Disease Patients Research Articles

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Modified Rankin Scale Disability Status at Day 4 Poststroke is an Informative Predictor of Long-Term Day 90 Outcome.

Long-term disability after stroke is standardly assessed 3 months post-onset, using the modified Rankin Scale (mRS). The value of an early, day 4 mRS assessment for projecting the 3-month disability outcome has not been formally investigated. In this cohort of patients with acute cerebral ischemia and intracranial hemorrhage, we analyzed day 4 and day 90 mRS assessments in the NIH Field Administration of Stroke Therapy- Magnesium (FAST-MAG) Phase 3 trial. The performance of day 4 mRS, alone and as part of multivariate models, in predicting day 90 mRS was assessed using correlation coefficients, percent agreement, and the kappa statistics. Among the 1573 acute cerebrovascular disease (ACVD) patients, 1206 (76.7%) had acute cerebral ischemia (ACI), while 367 (23.3%) had intracranial hemorrhage. Among all 1573 ACVD patients, day 4 mRS and day 90 mRS correlated strongly, Spearman's rho=0.79, in unadjusted analysis with weighted kappa of 0.59. For dichotomized outcomes, simple carry-forward of the day 4 mRS performed fairly well in agreeing with day 90 mRS: mRS 0-1 (kappa=0.67), 85.4%; mRS 0-2 (k=0.59), 79.5%; fatal outcome, 88% (k=0.33). Correlations of 4d and 90d mRS were stronger for ACI than ICH patients, 0.76 vs 0.71. In this acute cerebrovascular disease patient cohort, assessment of global disability performed on day 4 is highly informative regarding long-term, 3-month mRS disability outcome, alone, and even more strongly in combination with baseline prognostic variables. The day 4 mRS is a useful measure for imputing the final patient disability outcome in clinical trials and quality improvement programs.

Novel genes involved in vascular dysfunction of the middle temporal gyrus in Alzheimer's disease: transcriptomics combined with machine learning analysis.

Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease. The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease. Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discovery of novel targets for intervention. We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls, revealing obvious changes in vascular function. CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients, with altered intercellular communication of endothelial cells and pericytes being the most prominent. Differentially expressed genes were also identified. Using the CellChat results, AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor (VEGF)A-VEGF receptor (VEGFR) 2 pathway. AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity. Two subtypes of middle temporal gyrus cells showed significant alteration in AD: endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4 (ERBB4high) and pericytes with high expression of angiopoietin-like 4 (ANGPTL4high). Finally, combining bulk RNA sequencing data and two machine learning algorithms (least absolute shrinkage and selection operator and random forest), four characteristic Alzheimer's disease feature genes were identified: somatostatin (SST), protein tyrosine phosphatase non-receptor type 3 (PTPN3), glutinase (GL3), and tropomyosin 3 (PTM3). These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway. Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus. In conclusion, this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease. These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.

Spiking Laguerre Volterra networks—predicting neuronal activity from local field potentials

Objective. Understanding the generative mechanism between local field potentials (LFP) and neuronal spiking activity is a crucial step for understanding information processing in the brain. Up to now, most approaches have relied on simply quantifying the coupling between LFP and spikes. However, very few have managed to predict the exact timing of spike occurrence based on LFP variations. Approach. Here, we fill this gap by proposing novel spiking Laguerre–Volterra network (sLVN) models to describe the dynamic LFP-spike relationship. Compared to conventional artificial neural networks, the sLVNs are interpretable models that provide explainable features of the underlying dynamics. Main results. The proposed networks were applied on extracellular microelectrode recordings of Parkinson’s Disease patients during deep brain stimulation (DBS) surgery. Based on the predictability of the LFP-spike pairs, we detected three neuronal populations with unique signal characteristics and sLVN model features. Significance. These clusters were indirectly associated with motor score improvement following DBS surgery, warranting further investigation into the potential of spiking activity predictability as an intraoperative biomarker for optimal DBS lead placement.

A radiomics approach for predicting gait freezing in Parkinson's disease based on resting-state functional magnetic resonance imaging indices: a cross-sectional study.

