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Background This study aimed to investigate the association between handgrip strength (HGS) and cardiovascular disease (CVD) in individuals with metabolic dysfunction‐associated steatotic liver disease (MASLD) using data from the UK Biobank cohort. Methods A total of 201 563 participants were enrolled in this study. The HGS was measured using a Jamar J00105 hydraulic hand dynamometer. MASLD was defined as the presence of hepatic steatosis accompanied by one or more cardiometabolic criteria. Hepatic steatosis was identified using a fatty liver index ≥ 60. Advanced liver fibrosis was defined by a fibrosis‐4 (FIB‐4) score > 2.67. To examine the differences in the incidence of CVD, male and female participants were divided into non‐MASLD, MASLD with high HGS, MASLD with middle HGS, and MASLD with low‐HGS groups. Results Of the study participants, 75 498 (37.5%) were diagnosed with MASLD, with a mean age of 56.5 years, and 40.6% were male. The median follow‐up duration was 13.1 years. The frequency of incident CVD events increased significantly across groups: 10.9% in non‐MASLD, 13.3% in MASLD with high HGS, 14.8% in MASLD with middle HGS, and 18.4% in MASLD with low HGS for males (p < 0.001). In females, the frequency of incident CVD events was 6.1% in non‐MASLD, 9.2% in MASLD with high HGS, 10.7% in MASLD with middle HGS, and 13.3% in MASLD with low HGS (p < 0.001). Using the non‐MASLD group as a reference, multivariate‐adjusted hazard ratios (HRs) (95% confidence intervals [CI]) for CVD varied according to HGS in individuals with MASLD. In males with MASLD, HRs (95% CI) were 1.03 (0.96–1.10) for high HGS, 1.14 (1.07–1.21) for middle HGS, and 1.38 (1.30–1.46) for low HGS; in females with MASLD, they were 1.07 (0.97–1.18) for high HGS, 1.25 (1.14–1.37) for middle HGS, and 1.56 (1.43–1.72) for low HGS. The incidence of CVD events increased as HGS decreased in participants with MASLD, regardless of the presence or absence of advanced liver fibrosis (all p < 0.001). Conclusions This large prospective cohort study using the UK Biobank showed that in MASLD, a decrease in HGS was associated with increased CVD risk.

Objective One mechanism that may be responsible for drug resistance in epilepsy is the upregulation of P-glycoprotein (P-gp), a drug efflux pump, at the epileptogenic focus. In this study, we sought to evaluate the potential of a recently developed P-gp PET radiotracer, [ 11 C] N -desmethyl-loperamide ([ 11 C]dLop), for measuring P-gp function in the rat brain. Methods The precursor to [ 11 C]dLop was synthesized in two steps from commercially available starting materials and subsequently radiolabeled in one step using [ 11 C]methyl iodide. [ 11 C]dLop was then administered to two groups of rats, controls ( n  = 4) and those treated with a P-gp inhibitor ( n  = 8). Cyclosporin A (CsA, 50 mg/kg, n  = 3) and tariquidar (TQ, 20 mg/kg, n  = 5) were both used as P-gp inhibitors. MicroPET brain scans were performed for 120 min with arterial blood sampling. A one-tissue compartment model was used to estimate the distribution volume of radiotracer as the outcome measure of P-gp function. Results Plasma levels of parent [ 11 C]dLop decreased rapidly to <0.1 mean standardized uptake value (SUV) at 60 min. In controls, brain uptake of [ 11 C]dLop was very low (<0.1 mean SUV). In contrast, the mean SUVs were significantly higher in rats treated with CsA (0.51) or TQ (0.22). Estimation of distribution volumes was stable by 70 min. Estimated distribution volumes were significantly larger after P-gp inhibition (CsA = 7.3, TQ = 4.7) compared to controls (no inhibitor = 2.1). Conclusions The rat brain demonstrates significantly increased uptake of [ 11 C]dLop after P-gp inhibition. [ 11 C]dLop is a substrate of P-gp, and will serve as a promising radiotracer for studying P-gp function in the future.

The recent introduction of a number of new radiotracers suitable for imaging the serotonin transporters (SERT) has radically changed the field of SERT imaging. Whereas, until recently, only one selective SERT radiotracer was available ([11C]McN 5652) for SERT imaging with positron emission tomography (PET), several new C-11-labeled radiotracers of the N,N-dimethyl-2-(arylthio)benzylamine class have been described as appropriate imaging agents for the SERT. The aim of this study was to conduct a comparative evaluation of four of the most promising agents in this class ([11C]ADAM, [11C]DASB, [11C]DAPA, and [11C]AFM) with the reference tracer [11C]McN 5652 under standardized experimental conditions. This evaluation included in vitro measurements of affinity and lipophilicity, and in vivo PET imaging experiments in baboons. In vitro, DASB displayed significantly lower affinity for SERT than the other four tracers. In the blood, [11C]DASB and [11C]AFM display faster clearance and higher free fractions. Brain uptake was analyzed with kinetic modeling using a one-tissue compartment model and the metabolite-corrected arterial input function. The kinetic uptake of [11C]DASB was significantly faster compared with the other compounds, and the scan duration required to derive time-independent estimates of regional distribution volumes was shorter. [11C]DAPA exhibited the slowest brain kinetic. Regional-specific-to-nonspecific equilibrium partition coefficient (V3“) was the highest for [11C]AFM, followed by [11C]DASB and [11C]DAPA, which in turn provided higher V3” values than [11C]ADAM and [11C]McN 5652. From these experiments, two ligands emerged as superior radiotracers that provide a significant improvement over [11C]McN 5652 for PET imaging of SERT: [11C]DASB, because it enables the measurement of SERT availability in a shorter scanning time, and [11C]AFM, because its higher signal-to-noise ratios provide a more reliable measurement of SERT availability in brain regions with relatively low density of SERT, such as in the limbic system.

