bluuebunny/crossref_metadata_2025 huggingface dataset:
Prebiotics for Induction and Maintenance of Remission in Inflammatory Bowel Disease: Systematic Review and Meta-Analysis
Authors: Limketkai Berkeley N , Godoy-Brewer Gala , Shah Neha D , Maas Laura , White Jacob , Parian Alyssa M , Mullin Gerard E
Published: May 2024

Background

Prebiotics are nondigestible carbohydrates fermented by gut bacteria into metabolites that confer health benefits. However, evidence on their role for inflammatory bowel disease (IBD) is unclear. This study systematically evaluated the research on prebiotics for treatment of IBD.

Methods

A search was performed in PubMed, Embase, Cochrane, and Web of Science. Eligible articles included randomized controlled trials or prospective observational studies that compared a prebiotic with a placebo or lower-dose control in patients with IBD. Meta-analyses were performed using random-effects models for the outcomes of clinical remission, clinical relapse, and adverse events.

Results

Seventeen studies were included. For induction of clinical remission in ulcerative colitis (UC), the fructooligosaccharide (FOS) kestose was effective (relative risk, 2.75, 95% confidence interval, 1.05-7.20; n = 40), but oligofructose-enriched inulin (OF-IN) and lactulose were not. For maintenance of remission in UC, germinated barley foodstuff trended toward preventing clinical relapse (relative risk, 0.40; 95% confidence interval, 0.15-1.03; n = 59), but OF-IN, oat bran, and Plantago ovata did not. For Crohn’s disease, OF-IN and lactulose were no different than controls for induction of remission, and FOS was no different than controls for maintenance of remission. Flatulence and bloating were more common with OF-IN; reported adverse events were otherwise similar to controls for other prebiotics.

Conclusion

Prebiotics, particularly FOS and germinated barley foodstuff, show potential as effective and safe dietary supplements for induction and maintenance of remission in UC, respectively. The overall certainty of evidence was very low. There would be benefit in further investigation on the role of prebiotics as treatment adjuncts for IBD.
Singular Vortex Pairs Follow Magnetic Geodesics
Authors: Drivas Theodore D , Glukhovskiy Daniil , Khesin Boris
Published: May 2024

We consider pairs of point vortices having circulations $\Gamma _{1}$ and $\Gamma _{2}$ and confined to a two-dimensional surface $S$. In the limit of zero initial separation $\varepsilon $, we prove that they follow a magnetic geodesic in unison, if properly renormalized. Specifically, the “singular vortex pair” moves as a single-charged particle on the surface with a charge of order $1/\varepsilon ^{2}$ in an magnetic field $B$ that is everywhere normal to the surface and of strength $|B|=\Gamma _{1} +\Gamma _{2}$. In the case $\Gamma _{1}=-\Gamma _{2}$, this gives another proof of Kimura’s conjecture [11] that singular dipoles follow geodesics.
Microbial ecology of the deep terrestrial subsurface
Authors: Beaver Rachel C , Neufeld Josh D
Published: May 2024

The terrestrial subsurface hosts microbial communities that, collectively, are predicted to comprise as many microbial cells as global surface soils. Although initially thought to be associated with deposited organic matter, deep subsurface microbial communities are supported by chemolithoautotrophic primary production, with hydrogen serving as an important source of electrons. Despite recent progress, relatively little is known about the deep terrestrial subsurface compared to more commonly studied environments. Understanding the composition of deep terrestrial subsurface microbial communities and the factors that influence them is of importance because of human-associated activities including long-term storage of used nuclear fuel, carbon capture, and storage of hydrogen for use as an energy vector. In addition to identifying deep subsurface microorganisms, recent research focuses on identifying the roles of microorganisms in subsurface communities, as well as elucidating myriad interactions—syntrophic, episymbiotic, and viral—that occur among community members. In recent years, entirely new groups of microorganisms (i.e. candidate phyla radiation bacteria and Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoloarchaeota, Nanoarchaeota archaea) have been discovered in deep terrestrial subsurface environments, suggesting that much remains unknown about this biosphere. This review explores the historical context for deep terrestrial subsurface microbial ecology and highlights recent discoveries that shape current ecological understanding of this poorly explored microbial habitat. Additionally, we highlight the need for multifaceted experimental approaches to observe phenomena such as cryptic cycles, complex interactions, and episymbiosis, which may not be apparent when using single approaches in isolation, but are nonetheless critical to advancing our understanding of this deep biosphere.
Evaluation of GPT-4 ability to identify and generate patient instructions for actionable incidental radiology findings
Authors: Woo Kar-mun C , Simon Gregory W , Akindutire Olumide , Aphinyanaphongs Yindalon , Austrian Jonathan S , Kim Jung G , Genes Nicholas , Goldenring Jacob A , Major Vincent J , Pariente Chloé S , Pineda Edwin G , Kang Stella K
Published: May 2024

