Ultrafast fragmentation of highly-excited doubly-ionized deoxyribose: role of the liquid water environment.

Ab initio molecular dynamics simulations are used to investigate the fragmentation dynamics following the double ionization of 2-deoxy-D-ribose (DR), a major component in the DNA chain. Different ionization scenarios are considered to provide a complete picture. First focusing on isolated DR2+, fragmentation patterns are determined for the ground electronic state, adding randomly distributed excitation energy to the nuclei. These patterns differ for the two isomers studied. To compare thermal and electronic excitation effects, Ehrenfest dynamics are also performed, allowing to remove the two electrons from selected molecular orbitals. Two intermediate-energy orbitals, localized on the carbon chain, were selected. The dissociation pattern corresponds to the most frequent pattern obtained when adding thermal excitation. On the contrary, targeting the four deepest orbitals, localized on the oxygen atoms, leads to selective ultrafast C-O and/or O-H bond dissociation. To probe the role of environment, a system consisting of a DR molecule embedded in liquid water is then studied. The two electrons are removed from either the DR or the water molecules directly linked to the sugar through hydrogen bonds. Although the dynamics onset is similar to that of isolated DR when removing the same deep orbitals localized on the sugar oxygen atoms, the subsequent fragmentation patterns differ. Sugar damage also occurs following the Coulomb explosion of neighboring H2O2+ molecules due to interaction with the emitted O or H atoms.

Periportal macrophages protect against commensal-driven liver inflammation.

The liver is the main gateway from the gut, and the unidirectional sinusoidal flow from portal to central veins constitutes heterogenous zones, including the periportal vein (PV) and the pericentral vein zones1-5. However, functional differences in the immune system in each zone remain poorly understood. Here intravital imaging revealed that inflammatory responses are suppressed in PV zones. Zone-specific single-cell transcriptomics detected a subset of immunosuppressive macrophages enriched in PV zones that express high levels of interleukin-10 and Marco, a scavenger receptor that sequesters pro-inflammatory pathogen-associated molecular patterns and damage-associated molecular patterns, and consequently suppress immune responses. Induction of Marco+ immunosuppressive macrophages depended on gut microbiota. In particular, a specific bacterial family, Odoribacteraceae, was identified to induce this macrophage subset through its postbiotic isoallolithocholic acid. Intestinal barrier leakage resulted in inflammation in PV zones, which was markedly augmented in Marco-deficient conditions. Chronic liver inflammatory diseases such as primary sclerosing cholangitis (PSC) and non-alcoholic steatohepatitis (NASH) showed decreased numbers of Marco+ macrophages. Functional ablation of Marco+ macrophages led to PSC-like inflammatory phenotypes related to colitis and exacerbated steatosis in NASH in animal experimental models. Collectively, commensal bacteria induce Marco+ immunosuppressive macrophages, which consequently limit excessive inflammation at the gateway of the liver. Failure of this self-limiting system promotes hepatic inflammatory disorders such as PSC and NASH.

Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

INTRODUCTION: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs. METHODS: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression. RESULTS: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs. CONCLUSIONS: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases. PREVIOUS PRESENTATIONS: No portion of this study has been presented or published previously.

Combined simultaneous endoscopic endonasal and transcranial surgery using high-definition three-dimensional exoscope for malignant tumors of the anterior skull base.

BACKGROUND: Advanced surgical interventions are required to treat malignancies in the anterior skull base (ASB). This study investigates the utility of endoscopic endonasal and transcranial surgery (EETS) using a high-definition three-dimensional exoscope as an alternative to traditional microscopy. METHODS: Six patients with carcinomas of varying histopathologies underwent surgery employing the EETS maneuver, which synchronized three distinct surgical modalities: harvesting of the anterolateral thigh flap, initiation of the transnasal technique, and initiation of the transcranial procedure. RESULTS: The innovative strategy enabled successful tumor resection and skull base reconstruction without postoperative local neoplastic recurrence, cerebrospinal fluid leakage, or neurological deficits. CONCLUSION: The integration of the exoscope and EETS is a novel therapeutic approach for ASB malignancies. This strategy demonstrates the potential of the exoscope in augmenting surgical visualization, enhancing ergonomics, and achieving seamless alignment of multiple surgical interventions. This technique represents a progressive shift in the management of these complex oncological challenges.

