Association of the oral microbiome with cognitive function among older adults: NHANES 2011-2012.

BACKGROUND: An association between the gut microbiome and cognitive function has been demonstrated in prior studies. However, whether the oral microbiome, the second largest microbial habitant in humans, has a role in cognition remains unclear. DESIGN, SETTING, PARTICIPANTS: Using weighted data from the 2011 to 2012 National Health and Nutrition Examination Survey, we examined the association between oral microbial composition and cognitive function in older adults. The oral microbiome was characterized by 16S ribosomal RNA gene sequencing. Cognitive status was assessed using the Consortium to Establish a Registry for Alzheimer's Disease immediate recall and delayed recall, Animal Fluency Test, and Digit Symbol Substitution Test (DSST). Subjective memory changes over 12 months were also assessed. Linear and logistic regression models were conducted to quantify the association of α-diversity with different cognitive measurements controlling for potential confounding variables. Differences in ß-diversity were analyzed using permutational analysis of variance. RESULTS: A total of 605 participants aged 60-69 years were included in the analysis. Oral microbial α-diversity was significantly and positively correlated with DSST (ß, 2.92; 95% CI, 1.01-4.84). Participants with higher oral microbial α-diversity were more likely to have better cognitive performance status based on DSST (adjusted odds ratio, 2.35; 95% CI, 1.28-4.30) and were less likely to experience subjective memory changes (adjusted odds ratio, 0.43; 95% CI, 0.25-0.74). In addition, ß-diversity was statistically significant for the cognitive performance status based on DSST (P = 0.031) and subjective memory changes (P = 0.023). CONCLUSIONS: Oral microbial composition was associated with executive function and subjective memory changes among older adults among older U.S. adults in a nationally representative population sample. Oral dysbiosis is a potential biomarker or therapeutic target for cognitive decline. Further work is needed to elucidate the mechanisms underpinning the association between the oral microbiome and cognitive function.

Quality of Life and Emotional Problems of COVID-19 Patients after Discharge: A One-Month Longitudinal Study.

AIM: The first coronavirus disease 2019 (COVID-19) outbreak in Taiwan occurred in May 2021 and many individuals were infected. All COVID-19 patients were quarantined in designated facilities until they fully recovered to prevent the spread of the disease. Prolonged quarantine could adversely affect these patients. In this study, we focused on investigating changes in the quality of life and mental health of individuals discharged from hospital after recovering from COVID-19. METHODS: This study employed a longitudinal design and surveyed individuals discharged from a teaching hospital in northern Taiwan in 2021 within one week of their discharge and again after one month. An online questionnaire comprising the participants' background, respiratory function (COPD Assessment Test), quality of life (WHOQoL-BREF), and emotional problems (DASS-21) was administered to the participants. RESULTS: A total of 56 participants actively took part in both surveys. We observed that participants with abnormal respiratory function had a lower physical and psychological quality of life, especially those with severe symptoms requiring endotracheal intubation during the treatment period of COVID-19. Additionally, approximately 30% of participants experienced anxiety problems throughout this study period. Finally, patients with COVID-19 symptoms exhibited a lower quality of life and higher levels of severe emotional problems. CONCLUSIONS: According to our findings, it is necessary to monitor and provide appropriate interventions for individuals who have recovered from COVID-19, especially those who experienced severe symptoms that required endotracheal intubation during COVID-19 treatment. These interventions, such as symptom management and psychological support, can help improve their quality of life and reduce emotional problems. Therefore, after the participants are discharged, hospitals should regularly track the patients' status and provide appropriate support or referrals to help these individuals. Otherwise, future research could include more participants and follow up with them for longer to investigate the longitudinal impact of COVID-19.

Corrected QT Interval and Outcomes of Dialysis Patients with Symptomatic Peripheral Artery Disease: A Prospective Cohort Study.

