N-terminal Propeptide Research Articles

Chemotherapy effects on bone mineral density and microstructure in women with breast cancer.

Chemotherapy involves the administration of steroids to prevent nausea and vomiting; however, its effect on bone microstructure remains unknown. This study aimed to evaluate the changes in bone mineral density (BMD) and bone microstructure associated with chemotherapy using high-resolution peripheral quantitative computed tomography (HR-pQCT) in women with early breast cancer. This prospective single-arm observational study included non-osteoporotic, postmenopausal women with breast cancer. The patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide (P1NP) measurements at baseline, end of chemotherapy, and 6months after chemotherapy. The primary endpoint was the change in total volumetric BMD at the distal tibia and radius. Eighteen women were included in the study (median age: 57years; range: 55-62years). At 6months after chemotherapy, HR-pQCT indicated a significant decrease in total volumetric BMD (median: distal tibia -4.5%, p < 0.01; distal radius -2.3%, p < 0.01), cortical volumetric BMD (-1.9%, p < 0.01; -0.8%, p = 0.07, respectively), and trabecular volumetric BMD (-1.1%, p = 0.09; -3.0%, p < 0.01, respectively). The DXA BMD also showed a significant decrease in the lumbar spine (median: -4.5%, p < 0.01), total hip (-5.5%, p < 0.01), and femoral neck (-4.2%, p < 0.01). TRACP-5b and P1NP levels were significantly increased at the end of chemotherapy compared to baseline. Postmenopausal women undergoing chemotherapy for early breast cancer experienced significant BMD deterioration in weight-bearing bone, which was further reduced 6months after chemotherapy.

Bone and vascular effects of magnesium supplements in CKD patients (the MagicalBone Pilot Study)

Background and objectiveThe progression of chronic kidney disease (CKD) involves the development of alterations in mineral metabolism that are closely related to cardiovascular outcomes and bone disease. Hypomagnesemia is associated with more rapid progression of CKD and other comorbidities. Our objective was to analyze in CKD patients stages 3–4 the impact of the administration of magnesium (Mg) carbonate on bone mineral density (BMD) and hemodynamic changes associated with by vascular calcification (VC). Material and methodsPatients with CKD stages 3–4 were randomized into controls (n=12) or intervention (n=7) group receiving 360mg of Mg carbonate daily during a 15-month period. Parameters related to mineral metabolism, BMD, VC, and pulse wave velocity (PWV) were evaluated. ResultsSupplementation with Mg produced an increase in the urinary excretion of Mg while serum Mg levels remained stable and no episodes of hypermagnesemia were reported. In addition, no significant changes were found in the degree of VC assessed by Adragao index, however, both serum and urine Mg were significantly associated with a decrease in PWV, suggesting an increase in vascular compliance. Likewise, BMD did not change following treatment, but serum Mg significantly correlated with the levels of N-terminal propeptide of collagen alpha-1(I) chain (PINP), a marker of bone synthesis. ConclusionsIn sum, these results suggest a possible beneficial effect of Mg on vascular compliance with no detrimental effects on bone status. In addition, our results highlight the need to consider monitorization of urinary Mg status in CKD patients.

Natriuretic Peptide Concentrations and Echocardiography Findings in Patients with Micro-atrial Fibrillation.

