The association of prealbumin, transferrin, and albumin with immunosenescence among elderly males.

OBJECTIVE: As people get older, the innate and acquired immunity of the elderly are affected, resulting in immunosenescence. Prealbumin (PAB), transferrin (TRF), and albumin (ALB) are commonly used markers to monitor protein energy malnutrition (PEM). However, their relationship with the immune system has not been fully explored. METHODS: In our study, a total of 93 subjects (≥65 years) were recruited from Tongji Hospital between January 2015 and February 2017. According to the serum levels of these proteins (PAB, TRF, and ALB), we divided the patients into the high serum protein group and the low serum protein group. Then, we compared the percent expression of lymphocyte subsets between two groups. RESULTS: All the low serum protein groups (PAB, TRF, and ALB) had significant decreases in the percentage of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells and significant increases in the percentage of CD8+ cells, CD8+CD28- cells. PAB, TRF, and ALB levels revealed positive correlations with CD4/CD8 ratio, proportions of CD4+ cells, CD3+CD28+ cells, CD4+CD28+ cells, and negative correlation with proportions of CD8+ cells, CD8+CD28- cells. CONCLUSIONS: This study suggested PAB, TRF, and ALB could be used as immunosenescence indicators. PEM might accelerate the process of immunosenescence in elderly males.

Engulfment and cell motility protein 1 fosters reprogramming of tumor-associated macrophages in colorectal cancer.

Functional reprogramming of tumor-associated macrophages (TAMs) is crucial to their potent tumor-supportive capacity. However, the molecular mechanism behind the reprogramming process remains poorly understood. Here, we identify engulfment and cell motility protein 1 (ELMO1) as a crucial player for TAM reprogramming in colorectal cancer (CRC). The expression of ELMO1 in stromal but not epithelial tumor cells was positively associated with advanced clinical stage and poor disease-free survival in CRC. An increase in ELMO1 expression was specifically found in TAMs, but not in other multiple nonmalignant stromal cells. Gain- and loss-of-function assays indicated ELMO1 reprogrammed macrophages to a TAM-like phenotype through Rac1 activation. In turn, ELMO1-reprogrammed macrophages were shown to not only facilitate the malignant behaviors of CRC cells but exhibited potent phagocytosis of tumor cells. Taken together, our work underscores the importance of ELMO1 in determining functional reprogramming of TAMs and could provide new insights on potential therapeutic strategies against CRC.

Three-year outcomes of transanal total mesorectal excision versus standard laparoscopic total mesorectal excision for mid and low rectal cancer.

INTRODUCTION: Since transanal total mesorectal excision (taTME) was introduced, it has become an important topic in rectal cancer treatment. Many previous studies reported positive relevant short-term results, histopathological results, and associated complications. Recently, concerns regarding the oncological safety of taTME have been raised due to reports showing high local recurrences (LR) rates. Therefore, this study aimed to compare the 3-year outcomes between taTME and laparoscopic total mesorectal excision (laTME) for mid-low rectal cancer. METHODS: A total of 104 patients who underwent taTME were matched with 208 patients treated by laTME. The primary endpoint was 3-year LR rate; secondary endpoints in this matched-cohort study included the perioperative outcomes and histopathological outcomes. RESULTS: taTME was associated with lower permanent ostomy rate (1% vs 13.5%) and lower conversion rate (0% vs 3.4%) compared to laTME. A similar quality of resected specimens was detected for each group. In both groups, the local recurrence rate was 3.8%. Within 3 years after surgery, the disease-free survival (DFS) rates were 78.8% in the taTME group and 76.9% in the laTME group (P = 0.640), while the overall survival (OS) rates were 93.3% in the taTME group and 89.9% in the laTME group (P = 0.327). CONCLUSION: No significant differences regarding 3-year local recurrence rate (3.8%) were observed in the taTME group compared to laTME group.

Association Between Thromboelastography and Coronary Heart Disease.

