Search

Background Type 2 diabetes mellitus (T2DM) is increasingly being diagnosed in older adults. Our objective is to assess the advantages and potential drawbacks of different glucose-lowering medications in this specific population. Methods A network meta-analysis was conducted to identify randomized controlled trials that examined patient-centered outcomes in adults aged ≥65 years with T2DM. We searched PubMed, Cochrane CENTRAL, and Embase up to September 23, 2023. Quality of eligible studies were assessed using the Cochrane RoB 2.0 tool. Results A total of 22 trials that involved 41 654 participants were included, incorporating sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, sulfonylureas (SU) and acarbose. Our findings reveal that GLP-1RAs reduce the risk of major adverse cardiovascular events (risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.97) and body weight (mean difference [MD], −3.87 kg; 95% CI, −5.54 to −2.21). SGLT2 inhibitors prevent hospitalization for heart failure (RR, 0.66; 95% CI, 0.57 to 0.77), renal composite outcome (RR, 0.69; 95% CI, 0.53 to 0.89), and reduce body weights (MD, −1.85 kg; 95% CI, −2.42 to −1.27). SU treatment increases the risk of any hypoglycaemia (RR, 4.19; 95% CI, 3.52 to 4.99) and severe hypoglycaemia (RR, 7.06; 95% CI, 3.03 to 16.43). GLP-1RAs, SGLT2 inhibitors, metformin, SU and DPP-4 inhibitors are effective in reducing glycaemic parameters. Notably, the number of treatments needed decreases in most cases as age increases. Conclusions Novel glucose-lowering medications with benefits that outweigh risks should be prioritized for older patients with diabetes. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the most common cancers and is the second leading cause of cancer-related death in the world. Due to the westernization of diets, young patients with CRC are often diagnosed at advanced stages with an associated poor prognosis. Improved lifestyle choices are one way to minimize CRC risk. Among diet choices is the inclusion of bee propolis, long recognized as a health supplement with anticancer activities. Understanding the effect of propolis on the gut environment is worth exploring, and especially its associated intratumoral immune changes and its anticancer effect on the occurrence and development of CRC. In this study, early stage CRC was induced with 1,2-dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) for one month in an animal model, without and with propolis administration. The phenotypes of early stage CRC were evaluated by X-ray microcomputed tomography and histologic examination. The gut immunity of the tumor microenvironment was assessed by immunohistochemical staining for tumor-infiltrating lymphocytes (TILs) and further comparative quantification. We found that the characteristics of the CRC mice, including the body weight, tumor loading, and tumor dimensions, were significantly changed due to propolis administration. With further propolis administration, the CRC tissues of DMH/DSS-treated mice showed decreased cytokeratin 20 levels, a marker for intestinal epithelium differentiation. Additionally, the signal intensity and density of CD3+ and CD4+ TILs were significantly increased and fewer forkhead box protein P3 (FOXP3) lymphocytes were observed in the lamina propria. In conclusion, we found that propolis, a natural supplement, potentially prevented CRC progression by increasing CD3+ and CD4+ TILs and reducing FOXP3 lymphocytes in the tumor microenvironment of early stage CRC. Our study could suggest a promising role for propolis in complementary medicine as a food supplement to decrease or prevent CRC progression. [ABSTRACT FROM AUTHOR]