Resistive Pulse Sensing on a Capillary-Assisted Microfluidic Platform for On-Site Single-Particle Analyses.

Capillary-assisted flow is valuable for utilizing microfluidics-based electrical sensing platforms at on-site locations by simplifying microfluidic operations and system construction; however, incorporating capillary-assisted flow in platforms requires easy microfluidic modification and stability over time for capillary-assisted flow generation and sensing performance. Herein, we report a capillary-assisted microfluidics-based electrical sensing platform using a one-step modification of polydimethylsiloxane (PDMS) with polyethylene glycol (PEG). As a model of electrical sensing platforms, this work focused on resistive pulse sensing (RPS) using a micropore in a microfluidic chip for label-free electrical detection of single analytes, and filling the micropore with an electrolyte is the first step to perform this RPS. The PEG-PDMS surfaces remained hydrophilic after ambient storage for 30 d and assisted in generating an electrolyte flow for filling the micropore with the electrolyte. We demonstrated the successful detection and size analysis of micrometer particles and bacterial cells based on RPS using the microfluidic chip stored in a dry state for 30 d. Combining this capillary-assisted microfluidic platform with a portable RPS system makes on-site detection and analysis of single pathogens possible.

Five-Fraction Radiosurgery Using a Biologically Equivalent Dose of a Single Fraction of 24 Gy for a 3-cm Parasagittal Para-Central Sulcus Brain Metastasis From Adenocarcinoma of the Cecum.

An isolated single brain metastasis (BM) is an extremely rare manifestation of failure in patients with cecal adenocarcinoma (CAC). Total en bloc resection (while preserving function) of a 3-cm BM involving both the primary motor and sensory cortexes presents a conundrum: achieving long-term local control and safety of such a BM is also challenging for stereotactic radiosurgery (SRS). We describe the case of a 3.1-cm BM from CAC in the left parasagittal para-central sulcus region, which was treated using five-fraction SRS with a biologically effective dose (BED) of 81.6 Gy. In the SRS, the gross tumor volume (GTV, 7.14 cm3) was defined based on computed tomography (CT)/T1/T2 matching (enhancing lesion 11.66 cm3), and 98.7% of the GTV (CT/T2 mass) was covered with 43.6 Gy (58% isodose) using volumetric-modulated arcs. The maximum tumor response was partial (19.7% of the prior GTV) and sustained for 15.2 months, leaving minor neurological symptoms. However, the patient developed neurological worsening at six months, attributed to adverse radiation effects with a CT/T1/T2 mismatch, for which medical management, including the addition of bevacizumab (BEV), was effective for one year. Multi-fraction SRS with a high marginal and internal BED and sequential systemic therapy, including BEV, can be a minimally invasive, efficacious, and durable treatment option for a large CAC-BM involving the central sulcus. Early co-administration of BEV following SRS, dose escalation to the GTV boundary, and more than five fractions of SRS may be considered to improve the efficacy and safety further.

Chryseobacterium indologenes Peritonitis in a Peritoneal Dialysis Patient: A Case Report and Review of Literature.

