The Role of Biomarkers in Predicting Cognitive Impairment in Elderly Patients with Heart Failure.

OBJECTIVE: This study explores the impact of sST2, Growth Differentiation Factor 15 (GDF-15), and clinical factors on cognitive dysfunction in elderly patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A cohort of 101 chronic stable HFrEF patients aged over 65 years old participated in the study. Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA) test and the Mini Mental State Examination (MMSE). Levels of sST2, GDF-15, and N-terminal pro b-type natriuretic peptide (NT-proBNP) were also measured. RESULTS: Notably higher levels of NT-proBNP and GDF-15 were observed in the group with cognitive dysfunction, whereas sST2 levels were similar between the groups. The cognitive dysfunction group consisted of older patients. A higher proportion of patients with normal cognitive function had received influenza vaccinations. Furthermore, GDF-15 levels inversely correlated with MMSE score. Right ventricular diameter was negatively correlated, while hemoglobin levels were positively correlated with both MoCA and MMSE scores. Logistic regression analysis identified increased GDF-15 levels, older age, and advanced New York Heart Association (NYHA) classes as predictors of higher cognitive dysfunction risk, whereas influenza vaccination was linked to a reduced risk of cognitive dysfunction. CONCLUSION: Cognitive dysfunction in elderly patients with heart failure may be influenced by factors such as age, right ventricular enlargement, anemia, NYHA functional class, and levels of GDF-15 and NT-proBNP.

Impact of Tolvaptan Combined with Low-Dose Dopamine in Heart Failure Patients with Acute Kidney Injury.

The impact of tolvaptan and low-dose dopamine on heart failure (HF) patients with acute kidney injury (AKI) remains uncertain from a clinical standpoint.HF patients with AKI were selected and divided in a 1:1 fashion into the dopamine combined with the tolvaptan group (DTG), the tolvaptan group (TG), and the control group (CG). According to the standard of care, TG received tolvaptan 15 mg orally daily for a week. DTG received combination treatment, including 7 consecutive days of dopamine infusion (2 µg/kg・minutes) and oral tolvaptan 15 mg. Venous blood and urine samples were taken before and after therapy. The primary endpoint was the cardiorenal serological index after 7 days of treatment.Sixty-five patients were chosen randomly for the DTG (22 patients), TG (20 patients), and CG (23 patients), which were similar before the treatment. The serum indexes related to cardiac function (N-terminal probrain natriuretic peptide and cardiac troponin I) in DTG were decreased, compared with TG and CG (P < 0.05). Furthermore, the serological markers of renal function (serum cystatin C, serum creatinine, and neutrophil gelatinase-associated lipocalin) in DTG were lower than those in TG and CG (P < 0.05). There was no significant difference in the incidence of adverse reactions among groups.Low-dose dopamine combined with tolvaptan can markedly improve patients' cardiac and renal function. This may be considered a new therapeutic method for HF patients with AKI.

Serum Markers of Neurodegeneration Are Strongly Linked to Heart Failure Severity and Outcome.

