Modified stapled hemorrhoidopexy for lower postoperative stenosis: A five-year experience.

BACKGROUND: Stapled hemorrhoidopexy (SH) is currently a widely accepted method for treating the prolapse of internal hemorrhoids. Postoperative anal stenosis is a critical complication of SH. A remedy for this involves the removal of the circumferential staples of the anastomosis, followed by the creation of a hand-sewn anastomosis. Numerous studies have reported modified SH procedures to improve outcomes. We hypothesized that our modified SH technique may help reduce complications of anal stenosis after SH. AIM: To compare outcomes of staple removal at the 3- and 9-o'clock positions during modified SH in patients with mixed hemorrhoids. METHODS: This was a single-center, retrospective, observational study. Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1, 2015, and January 1, 2020, were included. The operation time, blood loss, length of hospital stay, and incidence of minor or major complications were recorded. RESULTS: Patients with grade III or IV hemorrhoids who underwent standard or modified SH at our colorectal center between January 1, 2015 and January 1, 2020, were included. Operation time, blood loss, length of hospital stay, and incidence of minor or major complications were recorded. We investigated 187 patients (mean age, 50.9 years) who had undergone our modified SH and 313 patients (mean age, 53.0 years) who had undergone standard SH. In the modified SH group, 54% of patients had previously undergone surgical intervention for hemorrhoids, compared with the 40.3% of patients in the standard SH group. The modified SH group included five (2.7%) patients with anal stenosis, while 21 (6.7%) patients in the standard SH group had complications of anal stenosis. There was a significant relationship between the rate of postoperative anal stenosis and the modified SH: 0.251 (0.085-0.741) and 0.211 (0.069-0.641) in multiple regression analysis. The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH. CONCLUSION: The modified SH technique is a safe surgical method for advanced grade hemorrhoids and might result in a lower rate of postoperative anal stenosis than standard SH.

Male Sex and Ageing are Independent Risk Factors for Sarcopenia Stage in Patients With Chronic Kidney Disease Not Yet on Dialysis.

BACKGROUND: The risk of sarcopenia in older adults with chronic kidney disease (CKD) not yet on dialysis is controversial. The aims of this study were to investigate the association among sarcopenia, diabetes and predialysis CKD and evaluate the impact of gender and ageing on the risk of sarcopenia statuses in older patients with predialysis CKD. METHODS: The participants aged ≥60 years old were recruited from the community of New Taipei City, Taiwan. Handgrip strength, appendicular skeletal muscle mass and the 6-m walk were measured. The diagnosis of sarcopenia was established based on the consensus of Asian Sarcopenia Working Group 2019. These older adults were categorised into G1, G2 and G3-5 according to the guidelines of Kidney Disease Improving Global Outcomes (KDIGO) after calculating the estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation. The Chi-square test and ANOVA were used to estimate the difference of categorical and continuous variables, respectively. Polytomous logistic regression was employed to assess the odds ratio (OR) and 95% confidence intervals (CIs) of the sarcopenia status and sarcopenia-associated risk factors in the predialysis CKD patients. All tests were two-sided, and p < 0.05 was defined as statistical significance. RESULTS: Among the 3648 older adults (mean age: 71.9 ± 6.07 years), including 1701 males and 1947 females, 870 (23.9%), 94 (2.58%) and 48 (1.32%) had possible sarcopenia, sarcopenia and severe sarcopenia, respectively. After adjustment, the risk for possible sarcopenia, sarcopenia and severe sarcopenia significantly increased with ageing (OR = 1.11, 1.10 and 1.23; 95% CI = 1.10-1.13, 1.07-1.15 and 1.18-1.30, respectively) and male gender (OR = 2.26, 20.3 and 25.4; 95% CI = 1.87-2.73, 11.5-36.0 and 11.3-57.2, respectively). Compared with KDIGO G1, no significant association between KDIGO G3-5 and the statuses of sarcopenia was observed (OR = 0.97, 0.88 and 0.91; 95% CI = 0.75-1.26, 0.43-1.78 and 0.37-2.27, p = 0.821, 0.718, 0.838, for possible sarcopenia, sarcopenia and severe sarcopenia, respectively). Ageing and male gender indicated a significant risk for higher sarcopenia status in older patients with predialysis CKD (0.027-fold/year and 0.284-fold, respectively) (p < 0.0001). CONCLUSIONS: This study illuminated the importance of the male sex and the ageing process on the risk of sarcopenia progression in patients with predialysis CKD. Early clinical screening and aggressive treatment for the prevention of higher sarcopenia status in advanced older male adults with predialysis CKD are recommended.