Objectives

To evaluate the proficiency of a HIPAA-compliant version of GPT-4 in identifying actionable, incidental findings from unstructured radiology reports of Emergency Department patients. To assess appropriateness of artificial intelligence (AI)-generated, patient-facing summaries of these findings.

Materials and Methods

Radiology reports extracted from the electronic health record of a large academic medical center were manually reviewed to identify non-emergent, incidental findings with high likelihood of requiring follow-up, further sub-stratified as “definitely actionable” (DA) or “possibly actionable—clinical correlation” (PA-CC). Instruction prompts to GPT-4 were developed and iteratively optimized using a validation set of 50 reports. The optimized prompt was then applied to a test set of 430 unseen reports. GPT-4 performance was primarily graded on accuracy identifying either DA or PA-CC findings, then secondarily for DA findings alone. Outputs were reviewed for hallucinations. AI-generated patient-facing summaries were assessed for appropriateness via Likert scale.

Results

For the primary outcome (DA or PA-CC), GPT-4 achieved 99.3% recall, 73.6% precision, and 84.5% F-1. For the secondary outcome (DA only), GPT-4 demonstrated 95.2% recall, 77.3% precision, and 85.3% F-1. No findings were “hallucinated” outright. However, 2.8% of cases included generated text about recommendations that were inferred without specific reference. The majority of True Positive AI-generated summaries required no or minor revision.

Conclusion

GPT-4 demonstrates proficiency in detecting actionable, incidental findings after refined instruction prompting. AI-generated patient instructions were most often appropriate, but rarely included inferred recommendations. While this technology shows promise to augment diagnostics, active clinician oversight via “human-in-the-loop” workflows remains critical for clinical implementation.
LC–MS-MS method for mitragynine and 7-hydroxymitragynine in hair and its application in authentic hair samples of suspected kratom abusers
Authors: Rhee Jongsook , Shin Ilchung , Kim Jihyun , Lee Juseun , Cho Byungsuk , Kim Junghyun , Park Meejung , Kim Eunmi
Published: May 2024

Kratom is a natural psychoactive product known primarily in Southeast Asia, including Thailand, Malaysia, etc. It is also known as krathom, kakuam, ithang, thom (Thailand), biak-biak, ketum (Malaysia) and mambog (Philippines) and is sometimes used as an opium substitute. It is stimulant at doses of 1–5 g, analgesic at doses of 5–15 g and euphoric and sedative at doses of >15 g. Mitragynine is the most abundant indole compound in kratom (Mitragyna speciosa) and is metabolized in humans to 7-hydroxymitragynine, the more active metabolite. Adverse effects include seizures, nausea, vomiting, diarrhea, tachycardia, restlessness, tremors, hallucinations and death. There are few studies on the analytical method for the detection of mitragynine and 7-hydroxymitragynine in hair. Therefore, this study proposes a liquid chromatography–tandem mass spectrometry (LC–MS-MS) method for the analysis of kratom in hair. Hair samples were first weighed to ∼10 mg and washed with methanol. Then the washed hair samples were cut into pieces and incubated in methanol with stirring and heating (16 h/38℃). Extracts were then analyzed by LC–MS-MS. This method was validated by determining the limit of detection (LOD), limit of quantification, linearity, intra- and inter-day accuracy and precision, recovery and matrix effects. The intra- and inter-day precision (CV%) and accuracy (bias%) were within ±20%, which was considered acceptable. Using this newly developed LC–MS-MS method, the simultaneous detection of mitragynine and 7-hydroxymitragynine in six authentic hair samples was achieved to provide the direct evidence of kratom use in the past. Mitragynine concentrations ranged from 16.0 to 2,067 pg/mg (mean 905.3 pg/mg), and 7-hydroxymitragynine concentrations ranged from 0.34 to 15 pg/mg (mean 7.4 pg/mg) in six authentic hair samples from kratom abusers. This may be due to the higher sensitivity of the LOD in this study, with values of 0.05 pg/mg for mitragynine and 0.2 pg/mg for 7-hydroxymitragynine in hair.
Chronic wasting disease effects on a breeding season behavior in White-tailed Deer (Odocoileus virginianus)
Authors: Huang Miranda H J , Demarais Steve , Strickland Bronson K , Houston Allan , Banda Alejandro , VerCauteren Kurt C
Published: May 2024