BACKGROUND: Cognitive impairment is prevalent in patients with heart failure with reduced ejection fraction (HFrEF), affecting self-care and outcomes. Novel blood-based biomarkers have emerged as potential diagnostic tools for neurodegeneration. OBJECTIVES: This study aimed to assess neurodegeneration in HFrEF by measuring neurofilament light chain (NfL), total tau (t-tau), amyloid beta 40 (Aß40), and amyloid beta 42 (Aß42) in a large, well-characterized cohort. METHODS: The study included 470 patients with HFrEF from a biobank-linked prospective registry at the Medical University of Vienna. High-sensitivity single-molecule assays were used for measurement. Unplanned heart failure (HF) hospitalization and all-cause death were recorded as outcome parameters. RESULTS: All markers, but not the Aß42:Aß40 ratio, correlated with HF severity, ie, N-terminal pro-B-type natriuretic peptide and NYHA functional class, and comorbidity burden and were significantly associated with all-cause death and HF hospitalization (crude HR: all-cause death: NfL: 4.44 [95% CI: 3.02-6.53], t-tau: 5.04 [95% CI: 2.97-8.58], Aß40: 3.90 [95% CI: 2.27-6.72], and Aß42: 5.14 [95% CI: 2.84-9.32]; HF hospitalization: NfL: 2.48 [95% CI: 1.60-3.85], t-tau: 3.44 [95% CI: 1.95-6.04], Aß40: 3.13 [95% CI: 1.84-5.34], and Aß42: 3.48 [95% CI: 1.93-6.27]; P < 0.001 for all). These associations remained statistically significant after multivariate adjustment including N-terminal pro-B-type natriuretic peptide. The discriminatory accuracy of NfL in predicting all-cause mortality was comparable to the well-established risk marker N-terminal pro-B-type natriuretic peptide (C-index: 0.70 vs 0.72; P = 0.225), whereas the C-indices of t-tau, Aß40, Aß42, and the Aß42:Aß40 ratio were significantly lower (P < 0.05 for all). CONCLUSIONS: Neurodegeneration is directly interwoven with the progression of HF. Biomarkers of neurodegeneration, particularly NfL, may help identify patients potentially profiting from a comprehensive neurological work-up. Further research is necessary to test whether early diagnosis or optimized HFrEF treatment can preserve cognitive function.

The effect of external fixator on bone metabolism in patients with open fracture of extremities.

This experiment aimed to explore the influence mechanism of external fixator on open fracture. A total of 128 patients with open tibiofibular fractures were included in this study. The patients were randomly divided into external fixator group (n=64) and control group (n=64) according to the order of admission. Double-blind controlled observation was used. The levels of osteocalcin (BGP), ß-CTX, P1 NP, BALP, including haptoglobin (Hp), ceruloplasmin (CER), serum adrenocorticotropic hormone (ACTH), cortisol (COR), C-reactive protein (CRP), white blood cell (WBC) and interleukin-6 (IL-6) were recorded in different groups. The postoperative VAS score and quality of life were recorded. Log-rank was used to analyze the difference in postoperative adverse reaction rates among different groups. External fixation stent treatment increased BGP, PINP, and BALP expression and decreased ß-CTX, Hp, CER, ACTH, COR, CRP, WBC, and IL-6 levels. Patients in the external fixation stent group had significantly lower VAS score quality of life scores and incidence of adverse events than the control group. External fixation stents protect open fracture patients by promoting bone metabolism.

Association between dietary inflammatory index and NT-proBNP levels in US adults: A cross-sectional analysis.

BACKGROUND: With cardiovascular diseases standing as a leading cause of mortality worldwide, the interplay between diet-induced inflammation, as quantified by the Dietary Inflammatory Index (DII), and heart failure biomarker NT-proBNP has not been investigated in the general population. METHODS: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, encompassing 10,766 individuals. The relationship between the DII and NT-proBNP levels was evaluated through multivariable-adjusted regression models. To pinpoint crucial dietary components influencing NT-proBNP levels, the LASSO regression model was utilized. Stratified analyses were then conducted to examine the associations within specific subgroups to identify differential effects of the DII on NT-proBNP levels across diverse populations. RESULTS: In individuals without heart failure, a unit increase in the DII was significantly associated with an increase in NT-proBNP levels. Specifically, NT-proBNP levels rose by 9.69 pg/mL (95% CI: 6.47, 12.91; p < 0.001) without adjustments, 8.57 pg/mL (95% CI: 4.97, 12.17; p < 0.001) after adjusting for demographic factors, and 5.54 pg/mL (95% CI: 1.75, 9.32; p = 0.001) with further adjustments for health variables. In participants with a history of heart failure, those in the second and third DII quartile showed a trend towards higher NT-proBNP levels compared to those in the lowest quartile, with increases of 717.06 pg/mL (95% CI: 76.49-1357.63, p = 0.030) and 855.49 pg/mL (95% CI: 156.57-1554.41, p = 0.018). Significant interactions were observed in subgroup analyses by age (<50: ß = 3.63, p = 0.141; 50-75: ß = 18.4, p<0.001; >75: ß = 56.09, p<0.001), gender (men: ß = 17.82, p<0.001; women: ß = 7.43, p = 0.061),hypertension (ß = 25.73, p<0.001) and diabetes (ß = 38.94, p<0.001). CONCLUSION: This study identified a positive correlation between the DII and NT-proBNP levels, suggesting a robust link between pro-inflammatory diets and increased heart failure biomarkers, with implications for dietary modifications in cardiovascular risk management.