BACKGROUND: Peripheral artery disease (PAD) is common and associated with a higher risk of cardiovascular morbidity and mortality in dialysis patients. A longer corrected QT (QTc) interval has been associated with adverse cardiovascular events and mortality in the general population and patients with end-stage kidney disease. However, little evidence is available on the predictive value of QTc in dialysis patients with PAD. METHODS: We conducted a prospective cohort study of 356 dialysis patients with symptomatic PAD undergoing endovascular therapy. We performed the resting 12-lead electrocardiogram (ECG) at baseline. Cox regression analyses were used to assess the association of QTc with all-cause mortality and major adverse cardiovascular events (MACEs), defined as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. RESULTS: The mean age was 67.3 ± 11.5 years; 41.6% of participants were women. The median QTc was 471 (interquartile ranges 448-491) milliseconds (ms). During a median follow-up of 2.2 years, 188 (52.8%) patients died, and MACEs occurred in 119 (33.4%) patients. In multivariable-adjusted models, patients in tertile 3 of QTc levels had a significantly greater risk of all-cause mortality (hazard ratio [HR] 2.41, 95% confidence intervals [CI] 1.58-3.69) and MACEs (HR 1.90, 95% CI 1.15-3.13) than those in tertile 1. Similarly, each 10-ms increase in the baseline QTc predicted a higher risk of all-cause death (HR 1.15, 95% CI 1.09-1.21) and MACEs (HR 1.15, 95% CI 1.07-1.23). CONCLUSIONS: QTc prolongation was independently associated with adverse outcomes among dialysis patients with symptomatic PAD.

Association of Frailty With Nutritional Status in Patients With Chronic Kidney Disease.

OBJECTIVES: Frailty is commonly observed in patients with chronic kidney disease (CKD) and is associated with adverse outcomes. Protein-energy wasting (PEW), a state of decreased body stores of protein and energy fuels, may be associated with frailty. However, few data are available on the possible association between frailty and PEW in CKD. METHODS: We examined the association between frailty and nutritional status assessed using anthropometric and body composition measurements, serum albumin, handgrip strength, the Malnutrition Inflammation Score (MIS), and dietary protein and calorie intake in a cross-sectional analysis of nondialysis patients with CKD stages 3-5. Body composition was assessed using multifrequency bioelectrical impedance. Frailty was defined as a Clinical Frailty Scale ≥4. We performed logistic regression with different nutrition assessment tools as the main predictors and age, sex, comorbidity, estimated glomerular filtration rate (eGFR), and hemoglobin as covariates. RESULTS: A total of 157 patients (93 men and 64 women; mean age 64 years; diabetes prevalence 38.9%) with CKD (eGFR 24.4 ± 13.4 mL/min/1.73 m2) were included. Overall, 29.3% of patients were frail. Patients with frailty were older and had a significantly higher fat tissue index and MIS but a significantly lower lean tissue index, eGFR, hemoglobin value, serum albumin value, handgrip strength value, and dietary protein intake. In multivariate logistic regression analyses, a higher body mass index category (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.03-2.31), higher fat tissue index (OR, 1.15; 95% CI, 1.03-1.28), larger waist circumference (OR, 1.05; 95% CI, 1.01-1.09), reduced handgrip strength (OR, 2.70; 95% CI, 1.17-6.21), PEW defined by MIS ≥5 (OR, 3.49; 95% CI, 1.35-9.01), and dietary protein intake ≤0.8 g/kg/day (OR, 2.70; 95% CI, 1.18-6.19) were associated with higher odds of frailty. CONCLUSION: Frailty is associated with nutritional status in patients with CKD. A comprehensive nutrition assessment may allow the implementation of strategies to prevent or reduce frailty.

Humoral immune response to an mRNA-1273 booster after chAdOx1-nCoV-19-priming among patients undergoing hemodialysis.