Peritonitis is one of the most important complications in patients with peritoneal dialysis (PD). Appropriate antibiotic treatment against PD-associated peritonitis is necessary to prevent PD catheter removal and withdrawal from PD. Chryseobacterium indologenes is a Gram-negative rod that occurs in the natural environment. C. indologenes is thought to acquire resistance to ß-lactam drugs through the production of metallo-ß-lactamase and to become resistant to antibiotic therapy through the formation of biofilms. Only a few cases of PD-associated peritonitis caused by C. indologenes have been reported to date, and appropriate treatment strategies have not been clarified. In the past, 5 cases of PD-associated peritonitis caused by C. indologenes have been reported and 2 patients required catheter removal because of recurrence or refractoriness. In this case, a 51-year-old man with PD-associated peritonitis caused by C. indologenes was treated with 2 susceptible antibiotics, including fluoroquinolones to prevent acquired resistance and biofilm formation. There was no recurrence, and catheter removal was not necessary in this case. Collectively, the present case highlighted that PD-associated peritonitis caused by C. indologenes should be treated with 2 susceptible antibiotics including fluoroquinolones for 3 weeks.

Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma.

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases.

A Case of High-Grade Glioma in an Eloquent Area Treated with Awake Craniotomy in an 85-year-old Patient.

An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices.

Intermittent Fasting Sustainably Improves Glucose Tolerance in Normal Weight Male Mice Through Histone Hyperacetylation.

To explore the mechanism by which intermittent fasting (IF) exerts prolonged effects after discontinuation, we examined mice that had been subjected to 4 cycles of fasting for 72 hours and ad libitum feeding for 96 hours per week (72hIF), followed by 4 weeks of ad libitum feeding, focusing on expression of genes for lipid metabolism in the skeletal muscle and histone acetylation in the promoter region. The 72hIF regimen resulted in metabolic remodeling, characterized by enhanced lipid utilization and mitochondrial activation in the muscle. This long-term IF (72hIF) caused stronger metabolic effects than alternate day fasting (24hIF) wherein fasting and refeeding are repeated every 24 hours. Upregulation of lipid oxidation genes and an increase in oxygen utilization were sustained even at 4 weeks after discontinuation of 72hIF, associated with histone hyperacetylation of the promoter region of uncoupling protein 3 (Ucp3) and carnitine palmitoyl transferase 1b (Cpt1b) genes. An increase in leucine owing to fasting-induced muscle degradation was suggested to lead to the histone acetylation. These findings support the previously unappreciated notion that sustainable promotion of histone acetylation in lipid oxidation genes of the muscle and adipose tissues during and after IF may contribute to sustained metabolic effects of IF.

Incorporation of a bromine atom into DNA-related molecules changes their electronic properties.

To understand the mechanism underlying the high radio-sensitisation of living cells possessing brominated genomic DNA, X-ray photoelectron spectroscopy (XPS) using synchrotron X-rays with energies of 2000 or 2500 eV was used to study brominated and nonbrominated nucleobases, nucleosides and nucleotides. The bromine atom significantly reduced the energy gap between the valence and conduction states, although the core level states were not greatly affected. This finding was supported by quantum chemical calculation for the nucleobases and nucleosides. Our findings strongly indicate that the energy gaps between the valence and conduction levels of the molecules are significantly reduced by bromination. Furthermore, the brominated molecules are more likely to produce inelastic scattering low energy electrons upon exposure to 2000 or 3000 eV X-rays. This modification of electronic properties around the brominated group may both facilitate electron transfer to the brominated site in DNA and increase the probability of reaction with low energy electrons. These processes can induce DNA damage, presumably resulting in debromination of the uracil moiety and a subsequent cytotoxic effect.

Structural study of wild-type and phospho-mimic XRCC4 dimer and multimer proteins using circular dichroism spectroscopy.

