-
Experimental and Clinical... Mar 2024Kidney transplant survival can be improved with better graft surveillance postoperatively. In the quest to explore new technologies, we explored the feasibility of an...
OBJECTIVES
Kidney transplant survival can be improved with better graft surveillance postoperatively. In the quest to explore new technologies, we explored the feasibility of an implantable Doppler probe as a blood flow monitoring device in kidney transplant patients. This qualitative study was embeddedin a feasibility trial and aimed to test the device's clinical acceptability and obtain suggestions for the development of the intervention. Objectives included exploring the experiences of feasibility study participants and identifying barriers to the implementation of implantable Doppler probes in clinical practice.
MATERIALS AND METHODS
We conducted semi-structured interviews containing open-ended questions with 12 feasibility study participants recruited by purposive sampling. All interviews were audio-recorded with verbatim transcription. Thematic data analysis was performed at the latent level by using an inductive approach with a previously published 6-phase guide.
RESULTS
Three key themes emerged: (1) perceived value of the intervention in clinical practice, (2) challenges and barriers to implementation of the intervention, and (3) suggestions forthe development of the intervention. Due to functional limitations and lack of research, medical professional participants revealed clinical equipoise regarding the utility of implantable Doppler probes. However,the device was well received by patient participants. Challenges included device training needs for medical professionals and educational sessions for patients. Innovative ideas for development included the insertion of a display screen, adopting disposable units to reduce overall cost, online access allowing remote monitoring, decreasing external monitoring unit size, and integrating a wireless connection with the probe to reduce signal errors and increase patient safety.
CONCLUSIONS
The clinical need for blood flow sensing technology in kidney transplants has been widely acknowledged. Implantable Doppler probes may be a beneficial adjunct in the early postoperative surveillance of kidney transplant patients. However, the device's technical limitations are the main challenges to its acceptance in clinical practice.
Topics: Humans; Kidney Transplantation; Feasibility Studies; Qualitative Research; Female; Male; Ultrasonography, Doppler; Middle Aged; Adult; Interviews as Topic; Predictive Value of Tests; Treatment Outcome; Equipment Design; Renal Circulation; Aged; Health Knowledge, Attitudes, Practice; Graft Survival; Blood Flow Velocity
PubMed: 38695588
DOI: 10.6002/ect.2023.0273 -
Cureus Apr 2024Rhabdomyolysis is characterised by muscle breakdown and the release of myoglobin. It is a potentially serious condition that can lead to acute kidney injury (AKI)....
Rhabdomyolysis is characterised by muscle breakdown and the release of myoglobin. It is a potentially serious condition that can lead to acute kidney injury (AKI). Factors, such as ischemia, trauma, muscle compression and drug toxicity, can trigger muscle breakdown. Treatment involves aggressive fluid resuscitation to maintain urine output and prevent renal injury. Severe cases with AKI may require temporary renal replacement therapy, such as haemodialysis. It has also been proposed that dialysis can speed up recovery by removing myoglobin that is secreted into the circulation by injured muscles. We present a case of a patient with alcohol abuse and prolonged immobility leading to severe rhabdomyolysis requiring hemodialysis. Our aim is to emphasise the importance of timely identification, and appropriate management of severe rhabdomyolysis not improving on fluids may require HD as soon as possible in order to minimise complications.
PubMed: 38694661
DOI: 10.7759/cureus.59316 -
Journal of Clinical Medicine Apr 2024in patients undergoing percutaneous coronary interventions (PCI), radial access should be favoured over femoral access as it reduces the risk of vascular complications...
in patients undergoing percutaneous coronary interventions (PCI), radial access should be favoured over femoral access as it reduces the risk of vascular complications and bleeding. Furthermore, a preventive role of radial access in the occurrence of acute kidney injury (AKI), mainly mediated by the reduction of bleeding and cholesterol crystal embolization into renal circulation, has been investigated in several studies, yielding conflicting results. we designed a retrospective study to appraise the effect of the use of a vascular access site on the occurrence of AKI in a cohort of 633 patients with acute myocardial infarction treated by PCI at our centre from 2018 to 2020. after propensity score adjustment, radial access was associated with a reduced, albeit statistically not significant, incidence of AKI (14.7% vs. 21.0%; = 0.06) and major bleeding (12.5% vs. 18.7%; = 0.04) as compared to femoral access. At multivariate analysis, femoral access was an independent predictor of AKI, together with in-hospital occurrence of BARC 3-5 bleeding, Killip class >1 at presentation, female gender, baseline eGFR <60 mL/min, and baseline haemoglobin <12 g/dL. although limited by the observational design, our study supports the hypothesis that radial access may exert a protective role on the occurrence of AKI in patients with acute myocardial infarction undergoing PCI.