Freezing of gait is a significant and debilitating motor symptom often observed in individuals with Parkinson's disease. Resting-state functional magnetic resonance imaging, along with its multi-level feature indices, has provided a fresh perspective and valuable insight into the study of freezing of gait in Parkinson's disease. It has been revealed that Parkinson's disease is accompanied by widespread irregularities in inherent brain network activity. However, the effective integration of the multi-level indices of resting-state functional magnetic resonance imaging into clinical settings for the diagnosis of freezing of gait in Parkinson's disease remains a challenge. Although previous studies have demonstrated that radiomics can extract optimal features as biomarkers to identify or predict diseases, a knowledge gap still exists in the field of freezing of gait in Parkinson's disease. This cross-sectional study aimed to evaluate the ability of radiomics features based on multi-level indices of resting-state functional magnetic resonance imaging, along with clinical features, to distinguish between Parkinson's disease patients with and without freezing of gait. We recruited 28 patients with Parkinson's disease who had freezing of gait (15 men and 13 women, average age 63 years) and 30 patients with Parkinson's disease who had no freezing of gait (16 men and 14 women, average age 64 years). Magnetic resonance imaging scans were obtained using a 3.0T scanner to extract the mean amplitude of low-frequency fluctuations, mean regional homogeneity, and degree centrality. Neurological and clinical characteristics were also evaluated. We used the least absolute shrinkage and selection operator algorithm to extract features and established feedforward neural network models based solely on resting-state functional magnetic resonance imaging indicators. We then performed predictive analysis of three distinct groups based on resting-state functional magnetic resonance imaging indicators indicators combined with clinical features. Subsequently, we conducted 100 additional five-fold cross-validations to determine the most effective model for each classification task and evaluated the performance of the model using the area under the receiver operating characteristic curve. The results showed that when differentiating patients with Parkinson's disease who had freezing of gait from those who did not have freezing of gait, or from healthy controls, the models using only the mean regional homogeneity values achieved the highest area under the receiver operating characteristic curve values of 0.750 (with an accuracy of 70.9%) and 0.759 (with an accuracy of 65.3%), respectively. When classifying patients with Parkinson's disease who had freezing of gait from those who had no freezing of gait, the model using the mean amplitude of low-frequency fluctuation values combined with two clinical features achieved the highest area under the receiver operating characteristic curve of 0.847 (with an accuracy of 74.3%). The most significant features for patients with Parkinson's disease who had freezing of gait were amplitude of low-frequency fluctuation alterations in the left parahippocampal gyrus and two clinical characteristics: Montreal Cognitive Assessment and Hamilton Depression Scale scores. Our findings suggest that radiomics features derived from resting-state functional magnetic resonance imaging indices and clinical information can serve as valuable indices for the identification of freezing of gait in Parkinson's disease.

Comparison of outcomes in small bowel surgery for Crohn’s disease: a retrospective NSQIP review

IntroductionDespite advances in medical therapy, approximately 33% of Crohn’s disease (CD) patients will need surgery within 5 years after initial diagnosis. Several surgical approaches to CD have been proposed including small bowel resection, strictureplasty, and combined surgery with resection plus strictureplasty. Here, we utilize the American College of Surgeons (ACS) national surgical quality registry (NSQIP) to perform a comprehensive analysis of 30-day outcomes between these three surgical approaches for CD.MethodsThe authors queried the ACS-NSQIP database between 2015 and 2020 for all patients undergoing open or laparoscopic resection of small bowel or strictureplasty for CD using CPT and IC-CM 10. Outcomes of interest included length of stay, discharge disposition, wound complications, 30-day related readmission, and reoperation.ResultsA total of 2578 patients were identified; 87% of patients underwent small bowel resection, 5% resection with strictureplasty, and 8% strictureplasty alone. Resection plus strictureplasty (combined surgery) was associated with the longest operative time (p = 0.002). Patients undergoing small bowel resection had the longest length of hospital stay (p = 0.030) and the highest incidence of superficial/deep wound infection (44%, p = 0.003) as well as the highest incidence of sepsis (3.5%, p = 0.03). Small bowel resection was found to be associated with higher odds of wound complication compared to combined surgery (OR 2.09, p = 0.024) and strictureplasty (1.9, p = 0.005).ConclusionOur study shows that various surgical approaches for CD are associated with comparable outcomes in 30-day related reoperation and readmission, or disposition following surgery between all three surgical approaches. However, small bowel resection displayed higher odds of developing post-operative wound complications.