Atrial fibrillation (AF) is a rhythm disorder characterized by very rapid and disorganized atrial-derived electrical activations with uncoordinated atrial contractions. Very short periods of AF-like activity (micro-AF) may be precursors of undetected, silent episodes of atrial fibrillation. Here, we examined the relationship between natriuretic peptide concentrations and echocardiography findings in patients with micro-AF. The electrocardiograms (ECGs) of patients complaining of palpitations were recorded with a 24‑hour Holter monitor, and the patients were consecutively included in the study. Micro-AF was defined as sudden, irregular atrial tachycardia lasting less than 30 sec with episodes of ≥5 consecutive supraventricular depolarizations with the absolute absence of p-waves. After a G-power test, patients were consecutively included in the study: 45 patients in the micro-AF group and 45 patients in the control group. Laboratory parameters, ECG and echocardiographic findings of the two groups were compared. N-terminal pro B-type natriuretic peptide (Pro-BNP) and serum troponin T concentrations were higher in the micro-AF group, (375.5±63.6 pg / ml vs. 63.1±56.8 pg / ml, p&lt;0.001; 13±11.4 ng / dl vs. 4.4±2.4 ng / dl, p&lt;0.001 respectively.) Each 1 pg / ml increase in serum Pro-BNP increased the risk of micro-AF by 1.8 %. In the ROC analysis, the cut-off value of Pro-BNP for the diagnosis of micro-AF was 63.4 pg / ml, with a sensitivity of 91.1 % and a specificity of 73.3 %. Atrial electro-mechanical delay durations were significantly higher in the micro-AF group. To predict micro-AF, the inter-annulus plane electromechanical delay time (inter-annulus plane AEMD) had a cut-off value of 18.5 sec, with a sensitivity of 93.3 % and a specificity of 91.1 %. Left intra-annulus plane electro-mechanical delay time (intra-annulus AEMD LEFT) had a cut-off value of 11.5 sec with a 95.6 % sensitivity and 75.6 % specificity. In the ECG evaluation, maximum P wave duration (Pmax) (113±10.2 ms vs. 98±10.4 ms; p&lt;0.001), minimum P wave duration (Pmin) (73.8±5.5 ms vs.70±6.3 ms; p&lt;0.001) and P wave dispersion (PWD) (39.1±7.9 ms vs.28±7.6 ms; p&lt;0.001) were longer in the micro-AF group. Micro-AF in patients may be predicted by evaluating ECG, echocardiographic, and serum natriuretic peptide data.

Predictive value of NT pro BNP for new-onset atrial fibrillation in heart failure and preserved ejection fraction.

The prognostic significance of N-terminal pro B-type natriuretic peptide (NT-proBNP) in heart failure with preserved ejection fraction (HFpEF) has been well established. HFpEF and atrial fibrillation (AF) commonly coexist, and each contributes to poor outcomes independently. Nevertheless, the ability of NT-proBNP to predict AF in HFpEF patients remains uncertain. A total of 367 HFpEF patients without baseline AF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were included. The Cox proportional hazard model was used to assess the association of NT-proBNP with the risk of AF. The C-statistic, categorical net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the ability of NT-proBNP in new-onset AF prediction. During a median follow-up of 2.91years, 17 (4.63%) new-onset AF cases occurred. Every 1000pg/mL increase in NT-proBNP was associated with a 16% increase in the risk of AF occurrence after adjustments (hazard ratio, 1.16 [95% CI, 1.02-1.32]). NT-proBNP showed a moderate performance for new-onset AF at 3years (C-statistic, 0.67). Adding NT-proBNP to CHADS2/R2CHADS2/CHA2DS2-VASc/C2HSET scores improved their predictive performance for AF risk (CHADS2: C-statistic, 0.63, CHADS2+NT: C-statistic, 0.69, NRI, 47.46%, IDI, 1.18%; R2CHADS2: C-statistic, 0.65, R2CHADS2+NT: C-statistic, 0.70, NRI, 48.03%, IDI, 0.51%; CHA2DS2-VASc: C-statistic, 0.67, CHA2DS2-VASc+NT: C-statistic, 0.72, NRI, 49.41%, IDI, 0.86%; C2HSET: C-statistic, 0.77, C2HSET+NT: C-statistic, 0.80, NRI, 50.32%, IDI, 1.58%). Among patients with HFpEF, the NT-proBNP level was positively associated with the incidence of new-onset AF and may be a promising predictor.

No effect of surgery on kidney and cardiovascular risk factors in mild primary hyperparathyroidism: secondary analyses from a 10-year randomized controlled trial.