PURPOSE: To investigate the structural features of wild-type and phospho-mimicking mutated XRCC4 protein, a protein involved in DNA double-strand break repair. MATERIALS AND METHODS: XRCC4 with a HisTag were expressed by E. coli harboring plasmid DNA and purified. Phospho-mimicking mutants in which one phosphorylation site was replaced with aspartic acid were also prepared in order to reproduce the negative charge resulting from phosphorylation. The proteins were separated into dimers and multimers by gel filtration chromatography. Circular dichroism (CD) spectroscopy was performed in the region from ultraviolet to vacuum-ultraviolet. The CD spectra were analyzed with two analysis programs to evaluate the secondary structures of the wild-type and phospho-mimicked dimers and multimers. RESULT AND DISCUSSION: The proportion of ß-strand in the wild-type dimers was very low, particularly in their C-terminal region, including the five phosphorylation sites. The secondary structure of the phospho-mimic hardly changed in the dimeric form. In contrast, the ß-strand content increased and the α-helix content decreased upon multimerization of the wild-type protein. The structural change of multimers slightly depended on the phospho-mimic site. These results suggest that the ß-strand structure stabilizes the multimerization of XRCC4 and it is regulated by phosphorylation at the C-terminal site in living cells. CONCLUSION: An increase in the ß-strand content in XRCC4 is essential for stabilization of the multimeric form through C-terminal phosphorylation, allowing the formation of the large double-strand break repair machinery.

IDH-mutant Astrocytoma Arising in the Brainstem with Symptom Improvement by Foramen Magnum Decompression: A Case Report.

Diffusely infiltrative midline gliomas are known to have a poor prognosis. The standard treatment for typical diffuse midline glioma in the pons is local radiotherapy as surgical resection is inappropriate. This case reports a brainstem glioma in which stereotactic biopsy and foramen magnum decompression were concomitantly performed to confirm the diagnosis and improve symptoms. A 23-year-old woman was referred to our department with a chief complaint of headache for six months. Magnetic resonance imaging (MRI) showed diffuse T2 hyperintense swelling of the brainstem with the pons as the main locus. Enlargement of the lateral ventricles was observed because of cerebrospinal fluid obstruction out of the posterior fossa. This was atypical for a diffuse midline glioma in terms of the longstanding slow progression of symptoms and patient age. Stereotactic biopsy was performed for diagnosis, and foramen magnum decompression (FMD) was concomitantly performed to treat the obstructive hydrocephalus. The histological diagnosis was astrocytoma, IDH-mutant. Post-surgery, the patient's symptoms were relieved, and she was discharged on the fifth day after surgery. The hydrocephalus was resolved, and the patient returned to normal life without any symptoms. The tumor size follow-up with MRI demonstrated no marked change for 12 months. Even though diffuse midline glioma is considered to have a poor prognosis, clinicians should contemplate if it is atypical. In atypical cases like the one described herein, surgical treatment may contribute to pathological diagnosis and symptom improvement.

Multidrug chemotherapy, whole-brain radiation and cytarabine therapy for primary central nervous system lymphoma in elderly patients with dose modification based on geriatric assessment: study protocol for a phase II, multicentre, non-randomised study.

INTRODUCTION: Multidrug chemoimmunotherapy with rituximab, high-dose methotrexate, procarbazine and vincristine (R-MPV) is a standard therapy for younger patients with primary central nervous system lymphoma (PCNSL); however, prospective data regarding its use in elderly patients are lacking. This multi-institutional, non-randomised, phase II trial will assess the efficacy and safety of R-MPV and high-dose cytarabine (HD-AraC) for geriatric patients with newly diagnosed PCNSL. METHODS AND ANALYSIS: Forty-five elderly patients will be included. If R-MPV does not achieve complete response, the patients will undergo reduced-dose, whole-brain radiotherapy comprising 23.4 Gy/13 fractions, followed by local boost radiotherapy comprising 21.6 Gy/12 fractions. After achieving complete response using R-MPV with or without radiotherapy, the patients will undergo two courses of HD-AraC. All patients will undergo baseline geriatric 8 (G8) assessment before HD-AraC and after three, five and seven R-MPV courses. Patients with screening scores of ≥14 points that decrease to <14 points during subsequent treatment, or those with screening scores <14 points that decrease from the baseline during subsequent treatment are considered unfit for R-MPV/HD-AraC. The primary endpoint is overall survival, and the secondary endpoints are progression-free survival, treatment failure-free survival and frequency of adverse events. The results will guide a later phase III trial and provide information about the utility of a geriatric assessment for defining chemotherapy ineligibility. ETHICS AND DISSEMINATION: This study complies with the latest Declaration of Helsinki. Written informed consent will be obtained. All participants can quit the study without penalty or impact on treatment. The protocol for the study, statistical analysis plan and informed consent form have been approved by the Certified Review Board at Hiroshima University (CRB6180006) (approval number: CRB2018-0011). The study is ongoing within nine tertiary and two secondary hospitals in Japan. The findings of this trial will be disseminated through national and international presentations and peer-reviewed publications. TRIAL REGISTRATION: jRCTs061180093.