Association of Plasma Amyloid, P-Tau, GFAP, and NfL With CSF, Clinical, and Cognitive Features in Patients With Dementia With Lewy Bodies.

BACKGROUND AND OBJECTIVES: Plasma ß-amyloid-1-42/1-40 (Aß42/40), phosphorylated-tau (P-tau), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) have been widely examined in Alzheimer disease (AD), but little is known about their reflection of copathologies, clinical importance, and predictive value in dementia with Lewy bodies (DLB). We aimed to evaluate associations of these biomarkers with CSF amyloid, cognition, and core features in DLB. METHODS: This cross-sectional multicenter cohort study with prospective component included individuals with DLB, AD, and healthy controls (HCs), recruited from 2002 to 2020 with an annual follow-up of up to 5 years, from the European-Dementia With Lewy Bodies consortium. Plasma biomarkers were measured by single-molecule array (Neurology 4-Plex E kit). Amyloid status was determined by CSF Aß42 concentrations, and cognition was assessed by Mini-Mental State Examination (MMSE). Biomarker differences across groups, associations with amyloid status, and clinical core features were assessed by analysis of covariance. Associations with cognitive impairment and decline were assessed by linear regression and linear mixed-effects models. RESULTS: In our cohort consisting of 562 individuals (HC n = 89, DLB n = 342, AD n = 131; 250 women [44.5%], mean [SD] age of 71 [8] years), sex distribution did not differ between groups. Patients with DLB were significantly older, and had less years of education and worse baseline cognition than HC, but not AD. DLB participants stratified for amyloid status differed significantly in plasma Aß42/40 ratio (decreased in amyloid abnormal: ß = -0.008, 95% CI -0.016 to -0.0003, p = 0.01) and P-tau (increased in amyloid abnormal, P-tau181: ß = 0.246, 95% CI 0.011-0.481; P-tau231: ß = 0.227, 95% CI 0.035-0.419, both p < 0.05), but not in GFAP (ß = 0.068, 95% CI -0.018 to 0.153, p = 0.119), and NfL (ß = 0.004, 95% CI -0.087 to 0.096, p = 0.923) concentrations. Higher baseline GFAP, NfL, and P-tau concentrations were associated with lower MMSE scores in DLB, and GFAP and NfL were associated with a faster cognitive decline (GFAP: annual change of -2.11 MMSE points, 95% CI -2.88 to -1.35 MMSE points, p < 0.001; NfL: annual change of -2.13 MMSE points, 95% CI -2.97 to -1.29 MMSE points, p < 0.001). DLB participants with parkinsonism had higher concentrations of NfL (ß = 0.08, 95% CI 0.02-0.14, p = 0.006) than those without. DISCUSSION: Our study suggests a possible utility of plasma Aß42/40, P-tau181, and P-tau231 as a noninvasive biomarkers to assess amyloid copathology in DLB, and plasma GFAP and NfL as monitoring biomarkers for cognitive symptoms in DLB.

Clinical significance of serum Ck18-M65 and M30 levels in patients with chronic hepatitis B combined with nonalcoholic steatohepatitis and liver fibrosis.

In this study, we aimed to explore the clinical significance of serum CK18-M65 and CK18-M30 levels in patients with chronic hepatitis B (CHB) complicated by nonalcoholic steatohepatitis (NASH) and liver fibrosis. The observation and control groups comprised 133 patients with CHB complicated by NASH and 50 healthy patients from our hospital, respectively. Liver function indices, including alanine aminotransferase, glutamic aminotransferase, γ-glutamyltransferase, total bilirubin, total protein, and total cholesterol, were determined using an automatic biochemical analyzer. Hyaluronic acid, type III procollagen, type IV collagen, laminin, and CK18-M65 and M30 levels were detected using ELISA. Serum CK18-M65 and M30 levels in patients with CHB complicated by NASH were positively correlated with the liver fibrosis stage (P < .05). While serum CK18-M65 demonstrated a low diagnostic value for liver fibrosis in the S0-1 stage, it exhibited good diagnostic value for S2-3 stage liver fibrosis. Serum CK18-M30 displayed good diagnostic value for S0-1 and S2-3 hepatic fibrosis, particularly for S2-3 hepatic fibrosis. Elevated serum CK18-M65 and CK18-M30 levels in patients with CHB complicated with NASH suggest their potential utility in evaluating the progression of liver fibrosis in this population. In particular, CK18-M30 exhibits superior diagnostic efficiency.