PubMed: 38673640
DOI: 10.3390/jcm13082367 -
World Journal of Emergency Surgery :... Apr 2024Hemorrhage is a major cause of preventable trauma deaths, and the ABC approach is widely used during the primary survey. We hypothesize that prioritizing circulation... (Observational Study)
Observational Study
Comparing outcomes in patients with exsanguinating injuries: an Eastern Association for the Surgery of Trauma (EAST), multicenter, international trial evaluating prioritization of circulation over intubation (CAB over ABC).
INTRODUCTION
Hemorrhage is a major cause of preventable trauma deaths, and the ABC approach is widely used during the primary survey. We hypothesize that prioritizing circulation over intubation (CAB) can improve outcomes in patients with exsanguinating injuries.
METHODS
A prospective observational study involving international trauma centers was conducted. Patients with systolic blood pressure below 90 who were intubated within 30 min of arrival were included. Prioritizing circulation (CAB) was defined as delaying intubation until blood products were started, and/or bleeding control was performed before securing the airway. Demographics, clinical data, and outcomes were recorded.
RESULTS
The study included 278 eligible patients, with 61.5% falling within the "CAB" cohort and 38.5% in the "ABC" cohort. Demographic and disease characteristics, including age, sex, ISS, use of blood products, and other relevant factors, exhibited comparable distributions between the two cohorts. The CAB group had a higher proportion of penetrating injuries and more patients receiving intubation in the operating room. Notably, patients in the CAB group demonstrated higher GCS scores, lower SBP values before intubation but higher after intubation, and a significantly lower incidence of cardiac arrest and post-intubation hypotension. Key outcomes revealed significantly lower 24-hour mortality in the CAB group (11.1% vs. 69.2%), a lower rate of renal failure, and a higher rate of ARDS. Multivariable logistic regression models showed a 91% reduction in the odds of mortality within 24 h and an 89% reduction at 30 days for the CAB cohort compared to the ABC cohort. These findings suggest that prioritizing circulation before intubation is associated with improved outcomes in patients with exsanguinating injuries.
CONCLUSION
Post-intubation hypotension is observed to be correlated with worse outcomes. The consideration of prioritizing circulation over intubation in patients with exsanguinating injuries, allowing for resuscitation, or bleeding control, appears to be associated with potential improvements in survival. Emphasizing the importance of circulation and resuscitation is crucial, and this approach might offer benefits for various bleeding-related conditions.
Topics: Humans; Male; Female; Prospective Studies; Adult; Exsanguination; Intubation, Intratracheal; Middle Aged; Wounds and Injuries; Trauma Centers; Injury Severity Score
PubMed: 38664763
DOI: 10.1186/s13017-024-00545-8 -
Clinical Cancer Research : An Official... Jun 2024ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell...
PURPOSE
ARO-HIF2 is an siRNA drug designed to selectively target hypoxia-inducible factor-2α (HIF2α) interrupting downstream pro-oncogenic signaling in clear cell renal cell carcinoma (ccRCC). The aims of this Phase 1 study (AROHIF21001) were to evaluate safety, tolerability, pharmacokinetics, and establish a recommended Phase 2 dose.
PATIENTS AND METHODS
Subjects with ccRCC and progressive disease after at least 2 prior therapies that included VEGF and immune checkpoint inhibitors were progressively enrolled into dose-escalation cohorts of ARO-HIF2 administered intravenously at 225, 525, or 1,050 mg weekly.
RESULTS
Twenty-six subjects received ARO-HIF2. The most common treatment emergent adverse events (AE) irrespective of causality were fatigue (50.0%), dizziness (26.9%), dyspnea (23.1%), and nausea (23.1%). Four subjects (15.4%) had treatment-related serious AEs. AEs of special interest included neuropathy, hypoxia, and dyspnea. ARO-HIF2 was almost completely cleared from plasma circulation within 48 hours with minimal renal clearance. Reductions in HIF2α were observed between pre- and post-dosing tumor biopsies, but the magnitude was quite variable. The objective response rate was 7.7% and the disease control rate was 38.5%. Responses were accompanied by ARO-HIF2 uptake in tumor cells, HIF2α downregulation, as well as rapid suppression of tumor produced erythropoietin (EPO) in a patient with paraneoplastic polycythemia.
CONCLUSIONS
ARO-HIF2 downregulated HIF2α in advanced ccRCC-inhibiting tumor growth in a subset of subjects. Further development was hampered by off-target neurotoxicity and low response rate. This study provides proof of concept that siRNA can target tumors in a specific manner.