Sickle Cell Disease and Lead Poisoning in New York City, 2005-2019.

OBJECTIVES: Previous analyses of New York City (NYC) health department's lead registry indicated that, among children with lead poisoning, an increased prevalence of sickle cell disease (SCD) exists. However, SCD is not considered a risk factor for lead poisoning. We assessed the association between SCD and childhood lead poisoning to determine if specific lead poisoning prevention efforts are needed for children with SCD. METHODS: We analyzed NYC's lead registry data for children with venous blood lead levels (BLLs) ≥15 mcg/dL during 2005 to 2019. t tests and χ2 tests were performed to compare demographic characteristics, BLLs, and lead exposure risks in non-Hispanic Black children with and without SCD. A t test was used to compare observed SCD prevalence among Black children with BLLs ≥15 mcg/dL with an estimated 0.43% SCD prevalence among Black NYC children. RESULTS: Among 1728 Black children with BLLs ≥15 mcg/dL identified, 37 (2.14%) had SCD. When comparing children with and without SCD, both mean age at peak BLL (62.8 versus 42.7 months; P = .003) and peak BLL (42.59 versus 23.06 mcg/dL; P = .008) were higher for children with SCD. Among risk factors for lead exposure, children with SCD had higher prevalence of pica. Observed SCD prevalence was 1.71% higher than estimated SCD prevalence among Black NYC children (P < .001). CONCLUSIONS: We found a potential association between SCD and childhood lead poisoning. Pica emerged as a potentially important risk factor. Our findings might have implications for lead poisoning prevention guidelines for children with SCD.

ERBB2 is a potential diagnostic and prognostic biomarker in renal clear cell carcinoma.

Renal clear cell carcinoma (ccRCC) is a common parenchymal tumor of the kidney, and the discovery of biomarkers for early and effective diagnosis of ccRCC can improve the early diagnosis of patients and thus improve long-term survival. Erb-b2 receptor tyrosine kinase 2 (ERBB2) mediates the processes of cell proliferation, differentiation, and apoptosis inhibition. The purpose of this study was to investigate the diagnostic and prognostic role of ERBB2 in ccRCC. We analyzed the expression levels of ERBB2 in various cancers from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. RNA-seq data were analyzed using R packages to identify differentially expressed genes between the high and low ERBB2 expression groups in the TCGA-KIRC dataset. Spearman correlation analysis was performed to determine the correlation between ERBB2 expression and immune cell infiltration, immune checkpoint expression, and PTEN expression. DNA methylation changes and genetic alterations in ERBB2 were assessed using the MethSurv and cBioPortal databases. Logistic regression analysis was performed to determine the correlation between ERBB2 expression and the clinicopathological characteristics of ccRCC patients. The diagnostic and prognostic value of ERBB2 was assessed using Kaplan‒Meier (K‒M) survival curves, diagnostic ROC curves, time-dependent ROC curves, nomogram models, and Cox regression models. The expression level of ERBB2 is lower in tumor tissues of ccRCC patients than in the corresponding control tissues. Differentially expressed genes associated with ERBB2 were significantly enriched in the pathways "BMP2WNT4FOXO1 pathway in primary endometrial stromal cell differentiation" and "AMAN pathway". In ccRCC tissues, ERBB2 expression levels were associated with immune cell infiltration, immune checkpoints, and PTEN. The DNA methylation status of 10 CpG islands in the ERBB2 gene was associated with the prognosis of ccRCC. ERBB2 expression levels in ccRCC tissues were associated with race, sex, T stage, M stage, histological grade, and pathological stage. Cox regression analysis showed that ERBB2 was a potential independent predictor of overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in ccRCC patients. ROC curve analysis showed that the expression level of ERBB2 could accurately distinguish between ccRCC tissue and adjacent normal renal tissue. Our study showed that ERBB2 expression in ccRCC tissues can be of clinical importance as a potential diagnostic and prognostic biomarker.

Molecular mechanics studies of factors affecting overall rate in cascade reactions: Multi-enzyme colocalization and environment.