Renal function and the skeleton are classic target organs in primary hyperparathyroidism (PHPT), affected by the chronic course of the disease. Most patients diagnosed today exhibit mild PHPT, characterized by slight hypercalcemia and no or unspecific symptoms. Concerns have been raised that PHPT could promote deteriorating kidney function and increase cardiovascular risk directly. To examine the effect of parathyroidectomy (PTX) on mild PHPT on renal function and markers for bone turnover, cardiovascular disease (CVD), and vascular inflammation. Prospective randomized controlled trial. ClinicalTrials.gov: NCT00522028. Eight Scandinavian referral centers. From 1998 to 2005, 191 patients with mild PHPT were included in Sweden, Norway, and Denmark. Of these 150 were included in the present analyses. Seventy patients were randomized to PTX and 80 to observation without intervention (OBS). e-GFR was calculated based on creatinine and cystatin C. Markers of CVD and systemic inflammation: osteoprotegerin, vascular cell adhesion molecule 1, soluble CD40 ligand, interleukin-1 receptor antagonist, von Willebrand factor. Bone turnover markers: C-terminal telopeptide of type 1 collagen (CTX-1) and serum Procollagen type 1 N-terminal propeptide. No differences in the development of renal function or vascular and systemic inflammation were detected. CTX-1 was lower in PTX after 10 years. Secondary analyses of a randomized controlled trial. PTX does not appear to affect renal function or markers of CVD and vascular inflammation in mild PHPT in a ten-year perspective.

Association between changes in serum bone metabolism markers and bone microarchitecture changes during basic combat training – The ARMI study

ImportanceU.S. Army Basic Combat Training (BCT) improves tibial volumetric bone mineral density (BMD) and structure in most, but not all soldiers. Few studies have investigated whether changes in serum bone biomarkers during BCT are associated with changes in tibial BMD and bone structure following BCT. ObjectiveTo characterize bone biomarker changes during BCT and to investigate the relationship between changes in bone biomarkers and changes in tibial BMD and bone structure. MethodsWe enrolled 235 trainees entering BCT in this ten-week prospective observational study. Trainees provided fasted blood samples and questionnaires weekly throughout BCT. Procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type 1 collagen (CTX) were measured by enzyme-linked immunoabsorbent assays every two weeks during BCT. We evaluated body composition and mass via dual-energy X-ray absorptiometry and bone structure, microarchitecture, and mineral density at the distal tibia via high-resolution peripheral quantitative computed tomography at baseline and post-BCT. ResultsBoth male (n = 110) and female trainees (n = 125) were young (20.9 ± 3.7 and 20.7 ± 4.3 years, respectively), with normal to overweight BMIs (25.2 ± 4.1 and 24.2 ± 3.6 kg/m2, respectively). In female trainees, PINP increased during and post-BCT compared to baseline, with the greatest increase in PINP at week four (45.4 % ± 49.6, p < 0.0001), whereas there were no changes in CTX. PINP also increased in male trainees, but only at weeks two and four (21.9 % ± 24.5, p = 0.0027 and 35.9 % ± 35.8, p < 0.0001, respectively). Unlike female trainees, in males, CTX was lower than baseline at weeks four, eight, and post-BCT. The change in PINP from baseline to week four of BCT was positively associated with changes in tibial BMD, Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po from the baseline to post-BCT. ConclusionThe bone formation marker PINP increases during U.S. Army BCT, especially during the first four weeks. Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia.

Correlations between Bone Turnover Marker Concentrations and Maxillary and Mandibular Cancellous Hounsfield Units: A Crosssectional Study.

Purpose: This study aimed to investigate the associations between the concentrations of bone turnover markers and maxillary and mandibular cancellous Hounsfield units to determine whether bone turnover marker assessments are effective for preoperative examinations for implant treatment. Materials and Methods: The study included 94 patients (37 males and 57 females) with a mean age of 62.0±11.9 years. Spearman's rank correlation and multivariate linear regression coefficients were used to determine the associations between the bone turnover markers and maxillary and mandibular cancellous Hounsfield units. Results: Multivariate bias correction showed that the concentrations of bone-specific alkaline phosphatase, procollagen type I N-terminal propeptide, and deoxypyridinoline were negatively associated with the maxillary Hounsfield units. The concentration of undercarboxylated osteocalcin tended to be negatively associated with the maxillary Hounsfield units but not significantly. The concentrations of deoxypyridinoline and tartrateresistant acid phosphatase 5b were significantly negatively associated, and the concentrations of bone-specific alkaline phosphatase and procollagen type I N-terminal propeptide only tended to be negatively associated with the mandibular Hounsfield units. Conclusion: Several bone formation and resorption markers were negatively correlated with the maxillary and mandibular Hounsfield units. BTM measurement is effective for preoperative examination for implant treatment.