Wildlife disease outbreaks can lead to population declines, which are usually attributed to increased direct or indirect mortality. Alternatively, behavior associated with sickness can lead to social isolation, potentially decreasing fitness of affected individuals. A useful case study to examine this dynamic is chronic wasting disease (CWD), a neurological disease of cervids, known to affect behavior and movement. In this study, we monitored scraping, a White-tailed Deer (Odocoileus virginianus; WTD) breeding season behavior, in an area of high CWD prevalence to determine if this reproductive behavior is affected by CWD. At 107 scrape sites, we detected 3,063 scrape interactions and 218 unique bucks. Bucks engaged with scrapes most often, performing 73% of interactions—compared to 23% by does, and 4% by fawns. Twenty-one bucks captured on camera traps at scrape sites were harvested through recreational hunting, 13 testing CWD-positive and 8 CWD not-detected. We found no significant effect of CWD status on specific scraping behaviors. There may, however, have been population-level effects, with shifts toward greater proportions of scraping by yearling bucks and during daylight hours compared to findings from past studies.
Using the Discontinuous Bi-viscosity model to analyze the three-dimensional flow field and local scour behavior around the Claviaster libycus
Authors: Lin Pin-Jie , Wu Tso-Ren , Lin Jih-Pai , Chuang Mei-Hui , Huang Yi-Xuan , Chi Jia-Jie
Published: May 2024

Previous studies have suggested that irregular echinoids exhibit higher survival rates than regular echinoids following mass extinctions. This study focuses on the irregular echinoid Claviaster libycus, investigating its flow field and scour behavior under extreme water flow conditions through numerical simulations and experiments. The numerical model Splash3D used in this study was modified from the open-source code Truchas developed by the U.S. National Laboratory. Splash3D solves the three-dimensional incompressible Navier-Stokes Eqs.. The fluid volume method describes the water surface kinematics and sand surface kinematics. Since Claviaster libycus is semi-submerged in the sand, a discontinuous bi-viscosity model describes the rheological behavior of the bed material. The research findings indicate that when the gonopore of Claviaster libycus faces downstream, there is no evident horseshoe vortex flow, which contributes to reducing the occurrence of localized scour. This also validates the hypothesis of this study: the transition of echinoids from pentaradial symmetry to bilateral symmetry assists in stabilizing bottom sediments and reducing localized scour.
Qualitative Analysis of the Lived Experience of Reproductive and Pediatric Health Care in the Military Health Care System
Authors: Musilli Megan G , Fuller Shara M , Wyatt Brelahn , Ryals Teri R , Haischer-Rollo Gayle , Drumm Caitlin M , Vereen Rasheda J , Plowden Torie C , Blevins Erin M , Spalding Carmen N , Konopasky Abigail , Lutgendorf Monica A
Published: May 2024

Introduction

Persistent inequities exist in obstetric and neonatal outcomes in military families despite universal health care coverage. Though the exact underlying cause has not been identified, social determinants of health may uniquely impact military families. The purpose of this study was to qualitatively investigate the potential impact of social determinants of health and the lived experiences of military individuals seeking maternity care in the Military Health System.

Materials and Methods

This was an Institutional Review Board-approved protocol. Nine providers conducted 31 semi-structured interviews with individuals who delivered within the last 5 years in the direct or purchased care market. Participants were recruited through social media blasts and clinic flyers with both maximum variation and homogenous sampling to ensure participation of diverse individuals. Data were coded and themes were identified using inductive qualitative research methods.

