Alternative dialysis access strategies: A case report of a patient with transrenal hemodialysis catheter due to exhausted traditional routes and review of literature.

Vascular access is the primary lifeline for patients with end-stage renal disease. While arteriovenous fistulas and grafts are the conventionally favored methods for dialysis therapy, certain patients may deplete these traditional vascular access options due to various reasons. In the quest for alternatives, unconventional vascular pathways could be considered, including transhepatic, trans-lumbar and trans-renal approaches. We present a case of a 61-year-old male who exhausted all the traditional vascular access options, therefore trans-renal hemodialysis catheter placement was performed. Overall, this case highlights the challenges of securing a reliable vascular access to perform dialysis therapy and implementing unconventional methods whenever regular means are exhausted.

Aberrant Right Subclavian Artery: Demographics, Morphological Features and Follow up CT Scans Dynamics.

Introduction: Aberrant right subclavian artery (ARSA) is the most common of the aortic arch anomalies, occurring in .5% to 1% of the population. There is no standardized follow up protocol, especially in the asymptomatic cases. The purpose of the present study was to evaluate the natural history of ARSA and the role of serial CT scans. Methods: This is a single-center retrospective study of patients with ARSA depicted on chest computed tomography (CT) scans between February 2013 and July 2022. Data were collected from their medical records. Measurements of the aorta at different segments including the aortic diameter at the orifice of ARSA, and ARSA at ostium followed by 1 cm intervals were collected, as well as for follow-up CT scans. Results: 65 patients were diagnosed with ARSA, 70.8% of whom were women. The average age for the cohort was 58.569 ± 16.99 years. The median follow up time was 4 years (range 0-10 years), KM estimated survival after ARSA diagnosis at 1 and 5 years as 97% and 93%, respectively. Nineteen patients had a second CT scan and were included in the morphological CT dynamic analysis, on average of 29 ± 27 months apart (range 7-108). The mean ARSA diameter at origin was larger in the second scan 16.91 ± 4.31 mm compared to the initial scan 16.31 ± 4.96 mm, (P = .04).The mean aortic arch diameter in the first and second CT were 28.54 ± 4.24 and 29.64 ± 5.14 (P = .10), respectively. All other measurements did not disclose any significant enlargement over time. Conclusions: Our cohort demonstrate a benign natural history of ARSA with slow growth rates. However, due to our small sample size we can't draw a clinically sound recommendation on the need for imaging follow up, and further larger cohort with longer follow up interval are required.

Humanin prevents intra-renal microvascular remodeling and inflammation in hypercholesterolemic ApoE deficient mice.

AIMS: Humanin (HN) is an endogenous mitochondrial-derived cytoprotective peptide that has shown protective effects against atherosclerosis and is expressed in human vessels. However, its effects on the progression of kidney disease are unknown. We hypothesized that HN would protect the kidney in the early phase of atherogenesis. MAIN METHODS: Forty-eight mice were studied in four groups (n=12 each). Twenty-four ApoE deficient mice were fed a 16-week high-cholesterol diet supplemented with saline or HN (4mg/kg/day, intraperitoneal). C57BL/6 mice were fed a normal diet supplemented with saline or HN. Microvascular architecture was assessed with micro-CT and vascular wall remodeling by alpha-SMA staining. The effects of HN on angiogenesis, inflammation, apoptosis and fibrosis were evaluated in the kidney tissue by Western blotting and histology. KEY FINDINGS: Cortical microvascular spatial density and media/lumen area ratio were significantly increased in high-cholesterol diet fed ApoE deficient mice, but restored by HN. HN up-regulated the renal expressions of anti-angiogenic proteins angiostatin and TSP-1, and inhibited angiopoietin-1. HN attenuated inflammation by down-regulating MCP-1, TNF-alpha and osteopontin. HN also tended to restore pSTAT3 and attenuated Bax expression, suggesting blunted apoptosis. Kidney collagen IV expression was alleviated by HN treatment. SIGNIFICANCE: HN attenuates renal microvascular remodeling, inflammation and apoptosis in the early stage of kidney disease in hypercholesterolemic ApoE(-/-) mice. HN may serve as a novel therapeutic target to mitigate kidney damage in early atherosclerosis.

Humanin, a cytoprotective peptide, is expressed in carotid atherosclerotic [corrected] plaques in humans.