Background: Spirometric abnormalities have been related to incident heart failure in general population, who generally have preserved left ventricular ejection fraction (LVEF). We aimed to investigate the association between spirometric indices, cardiac functions and clinical outcomes. Methods: Subjects presenting with exertional dyspnoea and received spirometry and echocardiography were eligible for this study. Forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1)/FVC ratio were measured to define the spirometry patterns: normal (FEV1/FVC ≥ 70%, FVC ≥ 80%), obstructive (FEV1/FVC < 70%, FVC ≥ 80%), restrictive pattern (FEV1/FVC ≥ 70%, FVC < 80%) and mixed (FEV1/FVC < 70%, FVC < 80%). The diastolic dysfunction index (DDi) was the counts of the indicators, including septal e′ velocity <7 cm/s, septal E/e′ > 15, pulmonary artery systolic pressure > 35 mmHg and left atrial dimension >40 mm. Results: Among a total of 8669 participants (65.8 ± 16.3 years, 56% men), 3739 (43.1%), 829 (9.6%), 3050 (35.2%) and 1051 (12.1%) had normal, obstructive, restrictive and mixed spirometry pattern, respectively. Subjects with restrictive or mixed spirometry pattern had higher DDi and worse long‐term survival than those with obstructive or normal ventilation. FVC but not FEV1/FVC was predictive of 5‐year mortality, independent of age, sex, renal function, LVEF, DDi, body mass index, and comorbidities (hazard ratio, 95% confidence intervals:.981,.977–.985). Furthermore, there was an inverse nonlinear relationship between FVC and DDi, suggesting the declined FVC may mediate 43% of the prognostic hazard of left ventricular diastolic dysfunction. Conclusions: The restrictive spirometry pattern or the declined FVC was associated with left ventricular diastolic dysfunction, which aggravated the long‐term mortality in the ambulatory dyspnoeic subjects. [ABSTRACT FROM AUTHOR]

Hypertension-related death is the leading cause of mortality worldwide, making blood pressure (BP) control an important issue. Salt substitute is a non-pharmaceutical strategy to improve hypertension control. The goal of this study was to evaluate the effect of salt substitute on BP and cardiovascular disease. The authors searched the Cochrane Library and PubMed databases through March 2022, and assessed the risk-of-bias for included studies by the Cochrane risk-of-bias tool. Twenty-three randomized controlled trials with 32073 patients were included in our systematic review. A meta-analysis with random effects was performed to analyze the effects of salt substitute on systolic and diastolic BP, 24-h urinary sodium and potassium, and cardiovascular and all-cause mortality. In the random-effects model, participants consuming salt substitute showed significant reduction in systolic BP (mean difference (MD) -4.80 mmHg, 95% confidence interval (CI) -6.12 to -3.48, P < 0.0001) and diastolic BP (MD -1.48 mmHg, 95% CI -2.06 to -0.90, P < 0.0001) compared with participants consuming normal salt. In the urine electrolyte analysis, the salt substitute group had significant reduction in 24-h urine sodium (MD -22.96 mmol/24-h, P = 0.0001) and significant elevation in 24-h urine potassium (MD 14.41 mmol/24-h, P < 0.0001). Of the five studies with mortality outcome data, salt substitute significantly reduced all-cause mortality (hazard ratio 0.88, P = 0.0003). In conclusion, our analyses showed that salt substitute has a strong effect on lowering BP and reducing all-cause mortality. By modifying the daily diet with salt substitute, the authors can improve BP control by using this non-pharmaceutical management. [ABSTRACT FROM AUTHOR]

The present study investigated the prognostic values for office brachial (OB), office central (OC), and ambulatory daytime brachial (AmDB) hypertension, as defined by a unifying threshold of 130/80 mmHg, and the incremental value of either OC or AmDB hypertension to OB hypertension. A total of 1219 community residents without receiving anti‐hypertensive treatment (671 men and 548 women, aged ≥ 30 years old) from central Taiwan and Kinmen islands had OB, OC, and AmDB blood pressure measurements during a cardiovascular survey conducted in 1992–1993. OB hypertension, OC hypertension, and AmDB hypertension were all defined in retrospect at the threshold of 130/80 mmHg. They were followed up for nonfatal and fatal cardiovascular events until December 31, 2017, by linking the baseline database to the National Health Insurance Research dataset and the National Death Registry. During a follow‐up of 25 612.5 person‐years (Average event‐free time: 21.0 years), there were 368 fatal and nonfatal cardiovascular events. In multivariable analyses, OB hypertension, OC hypertension, and AmDB hypertension had similar hazard ratios for cardiovascular events [2.03, 95% confidence interval: 1.47‐2.80]; 1.92 (1.47‐2.51); and 1.79 (1.41‐2.29), respectively. Using OB normotension as the reference, either the concordant OB and OC hypertension [2.24 (1.61‐3.12)], or the concordant OB and AmDB hypertension [2.52 (1.80‐3.54)] was significantly associated with cardiovascular events. Moreover, OB hypertension plus AmDB normotension was also significantly associated with increased risk for cardiovascular events. We concluded that OB hypertension, OC hypertension, and AmDB hypertension defined by a unifying threshold of 130/80 mmHg may provide similar estimates of long‐term risk for cardiovascular events. Cross‐classification analyses suggest that addition of OC hypertension or AmDB hypertension may improve the prognostic value of OB hypertension. [ABSTRACT FROM AUTHOR]