Millions of years of evolution have optimized many biosynthetic pathways by use of multi-step catalysis. In addition, multi-step metabolic pathways are commonly found in and on membrane-bound organelles in eukaryotic biochemistry. The fundamental mechanisms that facilitate these reaction processes provide strategies to bioengineer metabolic pathways in synthetic chemistry. Using Brownian dynamics simulations, here we modeled intermediate substrate transportation of colocalized yeast-ester biosynthesis enzymes on the membrane. The substrate acetate ion traveled from the pocket of aldehyde dehydrogenase to its target enzyme acetyl-CoA synthetase, then the substrate acetyl CoA diffused from Acs1 to the active site of the next enzyme, alcohol-O-acetyltransferase. Arranging two enzymes with the smallest inter-enzyme distance of 60 Å had the fastest average substrate association time as compared with anchoring enzymes with larger inter-enzyme distances. When the off-target side reactions were turned on, most substrates were lost, which suggests that native localization is necessary for efficient final product synthesis. We also evaluated the effects of intermolecular interactions, local substrate concentrations, and membrane environment to bring mechanistic insights into the colocalization pathways. The computation work demonstrates that creating spatially organized multi-enzymes on membranes can be an effective strategy to increase final product synthesis in bioengineering systems.

New insights on the phylogeny, evolutionary history, and ecological adaptation mechanism in cycle-cup oaks based on chloroplast genomes.

Cycle-cup oaks (Quercus section Cyclobalanopsis) are one of the principal components of forests in the tropical and subtropical climates of East and Southeast Asia. They have experienced relatively recent increases in the diversification rate, driven by changing climates and the Himalayan orogeny. However, the evolutionary history and adaptive mechanisms at the chloroplast genome level in cycle-cup oaks remain largely unknown. Therefore, we studied this problem by conducting chloroplast genomics on 50 of the ca. 90 species. Comparative genomics and other analyses showed that Quercus section Cyclobalanopsis had a highly conserved chloroplast genome structure. Highly divergent regions, such as the ndhF and ycf1 gene regions and the petN-psbM and rpoB-trnC-GCA intergenic spacer regions, provided potential molecular markers for subsequent analysis. The chloroplast phylogenomic tree indicated that Quercus section Cyclobalanopsis was not monophyletic, which mixed with the other two sections of subgenus Cerris. The reconstruction of ancestral aera inferred that Palaeotropics was the most likely ancestral range of Quercus section Cyclobalanopsis, and then dispersed to Sino-Japan and Sino-Himalaya. Positive selection analysis showed that the photosystem genes had the lowest ω values among the seven functional gene groups. And nine protein-coding genes containing sites for positive selection: ndhA, ndhD, ndhF, ndhH, rbcL, rpl32, accD, ycf1, and ycf2. This series of analyses together revealed the phylogeny, evolutionary history, and ecological adaptation mechanism of the chloroplast genome of Quercus section Cyclobalanopsis in the long river of earth history. These chloroplast genome data provide valuable information for deep insights into phylogenetic relationships and intraspecific diversity in Quercus.

2024 Guidelines of the Taiwan Society of Cardiology on the Primary Prevention of Atherosclerotic Cardiovascular Disease --- Part I.

Atherosclerotic cardiovascular disease (ASCVD) is one of the leading causes of death worldwide and in Taiwan. It is highly prevalent and has a tremendous impact on global health. Therefore, the Taiwan Society of Cardiology developed these best-evidence preventive guidelines for decision-making in clinical practice involving aspects of primordial prevention including national policies, promotion of health education, primary prevention of clinical risk factors, and management and control of clinical risk factors. These guidelines cover the full spectrum of ASCVD, including chronic coronary syndrome, acute coronary syndrome, cerebrovascular disease, peripheral artery disease, and aortic aneurysm. In order to enhance medical education and health promotion not only for physicians but also for the general public, we propose a slogan (2H2L) for the primary prevention of ASCVD on the basis of the essential role of healthy dietary pattern and lifestyles: "Healthy Diet and Healthy Lifestyles to Help Your Life and Save Your Lives". We also propose an acronym of the modifiable risk factors/enhancers and relevant strategies to facilitate memory: " ABC2D2EFG-I'M2 ACE": Adiposity, Blood pressure, Cholesterol and Cigarette smoking, Diabetes mellitus and Dietary pattern, Exercise, Frailty, Gout/hyperuricemia, Inflammation/infection, Metabolic syndrome and Metabolic dysfunction-associated fatty liver disease, Atmosphere (environment), Chronic kidney disease, and Easy life (sleep well and no stress). Some imaging studies can be risk enhancers. Some risk factors/clinical conditions are deemed to be preventable, and healthy dietary pattern, physical activity, and body weight control remain the cornerstone of the preventive strategy.

Impact of Abnormal Ankle Brachial Index on Sepsis Survival: One-Year Prospective Study Results.

