INTRODUCTION

Chronic Kidney Disease (CKD) is a leading cause of morbidity and mortality in the Philippines. Most Filipino CKD patients prefer hemodialysis due to barriers such as cost and availability of Kidney Transplant. End-stage kidney disease (ESKD) patients face high symptom burden and unmet palliative care needs. Even with advancement in dialysis technology, the annual mortality rate of dialysis patients remains between 20% and 25%. While Advance Care Planning (ACP) can help align care with patient preferences by facilitating discussions about values and future decisions, its utilization in dialysis population remains low due to barriers in implementation. There is limited research specifically addressing the preferences and influencing factors of Advance Care Planning among CKD patients on hemodialysis in the Philippines.

This study aimed to determine the ACP preferences of CKD patients undergoing hemodialysis and to identify the clinicodemographic factors associated with these preferences.

An analytic cross-sectional study was conducted involving 96 chronic kidney disease (CKD) patients undergoing hemodialysis at Baguio General Hospital and Medical Center (BGHMC) from October to November 2024. Data were collected using validated questionnaires administered either through face-to-face interviews or self-administration, depending on patients’ preferences and capabilities. Descriptive and inferential statistical methods were employed for data analysis.

The study revealed limited awareness of ACP among participants (86.5%), underscoring the need for education. Family-centered decision-making was prominent, with most participants preferring family members as surrogate decision-makers and confidants. Quality of life was prioritized over life extension, and preferences for “Do Not Resuscitate” (DNR) orders were notable. Educational attainment and ethnicity significantly influenced preferences, with higher education linked to greater awareness; and Ethnicity shaping preferences for decision-makers, confidants, timing of discussions, and resuscitation choices. Additionally, duration of dialysis was linked to care setting preferences, while social support systems influenced the preferred place for discussions.

The findings highlight critical associations between clinicodemographic factors and ACP preferences among hemodialysis patients. Addressing these associations through targeted education and culturally sensitive approach can promote high-quality end-of-life care, aligned with diverse patient needs, values, and preferences.

Peripheral nerve block (PNB) has been successfully used as the sole anesthetic for Peritoneal dialysis (PD) catheter insertion, and has been shown to provide satisfactory anesthesia and analgesia perioperatively, especially among critically – ill patients.

This report describes the anesthetic management of an 18 – year old underweight patient with End-stage renal disease (ESRD) and decompensated heart failure who was scheduled for PD catheter insertion. He was given a left lateral Transversus abdominis plane (TAP) block and a right Rectus sheath (RS) block as the main anesthetic. Fifteen mL of Isobaric Bupivacaine 0.375% with Epinephrine 1:400,000 dilution was injected for the TAP block, and 10mL for the RS block, for a total volume of 25mL (93.7mg). Sedation was given via a Remifentanil infusion at 0.1mcg/kg/min. Intraoperatively, the patient was awake, conversant, and comfortable, no pressors were used, and no conversion to general anesthesia was done. Post-operatively, he had good pain control, with a pain score of 1/10, and successfully underwent dialysis via the PD catheter on the 2ndhospital day.

This pediatric patient who is critically ill is not a good candidate for general or neuraxial anesthesia due to the risk of hemodynamic instability and perioperative decompensation. PNB was done to provide anesthesia, and ensure good pain control post-operatively, and a right TAP and left RS were done instead of a bilateral TAP to lower the LA volume and decrease the risk of LA toxicity.

Unilateral TAP with contralateral RS is a safe anesthetic technique among critically-ill pediatric patients who will undergo PD catheter insertion without the risk of hemodynamic instability with general or neuraxial anesthesia.

Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes.
Oxidative Stress/physiology* ; Humans ; Diabetes Mellitus/physiopathology* ; Diabetes Complications/metabolism* ; Reactive Oxygen Species/metabolism* ; Glycation End Products, Advanced/metabolism* ; Animals