Aim: To clarify the importance of HbA1c reduction and antidiabetic drug use in preventing major adverse cardiovascular events (MACE) for patients with type 2 diabetes (T2D). Materials and Methods: We conducted an updated systematic review of contemporary large randomized controlled trials assessing the relative efficacy and safety of antidiabetic drugs with less hypoglycaemia risk in adult T2D patients. Mixed‐effects meta‐regression was performed to examine the associations of HbA1c reduction with subsequent risk of macrovascular and microvascular events. We evaluated the potential mediating role of HbA1c reduction in the relationship between antidiabetic drugs and MACE. Results: Eighteen placebo‐controlled trials comprising 155 610 participants were included. The effects of treatment differed among antidiabetic drug classes for most adverse outcomes with high heterogeneity (I2: 63.7%‐95.8%). Mean HbA1c reduction was lowest with dipeptidyl peptidase‐4 inhibitors (0.30%), followed by sodium‐glucose co‐transporter‐2 inhibitors (0.46%), and was highest with glucagon‐like peptide‐1 receptor agonists (0.58%) and thiazolidinediones (0.60%). Lower relative risks of MACE were significantly associated with larger reductions in achieved HbA1c (β −0.3182; 95% CI: −0.5366 to −0.0998; P =.0043), even after adjusting for drug classes. When considering HbA1c lowering as a mediator to be controlled, beneficial effects owing to specific antidiabetic treatment for MACE were not observed (χ2 = 1.4494; P =.6940). The proportion mediated by HbA1c reduction was 50.0%‐63.5% for these antidiabetic agents. Conclusions: The main benefits of antidiabetic agents might result from the reduction in blood sugar levels and are generally independent of drugs used. Risk reduction in MACE was proportional to the magnitude of HbA1c decrease conferred by antidiabetic agents with less hypoglycaemic hazard. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is associated with dysbiosis and intestinal barrier dysfunction, as indicated by epithelial hyperpermeability and high levels of mucosal-associated bacteria. Changes in gut microbiota may be correlated with IBD pathogenesis. Additionally, microbe-based treatments could mitigate clinical IBD symptoms. Plasmon-activated water (PAW) is known to have an anti-inflammatory potential. In this work, we studied the association between the anti-inflammatory ability of PAW and intestinal microbes, thereby improving IBD treatment. We examined the PAW-induced changes in the colonic immune activity and microbiota of mice by immunohistochemistry and next generation sequencing, determined whether drinking PAW can mitigate IBD induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) and dysbiosis through mice animal models. The effects of specific probiotic species on mice with TNBS-induced IBD were also investigated. Experimental results indicated that PAW could change the local inflammation in the intestinal microenvironment. Moreover, the abundance of Akkermansia spp. was degraded in the TNBS-treated mice but elevated in the PAW-drinking mice. Daily rectal injection of Akkermansia muciniphila, a potential probiotic species in Akkermansia spp., also improved the health of the mice. Correspondingly, both PAW consumption and increasing the intestinal abundance of Akkermansia muciniphila can mitigate IBD in mice. These findings indicate that increasing the abundance of Akkermansia muciniphila in the gut through PAW consumption or other methods may mitigate IBD in mice with clinically significant IBD. [ABSTRACT FROM AUTHOR]