Results

Three main themes were identified: Requirements of Military Life (with subthemes of pregnancy notification and privacy during care, role of pregnancy instructions and policies, and role of command support), Sociocultural Aspects of the Military Experience (with subthemes of pregnancy as a burden on colleagues and a career detractor, postpartum adjustment, balancing personal and professional requirements, pregnancy timing and parenting challenges, and importance of friendship and camaraderie in pregnancy), and Navigating the Healthcare Experience (including subthemes of transfer between military and civilian care and TRICARE challenges, perception of military care as inferior to civilian, and remote duty stations and international care).

Conclusions

The unique stressors of military life act synergistically with the existing health care challenges, presenting opportunities for improvements in care. Such opportunities may include increased consistency of policies across services and commands. Increased access to group prenatal care and support groups, and increased assistance with navigating the health care system to improve care transitions were frequently requested changes by participants.
The Evolution of Transglutaminases Underlies the Origin and Loss of Cornified Skin Appendages in Vertebrates
Authors: Sachslehner Attila Placido , Surbek Marta , Holthaus Karin Brigit , Steinbinder Julia , Golabi Bahar , Hess Claudia , Eckhart Leopold
Published: May 2024

Transglutaminases (TGMs) cross-link proteins by introducing covalent bonds between glutamine and lysine residues. These cross-links are essential for epithelial cornification which enables tetrapods to live on land. Here, we investigated which evolutionary adaptations of vertebrates were associated with specific changes in the family of TGM genes. We determined the catalog of TGMs in the main clades of vertebrates, performed a comprehensive phylogenetic analysis of TGMs, and localized the distribution of selected TGMs in tissues. Our data suggest that TGM1 is the phylogenetically oldest epithelial TGM, with orthologs being expressed in the cornified teeth of the lamprey, a basal vertebrate. Gene duplications led to the origin of TGM10 in stem vertebrates, the origin of TGM2 in jawed vertebrates, and an increasing number of epithelium-associated TGM genes in the lineage leading to terrestrial vertebrates. TGM9 is expressed in the epithelial egg tooth, and its evolutionary origin in stem amniotes coincided with the evolution of embryonic development in eggs that are surrounded by a protective shell. Conversely, viviparous mammals have lost both the epithelial egg tooth and TGM9. TGM3 and TGM6 evolved as regulators of cornification in hair follicles and underwent pseudogenization upon the evolutionary loss of hair in cetaceans. Taken together, this study reveals the gain and loss of vertebrate TGM genes in association with the evolution of cornified skin appendages and suggests an important role of TGM9 in the evolution of amniotes.
#955 Real-world validation of the mortality box score to predict death following kidney transplantation: an international study
Authors: Lombardi Yannis , Rudrapatna Vivek , Truchot Agathe , Divard Gillian , Debiais Charlotte , Raynaud Marc , Butte Atul , Loupy Alexandre
Published: May 2024

Background and Aims

The mortality box score (mBox) is a validated risk prediction score developed by the Paris Transplant Group (NCT03474003), aimed at predicting mortality after kidney transplantation (KT) using data available at the time of surgery. However, its applicability using data routinely collected in institutions' electronic health records (EHRs), enabling automatic computation, needs to be investigated.

Method

We assessed the mBox's prediction performance in two EHR-based multicenter cohorts of adult kidney transplant recipients (KTRs) transplanted between 2017 and 2021 from: 1) the Greater Paris University Hospitals (AP-HP); and 2) the University of California San Francisco's Hospitals (UCSF). These cohorts were built using solely structured data, routinely collected in the institutions' EHRs. The mBox's discriminative ability to predict death at 3 years following KT was assessed by computing the AUC. Adequation between predicted and observed risk of death was assessed with calibration.