Description of Pre-Hemodialysis Serum Phosphate in Late-Stage Kidney Disease Patients of Productive Age (15-64 Years) at the Indonesian Christian University General Hospital

In Indonesia, end-stage kidney disease is still a health problem that needs attention. End-stage kidney disease or abbreviated as PGTA reflects the fifth stage of chronic kidney disease, at this stage, there is a buildup of toxins, fluids, electrolytes, and the remains of the body's metabolism. In stage 5 chronic kidney disease, the glomerular filtration rate decreases < 15 ml/minute / 1.73 m2 and has occurred for 3 months or more. One of the clinical complications of end-stage renal disease is an increase in phosphate levels in the patient's blood serum (hyperphosphatemia), this occurs due to disruption of the kidney's phosphate excretion function. Hyperphosphatemia in PGTA patients can result in hyperparathyroidism, soft tissue, and cardiovascular calcification, and affect bone mineral disorders. In kidney disease patients with a glomerular filtration rate < 30 ml/minute / 1.73m2, the prevalence of hyperphosphatemia complications increased to 23%. This study aims to determine the description of pre-hemodialysis inorganic phosphate levels in the serum of PGTA patients of productive age (15-64 years) undergoing hemodialysis at the Indonesian Christian University General Hospital for the period January 2022. The research conducted was a descriptive study, to determine the description of phosphate levels serum of PGTA patients. The data used in this study is primary data by directly taking the blood of 20 pre-hemodialysis patients with end-stage kidney disease and then examining it in the laboratory. In this study, the results showed that 10 PGTA patients (50%) experienced an increase in serum inorganic phosphate levels above normal (>5 mg/dl). Meanwhile, 9 people (45%) had normal serum phosphate levels (2.5 - 5 mg/dl), and 1 other person had below normal serum phosphate levels (<2.5 mg/dl). Keywords: Inorganic Phosphate, Hemodialysis, Hyperphosphatemia, End Stage Renal Disease

Impact of eccentric cycling in coronary rehabilitation program: a pragmatic randomized controlled trial versus conventional rehabilitation.

This randomized controlled trial examined the feasibility of adding eccentric exercise to a conventional cardiac rehabilitation program (CCRP) for coronary heart disease patients. Ninety-three patients were randomly assigned to either the MIX group (eccentric ergometer + CCRP) or the CON group (concentric ergometer + CCRP) for 7 weeks. Training effectiveness was assessed based on "good responders" showing improved functional capacities, such as 6-minute walk test (6MWT) distance and maximal voluntary contraction of the plantar flexors (ankle MVC). Safety was monitored with a visual analog scale for muscle soreness, perceived exertion, and heart rate during training. The proportion of good responders was similar between groups (26% in MIX, 29% in CON, P=0.744). Both groups improved in 6MWT (CON: 12.6%, MIX: 16.14%) and ankle MVC (CON: 15.5%, MIX: 11.30%), with no significant differences. Exercise tolerance did not differ significantly between the groups, but perceived effort was significantly lower in the MIX group (P<0.0001) compared to the CON group. Integrating eccentric exercise into cardiac rehabilitation is safe and well-tolerated. Nevertheless, this study did not find significant advantages over conventional programs for coronary heart disease patients. Further research should explore specific patient groups or conditions where eccentric exercise may be more beneficial, emphasizing personalized prescriptions and gradual workload progression for better cardiac rehabilitation outcomes.

Non-alcoholic Fatty Liver Disease in Overweight and Obese Children; Can Ultrasonography Substitute Laboratory Studies? A Case-Control Study