Aims: Impaired renal function (IRF) prevails in patients with acute heart failure. The study aimed to investigate the prevalence of on‐admission IRF and its association with short‐term and long‐term mortalities in patients hospitalized for HF with reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF) left ventricular ejection fraction (LVEF). Methods: Patients hospitalized for acute heart failure were enrolled and stratified by LVEF into three phenotypes as HFpEF (≥50%), HFmrEF (40–49%), and HFrEF (<40%). IRF was defined as an estimated glomerular filtration rate of ≤60 mL/min/1.73m2 on admission. National Death Registry was linked for the identification of mortality. Results: Of 2613 patients enrolled, 673 (25.7%) had HFrEF, 367 (14.0%) had HFmrEF, and 1573 (60.1%) had HFpEF, whereas IRF was prevalent among 63.7, 68.6, and 67.5% of them, respectively. IRF significantly correlated with higher long‐term mortality in each phenotype of HF. However, IRF was associated with 90‐day and 1‐year mortality in subjects with HFrEF and HFmrEF, but not HFpEF. After accounting for age, gender, hypertension, diabetes, coronary artery disease, atrial fibrillation, stroke, serum sodium, de novo heart failure, date of enrolment, and systolic blood pressure <90 mmHg or use of inotropic agents, IRF remained related to 5‐year mortality in patients with HFrEF (hazard ratio and 95% confidence interval: 1.346, 1.034–1.751), HFmrEF (2.210, 1.435–3.404), and HFpEF (1.493, 1.237–1.801). Conclusions: On‐admission IRF was independently predictive of long‐term mortality in patients hospitalized for HF, irrespective of HF phenotypes. Furthermore, IRF was also associated with short‐term mortality in HFrEF and HFmrEF, but not in HFpEF. [ABSTRACT FROM AUTHOR]

Use of prebiotics is a growing topic in healthcare. A lightweight molecule and water-soluble fiber ingredient, longish glucomannan hydrolysates (LGH), has been developed to improve the intestinal mucosal barrier and confer gut health benefits. This study aims to investigate the implications of continuous LGH intervening in intestinal epithelium integrity and protective immunity against chemical dextran sodium sulfate (DSS)-induced colitis. Twelve male BALB/c mice were randomly arranged into four groups. The LGH/DSS group had results in bodyweight variance, epithelial cell density, and aberrancy score as good as the LGH group, and both were equivalent to the control group. LGH consumption effectively protects the distal intestinal epithelium by activating innate T lymphocytes. Meanwhile, T-cell subsets in subepithelial interspersion take a bystander role in these microenvironmental alterations. Under this stress, the cluster of differentiation 3 (CD3)+ T cells infiltrate the epithelium, while CD4+ T cells inversely appear in submucosal large lymphoid aggregates/isolated lymphoid follicles (ILFs) in which significant CD3+, CD4+, and CD8+ T-cell populations agglomerate. Moreover, forkhead box P3 (Foxp3) and interleukin 17 (IL-17) are observed in these ILFs. Agglomerated CD4+ T-cell lineages may have roles with proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells in balancing responses to intraluminal antigens. Collectively, LGH administration may function in immune modulation to protect against DSS-induced inflammation. [ABSTRACT FROM AUTHOR]

Stem cell-based therapy has been evaluated in many different clinical trials for various diseases. This capability was applied in various neurodegenerative diseases, such as multiple sclerosis, which is characterized by demyelination, axonal injury, and neuronal loss. Dental pulp stem cells (DPSCs) are mesenchymal stem cells from the oral cavity that have been studied with potential application for the regeneration of different tissues. Heat shock protein 27 (HSP27) regulates neurogenesis in the process of neural differentiation of placenta multipotent stem cells. Here, we hypothesize that HSP27 expression is also critical for the neural differentiation of DPSCs. An evaluation of the possible role of HSP27 in the differentiation of DPSCs was performed using gene knockdown and neural immunofluorescent staining. We found that HSP27 played a role in the differentiation of DPSCs and that knockdown of HSP27 in DPSCs rendered cells to oligodendrocyte progenitors; i.e., small hairpin specific for HSP27 DPSCs exhibited NG2-positive immunoreactivity and gave rise to oligodendrocytes or type-2 astrocytes. This neural differentiation of DPSCs may have clinical significance in the treatment of patients with neurodegenerative diseases. In conclusion, our data provide an example of the oligodendrocyte differentiation of a DPSC model, which may be applied in human regenerative medicine. [ABSTRACT FROM AUTHOR]