Objectives: Patients who are undergoing dialysis due to end-stage kidney disease are susceptible to greater coronavirus disease 2019 (COVID-19) complications. While vaccination is seen as the most effective tactic against COVID-19, the dialysis population usually has impaired immune responses to vaccination. Owing to the global vaccine supply shortage in the early phase of the COVID-19 pandemic, hemodialysis patients in Taiwan were administered homologous ChAdOx1 nCoV-19/ChAdOx1 nCoV-19 at 12-week intervals, with a third booster shot of mRNA-1273 given 12 weeks after the second dose. We assessed the antibody responses of these patients to this extended-interval dosing protocol. Materials and Methods: A total of 168 hemodialysis patients (mean age: 67 ± 13 years) without prior COVID-19 infection were vaccinated between June 16, 2021, and January 5, 2022, and followed until February 10, 2022. The primary outcome was seroconversion with an antispike immunoglobulin G (IgG) antibody level ≥50 arbitrary units (AU)/mL at 4 weeks after the administration of an mRNA-1273 booster shot. The secondary outcome was the level of antispike IgG antibodies. Multivariable linear regression models were used to evaluate the associations between the baseline characteristics and the antispike IgG level. Results: A total of 163 (97.0%) patients reached the primary endpoint, with antibody levels after the third booster dose of mRNA-1273 being significantly higher than those after the second dose of ChAdOx1 nCoV-19 (median IgG titer 12,007 [4394-23,860] vs. 846 [interquartile range 295-2114] AU/mL; P < 0.001). Patients who were male, older, had a higher body mass index, had a lower total lymphocyte count, and used immunosuppressants had lower antibody levels. Conclusion: A third booster dose of mRNA-1273 after two consecutive priming doses of ChAdOx1 nCoV-19 with extended intervals resulted in adequate humoral immune responses among hemodialysis patients.

Dialysis Modality and Incident Stroke Among Patients With End-Stage Kidney Disease: A Registry-Based Cohort Study.

BACKGROUND: Patients with end-stage kidney disease undergoing dialysis are at significant risk of stroke. Whether dialysis modality is associated with cerebrovascular disease is unclear. This study compared the risk of incident stroke in patients undergoing peritoneal dialysis or hemodialysis. METHODS: Thirty-nine thousand five hundred forty-two patients without a history of stroke who initiated dialysis between January 1, 2010, and December 31, 2014 were retrospectively studied using Taiwan's National Health Insurance Research Database. We matched 3809 patients undergoing peritoneal dialysis (mean age 59±13 years; 46.5% women) and 11 427 patients undergoing hemodialysis (mean age 59±13 years; 47.3% women) by propensity score in a 1:3 ratio with follow-up through December 31, 2015. The primary outcome was incident acute ischemic stroke. Secondary outcomes included hemorrhagic stroke, acute coronary syndrome, and all-cause mortality. Cox proportional hazard models were conducted to determine hazard ratios of clinical outcomes according to the dialysis modality. RESULTS: During a median follow-up of 2.59 (interquartile range 1.50-3.93) years, acute ischemic stroke, hemorrhagic stroke, and acute coronary syndrome occurred in 783 (5.1%), 376 (2.5%), and 1350 (8.9%) patients, respectively. In a multivariable Cox model that accounted for the competing risk of death, acute ischemic stroke occurred more frequently in the peritoneal dialysis group than in the hemodialysis group (subdistribution hazard ratio, 1.32 [95% CI, 1.13-1.54]; P=0.0005). There were no significant treatment-related differences in the risk of hemorrhagic stroke (subdistribution hazard ratio, 0.89 [95% CI, 0.70-1.14]; P=0.3571) and acute coronary syndrome (subdistribution hazard ratio, 0.99 [95% CI, 0.88-1.12]; P=0.9080). Patients undergoing peritoneal dialysis were more likely to die from any cause than patients undergoing hemodialysis (adjusted hazard ratio, 1.24 [95% CI, 1.15-1.33]; P<0.0001). CONCLUSIONS: Peritoneal dialysis was associated with a significantly increased risk of acute ischemic stroke compared with hemodialysis. Further studies are needed to clarify whether more aggressive cerebrovascular preventive strategies might mitigate the excess risk for ischemic stroke among patients receiving peritoneal dialysis.

Anti-Inflammatory and Anti-Oxidative Effects of Polysaccharides Extracted from Unripe Carica papaya L. Fruit.