BACKGROUND Thromboelastography (TEG) is a novel blood viscoelasticity detection method revealing blood coagulation status and has been reported to be helpful in predicting clinical outcomes in patients with cardiovascular diseases (CVD). In this study, we aimed to investigate the association between TEG and CVD. MATERIAL AND METHODS A single-center case-control study was performed. Individuals who took TEG tests at Tongji Hospital in Wuhan, China from 2015 to 2019 were included. The nearest-neighbor Mahalanobis matching with replacement, within propensity score calipers of 0.25 was used to control the covariate imbalance between CVD patients and controls. Logistic regression analyses were conducted to assess the relationship between TEG and CVD. Subgroup and sensitivity analyses were performed to evaluate the robustness of the association between TEG and CVD. RESULTS After matching, a total of 151 participants were included in this study, with 83 patients having CVD (49 patients having coronary heart disease [CHD] and 34 patients having an ischemic stroke). By comparison, CHD patients had a significantly higher maximum amplitude (MA) (P=0.02) than controls. After multivariable adjustment, MA (OR 1.11, 95% CI 1.01-1.24, P=0.04) was independently associated with CHD. The association between MA and CHD remained robust across subgroups and in sensitivity analyses. CONCLUSIONS The current study suggests that MA is significantly associated with CHD. Enhanced platelet reactivity as described by high MA might be associated with risk of CHD. The exact role of MA in the measurement of CHD risk needs to be further examined in large-scale prospective cohort studies.

Use of lipid parameters to identify apparently healthy men at high risk of arterial stiffness progression.

BACKGROUND: Dyslipidemia contributes to the development and progression of arterial stiffness. We aimed to identify the most informative measures of serum lipids and their calculated ratios in terms of arterial stiffness progression risk. METHODS: Total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and brachial-ankle pulse wave velocity (baPWV) of 659 healthy males (47.4 ± 10.7 years) were measured at baseline. Values for non-HDL-C, TC/HDL-C, TG/HDL-C, LDL-C/HDL-C, and non-HDL-C/HDL-C were calculated. BaPWV was re-performed after 4.1 years follow-up. Elevated baPWV was defined as baPWV ≥ 1400 cm/s. RESULTS: Over the follow-up period, the mean baPWV value increased from 1340 cm/s to 1410 cm/s, and 331 individuals increased/persisted with high baPWV (outcome 1). Among the 448 subjects who had normal baseline baPWV, 100 incident elevated baPWV occurred (outcome 2). Only baseline logTG (OR 1.64 [95% CI: 1.14-2.37] for outcome 1; 1.89 [1.14-3.17] for outcome 2) and logTG/HDL-C (1.54 [1.15-2.10] for outcome 1; 1.60 [1.05-2.45] for outcome 2) were significantly associated with arterial stiffness progression after adjusting for confounding factors. Adding logTG or logTG/HDL-C to age and blood pressure improved the accuracy of risk predictions for arterial stiffness progression. These associations remained significant when lipids were analyzed as categorical variables. CONCLUSIONS: Baseline serum TG and TG/HDL-C were independently associated with increases in/persistently high baPWV and incident elevated baPWV, and they performed more effectively than other lipid variables in identifying healthy men at high risk of arterial stiffness progression.

The clinical characteristic of eight patients of COVID-19 with positive RT-PCR test after discharge.

Corona virus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The phenomenon of positive real time reverse transcription polymerase chain reaction (RT-PCR) result of SARS-CoV-2 in recovered patients had occurred and the research about these patients was rare. In our study, we did a retrospective review of medical records from COVID-19 patients admitted to one ward of Tongji Hospital of Hua Zhong University of Science and Technology from 10 February to 13 April 2020. From 10 February to 13 April 2020, there were 108 patients of COVID-19 admitted in the one ward of Tongji Hospital. Among them, eight cases were readmission patients because the RT-PCR result of SARS-CoV-2 was positive again after discharge. On the second admission, they had no symptoms and their chest computed tomography was almost normal. Data from laboratory tests of the readmission patients showed that all eight patients had normal white blood cell count, lymphocyte count. The inflammatory factors like procalcitonin and interleukin 6 were normal. After treatment, two patients met the standard and were discharged. The other six patients were still in the hospital because their RT-PCR of SARS-CoV-2 did not get three consecutive negative results and the course of two patients had persisted more than 90 days. We still needed to be alert that these patients could infect other people as a source of infection, and we also needed to be alert that these patients become chronic virus carriers. It also aroused our concern about the discharge standard of COVID-19.

Determinants of Brachial-Ankle Pulse Wave Velocity and Vascular Aging in Healthy Older Subjects.

