Background Septic associated acute kidney injury (SA-AKI) is common in the critically ill. Inadequate renal medullary tissue oxygenation has been linked to its pathogenesis. The aim of this preliminary study was to assess the feasibility of intermittent PuO2 monitoring using a blood gas analyzer in sepsis patients; to explore the effectiveness of time-weighted average PuO2 (PuO2TW) for predicting SA-AKI.Methods A total of 76 consecutive adult patients who were admitted to our intensive care unit (ICU) from September 2023 to March 2024 were prospectively recruited. PuO2 was measured with a blood gas analyzer at 0h, 3h, and 6h after ICU admission. PuO2TW was determined by the sum of the mean PuO2 values among consecutive time points multiplied by the period of time between consecutive time points and then dividing by the total time. All patients were followed throughout the ICU stay, and the development of SA-AKI during 48 h was evaluated.Results Approximately 23.68% developed AKI during the ICU stay. PuO2TW was lower in patients who developed AKI. The ROC curve analysis revealed that lower PuO2TW was associated with AKI development at the cutoff of <68 mmHg (area under the curve [AUC] 0.687; p = .008). In the logistic regression models, PuO2TW lower than 68 mmHg was associated with the development of AKI, when adjusted by confounding factors (OR 8.20; p = .002).Conclusions Measurement of PuO2 is feasible by collecting urine from a Foley catheter for analysis in a blood gas machine. 6h PuO2TW had a significant independent predictive value for AKI.
Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease. This study investigated the renoprotective effects and underlying mechanisms of Astragaloside IV (AS) in a rat model of type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. The rats received AS treatment (20, 40, or 80 mg/kg) for 13 weeks. AS significantly improved blood glucose and lipid profiles, enhanced the glomerular filtration rate, and reduced kidney injury without inducing hepatic toxicity. Histological staining, including hematoxylin and eosin, Masson’s trichrome, and periodic acid–Schiff staining, revealed attenuation of glomerular hypertrophy, mesangial expansion, and interstitial fibrosis. These improvements were corroborated by molecular analyses showing the downregulation of kidney injury molecule-1 and fibronectin, along with the restoration of nephrin expression at both the mRNA and protein levels. AS also attenuated high glucose-induced oxidative stress both in vivo and in vitro, as indicated by reduced reactive oxygen species and malondialdehyde levels and enhanced antioxidant enzyme activities, including superoxide dismutase and glutathione peroxidase in diabetic renal tissues and high glucose-stimulated HBZY-1 cells. Mechanistically, AS inhibited protein pinase C (PKC) beta expression and downstream NADPH Oxidase 4 activation, leading to suppression of mitogen-activated protein kinase (MAPK) signaling (ERK, p38, JNK) and NF-κB phosphorylation, thereby reducing inflammatory cytokine production. siRNA-based knockdown experiments further validated the PKC-β/NOX4 axis in mediating these protective effects. Collectively, AS alleviates diabetic renal injury by modulating the PKC-β/NOX4/MAPK pathway to reduce oxidative stress and inflammation, supporting its potential as a therapeutic candidate for DN.
Linghong Huang, Rowann Bowcutt, Alison Bigley
et al.