Intermittent tensile strain induces an increased response in bone formation markers compared to continuous load in mouse pre-osteoblasts when loading magnitude is matched

Intermittent and continuous mechanical loads are known to influence osteogenic activity. The present study examines the effects of matched intermittent and continuous load in vitro on bone formation markers. MC3T3 (mouse pre-osteoblasts) were cultured and placed in a bioreactor to undergo continuous, intermittent, or unloading for 1, 3 and 12 days. Loading conditions were matched for magnitude, duration and frequency. Each time point was analysed for alkaline phosphatase (ALP) activity, procollagen 1 N-terminal propeptide (PINP) and alizarin red staining (ARS). Intermittent load caused an increase in ALP activity across all time points compared to continuous loading (↑30%–59%) and unloaded conditions (↑70%–90%). PINP concentrations from intermittent load were lower than continuous load (↓112%) on day 3. However, no differences were observed in PINP concentrations between loading conditions at other time points. No differences were observed for ARS between loading conditions. Intermittent load caused an increase in bone formation marker ALP, but not PINP, when compared to continuous loading and unloaded conditions. These findings further our knowledge in bone formation response and provide additional tools for the analysis of osteogenesis in vitro.

The Influence of Nutrition Intervention on the P1NP and CTX-1 Response to an Acute Exercise Bout: A Systematic Review with Meta-Analysis.

Although nutrition and exercise both influence bone metabolism, little is currently known abouttheir interaction, or whether nutritional intervention can modulate the bone biomarker response to acute exercise. Improved understanding of the relationships between nutrition, exercise and bone metabolism may have substantial potential to inform nutritional interventions to protect the bone health of exercising individuals, and to elucidate mechanisms by which exercise and nutrition influence bone. The aim was to synthesise available evidence related to the influence of nutrition on the response of the bone biomarkers procollagen type 1 N-terminal propeptide (P1NP) and C-terminal telopeptide of type 1 collagen (CTX-1) to acute exercise, using a systematic review and meta-analytic approach. Studies evaluating the influence of nutritional status or intervention on the bone biomarker response to an acute exercise bout were included and separated into four categories: (1) feeding status and energy availability, (2) macronutrients, (3) micronutrients and (4) other. Studies conducted on healthy human populations of any age or training status were included. Meta-analysis was conducted when data from at least five studies with independent datasets were available. In the case of insufficient data to warrant meta-analysis, results from individual studies were narratively synthesised and standardised mean effect sizes visually represented. Twenty-two articles were included. Of these, three investigated feeding status or energy availability, eight macronutrients, eight micronutrients (all calcium) and six other interventions including dairy products or collagen supplementation. Three studies had more than one intervention and were included in all relevant outcomes. The largest and most commonly reported effects were for the bone resorption marker CTX-1. Meta-analysis indicated that calcium intake, whether provided via supplements, diet or infusion, reduced exercise-induced increases in CTX-1 (effect size - 1.1; 95% credible interval [CrI] - 2.2 to - 0.05), with substantially larger effects observed in studies that delivered calcium via direct infusion versus in supplements or foods. Narrative synthesis suggests that carbohydrate supplementation may support bone during acute exercise, via reducing exercise-induced increases in CTX-1. Conversely, a low-carbohydrate/high-fat diet appears to induce the opposite effect, as evidenced by an increased exercise associated CTX-1 response, and reduced P1NP response. Low energy availability may amplify the CTX-1 response to exercise, but it is unclear whether this is directly attributable to energy availability or to the lack of specific nutrients, such as carbohydrate. Nutritional intervention can modulate the acute bone biomarker response to exercise, which primarily manifests as an increase in bone resorption. Ensuring adequate attention to nutritional factors may be important to protect bone health of exercising individuals, with energy, carbohydrate and calcium availability particularly important to consider. Although a wide breadth of data were availablefor this evidence synthesis, there was substantial heterogeneity in relation to design and intervention characteristics. Direct and indirect replication is required to confirm key findings and to generate better estimates of true effect sizes.