BACKGROUND Vascular aging is characterized by increasing arterial stiffness as measured by pulse wave velocity. The present study evaluated the factors influencing vascular aging in Chinese healthy older subjects. MATERIAL AND METHODS Disease- and treatment-free aged (≥60 years) participants were recruited from 2014 to 2019. Cardiometabolic risk factors and brachial-ankle pulse wave velocity (baPWV) were assessed. We defined healthy vascular aging (HVA) as the lowest 10% and early vascular aging (EVA) as the highest 10% of the baPWV distribution, after adjustment for age and blood pressure (BP). We fitted linear and logistic regression models to assess the determinants. RESULTS In all, 794 subjects (mean age 66.5±6.8 years, 71.0% male) were recruited; the 10th and 90th percentiles of baPWV were 1278 cm/s and 1955 cm/s, respectively. Age, BP, heart rate, and triglycerides were all positively associated with baPWV, whereas male subjects and body mass index (BMI) were negatively associated with baPWV. The number of participants diagnosed with either HVA or EVA was 80. Logistic regression models showed that sex, BMI, heart rate, and triglycerides were associated with HVA and EVA after adjustment for age, BP, and other confounding factors. CONCLUSIONS Male, high BMI, low heart rate, and low triglycerides are protective factors for vascular aging in the healthy aged population. Management of BMI, heart rate, triglycerides in a reasonable range may help to alleviate the vascular aging process.

Identification, characterization and expression profiles of PSEN2 in the Chinese tree shrew (Tupaia belangeri chinensis).

The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase. Mutations in PSEN2 are not only related to Alzheimer's disease but are also involved in other diseases. The Chinese tree shrew (Tupaia belangeri chinensis) is a potential animal model for Alzheimer's disease, although little is known about its cDNA sequence, protein structure, and PSEN2 expression. To better understand PSEN2 in the tree shrew, we cloned this gene by rapid amplification of cDNA ends technology. Hence, we analyzed the sequence and molecular characteristics of PSEN2 mRNA, predicted its spatial structure, and analyzed its expression profiles. We found that tree shrew PSEN2 is 1539 base pairs in length and encodes 330 amino acids. It is homologous and genetically similar to humans (97.64% identity). The protein structure of tree shrew PSEN2 indicated similarities to human PSEN2, both being comprised of numerous transmembrane helices. However, tree shrew PSEN2 possesses seven α-helices, and thus lacks three compared with human PSEN2. Tree shrew PSEN2 mRNAs were ubiquitously detected in all tissues, with a tissue- and temporal-specific pattern. These results pave the way towards the function of tree shrew PSEN2, which will give insights into the mechanisms leading to neurodegenerative and other diseases in humans.

Impact of Long-Course Neoadjuvant Radiation on Postoperative Low Anterior Resection Syndrome and Quality of Life in Rectal Cancer: Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Neoadjuvant radiation is recommended for locally advanced rectal cancer, with proven benefit in local control but not in disease-free survival. However, the impact of long-course radiation on postoperative bowel function and quality of life (QOL) remains controversial. This study aimed to investigate the impact of long-course neoadjuvant radiation on bowel function and QOL, and to identify risk factors for severe bowel dysfunction. METHODS: Patients who underwent long-course neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by radical low anterior resection for locally advanced rectal cancer were recruited from the FOWARC randomized controlled trial. Low anterior resection syndrome (LARS) score and European Organisation for Research and Treatment of Cancer (EORTC) C30/CR29 questionnaires were used to assess bowel function and QOL, respectively. RESULTS: Overall, 220 patients responded after a median follow-up of 40.2 months, of whom 119 (54.1%) reported major LARS, 74 (33.6%) reported minor LARS, and 27 (12.3%) reported no LARS. Compared with the nCT group, the nCRT group reported more major LARS (64.4% vs. 38.6%, p < 0.001) and worse QOL. Long-course neoadjuvant radiation (OR 2.20, 95% CI 1.24-3.91; p = 0.007), height of anastomosis (OR 0.74, 95% CI 0.63-0.88; p < 0.001), and diverting ileostomy (OR 2.59, 95% CI 1.27-5.30; p = 0.009) were independent risk factors for major LARS. CONCLUSIONS: Long-course neoadjuvant radiation, along with low anastomosis, are likely independent risk factors for postoperative bowel function and QOL. Our findings might have implications for alleviating LARS and improving QOL by informing selection of neoadjuvant treatment.