AimsThis study evaluated the sex differences of sequential changes in coronary blood flows and microvascular function in patients with suspected angina but with no obstructed coronary arteries.MethodsA total of 202 consecutive patients who experienced chest pain but had no significant coronary artery stenosis and who underwent adenosine stress echocardiography were included in the study. Coronary blood flow (CBF) velocities were measured at 1, 2, and 3 min after adenosine infusion.ResultsThe mean age was 61 years, and 138 (68%) were women. Approximately 40% of patients had coronary microvascular dysfunction (CMD, coronary flow velocity reserve < 2.3), with women exhibiting higher CMD prevalence. The left ventricular (LV) mass index was similar between men and women, while women exhibited higher baseline rate pressure products (RPP). At baseline, coronary blood flow velocities were similar between the sexes. However, CBF velocities in women gradually increased during the examination; and in men, the increase was abrupt and steep during the early stages of examination (p = 0.015 for interaction between time and sex), even with similar RPP in stress. Coronary flow velocity reserve was steadily lower in women compared to men (1 min, 2.09 ± 0.86 vs 2.44 ± 0.87; 2 min, 2.39 ± 0.72 vs 2.63 ± 0.85; 3 min, 2.45 ± 0.70 vs 2.68 ± 0.73).ConclusionsIn patients with suspected angina but with no obstructed coronary arteries, CMD was especially prevalent among women. Women exhibited higher oxygen consumption, while exhibiting slower and gradual increases in CBF velocities. Conversely, men exhibited faster and steeper increases in CBF velocities even with similar RPP in stress.

Positron emission tomography (PET) and the high affinity D 2/3 radiotracer [ 18 F]fallypride allow the assessment of D 2/3 receptor occupancy of antipsychotic drugs in striatal and extrastriatal brain regions. We measured regional occupancy attained across a range of clinical dosing by the partial D 2 agonist aripiprazole using these methods. Twenty-eight PET scans were acquired on the ECAT EXACT HR+ camera in 19 patients with schizophrenia or schizoaffective disorder. Daily aripiprazole doses ranged from 2 to 40 mg, with a minimum of 10 days on steady dose. Mean regional occupancies, a model-independent estimate of aripiprazole effect on pituitary binding, and PANSS ratings changes were evaluated. Occupancy levels were high across regions of interest, ranging from 71.6±5.5% at 2 mg/day to 96.8±5.3% at 40 mg/day. Occupancy levels were higher in extrastriatal than striatal regions. Pituitary measures of aripiprazole effect correlated with doses and were unrelated to prolactin levels, which remained within the normal range under medication. PANSS positive (but not negative) symptom improvement correlated with striatal but not extrastriatal occupancies. These data show, for the first time, D 2 occupancy by aripiprazole in treated patients with schizophrenia in extrastriatal as well as striatal regions, with high occupancy for all doses. We discuss possible explanations for higher extrastriatal than striatal occupancy. Correlations of ratings of clinical improvement with regional occupancy suggest that aripiprazole, as do other antipsychotics, benefits positive symptoms of schizophrenia most directly through its modulation of striatal rather than cortical or other extrastriatal dopamine activity.

ObjectivePrevious studies that evaluated cardiovascular risk factors considered age as a potential confounder. We aimed to investigate the impact of cardiovascular disease (CVD) and its risk factors on fatal outcomes according to age in patients with COVID-19.MethodsA systematic literature review and meta-analysis was performed on data collected from PubMed and Embase databases up to 11 June 2020. All observational studies (case series or cohort studies) that assessed in-hospital patients were included, except those involving the paediatric population. Prevalence rates of comorbid diseases and clinical outcomes were stratified by mean patient age in each study (ranges: <50 years, 50–60 years and ≥60 years). The primary outcome measure was a composite fatal outcome of severe COVID-19 or death.ResultsWe included 51 studies with a total of 48 317 patients with confirmed COVID-19 infection. Overall, the relative risk of developing severe COVID-19 or death was significantly higher in patients with risk factors for CVD (hypertension: OR 2.50, 95% CI 2.15 to 2.90; diabetes: 2.25, 95% CI 1.89 to 2.69) and CVD (3.11, 95% 2.55 to 3.79). Younger patients had a lower prevalence of hypertension, diabetes and CVD compared with older patients; however, the relative risk of fatal outcomes was higher among the former.ConclusionsThe results of the meta-analysis suggest that CVD and its risk factors (hypertension and diabetes) were closely related to fatal outcomes in COVID-19 for patients across all ages. Although young patients had lower prevalence rates of cardiovascular comorbidities than elderly patients, relative risk of fatal outcome in young patients with hypertension, diabetes and CVD was higher than in elderly patients.Prospero registration numberCRD42020198152.