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

OBJECTIVES: To investigate the effect of serum advanced glycation endproducts (AGEs) on stenosis after first autologous arteriovenous fistula (AVF) in patients with end-stage renal disease (ESRD). METHODS: Patients with ESRD undergoing standard native arteriovenous fistula (AVF) for the first time in the Department of Nephrology, Affiliated Hospital of Guilin Medical University from February to June 2022 were prospectively enrolled. The preoperative general data, clinical examination results and ultrasound data of the operated limbs were collected. The patients with and without stenosis within 2 months after the operation were compared for preoperative serum AGEs levels detected using ELISA and the clinical parameters. Logistic regression analysis was used to analyze the independent risk factors of AVF stenosis, and the sensitivity and specificity of AGEs for predicting postoperative stenosis were analyzed using receiver-operating characteristic (ROC) curve. RESULTS: Of the 94 patients enrolled, 34 had postoperative arteriovenous stenosis and 60 had no stenosis. The number of diabetic patients differed significantly between stenosis group and non-stenosis group (P<0.001). Serum AGEs levels, which were negatively correlated with serum phosphorus level (P<0.05), were significantly higher in stenosis group than in non-stenosis group (Z=-2.837, P=0.005). Serum AGE level was an independent risk factor for postoperative stenosis after AVF (OR=1.251, 95% CI:1.096-1.423, P<0.001). For predicting AVF stenosis, the area under the ROC curve (AUC) of AGEs was 0.677 (P=0.007, 95% CI: 0.572-0.770), with a specificity of 90.00% and a sensitivity of 52.94% at the optimal cut-off value of 8.43 µg/mL; AGEs combined with fibrinogen had an AUC of 0.763 (P<0.001, 95% CI: 0.664-0.844), with a specificity of 73.33% and a sensitivity of 70.59% at the optimal cut-off value of 0.30. CONCLUSIONS Elevated serum AGEs level is an independent risk factor for postoperative AVF stenosis, and its combination with fibrinogen has a better efficacy for predicting postoperative AVF stenosis.
Humans ; Glycation End Products, Advanced/blood* ; Risk Factors ; Arteriovenous Shunt, Surgical/adverse effects* ; Kidney Failure, Chronic/blood* ; Male ; Constriction, Pathologic/etiology* ; Female ; Middle Aged ; Postoperative Complications/etiology* ; Renal Dialysis ; Aged ; Prospective Studies ; ROC Curve ; Adult

OBJECTIVES: To investigate the mechanism by which Guijianyu ameliorates podocyte injury in a mouse model of diabetic kidney disease (DKD) induced by advanced glycation endproducts (AGEs). METHODS: Sixty db/db mouse models of DKD were randomized equally into 5 groups for treatment with saline, Guijianyu extract at 3 doses or irbesartan for 12 weeks, and the changes in renal pathology and structure were observed using transmission electron microscopy, and the expressions of related genes and key proteins were detected using RT-qPCR and immunohistochemistry. In cultured MPC-5 cells incubated with 50 mg/L AGEs-BSA for 24 h, the effect of different concentrations of Guijianyu extract on cell viability was examined with CCK-8 assay; Western blotting was performed to detect the protein expressions of RAGE, VEGFA, TNF-α, NF-κB(p65), IL-6 and caspase-3, and the mRNA expressions of RAGE, NF-κB (p65), VEGFA and IL-6 were detected with RT-qPCR. RESULTS: In mouse models of DKD, treatment with high-dose Guijianyu extract significantly reduced renal expressions of RAGE, VEGFA, NF-κB(p65), and IL-6 proteins and the mRNA expressions of RAGE, NF-κB, and IL-6. In MPC-5 cells, exposure to AGEs significantly reduced cell viability and increased the protein expressions of RAGE, NF‑κB (p65), VEGFA, TNF-α, IL-6 and caspase-3 (P<0.05) and mRNA expressions of RAGE, NF-κB (p65), VEGFA, and IL-6. Treatment with Guijianyu extract obviously improved cell viability and reduced the expressions of RAGE, NF-κB(p65), VEGFA, TNF-α, IL-6, and caspase-3. Furthermore, Guijianyu extract effectively reversed RAGE agonist-induced elevation of protein expressions of RAGE, VEGFA, TNF-α, IL-6, and caspase-3 and mRNA expressions of RAGE, NF-κB (p65), IL-6, and VEGFA in MPC-5 cells. CONCLUSIONS Guijianyu extract ameliorates AGEs-induced mouse renal podocyte injury in DKD by inhibiting the activation of AGEs-RAGE signaling pathway and reducing the expressions of pro-inflammatory cytokines and vascular endothelial growth factors.
Animals ; Glycation End Products, Advanced ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Signal Transduction/drug effects* ; Podocytes/pathology* ; Diabetic Nephropathies/drug therapy* ; Receptor for Advanced Glycation End Products ; Vascular Endothelial Growth Factor A/metabolism* ; Interleukin-6/metabolism* ; Male

DNA double-strand breaks represent a common type of serious DNA damage in living organisms, causing instability of the genome and leading to cell death. Homologous recombination and non-homologous end-joining (NHEJ) are the two main ways to repair DNA double-strand breaks. The core components involved in the NHEJ pathway are highly conserved in both yeast and humans. A few bacteria such as Mycobacterium, Pseudomonas aeruginosa, and Bacillus subtilis also have the NHEJ mechanism. NHEJ plays a key role in the double strand repair of Mycobacterium in latency. This paper summarizes the mechanism and important components of NHEJ in Mycobacterium, introduces the application of NHEJ in gene editing, and reviews the research progress of the NHEJ pathway in Mycobacterium. We hope to bring new insights into the molecular mechanism and provide clues for the application of NHEJ in Mycobacterium.
DNA End-Joining Repair/physiology* ; Gene Editing/methods* ; Mycobacterium/physiology* ; DNA Breaks, Double-Stranded ; Humans