Obesity and heart failure with preserved ejection fraction.

OBJECTIVE: Aim: To perform an overall assessment of heart failure with preserved ejection fraction (HFpEF) adults with central obesity. PATIENTS AND METHODS: Materials and Methods: We enrolled HFpEF patients with central obesity (n =73, mean age 52.4 ± 6.3 years) and without obesity (n =70, mean age 51.9 ± 7.1 years) and compared with an age-matched healthy subjects who had not suffered from HF (n = 69, mean age 52.3 ± 7.5 years). Physical examination, routine laboratory tests such as fasting blood glucose, fasting insulin, insulin resistance (HOMA) index, serum lipids, haemoglobin, creatinine, ALT, AST, uric acide, hs CRP, TSH, N-terminal proB-type natriuretic peptide (NT-proBNP) and standard transthoracic echocardiogram (2D and Doppler) examinations were performed and assessed. RESULTS: Results: The average values of diastolic blood pressure (DBP), glucose and lipid profiles, uric acide, hs CRP were found to be significantly higher among obese patients with HFpEF than non-obese. Despite more severe symptoms and signs of HF, obese patients with HFpEF had lower NT-proBNP values than non-obese patients with HFpEF (129±36.8 pg/ml, 134±32.5 pg/ml vs 131±30.4 pg/ml, 139±33.8 pg/ml respectively; p < 0.05). However, it was found that patients with high central (visceral) adiposity have more pronounced obesity-related LV diastolic dysfunction, lower E/e' ratio, lower mitral annular lateral e' velocity, an increased LV diastolic dimension and LV mass index. Compared with non-obese HFpEF and control subjects, obese patients displayed greater right ventricular dilatation (base, 35±3.13 mm, 36±4.7 mm vs 33±2.8 mm, 34±3.2 mm and 29±5.3 mm, 30±3.9 mm; length, 74±5 mm, 76±8 mm vs 67±4 mm, 69±6 mm and 60±3 mm, 61±5 mm respectively; p < 0.05), more right ventricular dysfunction (TAPSE 16±2 mm, 15±3 mm vs 17±2 mm, 17±1 mm and 19±2 mm, 20±3 mm respectively; p < 0.05). CONCLUSION: Conclusions: Obese patients with HFpEF have higher diastolic BP, atherogenic dyslipidemia, insulin resistance index values and greater systemic inflammatory biomarkers, despite lower NT-proBNP values, which increase the risk of cardiovascular events in future. Echocardiography examination revealed not only significant LV diastolic dysfunction, but also displayed greater RV dilatation and dysfunction.

The impact of empagliflozin and metformin on cardiac parameters in patients with mid-range ejection fraction heart failure without diabetes.

Heart failure (HF) remains a significant problem for healthcare systems, requiring the use of intervention and multimodal management strategies. We aimed to assess the short-term effect of empagliflozin (EMPA) and metformin on cardiac function parameters, including ventricular dimension-hypertrophy, septal thickness, ejection fraction (EF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF and mildly reduced EF. A case-control study included 60 newly diagnosed patients with HF. Patients were divided into two groups: Group E received standard HF treatment (carvedilol, bumetanide, sacubitril-valsartan, spironolactone) plus EMPA 10 mg daily, and Group M received standard HF treatment plus metformin 500 mg daily. After three months of treatment, Group E had a significantly higher EF than Group M compared to initial measurements (a change of 9.2% versus 6.1%, respectively). We found similar results in the left ventricular end-systolic dimension (LVESD), with mean reductions of 0.72 mm for Group E and 0.23 mm for Group M. Regarding cardiac indicators, the level of NT-proBNP was considerably decreased in both groups. However, the reduction was significantly greater in group E than in group M compared to the initial level (mean reduction: 719.9 vs. 973.6, respectively). When combined with quadruple anti-heart failure therapy, metformin enhanced several echocardiographic parameters, showing effects similar to those of EMPA when used in the same treatment regimen. However, the benefits of EMPA were more pronounced, particularly regarding improvements in EF and LVESD.