Background: Facilitating the childbirth process is a global issue. Many strategies have been developed to cope with labor pain and improve the delivery experience and satisfaction of pregnant women. The results of different types of medical intervention on women's expectant pain have been varied. Therefore, this systematic review was aimed at summarizing the body of evidence regarding the effects of various non-pharmacological coping strategies for reducing labor pain. Methods: The review was conducted according to guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We systematically searched the articles published between 1989 and 2020 in six electronic databases: PubMed, MEDLINE, CINAHL, WOS, PsycARTICLES, and Airiti Library, and the reference lists of the Clinical Trial Registry. Twenty studies were identified, with eight eligible studies included in the Bayesian network meta-analysis. Results: Eight studies with 713 participants were included in the meta-analysis with nine different non-pharmacological strategies for reducing labor pain. The traditional meta-analysis demonstrated that the non-pharmacological coping strategies were effective in reducing labor pain. Of these interventional strategies, the ranking probabilities analysis of the network meta-analysis suggested that the Bonapace Method may be the most effective strategy in reducing labor pain, followed by acupressure. Conclusions: Non-pharmacological coping strategies can reduce labor pain while maintaining an effective and satisfactory delivery experience. This systematic review, by synthesizing the body of evidence, demonstrated that non-pharmacological coping strategies are effective in reducing labor pain. Furthermore, as demonstrated in the network meta-analysis, the Bonapace Method, modulating birth pain by involving the father, is the most effective non-pharmacological intervention for reducing labor pain. [ABSTRACT FROM AUTHOR]

Copyright of Acta Oto-Laryngologica is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sepsis is a state of host immune response triggered by virus or bacterial infection, in which the extent of regional and systemic inflammation and companion counter‐inflammatory reactions determines disease outcomes. Probiotics are known for the immunomodulatory effect on allergic disorders, but it is not clear whether the beneficiary effect extends to sepsis and increases survival. In this mouse model, we injected intraperitoneally lipopolysaccharides (LPS) to induce sepsis, and investigated whether the pretreatment of Lactobacillus rhamnosus GG (LGG) contributed to host survival and examined the alteration of the gut microbiota and blood cytokines/chemokines profile before sepsis induction. Four‐week‐old male BALB/c mice were divided into two groups: one group were fed daily with LGG as a dietary supplement for fourteen days, whereas the other group with sterile water. Before sepsis induction, some mice from each group were killed to collect stool in the intestine and blood for microbial metagenomic and cytokine/chemokine analyses, respectively, and the rest were monitored afterward for mortality. The relative abundance of several families in the gut microbiota after LGG treatment was altered as well as the ratio of Firmicutes/Bacteroidetes. In addition, several pro‐inflammatory cytokines such as G‐CSF, IL7, IL15, and MCP1 were lower in the LGG group than in the control group. The survival rate following LPS‐induced sepsis improved with LGG treatment. Our results indicated that dietary supplement of probiotic LGG improved survival from LPS‐induced sepsis, most likely through pre‐septic changes in the gut microbial constituents by LGG with reciprocal alteration of host immune system to a less reactive state to incoming pathogens. [ABSTRACT FROM AUTHOR]