Background: Non-alcoholic fatty liver disease (NAFLD) comprises a large burden on the global healthcare system with a high prevalence and lethal outcomes. Moreover, this disease is showing an incremental trend over time, partly due to the rise in obesity rates among children. Objectives: In this study, we aimed to elucidate the correlation of ultrasonographic and laboratory-assisted diagnosis of NAFLD in obese and normal-weight children. Methods: This study assessed 50 pediatric obese or overweight children with BMIs higher than the 85th percentile for their age and sex, as well as 50 age-and sex-matched control counterparts using ultrasonography and a liver enzyme panel. The prevalence of NAFLD and the differences in lab studies were evaluated. Then, receiver operating characteristics (ROC) curves were used to determine the optimal cut-off value for NAFLD based on liver enzymes. Results: A total of 100 participants were included in this study, 58% of whom were male. The mean age of the participants was 10.41 ± 2.224 years. The prevalence of sonographically diagnosed NAFLD in obese and overweight children was 34.0% (95% CI: 21.2% - 48.8%). The prevalence of NAFLD when assessed by lab values in this population was 58.0% (95% CI: 43.2% - 71.8%), with a low measure of agreement (K = 0.239, P = 0.058). High BMI increased the risk of NAFLD to about 8.5 times its baseline in the normal-BMI population. Non-alcoholic fatty liver disease patients had significantly higher values for aspartate aminotransferase (AST) (P &lt; 0.001), alanine aminotransferase (ALT) (P &lt; 0.001), and gamma-glutamyl transferase (GGT) (P &lt; 0.001), but not alkaline phosphatase (ALP) (P = 0.743). The ROC curves for AST, ALT, GGT, and BMI percentile had areas of 0.800, 0.899, 0.807, and 0.874, respectively, all of which could be used for screening NAFLD. A cut-off value of 43.5 IU/L for AST had a specificity and positive predictive value of 100% for the diagnosis of NAFLD in children. Conclusions: Obese and overweight children are 8.5 times more likely to develop NAFLD compared to their normal-BMI peers. For the evaluation of this disease, liver enzyme panels integrated with ultrasonographic assessment should be utilized.

Cardiovascular Care and Research in the Asia-Pacific Region during the COVID-19 Pandemic: Insights from Early and Mid-career Physicians

Background: The COVID-19 pandemic imposed a significant burden on healthcare systems in the Asia-Pacific region and has had a varying impact on physicians at different stages of their career. This study sought to evaluate the personal perspectives and the experiences of early and mid-career cardiologists and cardiothoracic surgeons with regard to the impact of the pandemic in the region. Methods: A cross-sectional web-based survey was conducted from June to July 2023 among members of the Asian Pacific Society of Cardiology (APSC) young community. The survey aimed to assess the impact of COVID-19 on cardiovascular clinical care and research activities that contained sections on demographic information, pandemic-related clinical and research experiences, personal stories, and interest in long-COVID research. Results: Overall, 60 physicians (44%) in the APSC young community responded to the survey. Cardiovascular disease patient numbers initially dropped in 2020 during the pandemic’s early stages but gradually increased in the following 3 years. Non-cardiovascular patient care workloads also rose during the first 2 years of the pandemic. Respondents observed notable changes in clinical care, research and personal life. Positive aspects included increased adaptability and telemedicine adoption, while challenges involved higher workloads and stress. More than 70% expressed interest in understanding the impact of long COVID, with Southeast Asian members showing the highest levels of interest. Conclusion: This survey conducted in the aftermath of the pandemic shed light on the challenges experienced by early to mid-career Asia-Pacific cardiovascular physicians. Physicians at this career stage encounter distinctive hurdles that require thoughtful consideration and effective solutions.

Construction of cirRNA-miRNA-mRNA network and MAPK1 protein signaling pathway in patients with valvular disease affected by artificial heart valve replacement surgery

The progress of modern medical technology has made artificial heart valve replacement an effective means to treat valvular disease, but the impact of cardiac function on patients after surgery is still a key issue. The purpose of this study was to construct the cirRNA-miRNA-mRNA network after artificial heart valve replacement in valvular disease patients, and to explore the regulatory mechanism related to MAPK1 protein, so as to reveal its potential role in affecting cardiac function. We downloaded cyclic cRNA expression profiles from the GEO database. Use the limma package to identify dec. WGCNA is used to identify key modules of circular rna. The target miRNAs of circular rna and the corresponding target genes of miRNAs were screened by ring intertome and target scan database. GO and KEGG analysis using the DAVID database. The genes associated with iron sag disease were derived from FerrDb database. The overlapping genes were obtained by Wien analysis. Next, the CircrNa-mirNa-mrna network was constructed based on the circRNA-miRNA pair and miRNA-mRNA pair and their cyclic landscape software. This study revealed the changes in the structure and expression of MAPK1 protein in the cirRNA-miRNA-mRNA network after artificial heart valve replacement in valvular disease patients, suggesting the potential role of MAPK1 protein in regulating cardiac function, and laying a foundation for further revealing its mechanism and clinical application.