Abstract Background Assessing target engagement (TE) and target occupancy (TO) of novel antifibrotic molecules is challenging, as the target organs are inaccessible. In clinical trials, this often requires biopsies of internal organs, which increases both risk and discomfort for participants. Zampilimab (UCB7858) is a humanized monoclonal antibody that specifically inhibits the extracellular activity of transglutaminase 2 (TG2). Blocking TG2 activity reduces fibrosis in experimental models of chronic kidney disease. Here, a low-risk skin ‘biopsy-on-biopsy’ approach has been developed as a surrogate to assess TO of zampilimab in the kidney, ahead of further investigation of zampilimab in clinical studies. Methods A dual-antibody competitive immunofluorescence assay was developed to assess TO of TG2 with zampilimab. A cynomolgus monkey unilateral ureteral obstruction model was used to assess zampilimab TO in the kidney and compare this with TE measured by an in situ TG activity assay. Data were compared with TO in dermal wounds in the same animals. A human skin ‘biopsy-on-biopsy’ dermal wound approach was developed to induce fibrosis-relevant pathways. Skin sections from healthy volunteers were incubated ex vivo with increasing doses of zampilimab to assess TO. Results Zampilimab TO in cynomolgus monkey kidney and skin were positively correlated using our immunofluorescence assay, with an inverse correlation between skin TO and kidney TE using our in situ TG activity assay. In the human dermal wound model, maximal TG2 staining was observed on days 4–6 post initial dermal wound (biopsy). TO measurements increased dose-dependently with zampilimab application. Conclusions Zampilimab inhibited TG2 in cynomolgus monkey kidney and skin. Skin is an accessible surrogate tissue to assess kidney TO and predict TE, and our ex vivo model of skin biopsy has potential for application in the development of other antifibrotic therapeutics. A phase I first-in-human study of zampilimab in healthy volunteers (NCT02879877; 26/08/2016) will provide further proof of concept.
Abstract Background Chronic kidney disease affects more than 10% of the world’s population and is a non-communicable disease of global concern and priority. There is a significant implementation gap between best practice guideline recommendations and current kidney disease management. Previous research has shown the need to partner with primary care to improve education, collaboration, and kidney disease awareness. This implementation trial will explore use of an innovative clinical decision support software, Future Health Today, to improve screening, diagnosis, and management of kidney disease in primary care. The program will be supported by tertiary care outreach services. The primary aim is to test the hypothesis that the Future Health Today implementation program will improve screening, diagnosis, and management of kidney disease. Secondary aims are to evaluate primary care satisfaction and broader health service impacts. Methods This pre-post implementation trial using an interrupted time series design will evaluate the clinical and service outcomes of Future Health Today, using a mixed methods study in twenty general practices with an estimated population size of 150,000. Deidentified patient data will be extracted from participating practices to examine the primary aims of the study. Surveys and semi-structured interviews with general practice will inform secondary hypotheses. Data linkage between primary care and tertiary care data will examine the broader health service impacts. Discussion This investigator driven trial will assess the impact of Future Health Today software coupled with education and clinical outreach support. Investigators hypothesise that there will be improvement in appropriate screening, diagnosis, and management of kidney disease. This program has the potential to be scaled more broadly. Trial Registration Australian New Zealand Clinical Trial Registry: ACTRN12623001096640.
The analysis of domestic and foreign literature on the epidemiology, etiology, and possible sexual transmission of urinary tract infections (UTI) was carried out. It has been established that more than 30 pathogens are currently classified as sexually transmitted infections (STI). The molecular genetic method has shown the identity of uropathogenic Escherichia coli in familial cases of UTI, which confirms the sexual route of infection transmission, which was not previously classified as a classic STI. Several works are cited that undoubtedly testify to the possible sexual transmission of Mycobacterium tuberculosis. Up to date, few reports of sexual transmission of UTI have been published, although tuberculosis is one of the most common infectious diseases worldwide. Perhaps because the partner of a patient with genital tuberculosis or other UTI is not actively evaluated. Thus, the possibility of sexual transmission may be underestimated. Sexual transmission of M. tuberculosis as well as uropathogenic E. coli is unlikely, but possible.
Abstract Introduction The increasing popularity of robotic assisted surgery (RAS) as it is implemented in to sub specialities poses many challenges to ensuring standards in quality and safety. The area of Reconstructive and Functional Urology (RFU) has a wide range and largely complex heterogeneous procedures. In recent years RFU has started to incorporate RAS as the primary method to undertake these procedures due to improved vision, dexterity, and access to deep cavities. To ensure patient safety majority of institutions maintain minimal requirements to operate using RAS however across specialities and institutions these greatly vary. Methods A narrative review of all the relevant papers known to the author was conducted. Results Specific challenges facing RFU is the inability to rely on case numbers as a surrogate means to measure competency as well the ongoing consideration of how to differentiate between surgeons with robotic training and those with the clinical experience specific to RFU. Conclusion This review explores current models of training and credentialling and assess how it can be adapted to suggest a standardised guideline for RFU to ensure the highest standards of patient care.