Fluconazole-induced long QT syndrome via impaired human ether-a-go-go-related gene (hERG) protein trafficking in rabbits.

AIMS: hERG protein trafficking deficiency has long been known in drug-induced long QT syndrome (LQTS). However, validated evidence from in vivo data kept scanty. Our goal was to investigate the proarrhythmic action of fluconazole and its underlying mechanism in an animal model. METHODS AND RESULTS: Twenty female Japanese long-eared white rabbits were randomly distributed into a control group and a fluconazole group for a chronic 2-week treatment. The control group was treated with 0.5% sodium carboxymethylcellulose (CMCNa), and the fluconazole group was treated with fluconazole. Electrocardiograms (ECGs) were recorded during the experimental period. Isolated arterially perfused left ventricular wedge preparations from the rabbits were made 2 weeks after treatment, and the arrhythmia events, the transmural ECG, and action potential from both the endocardium and epicardium were recorded. The changes in hERG protein expression were measured by western blot. The fluconazole group showed a longer QT interval 1 week after treatment (P < 0.05) and a higher arrhythmia occurrence 2 weeks after treatment (P < 0.05) than the control group. The fluconazole group also showed a longer transmural dispersion of repolarization and a higher occurrence of life-threatening torsades de pointes in arterially perfused left ventricular preparations. Furthermore, western blot analysis showed that the density of mature hERG protein was lower in the fluconazole group than that in the control group. CONCLUSION: Fluconazole can prolong the QT interval and possess proarrhythmic activity due to its inhibition of hERG protein trafficking in our experimental model. These findings may impact the clinical potential of fluconazole in humans.

Analysis of gene expression changes associated with human carcinoma-associated fibroblasts in non-small cell lung carcinoma.

BACKGROUND: This study aimed to investigate the gene expression changes associated with carcinoma-associated fibroblasts (CAFs) involving in non-small cell lung carcinoma (NSCLC). METHODS: We downloaded the GEO series GSE22862, which contained matched gene expression values for 15 CAF and normal fibroblasts samples, and series GSE27289 containing SNP genotyping for four matched NSCLC samples. The differentially expressed genes in CAF samples were identified using the limma package in R. Then we performed gene ontology (GO) and pathway enrichment analysis and protein-protein interaction (PPI) network construction using the identified DEGs. Moreover, aberrant cell fraction, ploidy, allele-specific copy number, and loss of heterozygosity (LOH) within CAF cells were analyzed using the allele-specific copy number analysis. RESULTS: We obtained 545 differentially expressed genes between CAF and normal fibroblasts samples. The up-regulated genes are mainly involved in GO terms such as positive regulation of cell migration and extracellular region, while the down-regulated genes participate in the lung development and extracellular region. Multiple genes including bone morphogenetic protein 4 (BMP4) and transforming growth factor, beta 3 (TGFB3) are involved in the TGF-ß signaling pathway. Genes including BMP4, TGFBI and matrix Gla protein (MGP) were hub genes. Moreover, no LOH event for BMP4 and MGP was found, that for sphingosine kinase 1 (SPHK1) was 70%, and for TGFBI was 40%. CONCLUSION: Our data suggested that BMP4, MGP, TGFBI, and SPHK1 may be important in CAFs-associated NSCLC, and the abnormal expression and high LOH frequency of them may be used as the diagnosis targets of CAFs in NSCLC.

Identification of crucial regulatory relationships between long non-coding RNAs and protein-coding genes in lung squamous cell carcinoma.

PURPOSE: This study aimed to analyze the relationships of long non-coding RNAs (lncRNAs) and protein-coding genes in lung squamous cell carcinoma (LUSC). METHODS: RNA-seq data of LUSC deposited in the TCGA database were used to identify differentially expressed protein-coding genes (DECGs) and differentially expressed lncRNA genes (DE-lncRNAs) between LUSC samples and normal samples. Functional enrichment analysis of DECGs was then performed. Subsequently, the target genes and regulators of DE-lncRNAs were predicted from the DECGs. Additionally, expression levels of target genes of DE-lncRNAs were validated by RT-qPCR after the silence of DE-lncRNAs. RESULTS: In total, 5162 differentially expressed genes (DEGs) were screened from the LUSC samples, and there were seven upregulated lncRNA genes in the DEGs. The upregulated DECGs were enriched in GO terms like RNA binding and metabolic process. Meanwhile, the downregulated DECGs were enriched in GO terms like cell cycle. Furthermore, the lncRNAs PVT1 and TERC targeted multiple DECGs. PVT1 targeted genes related to cell cycle (e.g. POLA2, POLD1, MCM4, MCM5 and MCM6), and reduced expression of PVT1 decreased expression of the genes. TERC regulated several genes (e.g. NDUFAB1, NDUFA11 and NDUFB5), and reduced expression of TERC increased expression of the genes. Additionally, PVT1 was regulated by multiple transcription factors (TFs) identified from DECGs, such as HSF1; and TERC was modulated by TFs, such as PIR. CONCLUSION: A set of regulatory relationships between PVT1 and its targets and regulators, as well as TERC and its targets and regulators, may play crucial roles in the progress of LUSC.