The variability of blood pressure (BPV) has been suggested as a clinical indicator for cognitive dysfunction, yet the results from clinical studies are variable. This study investigated the relationship between BPV and the risk of cognitive decline or dementia. Bibliographic databases, including PubMed, Scopus, and Embase, were searched systematically for longitudinal cohort studies with BPV measurements and neuropsychological examinations or dementia diagnosis. A traditional meta‐analysis with subgroup analysis, and a further dose‐response meta‐analysis were conducted. Twenty cohort studies with 7 924 168 persons were included in this review. The results showed that a higher systolic BPV (SBPV), when measured with the coefficient of variation (SBP‐CV) or standard deviation (SBP‐SD), was associated with a higher risk of all‐cause dementia diagnosis but not incidence of cognitive decline on neuropsychological examinations. In subgroup analysis, the effect was more prominent when using BPV of shorter timeframes, during shorter follow‐ups, or among the elderly aged more than 65 years. No dose‐response relationship could be found. Our study suggested possible positive associations between SBPV and the risk of dementia. Further studies are required to validate these findings. [ABSTRACT FROM AUTHOR]

Abstract Background This study is to analyze promoter methylation of various tumor suppressor genes in different types of ovarian carcinoma and to identify potential therapeutic targets of ovarian clear cell adenocarcinoma (OCCA). Materials and methods The promoter methylation statuses of 40 genes in primary ovarian carcinomas including 47 clear- and 63 non-clear-cell type tissues, 6 OCCA cell lines, 29 benign ovarian endometriotic cysts, and 31 normal controls were analyzed by methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The MS-MLPA results were correlated with clinicopathological features and outcomes of 47 OCCA patients. Functions of the target genes were further explored by Western Blot Analysis, apoptosis assay, and caspase-3/7 activity analysis. Results Frequencies of methylated RASSF1A, CDH13, CACNA1A, HIN-1, and sFRP5 genes in OCCA tissues were significantly higher than those in non-OCCA cancerous tissues and benign endometriotic cysts. The expected OS for patients with methylated promoters of HIN-1 was significantly worse than those for patients without methylated HIN-1 (30% vs. 62%, p = 0.002). The HIN-1 gene was over-expressed in ES2 cells, a significant reduction in cell growth and induction of apoptosis, and increasing paclitaxel sensitivity by reducing phosphorylation of Akt were observed. Conclusions Methylation of HIN-1 promoter is a novel epigenetic biomarker associated with poor outcomes in OCCA patients. Ectopic expression of the HIN-1 gene increased paclitaxel sensitivity which is partly through Akt pathway.

Abstract Background Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and the leading cause of cancer death. The identification of genes related to CRC is important for the development of successful therapies and earlier diagnosis. Methods Molecular analysis of feces was evaluated as a potential method for CRC detection. Expression of a predicted protein with unknown function, KIAA0247, was found in feces evaluated using specific quantitative real-time polymerase chain reaction. Its cellular function was then analyzed using immunofluorescent staining and the changes in the cell cycle in response to 5-fluorouracil (5-FU) were assessed. Results Gastrointestinal tissues and peripheral blood lymphocytes ubiquitously expressed KIAA0247. 56 CRC patients fell into two group categories according to fecal KIAA0247 mRNA expression levels. The group with higher fecal KIAA0247 (n = 22; ≥ 0.4897) had a significantly greater five-year overall survival rate than the group with lower fecal KIAA0247 (n = 30; < 0.4897) (66.0 ± 11.6%; p = 0.035, log-rank test). Fecal expression of KIAA0247 inversely related to CRC tumor size (Kendall's tau-b = -0.202; p = 0.047). Immunofluorescent staining revealed that the cytoplasm of CRC cells evenly expresses KIAA0247 without 5-FU treatment, and KIAA0247 accumulates in the nucleus after 40 μM 5-FU treatment. In HCT116 p53-/- cells, which lack p53 cell cycle control, the proportion of cells in the G2/M phase was larger (13%) in KIAA0247-silent cells than in the respective shLuc control (10%) and KIAA0247-overexpressing cells (7%) after the addition of low dose (40 μM) 5-FU. Expression of three cyclin genes (cyclin A2, cyclin B1, and cyclin B2) also downregulated in the cells overexpressing KIAA0247. Conclusions This is the first description of a linkage between KIAA0247 and CRC. The study's data demonstrate overexpression of KIAA0247 associates with 5-FU therapeutic benefits, and also identify the clinical significance of fecal KIAA0247 in CRC.