Trajectory of Irisin as a Predictor of Kidney-Related Outcomes in Patients with Asymptomatic Heart Failure.

The purpose of the study is to elucidate whether irisin is a promising predictive biomarker for kidney-related events in patients with T2DM and concomitant asymptomatic HF. We prospectively enrolled 146 T2DM patients who had either evidence of structural cardiac abnormality or elevated levels of N-terminal brain natriuretic pro-peptide (NT-proBNP) > 125 pmol/mL and followed them for 52 weeks. Structural cardiac abnormalities were used as the minimum from the following criteria: abnormal left ventricular (LV) global longitudinal strain (GLS) < -16%, LV hypertrophy, left atrial volume index > 34 mL/m2, abnormal ratio of early transmitral diastolic filling velocity/early mitral annular velocity ≥ 13 units. All the patients underwent echocardiographic and Doppler examinations by two blinded, highly experienced echocardiographers. NT-proBNP, irisin, TNF-alpha, and hs-CRP were quantified in the serum at baseline, at 26 weeks, and at the end of the study. The kidney-related outcomes consisted of an eGFR reduction by 40% from baseline, or end-stage kidney disease, or kidney replacement therapy. We found that levels of irisin at baseline < 4.15 ng/mL and/or its decrease > 20% from baseline in T2DM patients predicted kidney-related events better than baseline levels/dynamic NT-proBNP and the use of SGLT2 inhibitors. In conclusion, we established that a low baseline level of irisin and its 20% decrease correlated with newly kidney-related events in T2DM patients with asymptomatic HFpEF/HFmrEF.

[99mTc]Tc-hydroxydiphosphonate uptake in soft tissue is associated with amyloid load in subcutaneous abdominal fat tissue and mortality in wild-type transthyretin amyloidosis patients

PurposeBone scintigraphy is key to non-invasively diagnosing wild-type transthyretin (ATTRwt) amyloidosis, and is mainly used to assess cardiac radiotracer uptake. However, extracardiac radiotracer uptake is also observed. We investigated whether intensity of soft tissue radiotracer uptake is associated with amyloid load in subcutaneous abdominal fat tissue and with mortality.MethodsThis prospective cohort study included 94 ATTRwt amyloidosis patients and 26 amyloid-negative heart failure controls who underwent whole-body [99mTc]Tc-hydroxydiphosphonate scintigraphy. Site-to-background ratios were calculated for heart, elbows, subcutaneous tissue, shoulders and wrists on anterior planar bone scintigraphy images using rib and whole-body radiotracer uptake as background. Fat tissue aspirates were stained with Congo red to grade amyloid load. Site-to-rib ratios were compared between ATTRwt amyloidosis patients and controls, and associations of site-to-background ratio with Congo red score and all-cause mortality were studied.ResultsATTRwt amyloidosis patients had higher soft tissue-to-rib, heart-to-rib and heart-to-whole body ratios compared with controls. The intensity of soft tissue uptake was positively associated with amyloid load in fat tissue in ATTRwt amyloidosis patients. Estimated glomerular filtration rate, N-terminal brain natriuretic propeptide, high-sensitivity cardiac troponin T (hs-cTnT), and the prognostic Mayo and NAC staging system were associated with all-cause mortality in univariable models. Soft tissue/rib ratio, hs-cTnT and the prognostic staging systems were the only two variables that were independently associated withall-cause mortality.ConclusionSoft tissue radiotracer uptake on bone scintigraphy in ATTRwt amyloidosis patients is positively associated with amyloid load in abdominal fat tissue and is independently associated with mortality.

Effects of Aging on New Bone Regeneration in a Mandibular Bone Defect in a Rat Model.