Correlation between impedance cardiography and 6 min walk distance in atrial fibrillation patients.

BACKGROUND: The correlation between impedance cardiography (ICG) and 6 min walk distance (6MWD) in atrial fibrillation (AF) patients remains unknown. METHODS: We recruited 49 subjects in the study (21 AF patients and 28 patients without AF) and estimated hemodynamic parameters: cardiac output (CO), stroke volume (SV), stroke volume index (SVI), left stroke work (LSW), left stroke work index (LSWI), stroke systemic vascular resistance (SSVR), stroke systemic vascular resistance index (SSVRI); 6MWD, left ventricle ejection fraction (LVEF), NT-pro brain natriuretic peptide (NT-pro BNP) for the two groups. RESULTS: The AF group have apparently lower CO (2.26 ± 0.14 VS 4.11 ± 0.20 L/min, p = 0.039) and distinctly higher SVR (677.60 ± 69.10 VS 344.41 ± 22.98 dynes/cm(5), p = 0.001), SSVRI (396.97 ± 36.80 VS 199.01 ± 11.72 dynes/cm(5)/m(2), p < 0.001) than the control group. NT-pro BNP (1409.48 ± 239.90 VS 332.59 ± 68.85 pg/ml, p = 0.001) in the AF group was significantly higher than the control group and 6MWD (264.33 ± 14.55 VS 428.79 ± 29.98 m, p < 0.001) in the AF group was lower than the control group. There was no significant difference in LVEF between the two groups (62.67 ± 7.62 % VS 63.93 ± 5.03 %, p = 0.470). Pearson correlation analysis revealed that CO (R = 0.494, p = 0.023), SV (R = 0.633, p = 0.002), LSW (R = 0.615, p = 0.003) and LSWI (R = 0.491, p = 0.024) significantly correlated positively with 6MWD in AF patients. CONCLUSIONS: AF patients had lower cardiac output, shorter 6MWD and higher NT-pro BNP than patients with sinus rhythm. The cardiac output measured by impedance cardiography significantly correlated positively with 6MWD in AF patients.

Effect of the Kv1.3 voltage-gated potassium channel blocker PAP-1 on the initiation and progress of atherosclerosis in a rat model.

Acute coronary syndrome is a serious medical emergency. It occurs when an atherosclerotic plaque ruptures, leading to thrombus formation within a coronary artery. Previous studies have shown that T cells are involved in the initiation and progression of acute coronary syndrome. CD4(+)CD28(null) T lymphocytes increase in atherosclerotic plaque, and voltage-gated potassium channel Kv1.3 blockers can suppress the function of these cells in vitro by preventing exocytosis of their cytoplasmic granules. The purpose of this study was to investigate the effect of PAP-1, a small molecule voltage-gated potassium channel Kv1.3 blocker, on the development of atherosclerosis (AS) in a rat model and the potential mechanism for this effect. Plasma lipids, interferonγ, CRP, CD4(+)CD28(null) T cells, and perforin were increased and unstable atherosclerotic plaques developed in the rat model of AS. Blockade of the Kv1.3 potassium channel via PAP-1 administration decreased perforin levels and prevented plaque formation but had no effect on the other changes seen in this AS model. These findings suggest that the small molecule, voltage-gated potassium channel Kv1.3 blocker PAP-1 can suppress the development of AS in a rat model, most likely by inhibiting the exocytosis of cytoplasmic granules from CD4(+)CD28(null) T cells.

Antiarrhythmic peptide AAP10 prevents arrhythmias induced by protein kinase C activation in rabbit left ventricular wedges.