Genome editing in K562 cells suggests a functional role for the XmnI Gg polymorphism: a widely used genetic marker in β-thalassemia and sickle cell disease patients.

The XmnI Gg -158 C/T polymorphism has been widely associated with fetal hemoglobin (HbF) levels, the severity of disease, and the response to the drug hydroxyurea (HU) in both β-thalassemia (β-thal) and sickle cell disease (SCD) patients. However, the functional significance of this single nucleotide polymorphism (SNP) remains unclear. To gain insight, green fluorescence protein (GFP) cassettes harboring the XmnI C or T alleles in their left homology arms (i.e. Gg promoters) were knocked into the Gg gene(s) of K562 cells via CRISPR/Cas9. Subsequently, the GFP fluorescence levels were compared in the ensuing cell populations and isolated clones. In both instances, median fluorescence intensities (MFI) of the knockin cells having the inserted XmnI T allele were higher than those having the XmnI C allele. Our results suggest that the XmnI T allele can increase Gg expression in K562 cells. The possible functional significance of the XmnI Gg -158 C/T polymorphism provides a rationale for the aforementioned associations. Furthermore, the XmnI polymorphism as a functional SNP substantiates its importance as a prognostic marker.

Growth differentiation factor-15 predicts all-cause death and major adverse cardiovascular events in patients with coronary heart disease: a prospective cohort study.

The prognostic value of growth differentiation factor-15 (GDF-15) in predicting long-term adverse outcomes in coronary heart disease (CHD) patients remains limited. Our study examines the association between GDF-15 and adverse outcomes over an extended period in CHD patients and firstly assesses the incremental prognostic effect of incorporating GDF-15 into the Framingham risk score (FRS)-based model. This single-center prospective cohort study included 3,321 patients with CHD categorized into 2,479 acute coronary syndrome (ACS) (74.6%) and 842 non-ACS (25.4%) groups. The median age was 61.0 years (range: 53.0-70.0), and 917 (27.6%) were females. Mortality and major adverse cardiovascular events (MACEs) included cardiovascular mortality, myocardial infarction (MI), stroke, and heart failure (HF) (inclusive of HF episodes requiring outpatient treatment and/or hospital admission). Cox regression models assessed the associations between GDF-15 and the incidence of all-cause mortality and MACEs. Patients were stratified into three groups based on GDF-15 levels: the first tertile group (< 1,370 ng/L), the second tertile group (1,370-2,556 ng/L), and the third tertile group (> 2,556 ng/L). The C-index, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA) were used to assess incremental value. Over a median 9.4-year follow-up, 759 patients (22.9%) died, and 1,291 (38.9%) experienced MACEs. The multivariate Cox model indicated that GDF-15 was significantly associated with all-cause mortality (per ln unit increase, HR = 1.49, 95% CI: 1.36-1.64) and MACEs (per ln unit increase, HR = 1.29, 95% CI: 1.20-1.38). These associations persisted when GDF-15 was analyzed as an ordinal variable (p for trend < 0.05). Subgroup analysis of ACS and non-ACS for the components of MACEs separately showed a significant association between GDF-15 and both cardiovascular mortality and HF, but no association was observed between GDF-15 and MI /stroke in both ACS and non-ACS patients. The addition of GDF-15 to the FRS-based model enhanced the discrimination for both all-cause mortality (∆ C-index = 0.009, 95% CI: 0.005-0.014; IDI = 0.030, 95% CI: 0.015-0.047; continuous NRI = 0.631, 95% CI: 0.569-0.652) and MACEs (∆ C-index = 0.009, 95% CI: 0.006-0.012; IDI = 0.026, 95% CI: 0.009-0.042; continuous NRI = 0.593, 95% CI: 0.478-0.682). DCA suggested that incorporating GDF-15 into the FRS-based model demonstrated higher net benefits compared to FRS-based models alone (All-cause mortality: FRS-based model: area under the curve of DCA (AUDC) = 0.0903, FRS-based model + GDF-15: AUDC = 0.0908; MACEs: FRS-based model: AUDC = 0.1806, FRS-based model + GDF-15: AUDC = 0.1833). GDF-15 significantly associates with the long-term prognosis of all-cause mortality and MACEs in CHD patients and significantly improves the prognostic accuracy of the FRS-based model for both outcomes.