Background: Lower extremity peripheral artery disease (LE-PAD) has been linked to unfavorable cardiovascular outcomes. The impact of potentially undiagnosed LE-PAD, suspected by abnormal ankle-brachial index (ABI), on the survival of sepsis patients admitted to the intensive care unit (ICU) remains uncertain. Methods: We conducted a prospective cohort study and recruited adult patients admitted to the ICU with a primary diagnosis of sepsis (defined by a quick Sepsis-Related Organ Failure Assessment score of ≥ 2) between November 23, 2017 and July 22, 2018. ABI measurements were obtained within 24 hours of admission. The study compared the 30-day and 1-year all-cause mortality rates as well as the incidence of major adverse cardiovascular events (MACEs) between the groups with normal and abnormal ABI values. Results: Of the 102 sepsis patients admitted to the ICU, 38 (37%) were diagnosed with LE-PAD based on their ABI measurements. The overall 30-day mortality rate was 30.0% in patients with LE-PAD and 25.8% in those with normal ABI (p = 0.56). At 1 year, the overall mortality rate was 52.6% in the patients with abnormal ABI and 40.6% in those with normal ABI (p = 0.24). Additionally, the incidence of MACEs was significantly higher in the patients with abnormal ABI compared to those with normal ABI at 1-year follow-up (21.1% vs. 3.1%, respectively; p = 0.003). Conclusions: The patients with abnormal ABI had a higher incidence of MACEs within one year following hospital discharge. Future studies are needed to improve cardiovascular outcomes among sepsis survivors (ClinicalTrials.gov number, NCT03372330).

2024 Update of the TSOC Expert Consensus of Fabry Disease.

As an X-linked inherited lysosomal storage disease that is caused by α-galactosidase A gene variants resulting in progressive accumulation of pathogenic glycosphingolipid (Gb3) accumulation in multiple tissues and organs, Fabry disease (FD) can be classified into classic or late-onset phenotypes. In classic phenotype patients, α-galactosidase A activity is absent or severely reduced, resulting in a more progressive disease course with multi-systemic involvement. Conversely, late-onset phenotype, often with missense variants (e.g., IVS4+919G>A) in Taiwan, may present with a more chronic clinical course with predominant cardiac involvement (cardiac subtype), as they tend to have residual enzyme activity, remaining asymptomatic or clinically silent during childhood and adolescence. In either form, cardiac hypertrophy remains the most common feature of cardiac involvement, potentially leading to myocardial fibrosis, arrhythmias, and heart failure. Diagnosis is established through α-galactosidase enzyme activity assessment or biomarker analyisis (globotriaosylsphingosine, Lyso-Gb3), advanced imaging modalities (echocardiography and cardiac magnetic resonance imaging), and genotyping to differentiate FD from other cardiomyopathy. Successful therapeutic response relies on early recognition and by disease awareness from typical features in classic phenotype and cardiac red flags in cardiac variants for timely therapeutic interventions. Recent advances in pharmacological approach including enzyme replacement therapy (agalsidase alfa or beta), oral chaperone therapy (migalastat), and substrate reduction therapy (venglustat) aim to prevent from irreversible organ damage. Genotype- and gender-based monitoring of treatment effects through biomarker (Lyso-Gb3), renal assessment, and cardiac responses using advanced imaging modalities are key steps to optimizing patient care in FD.

The relationship between mindfulness and empathy with the oxytocinergic system in persons with schizophrenia spectrum disorders - A proof-of-concept randomized controlled trial (OXYGEN).

Background: The present study explored the feasibility and acceptability as well as the impact of mindfulness-based group therapy (MBGT) on oxytocin levels (OXT) and clinical parameters in outpatients with schizophrenia spectrum disorders (SSD). Methods: In a randomized-controlled design, outpatients with SSD (N = 48) were assigned to either MBGT in addition to German university-level treatment as usual (MBGT+TAU; n = 25) or TAU (n = 23). At baseline and at four-week post-intervention, clinical parameters and OXT levels were determined. Results: Results indicate high feasibility and acceptance with a 95.7% adherence- and 94% retention- rate of MBGT in SSD. While no significant changes in empathy were observed, MBGT+TAU demonstrated a significant reduction in positive symptoms (Positive and Negative Syndrom Scale) compared to TAU at post-intervention. OXT levels were significantly increased in MBGT+TAU at post-intervention, suggesting a potential link between mindfulness and the oxytocinergic system in SSD. Additionally, improvements in various clinical parameters were indicated. Conclusion: The study contributes to the growing evidence supporting feasibility, acceptability, and positive effects of MBGT in outpatients with SSD, emphasizing the need for further research to solidify these findings. Overall, this work sheds first evidence on the intersection of mindfulness, oxytocin, and clinical outcomes in SSD.