Automatic offline-capable smartphone paper-based microfluidic device for efficient biomarker detection of Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a prevalent neurodegenerative disease with no effective treatment. Efficient and rapid detection plays a crucial role in mitigating and managing AD progression. Deep learning-assisted smartphone-based microfluidic paper analysis devices (µPADs) offer the advantages of low cost, good sensitivity, and rapid detection, providing a strategic pathway to address large-scale disease screening in resource-limited areas. However, existing smartphone-based detection platforms usually rely on large devices or cloud servers for data transfer and processing. Additionally, the implementation of automated colorimetric enzyme-linked immunoassay (c-ELISA) on µPADs can further facilitate the realization of smartphone µPADs platforms for efficient disease detection. RESULTS: This paper introduces a new deep learning-assisted offline smartphone platform for early AD screening, offering rapid disease detection in low-resource areas. The proposed platform features a simple mechanical rotating structure controlled by a smartphone, enabling fully automated c-ELISA on µPADs. Our platform successfully applied sandwich c-ELISA for detecting the ß-amyloid peptide 1-42 (Aß 1-42, a crucial AD biomarker) and demonstrated its efficacy in 38 artificial plasma samples (healthy: 19, unhealthy: 19, N = 6). Moreover, we employed the YOLOv5 deep learning model and achieved an impressive 97 % accuracy on a dataset of 1824 images, which is 10.16 % higher than the traditional method of curve-fitting results. The trained YOLOv5 model was seamlessly integrated into the smartphone using the NCNN (Tencent's Neural Network Inference Framework), enabling deep learning-assisted offline detection. A user-friendly smartphone application was developed to control the entire process, realizing a streamlined "samples in, answers out" approach. SIGNIFICANCE: This deep learning-assisted, low-cost, user-friendly, highly stable, and rapid-response automated offline smartphone-based detection platform represents a good advancement in point-of-care testing (POCT). Moreover, our platform provides a feasible approach for efficient AD detection by examining the level of Aß 1-42, particularly in areas with low resources and limited communication infrastructure.

Value of 2D speckle tracking technique combined with real-time 3-dimensional echocardiography in the evaluation of the right atrial function in patients with 3-branch coronary artery disease without myocardial infarction.

To evaluate the right atrial function in patients with 3-branch coronary artery disease (TBCAD) without myocardial infarction by 2D speckle tracking echocardiography (2D-STE) combined with real-time 3-dimensional echocardiography (RT-3DE). Fifty-six patients admitted to our hospital without myocardial infarction with TBCAD were selected. We divided them into 2 groups according to the coronary angiography results: 28 patients in group B (the rate of stenosis is 50% ~< 75%); 28 patients in group C (the rate of stenosis is ≥75%); in addition, 30 healthy volunteers were screened as group A. All subjects underwent RT-3DE to obtain the right atrial volume (RAVmax, RAVmin, and RAVp), and then we calculated the right atrial passive and active ejection fraction (RAPEF, RAAEF), and maximum volume index (RAVImax). In addition, to measure the strain rates (RASRs, RASRe, RASRa) of the right atrium during systole, early diastole, and late diastole, 2D-STE was applied. Correlations between the 2D-STE parameters and the results of N-terminal pro-brain natriuretic peptide (NT-proBNP) and Gensini scores were analyzed by Pearson linear analysis. Compared with group A, RAPEF and RASRe were reduced, while RAAEF and RASRa were elevated in group B (P < .05). RAPEF, RASRs, RASRe, and RASRa were decreased compared with groups A and B, while RAVmax, RAVmin, RAVp, RAVImax, and RAAEF were increased in group C (P < .05). There was a significant correlation between 2D-STE parameters and the results of NT-proBNP and Gensini scores (P < .05). The storage, conduit, and pump functions of the right atrium are reduced in patients with 3-branch coronary artery disease without myocardial infarction; 2D-STE combined with RT-3DE is valuable in the evaluation of the right atrium in patients with coronary artery disease.