The effects of aging on the healing capacity of maxillofacial bone defects have not been studied. The aim of this study was to evaluate the effects of aging on the regeneration of round bony defects in the mandible. We created a round-shaped bony defect in the mandibular angle area in rats of different ages (2-[2 M], 10-[10 M], and 20-month-old [20 M]) and evaluated new bone regeneration in these groups. Changes in bone turnover markers such as alkaline phosphatase, procollagen type I N-terminal propeptide (PINP), cross-linked C-telopeptide of type I collagen, and tartrate-resistant acid phosphatase 5B (TRAP5b) were investigated. The bone volume/total volume and bone mineral density of the 20 M group were significantly higher than those of the 2 M group (p = 0.029, 0.019). A low level of the bone formation marker PINP was observed in the 20 M group, and a high level of the bone resorption marker TRAP5b was observed in the 10 M and 20 M groups. Micro-computed tomography (µ-CT) results showed that older rats had significantly higher bone formation than younger rats, with lower serum levels of PINP and higher levels of TRAP5b. The local environment of the old rat bone defects, surrounded by thickened bone, may have affected the results of our study. In conclusion, old rats showed greater new bone regeneration and healing capacity for round mandibular bone defects. This result was related to the fact that the bone defects in the 20 M rat group provided more favorable conditions for new bone regeneration.

Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure.

Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.

Risk Factors for All-Cause Mortality in Patients Diagnosed with Advanced Heart Failure: A Scoping Review.

Introduction: Identifying the evolving needs of patients with advanced heart failure (AdHF) and triaging those at high risk of death can facilitate timely referrals to palliative care and advance patient-centered individualized care. There are limited models specific for patients with end-stage HF. We aim to identify risk factors associated with up to three-year all-cause mortality (ACM) and describe prognostic models developed or validated in AdHF populations. Methods: Frameworks proposed by Arksey, O'Malley, and Levac were adopted for this scoping review. We searched the Medline, EMBASE, PubMed, CINAHL, Cochrane library, Web of Science and gray literature databases for articles published between January 2010 and September 2020. Primary studies that included adults aged ≥ 18 years, diagnosed with AdHF defined as New York Heart Association class III/IV, American Heart Association/American College of Cardiology Stage D, end-stage HF, and assessed for risk factors associated with up to three-year ACM using multivariate analysis were included. Studies were appraised using the Quality of Prognostic Studies tool. Data were analyzed using a narrative synthesis approach. Results: We reviewed 167 risk factors that were associated with up to three-year ACM and prognostic models specific to AdHF patients across 65 articles with low-to-moderate bias. Studies were mostly based in Western and/or European cohorts (n = 60), in the acute care setting (n = 56), and derived from clinical trials (n = 40). Risk factors were grouped into six domains. Variables related to cardiovascular and overall health were frequently assessed. Ten prognostic models developed/validated on AdHF patients displayed acceptable model performance [area under the curve (AUC) range: 0.71-0.81]. Among the ten models, the model for end-stage-liver disease (MELD-XI) and acute decompensated HF with N-terminal pro b-type natriuretic peptide (ADHF/proBNP) model attained the highest discriminatory performance against short-term ACM (AUC: 0.81). Conclusions: To enable timely referrals to palliative care interventions, further research is required to develop or validate prognostic models that consider the evolving landscape of AdHF management.

Electroacupuncture ameliorates senile osteoporosis by promoting bone remodeling and regulating autophagy.

Osteoporosis is widely regarded as a typical aged-related disease caused by impaired bone remodeling. This research was designed to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in a rat model and investigate the underlying mechanisms. Three-month-old rats were randomly selected as the youth group, and 24-month-old rats were randomly assigned to the elderly and EA groups. Rats in the EA group received 30 min of EA at bilateral SP10, ST36, K13 and GB34 daily, 5 days a week for 8 weeks. Bone mineral density (BMD), microstructure of the bone tissue, bone turnover biomarkers and expression level of autophagy-related proteins were detected. Compared with the elderly group, EA treatment significantly increased BMD of the femur and ameliorated the microstructure. EA treatment increased trabecular bone volume ratio (= bone volume / total volume [BV/TV]) and trabecular number (Tb.N) and decreased trabecular separation (Tb.Sp) in senile osteoporosis rats. Compared with the elderly group, the serum N-terminal telopeptide of type I collagen (NTX1) level in the EA group was lower, and the serum procollagen type I N-terminal propeptide (PINP) concentration was higher. In addition, the expression of Beclin 1, microtubule-associated protein I light chain 3 (LC3B) and P62 was inhibited in the senile osteoporosis rats after EA treatment. EA can effectively alleviate aging-related bone loss and improve the microstructure of bone tissue in senile osteoporosis rats, and the regulation of autophagy might be one of the important mechanisms.

Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure.

Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.

Relationship of changes in QRS duration with left ventricular ejection fraction in patients with acute ST segment elevation myocardial infarction treated with primary percutaneous coronary intervention

ObjectiveTo assess the changes in QRS duration (△QRSd) before and after primary percutaneous coronary intervention(PPCI) regarding the relation of left ventricular ejection fraction (LVEF) in patients after a first acute ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PPCI). MethodsA total of 244 patients with STEMI were enrolled, and clinical, biochemical, and angiographic parameters were compared between two groups based on LVEF at 6 months post-discharge. QRS duration (QRSd) was analyzed in relation to LVEF, and feature selection using least absolute shrinkage and selection operator(LASSO) regression was performed. Logistic regression analysis and receiver operating characteristic (ROC) curve evaluation were conducted to identify predictors and assess model efficacy. ResultsSignificant differences were observed between the two groups in terms of various parameters, including age, time from symptom onset to balloon dilation (STB), N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, Left ventricular end-diastolic volume(LVEDV) at baseline, left ventricular end-systolic volume(LVESV)at baseline, left ventricular end-diastolic diameter (LVDD)at baseline and six months, hospital length of stay(days), ST-segment resolution (STR), the left anterior descending artery as the infarction-related artery (IRA-LAD), frequency of TIMI 3 flow post PPCI, thrombus aspiration and/or intracoronary thrombolysis, the use of tirofiban, and the number of implanted stents(stents).In addition, postoperative QRSd and △QRSd were significantly higher in patients with left ventricular systolic dysfunction(LVSD). LASSO regression selected six variables as predictors of postoperative LVEF. Logistic regression analysis identified age, STB, NT-proBNP, LVESV at baseline,△QRSd, and stents, as independent factors associated with LVSD within six months for patients with a first occurrence of STEMI. The models achieved AUC values of 0.906 (using ΔQRSd),0.922(using 6 variables excluding ΔQRSd) and 0.962 (using 6 variables). ConclusionThis study identified ΔQRSd as a potential predictor of LVSD in patients with STEMI. The developed models showed good efficacy in predicting postoperative LVEF changes. These findings may contribute to risk stratification and individualized management strategies for STEMI patients.

Bioimpedance analysis predicts worsening events in outpatients with heart failure and reduced ejection fraction.

Heart failure (HF) with reduced left ventricle ejection fraction (LVEF) is an entity with poor prognosis characterized by decompensations. Bioelectrical impedance analysis (BIA) is used to assess volume overload (VO) and may be useful to identify apparently stable HF outpatients at risk of decompensation. The aim of this study is to analyse whether VO assessed by BIA is associated with worsening heart failure (WHF) in stable outpatients with HF and reduced LVEF (HFrEF). This is a prospective single-centre observational study. Consecutive stable HF outpatients with LVEF below 40% underwent BIA, transthoracic echocardiography, blood sampling, and physical examination and were followed up for 3months. VO was defined as the difference between the measured weight and the dry weight assessed by BIA. Demographic, clinical, anthropometric, echocardiographic, and analytical parameters were recorded. The primary endpoint was WHF, defined by visits to the emergency department for HF or hospitalization for HF. A total of 100 patients were included. The median VO was 0.5L (interquartile range 0-1.6L). Eleven patients met the primary endpoint. Univariate binary logistic regression analysis showed that left ventricle filling pressures assessed by E/e', N-terminal pro B-type natriuretic peptide, inferior vena cava dilatation (≥21mm), signs of congestion, and VO were associated with the primary endpoint. Binary logistic regression multivariate analysis showed that VO was the only independent predictor for the primary endpoint (adjusted OR 2.7; 95% CI 1.30-5.63, P=0.008). Multivariate Cox regression analysis also showed an adjusted hazard ratio (HR) for VO of 2.03; 95% CI 1.37-3.02, P<0.001. Receiver-operating characteristic curve analysis showed an area under the curve for VO of 0.88 (95% CI 0.79-0.97, P<0.001) with an optimal cut-off of 1.2L. VO assessed by BIA is independently associated with WHF in stable outpatients with HFrEF at 3months.