Abstract Background Colorectal cancer (CRC) is one of the leading causes of malignant death worldwide. Because young age of onset is often considered a poor prognostic factor for CRC, it is important to identify the poor outcomes of CRC in a younger population and to consider an aggressive approach by implementing early treatment. Our aim was to specifically quantify the fecal cytokeratin 19 (CK19) transcript from CRC patients and investigate its correlation with clinical stage, tumor malignancy, and age. Methods The quantitation of fecal CK19 transcript was determined by a quantitative real-time reverse transcription polymerase chain in 129 CRC patients (45 younger than 60 years at diagnosis) and 85 healthy controls. The levels of CK19 protein were examined both in colonic cell lines and tissues. Results The analysis of 45 younger CRC patients (age ≤ 60 years) revealed that patients at the M1 stage had significantly higher expression levels of fecal CK19 mRNA when compared with healthy controls (p < 0.001) and patients at the M0 stage (p = 0.004). Additionally, the degree of consistency between the mean level of fecal CK19 mRNA and the distant metastatic rate in each age interval was up to 89% (p = 0.042). Conclusion These results indicate that high levels of fecal CK19 mRNA represent a potential marker for colorectal malignancy and for aggressive treatment of younger CRC patients.

Abstract Background Chromosome 22q11 deletion syndrome (22q11DS) causes a developmental disorder during the embryonic stage, usually because of hemizygous deletions. The clinical pictures of patients with 22q11DS vary because of polymorphisms: on average, approximately 93% of affected individuals have a de novo deletion of 22q11, and the rest have inherited the same deletion from a parent. Methods using multiple genetic markers are thus important for the accurate detection of these microdeletions. Methods We studied 12 babies suspected to carry 22q11DS and 18 age-matched healthy controls from unrelated Taiwanese families. We determined genomic variance using microarray-based comparative genomic hybridization (array-CGH), quantitative real-time polymerase chain reaction (qPCR) and multiplex ligation-dependent probe amplification (MLPA). Results Changes in genomic copy number were significantly associated with clinical manifestations for the classical criteria of 22q11DS using MPLA and qPCR (p < 0.01). An identical deletion was shown in three affected infants by MLPA. These reduced DNA dosages were also obtained partially using array-CGH and confirmed by qPCR but with some differences in deletion size. Conclusion Both MLPA and qPCR could produce a clearly defined range of deleted genomic DNA, whereas there must be a deleted genome that is not distinguishable using MLPA. These data demonstrate that such multiple genetic approaches are necessary for the unambiguous molecular detection of these types of complicated genomic syndromes.

Aims: Atrial fibrillation (AF) is a frequent comorbidity among patients with severe mitral regurgitation (MR). Direct current (DC) cardioversion is one of the strategies for rhythm control. However, the safety and feasibility of immediate DC cardioversion after MitraClip are not elucidated. Methods and Results: In this study, patients with symptomatic severe MR who underwent MitraClip were included. After fixing the MR, synchronized DC cardioversion was attempted for those with AF. A total of consecutive 60 patients, 36 subjects (60%), comorbid with AF. DC cardioversion was performed in 30 patients (mean age of 76.0 ± 9.3 years), and the successful conversion was achieved in 15 patients (50%). There was no any adverse event related to the cardioversion. Subjects with sustained conversion to SR experienced significant improvement in 6MWT (failed: 285 ± 110‐308 ± 135 m, P =.278; successful: 269 ± 109 m‐328 ± 78, P =.047) and reduction in NT‐proBNP level (failed: 4411 ± 7401‐3296 ± 4299 ng/mL, P =.217; successful: 4094 ± 2735‐2353 ± 2856 ng/mL, P =.026) at 1 month. Conclusions: Direct current cardioversion seemed to be safe and feasible immediately after the transcatheter edge‐to‐edge mitral valve repairs. Subjects who maintain SR experienced better functional improvement. [ABSTRACT FROM AUTHOR]