: Peripheral nerve block (PNB) has been successfully used as the sole anesthetic for Peritoneal dialysis (PD) catheter insertion, and has been shown to provide satisfactory anesthesia and analgesia perioperatively, especially among critically – ill patients. : This report describes the anesthetic management of an 18 – year old underweight patient with End-stage renal disease (ESRD) and decompensated heart failure who was scheduled for PD catheter insertion. He was given a left lateral Transversus abdominis plane (TAP) block and a right Rectus sheath (RS) block as the main anesthetic. Fifteen mL of Isobaric Bupivacaine 0.375% with Epinephrine 1:400,000 dilution was injected for the TAP block, and 10mL for the RS block, for a total volume of 25mL (93.7mg). Sedation was given via a Remifentanil infusion at 0.1mcg/kg/min. Intraoperatively, the patient was awake, conversant, and comfortable, no pressors were used, and no conversion to general anesthesia was done. Post-operatively, he had good pain control, with a pain score of 1/10, and successfully underwent dialysis via the PD catheter on the 2nd hospital day. : This pediatric patient who is critically ill is not a good candidate for general or neuraxial anesthesia due to the risk of hemodynamic instability and perioperative decompensation. PNB was done to provide anesthesia, and ensure good pain control post-operatively, and a right TAP and left RS were done instead of a bilateral TAP to lower the LA volume and decrease the risk of LA toxicity. Unilateral TAP with contralateral RS is a safe anesthetic technique among critically-ill pediatric patients who will undergo PD catheter insertion without the risk of hemodynamic instability with general or neuraxial anesthesia.
Human ; Male ; Adolescent: 13-18 yrs old ; End-stage Renal Disease (ESRD) ; kidney failure, chronic ; heart failure

OBJECTIVE

To describe the treatment outcomes of patients who underwent Percutaneous Transluminal Angioplasty (PTA) for Central Vein Occlusive Disease (CVOD) in end-stage kidney disease and determine the association between patient profile and treatment outcomes.

A single-institution, retrospective review of patients aged 18 and above with end-stage kidney disease who underwent PTA for CVOD in the University of the Philippines - Philippine General Hospital (UP-PGH) from January 1, 2013, to December 31, 2022, was performed. These patients’ demographic and clinical profiles were evaluated using means, frequencies, and percentages. The relationship between patient profile and success of PTA was assessed using Chi-square and Mann-Whitney U tests.

One hundred one patients were included in the study. Eighty-two had a first intervention, and 19 had a recurrent first intervention. The mean age was 49.8 years, with forty-six (45.5%) males and fifty-five (54.5%) females. The most common comorbidity was hypertension (59.4%). This was followed by diabetes (35.6%), chronic glomerulonephritis (18.8%), and NSAID nephropathy (4.9%). Other comorbidities include lupus nephritis, urate nephropathy, and polycystic kidney disease. The interval between symptoms and intervention ranged from two weeks to ninety-six weeks. Eleven patients (10.9%) had an arterio-venous fistula (AVF) before initiating dialysis and did not have a history of dialysis catheter use. Temporary catheters comprise most of the central vein catheters (CVC) (84.2%), while tunneled catheters were a minority (8.9%). The overall central line insertions of one hundred one patients were one hundred fifty-five, most via the right internal jugular vein (86%). There was a total of one hundred twenty-seven lesions seen during venography. Most of these lesions were in the left Innominate vein (38.6%, 39/101) and the right innominate vein (32.7%, 33/101). The most common type of lesion was stenosis (47.5%), followed by abrupt occlusions (31.7%) and tapered occlusions (20.8%). The overall success rate of PTA was 74.2%. In the second intervention for recurrence (n=19), the success rate was 78.9% (15/19). Third-time intervention in three patients was all successful. The success rate in stenotic, tapered, and abrupt lesions were 100%, 85.7%, and 28.1%, respectively. Symptomfree intervals ranged from twelve to one hundred ninetytwo weeks. After a failed intervention, a new fistula or graft was the most common access option (50%). This was followed by central catheter (38.5%), venous bypass (7.7%), and peritoneal dialysis catheter (3.8%). Morbidity was 0.99%. The in-hospital mortality was zero.

Overall PTA success rate for non-recurrent and first operation of recurrent patients with CVOD was high (74%). Stenotic type of lesions were the best vessels to dilate. Failure of PTA was directly related to previous right subclavian catheter insertion, multiple central vein catheter insertions, lesions in the right innominate vein, and an abrupt type of central vein occlusion. The current strategy of PTA for CVOD is both safe and effective. Early AVF creation can prevent patients from requiring multiple catheter insertions and developing CVOD. The right internal jugular vein is the optimal choice for access, while subclavian vein access should be avoided.