Acute myocardial infarction (AMI) is highly prevalent and remains the leading cause of mortality. Particularly in women, under-recognition and management of AMI have been raised. The aim of this study was to investigate the long-term trends of prevalence, treatment methodologies, and mortality of AMI by gender. The subjects of this study were patients hospitalized for AMI according to the Korean National Health Insurance Claims Database from 2002 to 2018. Total 633,097 AMI patients were hospitalized, 40% women. The incidence of AMI has been increasing since 2011, with a lower incidence in women. Overall, 53.1% of patients underwent CAG, with a lower tendency in women than in men (39.8% vs. 62.3%). Furthermore, fewer women underwent PCI than men (77.5% vs. 85.8% in 2018, p  < 0.0001). Of the 336,463 AMI patients undergoing CAG, women were undertreated with a lower prescription rate of beta-blockers or statins at discharge. When adjusted for age, women showed higher 7-day mortality but lower 1-year mortality relative to men. According to the Korean National Health Insurance Claims Database, women with AMI have been under-recognized, underdiagnosed, and undertreated in terms of revascularization or medical therapy for years suggesting that efforts to close the gender gap are necessary.

We aimed to evaluate the utility of left atrial reservoir strain (LASr) as a predictor of left ventricular (LV) filling pressure measured via catheterization in patients with sinus rhythm. This prospective study collected data including pre-atrial contraction (pre-A) pressure and LV end-diastolic pressure (LVEDP) from patients undergoing LV catheterization. Transthoracic echocardiography was performed within 24 h to assess LA strain. Patients with supraventricular tachycardia or acute coronary syndrome were excluded. From June 2021 to September 2022, 365 patients (mean age 61.7 ± 11.5 years, 25.5% female) were enrolled. Mean LASr was 28.7 ± 7.4%. LASr demonstrated good discrimination for predicting LV pre-A pressure ≥ 15 mmHg (0.754, 95% CI 0.641–0.820), being significantly better than that of LVEDP ≥ 16 mmHg (0.655, 95% CI 0.592–0.719) using a 24% cutoff ( p  = 0.021). Adding LASr to a model based on HFA-PEFF components improved diagnostic performance (continuous net reclassification index 0.404, 95% CI 0.037–0.807, p  = 0.032). In patients with indeterminate diastolic function, LASr ≥ 24% reclassified them as normal with 76.9% accuracy. When the 198 patients within the intermediate score group with LASr > 24% were reclassified as ‘HFpEF unlikely,’ 192 (97.0%) showed normal LV filling pressure. LASr is an independent predictor of LV filling pressure, especially LV pre-A pressure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), have shown benefits in patient with heart failure (HF), however, adherence remains a significant issue: with only 60% of patients continuing usage beyond a year. This study aims to identify patients at risk of discontinuing SGLT2i and promote its judicious use to reduce hospitalizations and improve cardiovascular outcomes. Using the Korean National Health Insurance Service database, patients diagnosed with HF and diabetes mellitus (n = 1,665,565) between 2013 and 2018 were identified. Among them, 55,694 participants prescribed SGLT2i were enrolled. The primary endpoint included 1) all-cause mortality and 2) SGLT2i-related hospitalization, encompassing incidents such as ketoacidosis, acute kidney injury, urinary tract infections, fall-related fractures, and other unplanned hospitalizations. During the follow-up period (median: 2.3 years; range: 1.2–3.6 years), 8,463 participants reached the primary endpoint (25.5 for all-cause death and 39.4 for SGLT2i-related hospitalizations per 1,000 person-years). Independent risk factors for the primary endpoint in multivariate Cox regression and propensity-score matching analyses included age of ≥ 70 years, body mass index (BMI) <18.5 kg/m 2 , body weight <60 kg, anemia, chronic kidney disease, and the use of diuretics. Age (hazard ratio [HR] 1.45, 95% confidence interval [CI]: 1.36–1.54), BMI (HR 1.78, 95% CI: 1.29–2.45), body weight (HR 1.17, 95% CI: 1.09–1.26) and the use of furosemide (HR 1.45, 95% CI: 1.22–1.74) (all p <0.001) were consistent independent risk factors in the propensity score-matched cohort. Having three or more risk factors was associated with an adjusted HR that was 3.04 times higher than cases with no risk factor (95% CI: 2.83–3.28, p <0.001). Old age, low weight or BMI, and the use of diuretics are risk factors that hinder the continuous use of SGLT2i in diabetic patients with HF. Close monitoring for side effects is essential when prescribing SGLT2i, particularly for those with multiple risk factors.