Accuracy of brain natriuretic peptide and N-terminal brain natriuretic peptide for detecting paediatric pulmonary hypertension: a systematic review and meta-analysis.

OBJECTIVE: Pulmonary hypertension (PH) is a life-threatening disease, especially in paediatric population. Symptoms of paediatric PH are non-specific. Accurate detection of paediatric PH is helpful for early treatment and mortality reduction. Therefore, we assessed the overall performance of brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) for diagnosing PH in paediatric population. METHODS: PubMed, Web of Science, Cochrane Library and Embase databases were screened since their respective inceptions until August 2023. A bivariate random model and a hierarchical summary receiver operating characteristic model were used together to evaluate and summarize the overall performance of BNP and NT-proBNP for diagnosing paediatric PH. RESULTS: Eighteen studies using BNP/NT-proBNP were assessed, comprising 1127 samples. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUROC) of BNP/NT-proBNP were separately as 0.81, 0.87, 6.33, 0.21, 29.50 and 0.91, suggesting a good diagnostic performance of BNP/NT-proBNP for detecting PH in paediatric population. For BNP, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.83, 0.89, 7.76, 0.19, 40.90 and 0.93, indicating the diagnostic accuracy of BNP for paediatric PH patients was good. For NT-proBNP, the pooled sensitivity, specificity, PLR, NLR, DOR and AUROC were 0.81, 0.86, 5.59, 0.22, 24.96 and 0.90, showing that NT-proBNP could provide a good value for detecting paediatric PH. CONCLUSIONS: Both BNP and NT-proBNP are good markers for differentiating paediatric PH patients from non-PH individuals.

Accurate detection of paediatric PH is helpful for early treatment and mortality reduction. This study shows that both BNP and NT-proBNP are good markers for detecting paediatric PH. In clinical practice, we recommend that BNP and NT-proBNP are auxiliary biomarkers in diagnosing paediatric PH.

Higher N-terminal pro-brain natriuretic peptide level at onset of peritoneal dialysis-related peritonitis is a risk factor for technique failure.

BACKGROUND: Recent studies have suggested that the N-terminal fragment of B-type natriuretic peptide (NT-proBNP) level serve as a significant risk factor for mortality in patients with end-stage renal disease. However, the relationship between NT-proBNP levels and technique failure in peritoneal dialysis-associated peritonitis (PDAP) remains unclear. This study investigated the relationship between NT-proBNP levels at the onset of PDAP and the risk of technique failure in patients with PDAP. METHODS: A retrospective analysis was conducted on patients with PDAP from December 1, 2009, to December 31, 2021, at our peritoneal dialysis center. We recorded all demographic and baseline clinical data at the time of admission for each PDAP episode. Logistic and Cox regression analyses were performed to assess the association between NT-proBNP levels and technique failure. RESULTS: Of 485 PDAP episodes included in this study, 130 episodes of technique failure were observed. Multivariate logistic analysis revealed that hospital stay, Na and NT-proBNP levels, and peritoneal dialysate white blood cell counts on days 3 and 5 were independently associated with technique failure. The receiver operating characteristic curve demonstrated that the NT-proBNP level was a better indicator than the other four variables in indicating technique failure. In the multivariate Cox regression analysis, after adjusting for confounding factors, higher NT-proBNP levels (HR of 3.020, 95% CI 1.771, 5.150, P < 0.001) were associated with PDAP technique failure. CONCLUSIONS: This retrospective study identified the serum NT-proBNP level at the onset of PDAP as an independent risk factor for technique failure in these patients.

Clinical usefulness of NT-proBNP as a prognostic factor for septic shock patients presenting to the emergency department.