Nature of the physicochemical process in water photolysis uncovered by a computer simulation.

In this work, we investigate the physicochemical process of water photolysis to bridge physical and chemical processes by a newly developed first-principles calculation code. The deceleration, thermalization, delocalization, and initial hydration of the extremely low-energy electrons ejected by water photolysis are sequentially tracked in the condensed phase. We show herein the calculated results for these sequential phenomena during 300 fs. Our results indicate that the mechanisms heavily depend on the intermolecular vibration and rotation modes peculiar to water and the momentum transfer between the electrons and the water medium. We suggest that using our results for the delocalized electron distribution will reproduce successive chemical reactions measured by photolysis experiments using a chemical reaction code. We expect our approach to become a powerful technique for various scientific fields related to water photolysis and radiolysis.

Utility of genome-wide DNA methylation profiling for pediatric-type diffuse gliomas.

Despite the current progress of treatment, pediatric-type diffuse glioma is one of the most lethal primary malignant tumors in the central nervous system (CNS). Since pediatric-type CNS tumors are rare disease entities and highly heterogeneous, the diagnosis is challenging. An accurate diagnosis is essential for the choice of optimal treatment, which leads to precision oncology and improvement of the patient's outcome. Genome-wide DNA methylation profiling recently emerged as one of the most important tools for the diagnosis of CNS tumors, and the utility of this novel assay has been reported in both pediatric and adult patients. In the current World Health Organization classification published in 2021, several new entities are recognized in pediatric-type diffuse gliomas, some of which require methylation profiling. In this review, we investigated the utility of genome-wide DNA methylation profiling in pediatric-type diffuse glioma, as well as issues in the clinical application of this assay. Furthermore, the combination of genome-wide DNA methylation profiling and other comprehensive genomic assays, which may improve diagnostic accuracy and detection of the actionable target, will be discussed.

X-ray induced luminescence spectroscopy for DNA damaging intermediates aided by a monochromatic synchrotron radiation.

PURPOSE: To identify the bonding sites of initial radiation interaction with DNA and to trace the following chemical reaction sequences on the pathway of damage induction, we carry out a spectroscopy XIL (X-ray induced luminescence) using soft X-ray synchrotron radiation. This is a nondestructive analysis of the excited intermediate species produced in a molecular mechanism on the damage induction pathway. MATERIALS AND METHODS: We introduce aqueous samples of UMP (uridine-5'-monophosphate) in the vacuum by the use of a liquid micro-jet technique. The luminescence in the region of UV-VIS (from visible to ultraviolet) radiation induced after the absorption of monochromatic soft X-ray by aqueous UMP is measured with sweeping the soft X-ray energy in the region of 370-560 eV. RESULTS: The enhanced XIL intensities for aqueous UMP in the region of soft X-ray of 410-530 eV (in "water window" region) are obtained. The enhancement of XIL intensities in the UV-VIS region, relative to the water control, is explained by the excitation and ionization of a K-shell electron of nitrogen atoms in the uracil moiety. The enhanced XIL intensities do not match the structure of XANES (X-ray absorption near-edge structure) of the aqueous UMP. This suggests that the XIL intensities reflect the quantum yields of luminescence, or the quantum yields for conversion by UMP of an absorbed X-ray into UV-VIS radiation. In this paper, spectra of luminescence are shown to be resolved by combining low pass filters. The filtered luminescence spectra are obtained at the center of gravity (λc) of the band pass wavelength regions at λc = 270nm, 295 nm, 340 nm, 385 nm, 450 nm, and 525 nm., which show a trend similar to the fluorescence of nucleobases induced by ultraviolet radiation. CONCLUSION: It is concluded that the origin of the observed XIL is the hydrated uracil moiety in aqueous UMP, decomposition of which is suppressed by the migration of excess charge and internal energy after the double ionization due to Auger decay.