Comparing the Saccule-to-Utricle Ratio in Early- Versus Late-Stage Meniere's Disease Patients.

To compare the saccule-to-utricle ratio in early- versus late-stage Meniere's disease (MD) patients based on magnetic resonance imaging (MRI) images. In this retrospective study, we performed 3-dimensional real inversion recovery (3D-real IR) MRI 24 h after intratympanic gadolinium administration in unilateral MD patients at early-stage (n = 56) and late-stage (n = 70). Two radiologists independently graded endolymphatic hydrops (EH) and the saccule-to-utricle ratio inversion (SURI) was compared between the two groups. Furthermore, early-stage MD patients were further divided into two subgroups based on disease duration: ≤6 months (n = 20) and >6 months (n = 36) and the SURI was compared. Among the 56 patients in the early-stage group, 26 cases (46.43%) exhibited an enlarged saccule that is larger than the utricle, showing SURI. In contrast, among the late-stage MD, only four cases (5.71%) showed SURI (p < 0.001). In the early-stage MD subgroup with a disease duration of ≤6 months, the proportion of SURI was 70% (14/20), which was higher than that in the subgroup with a disease duration of >6 months (33.33%, 12/36, p = 0.02). SURI may serve as an effective imaging marker for diagnosis of early-stage MD. Our finding suggests that endolymphatic hydrops in MD may primarily originate from the saccule. Level 3 Laryngoscope, 2024.

Effect of online hemodiafiltration on quality of life, fatigue and recovery time: a systematic review and meta-analysis.

The present systematic review and meta-analysis aims to compare the effect of bicarbonate hemodialysis and HDF on quality of life (QoL), fatigue, and time to recovery in end-stage renal disease (ESRD) patients. Searches were run on January 2024 and updated on 3 March 2024 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); PubMed (1985 to present). Ten articles were fully assessed for eligibility and included in the investigation. Compared to HD, online HDF had a pooled MD of the mental component score (MCS) of the SF-36of 0.98 (95% CI -0.92, 2.87; P = 0.31). and of the physical component score (PCS) of 0.08 (95% CI -1.32, 1.48; P = 0.91). No significant heterogeneity was observed (Chi2 = 4.85; I2 = 38%; P = 0.18 and Chi2 = 3.85; I2 = 22%; P = 0.28, respectively). Studies that compared the QoL assessed through the Kidney Disease Questionnaire or KDQOL-SF and show that HDF does not improve QoL when compared with HD, in most studies. In five out of seven studies, HDF was not significantly more effective than HD in improving fatigue. The length of the recovery time resulted in similar in patients receiving HDF and HD in all studies included in the present review. HDF is not more effective than HD in improving QoL and fatigue and in reducing the length of time of recovery after dialysis.

Differences in gray matter atrophy and functional connectivity between motor subtypes of Parkinson's disease.

Parkinson's disease (PD) patients with postural gait abnormalities exhibit poorer motor function scores, more severe non-motor symptoms, faster cognitive function deterioration, and a less favorable response to drugs and surgery compared to PD patients with tremor. This discrepancy is believed to be associated with more pronounced gray matter atrophy and abnormal functional connectivity. To investigate the distinctive pathological mechanisms between PD subtypes, we examined gray matter volume (GMV) and functional connectivity in patients with Parkinson's disease presenting with postural instability/gait difficulty (PD-PIGD), patients with tremor-dominant Parkinson's disease (PD-TD), and healthy controls. Voxel-based morphometry (VBM) of T1-weighted images was conducted to compare GMV among 64 PD-PIGD patients, 44 PD-TD patients, and 32 controls. Subsequently, functional connectivity within regions showing reduced GMV was compared across the groups. We analyzed whether differences among the groups were associated with clinical characteristics and neuroimaging biomarkers using partial correlation and binary logistic regression. Our comparison between PD-PIGD and PD-TD patients revealed a link between PD-PIGD and more extensive frontotemporal atrophy, potentially indicating increased basal ganglia activity accompanied by decreased cerebellum activity. Furthermore, in addition to the smaller GMV in the left middle temporal gyrus, the increased functional connectivity between this brain region and the right caudate was also the independent risk factor for PD-PIGD. In addition, we compared brain network connectivity between the PIGD and TD subtypes, using an independent component analysis (ICA). We found that Compared to PD-TD, PD-PIGD patients showed an enhanced sensorimotor network (SMN) around the left supplementary motor area. These findings suggest that severe gray matter atrophy and abnormal functional connectivity and brain networks may serve as pathophysiological mechanisms distinguishing PD-PIGD patients from other subtypes.