Plasma N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level is primarily used as a biomarker for left ventricular (LV) dysfunction. It is influenced by various conditions, such as myocardial strain and situations affecting the clearance of NT-proBNP, including sepsis and shock. In this study, we investigated the appropriateness of NT-proBNP as a prognostic factor for septic shock. Patients with septic shock who visited the emergency department of the Ewha Womans' University Mokdong Hospital between January 1, 2018, and December 31, 2020, were classified into the survival group (those who survived in the hospital and were discharged) and the death group (those who died in the hospital). The effectiveness of NT-proBNP, lactate, and blood urea nitrogen as predictive factors of in-hospital mortality was evaluated using the area under the receiver operating characteristic (AUROC) curve. The AUROC curve was 0.678 and 0.648 for lactate and NT-proBNP, respectively, with lactate showing the highest value. However, there was no significant difference between lactate and NT-proBNP levels in the comparison of their AUROC curve (p = 0.6278). NT-proBNP could be a useful predictor of in-hospital mortality in patients with septic shock who present to the emergency department.

Comparison of plasma and neuroimaging biomarkers to predict cognitive decline in non-demented memory clinic patients.

BACKGROUND: Plasma biomarkers of Alzheimer's disease (AD) pathology, neurodegeneration, and neuroinflammation are ideally suited for secondary prevention programs in self-sufficient persons at-risk of dementia. Plasma biomarkers have been shown to be highly correlated with traditional imaging biomarkers. However, their comparative predictive value versus traditional AD biomarkers is still unclear in cognitively unimpaired (CU) subjects and with mild cognitive impairment (MCI). METHODS: Plasma (Aß42/40, p-tau181, p-tau231, NfL, and GFAP) and neuroimaging (hippocampal volume, centiloid of amyloid-PET, and tau-SUVR of tau-PET) biomarkers were assessed at baseline in 218 non-demented subjects (CU = 140; MCI = 78) from the Geneva Memory Center. Global cognition (MMSE) was evaluated at baseline and at follow-ups up to 5.7 years. We used linear mixed-effects models and Cox proportional-hazards regression to assess the association between biomarkers and cognitive decline. Lastly, sample size calculations using the linear mixed-effects models were performed on subjects positive for amyloid-PET combined with tau-PET and plasma biomarker positivity. RESULTS: Cognitive decline was significantly predicted in MCI by baseline plasma NfL (ß=-0.55), GFAP (ß=-0.36), hippocampal volume (ß = 0.44), centiloid (ß=-0.38), and tau-SUVR (ß=-0.66) (all p < 0.05). Subgroup analysis with amyloid-positive MCI participants also showed that only NfL and GFAP were the only significant predictors of cognitive decline among plasma biomarkers. Overall, NfL and tau-SUVR showed the highest prognostic values (hazard ratios of 7.3 and 5.9). Lastly, we demonstrated that adding NfL to the inclusion criteria could reduce the sample sizes of future AD clinical trials by up to one-fourth in subjects with amyloid-PET positivity or by half in subjects with amyloid-PET and tau-PET positivity. CONCLUSIONS: Plasma NfL and GFAP predict cognitive decline in a similar manner to traditional imaging techniques in amyloid-positive MCI patients. Hence, even though they are non-specific biomarkers of AD, both can be implemented in memory clinic workups as important prognostic biomarkers. Likewise, future clinical trials might employ plasma biomarkers as additional inclusion criteria to stratify patients at higher risk of cognitive decline to reduce sample sizes and enhance effectiveness.

Eligibility for omecamtiv mecarbil in a real-world heart failure population: Data from the Swedish Heart Failure Registry.