Anne Crochard, Alexandre Gherardi, Mélanie Hueber Kollen
et al.
Abstract Psoriasis can affect diverse facets of patients' lives over time and may lead to irreversible cumulative life course impairment (CLCI). The CLCI concept initially described in 2010 in the context of psoriasis encompasses the intricate interaction between physical, psychological, social and economic burden and is influenced by several factors such as coping mechanisms, personality and external factors. CLCI assessment is conducted to characterise and ultimately mitigate or prevent the patient's burden over the life course. This review aims to give a comprehensive overview of the development and use of the CLCI concept in psoriasis since its inception. A narrative literature review was conducted from 2010 to 2022 and included 19 publications. As original studies on CLCI are scarce, this review primarily relied on case studies and those without longitudinal assessment. The core components of CLCI burden identified in patients' narratives include physical impairment, psychological impairment, stigma, socioeconomic burden and modulating factors. Modulating factors are crucial to mitigate the burden but are not equally explored. The burden associated with psoriasis stands across all dimensions covered by CLCI, thus confirming its suitability in clinical management and future studies. A better understanding of CLCI can support physicians and researchers in improving patients' lives and raising awareness on the necessity to develop early, efficient and patient‐centric interventions. The practical and systematic adoption of CLCI yet relies on the development and psychometric validation of a questionnaire that measures it.
Dermatology, Diseases of the genitourinary system. Urology
Dylan Burger, Amira Abdelrasoul, R. Todd Alexander
et al.
Purpose of conference: New discoveries arising from investigations into fundamental aspects of kidney development and function in health and disease are critical to advancing kidney care. Scientific meetings focused specifically on fundamental biology of the kidney can facilitate interactions, support the development of collaborative groups, and accelerate translation of key findings. The Canadian fundamental kidney researcher community has lacked such a forum. On December 3 to 4, 2021, the first Molecules and Mechanisms Mediating Kidney Health and Disease (M3K) Scientific Meeting and Investigator Summit was held to address this gap with the goal of advancing fundamental kidney research nationally. The meeting was held virtually and was supported by a planning and dissemination grant from the Canadian Institutes of Health Research. Attendees included PhD scientists, nephrology clinician scientists, engineers, industry representatives, graduate students, medical residents, and fellows. Sources of information: This report was prepared from the scientific program, registration numbers, and details obtained from the online platform WHOVA, and summaries written by organizers and participants of the 2021 meeting. Methods: A 21-person team, consisting of the organizing committee members and participants from the meeting, was assembled. Key highlights of the meeting and future directions were identified and the team jointly assembled this report. Key findings: Participation in the meeting was strong, with more than 140 attendees across a range of disciplines. The program featured state-of-the-art presentations on diabetic nephropathy, the immune system, kidney development, and fibrosis, and was heavily focused on trainee presentations. The moderated “Investigator Summit” identified key barriers to research advancement and discussed strategies for overcoming them. These included establishment of a pan-Canadian fundamental kidney research network, development of key resources, cross-pollination with clinical nephrology, better reintegration into the Canadian Society of Nephrology, and further establishment of identity and knowledge translation. Limitations and implications: The 2021 M3K meeting represented a key first step in uniting fundamental kidney researchers in Canada. However, it was universally agreed that regular meetings were necessary to sustain this momentum. The proceedings of this meeting and future actions to sustain the M3K Scientific Meeting and Investigator Summit are presented in this article.
Eliyahu Kresch, Justin Achua, Russell Saltzman
et al.
Purpose: A pilot study to describe histopathological features of penile tissue of patients who recovered from symptomatic COVID-19 infection and subsequently developed severe erectile dysfunction (ED).
