association was most robust for an intimal type of IICA calcification pattern, while no such relationship could be demonstrated for other types of vascular calcifications.

The combined effect of cardiorespiratory and muscular fitness on the incidence of metabolic syndrome before midlife.

Cardiorespiratory fitness (CRF) could reduce the risk of metabolic syndrome (MetS) while the association between muscular endurance capacity (MEC) and incident MetS has rarely been investigated in young adults. A total of 2890 military men and women, aged 18-39years, free of baseline MetS in Taiwan, were followed for incident MetS from baseline (2014) until the end of 2020. All subjects received annual health examinations for assessment of MetS. Physical fitness was assessed by CRF (estimated maximal oxygen uptake, VO2 max [mL/kg/min], in a 3000-m run) and MEC (numbers of 2-min push-ups). MetS was defined according to the International Diabetes Federation (IDF) criteria. Multiple Cox regression analysis was conducted with adjustments for baseline age, sex, substance use status and physical activity to determine the associations of CRF and MEC with incidences of new-onset MetS and related features, for example, central obesity, hypertension, dyslipidaemia and prediabetes or diabetes. To examine the combined effects of CRF and MEC status on incidence of MetS, high and low levels of CRF and MEC were separately defined by over and under the sex-specific median in each exercise test. During a median follow-up of 5.8years, there were 673 (23.3%) new-onset MetS. Higher CRF was associated with a lower incidence of MetS (hazard ratio [HR] and 95% confidence interval: 0.905 [0.877-0.933]), and its components separately, except hypertension. No association was observed between MEC and incident MetS, and its components separately, except hypertension. When evaluating the combined effects of MEC and CRF status on the incidence of MetS, it was observed that compared with the low CRF/low MEC, the high CRF/high MEC (HR: 0.553 [0.439-0.697]) and the high CRF/low MEC (HR: 0.730 [0.580-0.918]) had a lower incidence of new-onset MetS (P value for the intergroup difference=0.04). There was no significant result for the low CRF/high MEC. This study highlights that although the protective effects of MEC to reduce the incidence of MetS and most of its related features were mainly driven by CRF in young adults, there was an addictive effect of greater MEC on CRF to prevent the development of new-onset MetS before midlife.

Binge drinking and progression of white matter hyperintensities of presumed vascular origin in older men

BackgroundInformation on trajectories of diffuse subcortical brain damage of vascular origin associated with binge drinking in older adults is limited. We sought to evaluate the impact of this drinking pattern on the progression of white matter hyperintensities (WMH) of presumed vascular origin in individuals aged ≥60 years taken from the community. MethodsFollowing a longitudinal prospective design, participants of the Atahualpa Project Cohort received interviews to assess patterns of alcohol intake as well as baseline and follow-up brain MRIs. Only men were included because alcohol consumption in women is negligible and tend not to engage in binge drinking in our studied population. Poisson regression models were fitted to assess the incidence rate ratio of WMH progression by patterns of alcohol use (binge drinking or not), after adjusting for demographics, level of education and cardiovascular risk factors. ResultsThe study included 114 men aged ≥60 years (mean age: 65.1±5.4 years). Thirty-seven participants (32%) reported binge drinking for more than 30 years. Follow-up MRIs revealed WMH progression in 45 participants (39%) after a median of 7.2 years. In unadjusted analysis, the risk of WMH progression among individuals with binge drinking was 2.08 (95% C.I.: 1.16–3.73). After adjustment for age, education level and vascular risk factors, participants with this drinking pattern were 2.75 times (95% C.I.: 1.42–5.30) more likely to have WMH progression than those who did not. ConclusionsStudy results show an independent association between binge drinking and WMH progression in community-dwelling older men.

Differences in impact of current and former shift work on cardiovascular risk factors, carotid atherosclerosis and white matter integrity

Abstract Study Objectives The association of shift work and disrupted circadian rhythm with markers of large artery atherosclerosis and cerebral small vessel disease is uncertain. We aimed to study the separate association of current and former shift work (SW) with these markers. Methods We included participants from the population-based Hamburg City Health Study. SW was defined by monthly working hours between 6 p.m. and 7 a.m. containing night shifts for at least 12 months. Cross-sectional data were obtained from structured questionnaires, laboratory analyses, physical examinations, brain MRI, and carotid ultrasound. We performed multivariable regression analysis with carotid intima media thickness (CIMT), and peak-width skeletonized mean diffusivity (PSMD) as dependent variables. Results 344 current, 238 former and 7’162 never-shift workers were included. The median age was 60 years for both current and former shift workers, and total duration of SW was comparable for the two groups. Current shift workers were less frequently female (27.3% vs 44.5%; p&amp;lt;0.001), had more frequent hyperlipidemia (31.5% vs 22.3%; p=0.024), and diabetes (16.2% vs 3.2%; p&amp;lt;0.001). After adjustment for age and sex, reduced quality of sleep (β=1.61,p=0.001) and low education (β=2.63,p&amp;lt;0.001) were associated with current but not former SW. Adjusted for age and sex, current SW was associated with higher CIMT (β=0.02,p=0.001) and PSMD (β= 9.06e-06,p=0.006), whereas former SW was not. Adjusted for risk factors, current SW remained associated with PSMD (β=9.91e-06,p=0.006) but not with CIMT. Conclusions Current SW was associated with CIMT and with PSMD, with the latter association remaining after adjustment for risk factors. Former SW showed no associations with CIMT or PSMD. This may indicate that current shift work is linked with increased neurovascular risk through disrupted circadian rhythms.