As the mechanisms underlying PKC activation induced arrhythmias are not yet fully verified, we investigated the role of gap junctions in arrhythmias induced by PKC activation.Arterially-perfused rabbit left ventricular preparations were randomly assigned to perfusion with phorbol ester (PMA) or in combination with AAP10. Transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded throughout all experiments. Changes in connexin43 (Cx43) and nonphosphorylated Cx43 on S368 were measured by Western blot analysis.In the PMA group, the QT interval was shortened, the interval from the peak to the end of the electrocardiographic T wave (Tp-e) and induced nonsustained ventricular tachycardia (VT) were increased, and the expressions of Cx43 and nonphosphorylated Cx43 on S368 were decreased compared with the control group. Compared with the PMA group, without significant changes in the QT interval and the expression of nonphosphorylated connexin43 on S368, Tp-e and induced VT decreased and the expression of Cx43 increased in the AAP10 group.AAP10 can prevent PMA-induced rabbit ventricular arrhythmias by attenuating the increase of Tp-e and the decrease of expression of Cx43. These data suggest that increasing gap junction coupling prevents arrhythmias induced by protein kinase C activation.

Speckle tracking echocardiography assessment of global and regional contraction dysfunction in the mice model of pressure overload.

Speckle tracking echocardiography (STE) has been applied to the evaluation of cardiac contraction dysfunction. However, there were few studies on alteration of global and regional STE parameters in the process of myocardial hypertrophy and heart failure. In this study, STE was applied to evaluate the global and regional cardiac function under heart failure and hypertrophy in the mice model of pressure overload. Adult mice were subjected to mild or severe aortic banding with a 25 Gauge (G) or 27 G needle. After surgery, STE and conventional echocardiography were used in the sham group (n=10), mild trans-aortic banding (TAB) group (n=14) and severe TAB group (n=10) for 8 weeks. The results showed that the mice subjected to severe TAB showed a significant change in fractional shortening (FS), left ventricular (LV) mass, and left ventricular end diastolic diameter (LVEDD) (P<0.05 for each). Meanwhile, there were no significant differences in FS and LVEDD between the sham group and mild TAB group during the experimental procedures (P>0.05 for both). STE analysis revealed that longitudinal strain (LS) was significantly decreased in the severe TAB group as compared with the sham and mild TAB groups (P<0.05 for both) from the postoperative week 1. LS in the mild TAB group was reduced as compared to the sham group (P<0.05). Radial strain (RS) and circumferential strain (CS) were significantly decreased in the severe TAB group as compared to the sham group and the mild TAB group (P<0.05 for both) from the postoperative week 1 (P<0.05 for both). Compared to the sham group, CS in the mild TAB group maintained unchanged during the test period, and RS was reduced only on the postoperative week 6 (P<0.05). Finally, regional contraction dysfunction was analyzed in both hypertrophic and failing myocardium in longitudinal and radial directions. It was found that LS was largest in the apex region and RS was smallest in the apex region in the healthy and hypertrophic myocardium. It was also found that compared to the sham group, only base longitudinal strain in the mild TAB group was decreased. Each of regional strain in the severe TAB group was uniformly depressed in radial and longitudinal directions. It is concluded that STE has provided a non-invasive and highly feasible way to explore the global and regional contraction dysfunction in hypertrophic and heart failure myocardium in the murine model of pressure overload.

Ability of ambulatory ECG-based T-wave alternans to modify risk assessment of cardiac events: a systematic review.

BACKGROUND: Exercise-based spectral T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death (SCD) and cardiac mortality. Prior studies have indicated that ambulatory electrocardiogram (AECG)-based TWA is an important alternative platform to exercise for risk stratification of cardiac events. This study sought to review data regarding 24-hour AECG-based TWA and to discuss its potential role in risk stratification of fatal cardiac events across a series of patient risk profiles. METHODS: Prospective clinical studies of the predictive value of AECG-based TWA obtained with daily activity published between January 1990 and November 2014 were retrieved. Major endpoints included composite endpoint of SCD, cardiac mortality, and severe arrhythmic events. RESULTS: Data were accumulated from 5 studies involving a total of 1,588 patients, including 317 positive and 1,271 negative TWA results. Compared with the negative group, positive group showed increased rates of SCD (hazard ratio [HR]: 7.49, 95% confidence interval [CI]: 2.65 to 21.15), cardiac mortality (HR: 4.75, 95% CI: 0.42 to 53.55), and composite endpoint (SCD, cardiac mortality, and severe arrhythmic events, HR: 5.94, 95% CI: 1.80 to 19.63). For the 4 studies evaluating TWA measured using the modified moving average method, the HR associated with a positive versus negative TWA result was 9.51 (95% CI: 4.99 to 18.11) for the composite endpoint. CONCLUSIONS: The positive group of AECG-based TWA has a nearly six-fold risk of severe outcomes compared with the negative group. Therefore, AECG-based TWA provides an accurate means of predicting fatal cardiac events.