Materials and Methods:Materials and Methods: Penile tissue was collected from patients undergoing surgery for penile prosthesis for severe ED. Specimens were obtained from two men with a history of COVID-19 infection and two men with no history of infec-tion. Specimens were imaged with TEM and H&E staining. RT-PCR was performed from corpus cavernosum biopsies. The tissues collected were analyzed for endothelial Nitric Oxide Synthase (eNOS, a marker of endothelial function) and CO-VID-19 spike-protein expression. Endothelial progenitor cell (EPC) function was assessed from blood samples collected from COVID-19 (+) and COVID-19 (-) men.
Results:Results: TEM showed extracellular viral particles ~100 nm in diameter with peplomers (spikes) near penile vascular endo-thelial cells of the COVID-19 (+) patients and absence of viral particles in controls. PCR showed presence of viral RNA in COVID-19 (+) specimens. eNOS expression in the corpus cavernosum of COVID-19 (+) men was decreased compared to COVID-19 (-) men. Mean EPC levels from the COVID-19 (+) patients were substantially lower compared to mean EPCs from men with severe ED and no history of COVID-19.
Conclusions:Conclusions: Our study is the first to demonstrate the presence of the COVID-19 virus in the penis long after the initial infec-tion in humans. Our results also suggest that widespread endothelial cell dysfunction from COVID-19 infection can contrib-ute to ED. Future studies will evaluate novel molecular mechanisms of how COVID-19 infection leads to ED.
Medicine, Diseases of the genitourinary system. Urology
Borzoueisileh S, Shabestani Monfared A, Ghorbani H
et al.
Sajad Borzoueisileh,1,2 Ali Shabestani Monfared,3 Hossein Ghorbani,4 SMJ Mortazavi,5 Ebrahim Zabihi,1 Mehdi Pouramir,1 Mohsen Shafiee,6 Fatemeh Niksirat7 1Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 2Student Research Committee, Babol University of Medical Sciences, Babol, Iran; 3Cancer Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; 4Pathology Department, Babol University of Medical Sciences, Babol, Iran; 5Department of Medical Physics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; 6Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran; 7Department of Medical Physics Radiobiology and Radiation Protection, School of Medicine, Babol University of Medical Sciences, Babol, IranCorrespondence: Ali Shabestani MonfaredCancer Research Center, Babol University of Medical Sciences, Ganjafrooz St., Babol, IranTel +989111230475Fax +981135289733Email monfared_ali@yahoo.comPurpose: Biochemical and histopathological properties of renal tissues were reported to be affected by both radiofrequency electromagnetic fields (RF-EMF) and ionizing radiation. The radiation-induced changes in the kidney, including the serum levels of blood urea nitrogen (BUN) and creatinine (Cr), could lead to adverse health outcomes such as chronic kidney disease. These complications signify the importance of the research in this field. Thus, in this study, the effects of ionizing and non-ionizing radiations, as well as their combination, were assessed by evaluating the alteration in BUN, Cr, and histopathological changes in kidney tissue.Materials and Methods: Ninety-six male Wistar rats were randomly divided into six groups and were exposed to either 900/1800MHz (mobile phone) or 2.4 GHz RF-EMF (Wi-Fi) radiation for 14 days, 8Gy x-ray, or their combination. Sera were collected from 2 mL of rat blood, then BUN and Cr levels were determined. Also, renal samples were stained with hematoxylin and eosin and evaluated histopathologically.Results: Both BUN and Cr levels raised non-significantly after exposure to 8 Gy x-rays. Moreover, all measurements in the samples of x-ray groups were in borderline or higher than normal values. The BUN levels of control, Wi-Fi, x-ray, and Wi-Fi+x-ray groups were not significantly different. However, Cr levels in the Wi-Fi group were significantly higher than those of the controls, and BUN to Cr ratio levels were significantly lower than those of the controls. Also, tubular atrophy and vessel wall thickening were associated with these exposures.Conclusion: Exposure to 900/1800MHz, 2400 MHz EMF can alter the kidney function. However, pre-exposure to 900/1800MHz EMF could modulate the acute adverse effects of lethal x-ray dose, which addresses the adaptive response in the kidney.Keywords: EMF, RF, kidney, mobile phone radiation, Wi-Fi radiation
Joanne Wong, Almas R Juma, Stephanie C Tran
et al.