AIMS: We assessed eligibility for omecamtiv mecarbil (OM) in a real-world cohort with heart failure with reduced ejection fraction (HFrEF) according to the selection criteria of the GALACTIC-HF trial (trial scenario) and selected trial´s criteria more likely to impact real-world use (pragmatic scenario). METHODS AND RESULTS: We included 31,015 patients with HFrEF lasting ≥3 months and registered in the Swedish HF registry between 2000-2021. Trial eligibility was calculated by applying all the GALACTIC-HF selection criteria. The pragmatic scenario considered only the New York Heart Association class, history of worsening HF, N-terminal pro-B-type natriuretic peptides (NT-proBNP), blood pressure and renal failure criteria defined as in the trial. Eligibility for OM in chronic HFrEF was 21% and 36% in the trial and pragmatic scenarios, respectively. Eligibility was higher in those with EF<30% (trial: 27%, pragmatic: 44%), in-patients (trial:30%, pragmatic:57%), severe HF (trial: 35%, pragmatic: 60%), NYHA class III-IV (trial: 26%, pragmatic: 45%), and NT-proBNP≥5,000pg/mL (trial: 30%, pragmatic: 51%). The criteria that most limited eligibility were history of a recent worsening HF event (60% eligible in chronic HFrEF), elevated NT-proBNP (82% eligible), and deviating blood pressure (82% eligible). Overall, eligible patients were characterized by more severe HF and higher CV event-rates in both scenarios, and higher comorbidity burden in the pragmatic scenario. CONCLUSION: Approximately 21% of real-world chronic HFrEF patients would be eligible for OM according to the GALACTIC-HF selection criteria, and 36% according to the criteria more likely to affect OM use in clinical practice. Criteria in both scenarios identified a patient-group with severe HF and high CV event-rates.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Association between CTX-1 and Fibulin-1 Serum Levels with Pathogenesis of Multiple Myeloma Cancer.

BACKGROUND: Multiple myeloma (MM) is the second most prevalent blood cancer after non-Hodgkin lymphoma. It is identified by the excessive production of abnormal monoclonal immunoglobulins, which can result in various clinical symptoms such as destructive bone lesions, renal dysfunction, anemia, and immunodeficiency. The current study aims to evaluate the serum levels of carboxy-terminal collagen crosslinks 1 (CTX-1), Fibulin-1, vitamin D3, LDH, and albumin in MM patients and their significance for early diagnosis. MATERIALS AND METHODS: This study included 30 healthy controls (11 males, 19 females) and 60 patients with multiple myeloma (37 males and 23 females), aged between 40-60 years. Five-milliliter blood samples were collected and stored at -20°C. Afterward, enzyme-linked immunosorbent assay (ELISA) kits were used to estimate the concentrations of CTX-1, Fibulin-1, and vitamin D3. Additionally, LDH and albumin levels were determined using the automated biochemistry analyzer. RESULTS: This study revealed that the majority of patients with multiple myeloma are between the ages of 51 and 60 years. The serum concentrations of CTX-1, Fibulin-1, and LDH were significantly increased in the multiple myeloma patients compared to the healthy control group. In contrast, the serum level of vitamin D3 was significantly decreased in patients with MM. CONCLUSION: Our results indicate that the incidence of multiple myeloma is higher in males than in females. Additionally, the serum concentrations of CTX-1 and Fibulin-1 were significantly higher in the multiple myeloma patients compared to the healthy control group, indicating their potential for early detection and as therapeutic targets.

Acute Hyperglycemia Induced by Hyperglycemic Clamp Affects Plasma Amyloid-ß in Type 2 Diabetes.

Background: Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer's disease (AD). Mis-metabolism with aggregation of amyloid-ß peptides (Aß) play a key role in AD pathophysiology. Therefore, human studies on Aß metabolism and T2D are warranted. Objective: The objective of this study was to examine whether acute hyperglycemia affects plasma Aß1-40 and Aß1-42 concentrations in individuals with T2D and matched controls. Methods: Ten participants with T2D and 11 controls (median age, 69 years; range, 66-72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in a randomized order, each lasting 4 hours. Aß1-40, Aß1-42, and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4 hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aß1-40 and Aß1-42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration. Results: At baseline, Aß1-40 and Aß1-42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aß decreased in the control group, compared to the placebo clamp (Aß1-40: p = 0.034, Aß1-42: p = 0.020), IDE increased (p = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aß or IDE was noted in the T2D group. Conclusions: Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aß40 and Aß42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D.

HF Etiology and cardiac contractility modulation therapy.

OBJECTIVES: Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology. METHODS: We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation. RESULTS: The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032). CONCLUSION: In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.