[Comparison of ultrasound-guided transrectal and transperineal prostate biopsies in clinical application].

OBJECTIVE: To compare the positive rates and complications of ultrasound-guided transrectal and transperineal prostate biopsies. METHODS: We retrospectively analyzed 156 cases of ultrasound-guided transrectal (n = 97) and transperineal (n = 59) prostate biopsy, and compared the positive rate and post-biopsy complications between the two approaches. RESULTS: The positive rates in the transrectal and transperineal groups were 48.4% and 44.1%, respectively, with no significant difference between the two approaches according to different PSA levels (P >0.05). No statistically significant differences were observed between the transrectal and transperineal groups in the post-biopsy incidence rates of such complications as hematuria (54.6% vs 42.4%, P >0.05), lower urinary tract symptoms (17.5% vs 22.0%, P >0.05), dysuria (9.3% vs 6.8%, P >0.05), and acute urinary retention (7.2% vs 6.8%, P >0.05). However, the incidence rates of post-biopsy infection and rectal bleeding were remarkably higher (15.5% vs 3.4%, P<0.05 and 50.5% vs 3.4%, P >0.01) while that of perineal swelling markedly lower in the former than in the latter (3.1% vs 13.6%, P <0.05). CONCLUSION: Transrectal and transperineal biopsies are both effective for the diagnosis of prostate cancer. Since their complications vary, the choice between the two methods depends on the specific condition of the patient.

Association between Life's Essential 8 and estimated pulse wave velocity among adults in the US: a cross-sectional study of NHANES 2011-2018.

Background: Arterial stiffness, typically evaluated via estimated pulse wave velocity (ePWV), is believed to have a significant association with cardiovascular diseases. The objective of this study was to investigate the correlation between Life's Essential 8 (LE8), a newly revised metric of cardiovascular health, and ePWV among adult population in the United States. Methods: This research employed a cross-sectional methodology, drawing upon data from the National Health and Nutrition Examination Survey (NHANES) spanning from 2011 to 2018. To explore the relationship between LE8 and ePWV among adults in the US, both univariate and multivariate linear regression analyses were carried out. Additionally, the restricted cubic splines method was utilized to examine any non-linear correlation. Results: The study comprised 6,742 participants with an average age of 48.30 ± 0.35 years. Among these, 3,236 were males, representing a weighted percentage of 48%. The population's weighted average LE8 score was 68.68 ± 0.37, while the average ePWV was 8.18 ± 0.04. An entirely adjusted model revealed a negative correlation between ePWV and LE8 scores [in the moderate LE8 group, coefficient - 0.17, 95% CI -0.28 to -0.06, p = 0.004; in the high LE8 group, coefficient - 0.44, 95% CI -0.56 to -0.32, p < 0.0001]. This negative correlation was consistent with the findings in demographic subgroup analysis, with the effect size being more pronounced among adults under the age of 60, and individuals without hypertension, cardiovascular disease, or diabetes. Conclusion: Our study reveals a negative correlation between LE8 and ePWV in the adult population of the US, suggesting that LE8 could potentially serve as an indicative marker for evaluating the risk of vascular stiffness. This inverse relationship is markedly stronger in adults below 60 years and those without diagnosed vascular diseases. This implies that lifestyle upgrades and risk factor management could be especially advantageous in curbing arterial stiffness within these groups. These conclusions underscore the importance of primary prevention in mitigating the risk of vascular aging in a relatively healthy group, emphasizing the significance of early intervention and risk factor management in cardiovascular disease.

Physical frailty, genetic predisposition, and incident arrhythmias.

BACKGROUND: Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. METHODS: In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. RESULTS: This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. CONCLUSIONS: Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.