Mice deficient in the transcription factor pleomorphic adenoma gene 1 (PLAG1) exhibit reproductive issues that are characterized, in part, by decreased progressive sperm motility in the male. However, the underlying cause of this impairment is unknown. As epididymal transit is critical for sperm maturation and motility, the morphology of the epididymis of Plag1-deficient mice was investigated and the spatial expression patterns of PLAG1 protein and mRNA were identified. Using X-gal staining and in situ hybridization, PLAG1 was shown to be widely expressed in both the epithelium and stroma in all regions of the mouse epididymis. Interestingly, the X-gal staining pattern was markedly different in the cauda, where it could be suggestive of PLAG1 secretion into the epididymal lumen. At all ages investigated, the morphology of epididymides from Plag1 knockout (KO) mice was aberrant; the tubule failed to elongate and coil, particularly in the corpus and cauda, and the cauda was malformed, lacking its usual bulbous shape. Moreover, the epididymides from Plag1 KO mice were significantly reduced in size relative to body weight. In 20% of Plag1-deficient mice, the left testicle and epididymis were lacking. The impaired morphogenesis of the epididymal tubule is likely to be a major contributing factor to the fertility problems observed in male Plag1-deficient mice. These results also establish PLAG1 as an important regulator of male reproduction, not only through its involvement in testicular sperm production, but also via its role in the development and function of the epididymis.
Objective:Ureterorenoscopic stone surgery (USS) is the primary method of ureteral stone treatment. Double-J (JJ) stenting is an integral part of a USS, and most urologists prefer to use it without an extraction string. The probable reason for such preference could be the lack of reliable and sufficient data on JJ stent use with an extraction string.Materials and Methods:A total of 177 patients who underwent USS were divided into four groups: Group 1 men (JJ stent was manually removed), group 2 men (JJ stent was cystoscopically removed), group 3 women (JJ stent was manually removed), and group 4 women (JJ stent was cystoscopically removed). We investigated the impact of two different JJ stent removal techniques on pain perception, lower urinary tract symptoms (LUTS), depressive symptomatology, complications, and cost.Results:Compared to groups 1 and 3, the mean surgery times were higher in groups 2 and 4 (p=0.001). Preoperative LUTS scores were similar in all groups (p>0.05). Postoperative pain scores in groups 3 and 4 were similar (p=0.06), but they were lower in group 1 than in group 2 (p=0.004). Postoperative Beck depression inventory scores were lower in groups 1 and 3 (p<0.02). The total cost of USS was 28.5% higher in groups 2 and 4 compared to groups 1 and 3.Conclusion:It is concluded that JJ stent removal with an extraction string is a reliable method with low treatment costs that does not adversely affect surgical outcomes.
Surgery, Diseases of the genitourinary system. Urology
Antonio B. Porcaro, Alessandro Tafuri, Marco Sebben
et al.
Background: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume (CTZV) to the peripheral zone volume (PZV), and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) load in patients presenting with normal digital rectal exam (DRE) and prostate-specific antigen (PSA) ⩽ 10 ng/ml at baseline random biopsies. Methods: Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core transperineal randomized biopsies. We considered small and high PCA load patients with no more than three (limited tumor load) and greater than three (extensive tumor load) positive biopsy cores, respectively. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing different multivariate models. Results: 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases, respectively. On multivariate analysis, PVI and PCI were independent predictors of the risk of detecting limited or extensive tumor load. The risk of detecting extensive tumor load at baseline biopsies was increased by PSAD above the median and third quartile as well as PVI ⩽ 1 [odds ratio (OR)=1.971] but decreased by PCI (OR=0.185; 95% CI: 0.088–0.388). Conclusions: Higher PVI and the presence of PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ⩽ 10 ng/ml at baseline random biopsy. In this subset of patients, a PVI ⩽ or >1 is able to differentiate patients with PCA or PCI.