Topics: Humans; Carcinoma, Renal Cell; Basic Helix-Loop-Helix Transcription Factors; Male; Female; Middle Aged; Aged; Kidney Neoplasms; RNA, Small Interfering; Adult; RNA Interference; Antineoplastic Agents; Aged, 80 and over
PubMed: 38652038
DOI: 10.1158/1078-0432.CCR-23-3029 -
ELife Apr 2024Transporter research primarily relies on the canonical substrates of well-established transporters. This approach has limitations when studying transporters for the...
Transporter research primarily relies on the canonical substrates of well-established transporters. This approach has limitations when studying transporters for the low-abundant micromolecules, such as micronutrients, and may not reveal physiological functions of the transporters. While d-serine, a trace enantiomer of serine in the circulation, was discovered as an emerging biomarker of kidney function, its transport mechanisms in the periphery remain unknown. Here, using a multi-hierarchical approach from body fluids to molecules, combining multi-omics, cell-free synthetic biochemistry, and ex vivo transport analyses, we have identified two types of renal d-serine transport systems. We revealed that the small amino acid transporter ASCT2 serves as a d-serine transporter previously uncharacterized in the kidney and discovered d-serine as a non-canonical substrate of the sodium-coupled monocarboxylate transporters (SMCTs). These two systems are physiologically complementary, but ASCT2 dominates the role in the pathological condition. Our findings not only shed light on renal d-serine transport, but also clarify the importance of non-canonical substrate transport. This study provides a framework for investigating multiple transport systems of various trace micromolecules under physiological conditions and in multifactorial diseases.
Topics: Serine; Monocarboxylic Acid Transporters; Amino Acid Transport System ASC; Animals; Humans; Kidney; Mice; Sodium; Biological Transport; Male
PubMed: 38650461
DOI: 10.7554/eLife.92615 -
Advances in Kidney Disease and Health Mar 2024Acute kidney injury is a common complication of decompensated cirrhosis, frequently requires hospitalization, and carries a high short-term mortality. This population... (Review)
Review
Acute kidney injury is a common complication of decompensated cirrhosis, frequently requires hospitalization, and carries a high short-term mortality. This population experiences several characteristic types of acute kidney injury: hypovolemic-mediated (prerenal), ischemic/nephrotoxic-mediated (acute-tubular necrosis), and hepatorenal syndrome. Prerenal acute kidney injury is treated with volume resuscitation. Acute-tubular necrosis is treated by optimizing perfusion pressure and discontinuing the offending agent. Hepatorenal syndrome, a unique physiology of decreased effective arterial circulation leading to renal vasoconstriction and ultimately acute kidney injury, is treated with plasma expansion with albumin and splanchnic vasoconstrictors such as terlipressin or norepinephrine. Common acute stressors such as bleeding, infection, and volume depletion often contribute to multifactorial acute kidney injury. Even with optimal medical management, many clinicians are faced with the challenge of initiating renal replacement therapy in these patients. This article reviews the epidemiology, indications, and complex considerations of renal replacement therapy for acute kidney injury in decompensated cirrhosis.
Topics: Humans; Liver Cirrhosis; Acute Kidney Injury; Renal Replacement Therapy; Hepatorenal Syndrome
PubMed: 38649217
DOI: 10.1053/j.akdh.2024.01.003 -
Frontiers in Cardiovascular Medicine 2024Although the adverse effects of atrial fibrillation (AF) on cancers have been well reported, the relationship between the AF and the adverse outcomes in prostate cancer...
PURPOSE
Although the adverse effects of atrial fibrillation (AF) on cancers have been well reported, the relationship between the AF and the adverse outcomes in prostate cancer (PC) remains inconclusive. This study aimed to explore the prevalence of AF and evaluate the relationship between AF and clinical outcomes in PC patients.
METHODS
Patients diagnosed with PC between 2008 and 2017 were identified from the National Inpatient Sample database. The trends in AF prevalence were compared among PC patients and their subgroups. Multivariable regression models were used to assess the associations between AF and in-hospital mortality, length of hospital stay, total cost, and other clinical outcomes.
RESULTS
256,239 PC hospitalizations were identified; 41,356 (83.8%) had no AF and 214,883 (16.2%) had AF. AF prevalence increased from 14.0% in 2008 to 20.1% in 2017 ( < .001). In-hospital mortality in PC inpatients with AF increased from 5.1% in 2008 to 8.1% in 2017 ( < .001). AF was associated with adverse clinical outcomes, such as in-hospital mortality, congestive heart failure, pulmonary circulation disorders, renal failure, fluid and electrolyte disorders, cardiogenic shock, higher total cost, and longer length of hospital stay.
CONCLUSIONS
The prevalence of AF among inpatients with PC increased from 2008 to 2017. AF was associated with poor prognosis and higher health resource utilization. Better management strategies for patients with comorbid PC and AF, particularly in older individuals, are required.