S-Equol Ameliorates Menopausal Osteoarthritis in Rats through Reducing Oxidative Stress and Cartilage Degradation.

Osteoarthritis (OA) is a chronic degenerative disease leading to articular cartilage destruction. Menopausal and postmenopausal women are susceptible to both OA and osteoporosis. S-equol, a soy isoflavone-derived molecule, is known to reduce osteoporosis in estrogen-deficient mice, but its role in OA remains unknown. This study aimed to explore the effect of S-equol on different degrees of menopausal OA in female Sprague-Dawley (SD) rats induced by estrogen deficiency caused by bilateral ovariectomy (OVX) combined with intra-articular injection of mono-iodoacetate (MIA). Knee joint histopathological change; serum biomarkers of bone turnover, including N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (CTX-I) and N-terminal telopeptide of type I collagen (NTX-I); the cartilage degradation biomarkers hyaluronic acid (HA) and N-terminal propeptide of type II procollagen (PIINP); and the matrix-degrading enzymes matrix metalloproteinases (MMP)-1, MMP-3 and MMP-13, as well as the oxidative stress-inducing molecules nitric oxide (NO) and hydrogen peroxide (H2O2), were assessed for evaluation of OA progression after S-equol supplementation for 8 weeks. The results showed that OVX without or with MIA injection induced various severity levels of menopausal OA by increasing pathological damage, oxidative stress, and cartilage matrix degradation to various degrees. Moreover, S-equol supplementation could significantly reduce these increased biomarkers in different severity levels of OA. This indicates that S-equol can lessen menopausal OA progression by reducing oxidative stress and the matrix-degrading enzymes involved in cartilage degradation.

Influence of perch provision during rearing on activity and musculoskeletal health of pullets.

Prior research suggests exercise during pullet rearing can mitigate lay-phase bone fractures by strengthening muscles, enhancing balance, and increasing bone mass. This study aimed to confirm that Hy-Line brown pullets with multi-tier perches show increased activity and improved musculoskeletal health. Pullets (n = 810) were randomly allocated to housing systems, either with multi-tier perches (P; n = 15 pens) or without (NP; n = 15 pens), spanning from 0-17 weeks of age. At 5, 11, and 17 weeks, individual birds were meticulously monitored for activity using accelerometers over three consecutive days (n = 90 randomly selected birds/week). At 11 and 17 weeks, 60 birds underwent euthanasia and computed tomography (CT) scans to ascertain tibiotarsal bone mineral density and cross-sectional area measurements. Post-CT scanning, birds were dissected for muscle size, tibiotarsal breaking strength, and tibiotarsal ash percentage measurements. Additionally, serum concentrations of bone-specific alkaline phosphatase and procollagen type 1 N-terminal propeptide were assessed as markers of bone formation (n = 90 birds/week). Pullet group P exhibited heightened vertical activity (P<0.05), with no discernible differences in overall activity (P>0.05) during weeks 5, 11, and 17 compared to group NP. Tibiotarsal bones of P pullets demonstrated superior total and cortical bone mineral density at week 11, alongside increased cortical bone cross-sectional areas and heightened total and cortical bone mineral densities at week 17 (P<0.05) compared to NP pullets. At week 11, P pullets displayed larger leg muscles, including triceps, pectoralis major and minor, and leg muscles at week 17 (P<0.05) compared to NP pullets. Notably, at both weeks, P pullets' tibiae exhibited greater breaking strengths, higher ash percentages, and elevated concentrations of bone-specific alkaline phosphatase and procollagen type 1 N-terminal propeptide compared to NP pullets (P<0.05). The study findings underscore the benefits of providing multi-tier perches for pullets, serving as a valuable tool for enhancing bird activity and musculoskeletal health preceding the lay phase.