This study evaluated the antioxidative and anti-inflammatory activities of polysaccharides extracted from unripe Carica papaya L. (papaya) fruit. Three papaya polysaccharide (PP) fractions, namely PP-1, PP-2, and PP-3, with molecular weights of 2252, 2448, and 3741 kDa, containing abundant xylose, galacturonic acid, and mannose constituents, respectively, were obtained using diethylaminoethyl-Sepharose™ anion exchange chromatography. The antioxidant capacity of the PPs, hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay revealed that the PP-3 fraction had the highest antioxidant activity, with an EC50 (the concentration for 50% of the maximal effect) of 0.96 mg/mL, EC50 of 0.10 mg/mL, and Abs700 nm of 1.581 for the hydroxyl radical scavenging assay, ferrous ion-chelating assay, and reducing power assay, respectively. In addition, PP-3 significantly decreased reactive oxygen species production by 45.3%, NF-κB activation by 32.0%, and tumor necrosis factor-alpha and interleukin-6 generation by 33.5% and 34.4%, respectively, in H2O2-induced human epidermal keratinocytes. PP-3 exerts potent antioxidative and anti-inflammatory effects; thus, it is a potential biofunctional ingredient in the cosmetic industry.

Immunosenescence, gut dysbiosis, and chronic kidney disease: Interplay and implications for clinical management.

Immunosenescence refers to the immune system changes observed in individuals over 50 years old, characterized by diminished immune response and chronic inflammation. Recent investigations have highlighted similar immune alterations in patients with reduced kidney function. The immune system and kidney function have been found to be closely interconnected. Studies have shown that as kidney function declines, both innate and adaptive immunity are affected. Chronic kidney disease (CKD) patients exhibit decreased levels of naive and regular T cells, as well as naive and memory B cells, while memory T cell counts increase. Furthermore, research suggests that CKD and end-stage kidney disease (ESKD) patients experience early thymic dysfunction and heightened homeostatic proliferation of naive T cells. In addition to reduced thymic T cell production, CKD patients display shorter telomeres in both CD4+ and CD8+ T cells. Declining kidney function induces uremic conditions, which alter the intestinal metabolic environment and promote pathogen overgrowth while reducing diversity. This dysbiosis-driven imbalance in the gut microbiota can result in elevated production of uremic toxins, which, in turn, enter the systemic circulation due to compromised gut barrier function under uremic conditions. The accumulation of gut-derived uremic toxins exacerbates local and systemic kidney inflammation. Immune-mediated kidney damage occurs due to the activation of immune cells in the intestine as a consequence of dysbiosis, leading to the production of cytokines and soluble urokinase-type plasminogen activator receptor (suPAR), thereby contributing to kidney inflammation. In this review, we delve into the fundamental mechanisms of immunosenescence in CKD, encompassing alterations in adaptive immunity, gut dysbiosis, and an overview of the clinical findings pertaining to immunosenescence.

Association of diabetic retinopathy with risk of developing cardiovascular diseases in patients undergoing hemodialysis: A population-based cohort study.

BACKGROUND AND AIMS: While patients undergoing dialysis have substantially increased cardiovascular event rates compared with the general population, predicting individual risk remains difficult. Whether diabetic retinopathy (DR) is associated with cardiovascular diseases in this population is unclear. METHODS AND RESULTS: We conducted a nationwide cohort study of 27,686 incident hemodialysis patients with type 2 diabetes who were enrolled in Taiwan's National Health Insurance Research Database between January 1, 2010, and December 31, 2014, and had follow-up data until December 31, 2015. The primary outcome was a composite of macrovascular events, including acute coronary syndrome (ACS), acute ischemic stroke, and peripheral artery disease (PAD). A total of 10,537 (38.1%) patients had DR at baseline. We matched 9164 patients without DR (mean age, 63.7 years; 44.0% women) to 9164 patients with DR (mean age, 63.5 years; 43.8% women) by propensity score. During a median follow-up of 2.4 years, 5204 patients in the matched cohort experienced a primary outcome. The presence of DR was associated with a higher risk of a primary outcome (subdistribution hazard ratio [sHR] 1.07; 95% CI, 1.01-1.13), which reflected a higher risk of acute ischemic stroke (sHR 1.26; 95% CI, 1.14-1.39) and PAD (sHR 1.14; 95% CI, 1.05-1.25) but not ACS (sHR 0.99; 95% CI, 0.92-1.06). CONCLUSIONS: The presence of DR signifies an increased risk of acute ischemic stroke and PAD in hemodialysis patients with type 2 diabetes, independent of the known risk factors. These results highlight the need for more comprehensive cardiovascular assessment and management in hemodialysis patients with DR.