PubMed: 38638883
DOI: 10.3389/fcvm.2024.1382166 -
Iranian Journal of Basic Medical... 2024Rhabdomyolysis leads to the release of myoglobin, sarcoplasmic proteins, and electrolytes into the blood circulation causing acute kidney injury (AKI). Thymoquinone, a...
OBJECTIVES
Rhabdomyolysis leads to the release of myoglobin, sarcoplasmic proteins, and electrolytes into the blood circulation causing acute kidney injury (AKI). Thymoquinone, a natural compound found in seeds, has antioxidant and anti-inflammatory effects. This investigation assessed the renoprotective effect of thymoquinone on rhabdomyolysis-induced AKI in rats.
MATERIALS AND METHODS
Male Wistar rats were categorized into six groups (n = 6): 1. Control: (normal saline), 2. Glycerol (50 ml/kg, single dose, IM), 3-5: Glycerol + thymoquinone (1, 2.5 and 5 mg/kg, 4 days, IP), 6. Thymoquinone (5 mg/kg). On day 5, serum and kidney tissue were isolated and the amounts of serum creatinine and blood urea nitrogen (BUN), renal malondialdehyde (MDA), glutathione (GSH.), tumor necrosis factor-alpha (TNF-α), neutrophil gelatinase-associated lipocalin (NGAL), and pathological changes were evaluated.
RESULTS
Glycerol increased creatinine, BUN, MDA, TNF-α, and NGAL levels. It decreased GSH amounts and caused renal tubular necrosis, glomerular atrophy, and myoglobin cast in kidney tissue. Co-administration of glycerol and thymoquinone reduced creatinine, BUN, histopathological alterations, and MDA levels, and enhanced GSH amounts. Administration of glycerol and thymoquinone (5 mg/kg) had no significant effect on TNF-α amount but decreased NGAL protein levels. The administration of thymoquinone (5 mg/kg) alone did not display a significant difference from the control group.
CONCLUSION
Rhabdomyolysis from glycerol injection in rats can cause kidney damage. Thymoquinone may attenuate renal dysfunction and oxidative stress. However, the TNF-α level was not significantly affected. Further studies are needed to explore the potential therapeutic effects of thymoquinone in managing AKI.
PubMed: 38629092
DOI: 10.22038/IJBMS.2023.72797.15838 -
BMC Neurology Apr 2024Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood...
OBJECTIVE
Restless legs syndrome (RLS) stands as a prevalent neurological complication within maintenance hemodialysis (MHD) patients. However, the alterations in cerebral blood flow (CBF) among MHD-RLS patients remain uncharted. Through the utilization of the arterial spin labeling (ASL) technique, we evaluated the fluctuations in CBF within distinct brain regions and analyzed the risk factors for the development of RLS in MHD patients in the context of the clinic.
METHODS
Thirty-one MHD patients with concomitant RLS (MHD-RLS group) and thirty-one non-RLS patients matched based on age, gender, as well as cognitive function (MHD-nRLS group) were included. Through image preprocessing and data analysis, the changes in CBF values in distinct brain regions were obtained, and the CBF values of brain regions with substantial differences between the two groups were correlated with the RLS scores. Furthermore, the differences in baseline data were compared, and through the utilization of multifactorial logistic regression, the independent risk factors for the development of RLS were examined.
RESULTS
Compared with the MHD-nRLS group, the MHD-RLS group had increased CBF in the right superior temporal gyrus, reduced CBF in the right hippocampus, left middle frontal gyrus, inferior frontal gyrus of right triangle, middle frontal gyrus of left orbit, left precentral gyrus, and left precuneus. Only left precentral gyrus CBF were negatively correlated with RLS scores after correction for dialysis duration(r = -0.436, P = 0.016). Accordingly, multifactorial regression analysis by stepwise method yielded that the left precentral gyrus CBF values(OR: 0.968, 95%CI: 0.944-0.993, P = 0.012) remained an independent risk factor for RLS in MHD patients. In addition, the results showed that hemodialysis duration (OR: 1.055, 95%CI: 1.014-1.098, P = 0.008) and serum iron levels (OR: 0.685, 95%CI: 0.551-0.852, P = 0.001) were also risk factors for the development of RLS.
CONCLUSION
Patients afflicted with MHD-RLS exhibit alterations in CBF across several brain regions. Notably, the left precentral gyrus might serve as a pivotal region influencing the onset of RLS among MHD patients. Furthermore, extended hemodialysis duration and a relative insufficiency in serum iron levels independently contribute as risk factors for RLS development within the MHD patient population.
Topics: Humans; Restless Legs Syndrome; Cross-Sectional Studies; Case-Control Studies; Renal Dialysis; Cerebrovascular Circulation; Motor Cortex; Iron; Magnetic Resonance Imaging
PubMed: 38627680
DOI: 10.1186/s12883-024-03636-w