Risk Factors and Drug Therapy Monitoring in CKD Patients (Chronic Kidney Disease)

Chronic Kidney Disease (CKD) is a global health problem that affects millions of people, characterized by a progressive decline in kidney function. This study aims to determine Drug Related Problems (DRPs) in the treatment management of CKD (Chronic Kidney Disease) patients. This study used the literature review method. The research results from the collected literature will be summarized and presented in the form of descriptive analysis. Researchers will conduct literature searches through online sites such as Google Scholar, PubMed, ResearchGate, Elsevier, and NCBI. The keywords used are “CKD risk factors” and “drug therapy for CKD patients”. The results of the search for relevant literature will be collected and selected according to the inclusion criteria. The research results from the collected literature will be presented in the form of a descriptive table. The table will include information such as author, year of publication, article title, and summary of the study results. The prevalence of drug-related problems (DRP) in CKD patients ranges from 12% to 87%. Commonly found problems include ineffective treatment, inappropriate drug selection, and drug dosing issues. Regular drug monitoring and dose adjustment are essential to reduce adverse drug reactions and improve patient outcomes. Effective drug therapy management and patient education are essential to improve the quality of care and life of CKD patients. In conclusion, this study emphasizes the importance of identifying and addressing drug-related problems (DRPs) to improve treatment effectiveness in CKD patients. Close drug monitoring and comprehensive patient education are key components in the optimal management of CKD.

The Effects of Different Dosages on Micronized Purified Flavonoid Fraction's Treatment of Lower Limb Chronic Venous Disease: A Meta-Analysis.

Micronized purified flavonoid fraction (MPFF) is a widely prescribed and extensively investigated venoactive drug (VAD). The standard dosage for MPFF is 500 mg administered twice daily. However, a new daily dose of 1000 mg has just been introduced. This study investigated whether a daily dose of 1000 mg MPFF could be implemented and embraced by the public and still has the same therapeutic effects as conventional pharmaceuticals. For this meta-analysis, we searched MEDLINE, Embase, Science of Web, Cochrane, and PubMed databases and forward and backward citations for studies published between database inception and March 2023. Three randomized controlled trials (RCTs) of comparison of different dosages of MPFF to evaluate whether there is a significant difference between them were included, without language or date restrictions. Due to the small sample size of the study included, we conducted a simple sensitivity test using a one-by-one exclusion method, and the results showed that the study did not affect the final consolidation conclusion. The quality of the evidence was assessed using the Cochrane risk-of-bias tool. Out of 232 studies, 99 were eligible and 39 RCTs had data, all with low to moderate bias. Overall, 1924 patients (experimental group: 967, control group: 957) in 3 RCTs met the criteria. There is no significant difference in patient compliance, efficacy, clinical adverse events, and quality of life scores between MPFF 1000 mg once daily and MPFF 500 mg twice daily (standardized mean difference [SMD]: 0.049 [0.048, 0.145], p=0.321, risk ratio [RR]: 0.981 [0.855, 1.125], p=0.904, and SMD: 0.063 [0.034, 0.160], p=0.203). In symptomatic chronic venous disease patients, MPFF 1000 mg once daily and MPFF 500 mg twice daily improve patient compliance, lower limb discomfort, clinical adverse events, and quality of life scores similarly. Regular medical care should recommend MPFF 1000 mg daily more often. Micronized purified flavonoid fraction (MPFF) is a popular venoactive medication (VAD) in modern medicine.MPFF is effective in treating lower extremity venous problems.Currently, besides conventional 500 mg tablets, there exist alternative dosage forms such as solutions, chewable tablets, and other novel formulations for MPFF.The excessive frequency and amount of medication may have a negative impact on patient adherence.