Aims: Volume overload and perturbations of pulsatile haemodynamics may precipitate acute heart failure (AHF). Nocturnal thoracic volume overload due to rostral fluid shift during recumbency undetected by daytime measures may impact nighttime haemodynamics and post‐discharge outcomes. Methods and results: A total of 63 patients (median 60 years, 79.4% men, and left ventricular ejection fraction 29.4%) hospitalized for AHF were enrolled. Once clinical euvolaemia was achieved, noninvasive pulsatile haemodynamics were assessed during daytime followed by circadian monitoring (6 p.m. to 5 a.m.) of thoracic fluid content and thoracic fluid content index (TFCi) using impedance cardiography, normalized electromechanical activation time ratio (EMAT%) using acoustic cardiography, and mean blood pressure using ambulatory blood pressure monitoring before discharge. The primary endpoints were composited of the first hospitalization for heart failure and death from any cause. Patients were also followed for the repeated heart failure hospitalizations. During a median follow‐up duration of 16 months, 33 patients encountered primary composite endpoints (52.4%), and there were 42 hospitalizations developed among 25 patients. An overnight increase in TFCi along with persistently prolonged EMAT% and low mean blood pressure was observed in the eventful group. Overnight increase in TFCi (ΔTFCi, the difference between the measures at 4 a.m. and 6 p.m.) was an independent predictor of primary composite events (hazard ratio and 95% confidence interval: 1.58, 1.07–2.33; P = 0.022) and recurrent composite events (2.22, 1.51–3.26; P < 0.001), after adjusting for potential confounding factors. A high ΔTFCi (≥0.5/kΩ/m2) significantly correlated with higher post‐discharge events (hazard ratio 6.25; 95% confidence interval 2.30–16.96; P < 0.001) in comparison with a low ΔTFCi (<0.5/kΩ/m2). ΔTFCi was significantly associated with EMAT%, estimated glomerular filtration rate, and left ventricular ejection fraction, but not with parameters of pulsatile haemodynamics. Conclusions: Nocturnal thoracic volume overload in AHF before discharge, indicating the presence of residual volume overload unidentified by daytime measures, may predict post‐discharge outcomes. [ABSTRACT FROM AUTHOR]

Background: The prognostic value of chronic obstructive pulmonary disease (COPD) as a comorbidity in heart failure has been well documented. However, the role of pulmonary function indices in patients with heart failure and preserved ejection fraction (HFpEF) remains to be elucidated. Methods: Subjects with HFpEF received pulmonary function tests and echocardiogram. Total lung capacity (TLC), residual volume (RV), forced expiratory flow rate between 25% and 75% of vital capacity (FEF25-75), forced expiratory volume in the 1st second (FEV1), forced vital capacity (FVC), and vital capacity (VC) were measured. Echocardiographic indices, including pulmonary artery systolic pressure (PASP), the ratio of early ventricular filling flow velocity to the septal mitral annulus tissue velocity (E/e'), and left ventricular mass (LVM), were recorded. National Death Registry was linked for the identification of mortality. Results: A total of 1194 patients (72.4±13.2 years, 59% men) were enrolled. PASP, E/e' and LVM were associated with either obstructive (RV/TLC, FEV1 and FEF25-75) or restrictive (VC and TLC) ventilatory indices. During a mean follow-up of 23.0±12.8 months, 182 patients died. Subjects with COPD had a lower survival rate than those without COPD. While VC, FVC, RV/TLC, and FEV1 were all independently associated with all-cause mortality in patients without COPD, only FEF25-75 was predictive of outcomes in those with COPD. Conclusions: The abnormalities of pulmonary function were related to the cardiac hemodynamics in patients with HFpEF. In addition, these ventilatory indices were independently associated with long-term mortality, especially in those without COPD. [ABSTRACT FROM AUTHOR]