OBJECTIVE: The mechanism of atherosclerotic plaque progression leading to instability, rupture, and ischemic manifestation involves oxidative stress and apoptosis. Humanin (HN) is a newly emerging endogenously expressed cytoprotective peptide. Our goal was to determine the presence and localization of HN in carotid atherosclerotic plaques. METHODS AND RESULTS: Plaque specimens from 34 patients undergoing carotid endarterectomy were classified according to symptomatic history. Immunostaining combined with digital microscopy revealed greater expression of HN in the unstable plaques of symptomatic compared to asymptomatic patients (29.42±2.05 vs. 14.14±2.13% of plaque area, p<0.0001). These data were further confirmed by immunoblot (density of HN/ß-actin standard symptomatic vs. asymptomatic 1.32±0.14 vs. 0.79±0.11, p<0.01). TUNEL staining revealed a higher proportion of apoptotic nuclei in the plaques of symptomatic patients compared to asymptomatic (68.25±3.61 vs. 33.46±4.46% of nuclei, p<0.01). Double immunofluorescence labeling revealed co-localization of HN with macrophages (both M1 and M2 polarization), smooth muscle cells, fibroblasts, and dendritic cells as well as with inflammatory markers MMP2 and MMP9. CONCLUSIONS: The study demonstrates a higher expression of HN in unstable carotid plaques that is localized to multiple cell types within the plaque. These data support the involvement of HN in atherosclerosis, possibly as an endogenous response to the inflammatory and apoptotic processes within the atheromatous plaque.

Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice.

OBJECTIVE: Humanin (HN) is a cytoprotective peptide derived from endogenous mitochondria, expressed in the endothelial layer of human vessels, but its role in atherogenesis in vivo is not known. In vitro study, however, HN reduced oxidized low-density lipoprotein induced formation of reactive oxygen species and apoptosis. The present study tested the hypothesis that long term treatment with HN will have a protective role against endothelial dysfunction and progression of atherosclerosis in vivo. METHODS AND RESULTS: Daily intraperitonial injection of the HN analogue HNGF6A for 16 weeks prevented endothelial dysfunction and decreased atherosclerotic plaque size in the proximal aorta of ApoE-deficient mice fed on a high cholesterol diet, without showing direct vasoactive effects or cholesterol-reducing effects. HN was expressed in the endothelial layer on the aortic plaques. HNGF6A treatment reduced apoptosis and nitrotyrosine immunoreactivity in the aortic plaques without affecting the systemic cytokine profile. HNGF6A also preserved expression of endothelial nitric oxide synthase in aorta. CONCLUSIONS: HN may have a protective effect on endothelial function and progression of atherosclerosis by modulating oxidative stress and apoptosis in the developing plaque.

Humanin is expressed in human vascular walls and has a cytoprotective effect against oxidized LDL-induced oxidative stress.

AIMS: Humanin (HN) is a 24-amino acid peptide that has been shown to have an anti-apoptotic function against neuronal cell death caused by Alzheimer's disease. Increased oxidative stress, one of the major factors contributing to this cell death, also plays an important role in the inflammatory process of atherosclerosis. The current study was designed to test the hypothesis that HN is expressed in the human vascular wall and may protect against oxidative stress. METHODS AND RESULTS: HN expression in the vascular wall was detected by immunostaining in the endothelial cell layer of human internal mammary arteries (n = 5), atherosclerotic coronary arteries (n = 17), and sections of the greater saphenous vein (n = 3). HN mRNA was expressed in the human aortic endothelial cells (HAECs). Cytoprotective effects of HN against oxidative stress were tested in vitro in HAECs. Pre-treatment with 0.1 µM HN reduced oxidized LDL (Ox-LDL)-induced (i) formation of reactive oxygen species by 50%, (ii) apoptosis by ∼50% as determined by TUNEL staining, and (iii) formation of ceramide, a lipid second messenger involved in the apoptosis signalling cascade, by ∼20%. CONCLUSION: The current study demonstrates for the first time the expression of HN in the endothelial cell layer of human blood vessels. Exogenous addition of HN to endothelial cell cultures was shown to be effective against Ox-LDL-induced apoptosis. These findings suggest that HN may play a role and may have a protective effect in early atherosclerosis in humans.