Safety and tolerability of the protein C activator AB002 in end-stage renal disease patients on hemodialysis: a randomized phase 2 trial

BackgroundThe protein C system regulates blood coagulation, inflammation, and vascular integrity. AB002 is an injectable protein C activating enzyme under investigation to safely prevent and treat thrombosis. In preclinical models, AB002 is antithrombotic, cytoprotective, and anti-inflammatory. Since prophylactic use of heparin is contraindicated during hemodialysis in some end-stage renal disease (ESRD) patients, we propose using AB002 as a short-acting alternative to safely limit blood loss due to clotting in the dialysis circuit.MethodsThis phase 2, randomized, double-blind, placebo-controlled, single-dose study evaluates the safety and tolerability of AB002 administered into the hemodialysis line of ESRD patients during hemodialysis at one study center in the United States (ClinicalTrials.gov: NCT03963895). In this study, 36 patients were sequentially enrolled into two cohorts and randomized to AB002 or placebo in a 2:1 ratio. In cohort 1, patients received 1.5 µg/kg AB002 (n = 12) or placebo (n = 6); in cohort 2, patients received 3 µg/kg AB002 (n = 12) or placebo (n = 6). Patients underwent five heparin-free hemodialysis sessions over 10 days and were dosed with AB002 or placebo during session four.ResultsHere we show that AB002 is safe and well-tolerated in ESRD patients, with no treatment-related adverse events. Clinically relevant bleeding did not occur in any patient, and the time to hemostasis at the vascular access sites is not affected by AB002.ConclusionsAs far as we are aware, this proof-of-concept study is the first clinical trial assessing the therapeutic potential of protein C activation. The results herein support additional investigation of AB002 to safely prevent and treat thrombosis in at-risk populations.

Efficacy of oral anticoagulants in chronic kidney disease and hemodialysis patients with atrial fibrillation: a systematic review and meta-analysis.

This meta-analysis seeks to evaluate the efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKA) in individuals with chronic kidney disease (CKD), end-stage renal disease (ESRD), and undergoing hemodialysis (HD) who also have atrial fibrillation (AF). A comprehensive search of MEDLINE, clinicaltrials.gov, EMBASE, and Cochrane Database for relevant studies reporting the usefulness of OAC therapy for CKD, ESRD, and HD patients with AF was conducted from its inception until 1st May 2023. The studies that reported OR, RR, or HR for adult AF patients to investigate the efficacy of OAC in CKD, ESRD, and HD were included. Statistical analysis was completed using a generic inverse variance and random-effects model to calculate the combined HR and their corresponding 95% CIs for all outcomes. The meta-analysis included 33 studies with 178,956 patients. The analysis revealed that the DOACs, when compared to VKA, significantly lowered the risk of stroke or systemic embolism (HR: 0.81 [95% CI: 0.70, 0.93]; P=0.002; I2=62%), bleeding (HR: 0.77, [95% CI: 0.67, 0.89]; P=0.0003; I2=83%), and intracranial hemorrhage (HR: 0.56, [95% CI 0.47, 0.66]; P<0.00001; I2=0%). Similarly, the risks of cardiovascular death (HR: 0.88, [95% CI 0.78, 1.00]; P=0.05; I2=0%), all-cause mortality (HR: 0.88, [95% CI 0.70, 1.10]; P=0.25; I2=96%), and myocardial infarction (HR: 0.80, [95% CI 0.54, 1.17]; P= 0.25; I2= 0%) were lowered by DOAC, but the result was insignificant. No significant difference was seen in the risk of gastrointestinal bleeding between DOAC and VKA as well (HR: 0.95, [95% CI 0.75, 1.20]; P=0.65; I2=83%). Our meta-analysis confirms that DOACs are effective for managing AF in patients with kidney disease, with potential clinical implications for AF and CKD management. Further research should explore DOACs' reno-protective effects.