Electronic properties of DNA-related molecules containing a bromine atom.

PURPOSE: To clarify the radiosensitization mechanism masking the Auger effect of the cells possessing brominated DNA, the electronic properties of DNA-related molecules containing Br were investigated by X-ray spectroscopy and specific heat measurement. MATERIALS AND METHODS: X-ray absorption near-edge structure (XANES) and X-ray photoemission spectroscopy (XPS) were used to measure the electronic properties of the nucleotides with and without Br. We determined the specific heat of 5-bromouracil crystals with thymine as a reference molecule at low temperatures of 3-48 K to calculate the microscopic state numbers. RESULTS: Obtained XANES and XPS spectra indicated that both the lowest unoccupied molecular orbital (LUMO) and the core-levels were not affected by the Br incorporation. The state numbers of 5-bromouracil calculated from the specific heats obtained around 25 K was about 1.5 times larger than that for thymine below 20 K, although the numbers were almost the same below 5 K. DISCUSSION: Our results suggest that the Br atom may not contribute substantially to the LUMO and core-level electronic states of the molecule, but rather to the microscopic states related to the excitation of lattice vibrations, which may be involved in valence electronic states.

Progressive differentiation toward the long-lived plasma cell compartment in the bone marrow.

The longevity of plasma cells is dependent on their ability to access and reside in so-called niches that are predominantly located in the bone marrow. Here, by employing a traceable method to label recently generated plasma cells, we showed that homeostatic plasma cells in the bone marrow and spleen were continuously replenished by newly generated B220hiMHC-IIhi populations that progressively differentiated into B220loMHC-IIlo long-lived plasma cell (LLPC) populations. We also found that, in the bone marrow, germinal center (GC)-independent and GC-dependent plasma cells decayed similarly upon NP-CGG engagement, and both entered the B220loMHC-IIlo LLPC pool. Compared with NP+B220hiMHC-IIhi plasma cells, NP+B220loMHC-IIlo cells were more immobilized in the bone marrow niches and showed better survival potential. Thus, our results suggest that the adhesion status of bone marrow plasma cells is dynamically altered during their differentiation and is associated with provision of survival signals.

Ultra-Low-Dose Contrast Using Transluminal Renal Angioplasty: The ULTRA Study.

BACKGROUND: Although severe atherosclerotic renal artery stenosis (ARAS) is a predictor of future cardiovascular events, large trials have not shown the benefits of percutaneous transluminal renal angioplasty (PTRA). This study aimed to validate the safety and efficacy of PTRA using low-concentration digital subtraction angiography (LC-DSA) in patients with severe ARAS and advanced chronic kidney disease (CKD). MATERIALS AND METHODS: This prospective study was conducted between August 2018 and October 2021. Eighteen patients with 20 lesions, CKD stage 3b or worse, and significant renal artery stenosis were included and underwent PTRA using ultra-low-dose contrast medium. The primary endpoint was a change in renal function based on serum creatinine (sCr) level. RESULTS: The mean sCr level significantly improved from 3.34 ± 1.8 mg/dL pre-PTRA to 2.48 ± 1.19 mg/dL at 1 month post-PTRA (P = .02). The mean amount of contrast used was 8.3 ± 3.9 mL per vessel. More severe stenosis and rapid deterioration of renal function before treatment were associated with improved kidney function. No cardiovascular or renal complications such as stroke or contrast-induced nephropathy were observed during the 30-day period. CONCLUSIONS: PTRA using an ultra-low-dose contrast medium is safe and provides acceptable results.