Results

Out of 10 367, 191 and 5 885 623 patients, we identified 2 560 and 2 028 consecutive KTRs meeting the inclusion criteria in the AP-HP and UCSF cohorts, respectively. In the AP-HP cohort, 344 (13.4%) patients died, during a median follow-up of 3.1 years (interquartile range [IQR]: 1.8 to 4.1). In the UCSF cohort, 150 (7.4%) patients died, during a median follow-up of 2.7 years (IQR: 1.2 to 4.1). The mBox's AUC to predict death within 3 years following KT was 0.780 (95% confidence interval [CI]: 0.752 to 0.801) in the AP-HP cohort and 0.720 (95% CI: 0.672 to 0.768) in the UCSF cohort. Visual examination of the calibration curves showed that the mBox accurately estimated the actual risk of death in the UCSF cohort, and tended to underestimate the actual risk of death in the AP-HP cohort.

Conclusion

In this real-world international study, performed on 4 588 kidney transplant recipients, relying solely on data routinely collected in institutions' electronic health records, we demonstrate a fair accuracy of the mBox risk prediction score in predicting patient death following transplantation.
#1640 Alternative complement pathway disorders in the transplant setting—experience from a large volume center
Authors: Simunov Bojana , Jurekovic Zeljka , Zibar Lada , Laganovic Mario
Published: May 2024

Background and Aims

Complement alternative pathway disorders, atypical hemolytic-uremic syndrome (aHUS) and C3 glomerulopathy (C3G), are rare diseases with a high rate of recurrence after kidney transplantation. Due to limited availability of testing, patients may go undiagnosed, indicating testing during pretransplant evaluation. Posttransplant thrombotic microangiopathy (TMA) is a rare complication of transplantation. A large number of post transplant TMAs is regarded as secondary, either to immunosuppressive drugs or transplant itself. In select cases, complement alternative pathway disorders analysis is warranted.

Method

We retrospectively reviewed all patients in whom complement system diagnostic work-up was performed in the transplant setting in our center, from 2017 to 2022. Complement system analysis in isolated histological TMA of the allograft, without extrarenal manifestations and with known cause of native kidneys ESRD, was not performed routinely.

Patients in whom alternative pathway disorders were confirmed were compared with those with no abnormalities detected by complement system analysis.

Results

12 patients were identified, 75% male, median age 39.5 years (IQR 28-60.25). 8 patients were evaluated before transplantation. 4 of the 8 patients were referred for transplantation with diagnosed aHUS. Genetic testing was used for recurrence risk stratification. In living donor transplantations 2 donors were tested as well. One patient was referred from a neighboring resource poor country and was not on eculizumab therapy. He was homozygous for a high risk causative mutation. He was declined for living related donor kidney transplant, due to risk to the donor and unavailability of eculizumab. Compassionate use request was initiated. One patient was referred as possible C3G and repeat complement analysis revealed elevated C3Nef. Out of 3 patients, previously diagnosed as CKD of unknown origin or immune complex-mediated membranoproliferative glomerulonephritis, 2 were diagnosed during pretransplant evaluation: one as C3G and the other as aHUS. 4 patients were evaluated posttransplant. One analysis was performed due to recurrent C3G of the allograft, with confirmed competent dysregulation. 2 analyses were in liver transplant recipients, both with systemic TMA. Severe overactivation with consumption of complement was proven in one and treated with eculizumab. The characteristics of patients with diagnosed disorders of the complement system and those without are shown in Table 1.

Conclusion

Transplant physicians should keep a high volume of suspicion for complement dysregulation disorders, both during the pretransplant work-up and when evaluating TMA and recurrent GN posttransplant. Special caution should be advised when a patient is referred as chronic GN, MPGN or unknown cause ESKD at a young age.
#1206 Combination therapy with Lisinopril and Dapagliflozin rescues GFR decline and glomerular damage in the KKAy mouse model of diabetic kidney disease
Authors: van Koppen Arianne , Hinke Simon , Nguyen Tri , Dendooven Amélie , Tseng Tzu-Ling , Hsu Wei-Chan , Bajema Ingeborg , Menke Aswin , van Goor Harry , Stoop Reinout
Published: May 2024

Background and Aims

Male KKAy mice develop diabetic kidney disease (DKD) with progressive decline of GFR upon high fat diet feeding which is accelerated by the vasoconstrictor LNNA. In this study, efficacy of combination therapy with clinical relevant therapeutics in the form of an ACE-inhibitor (Lisinopril) and SGLT2-inhibitor (Dapagliflozin) on renal function and histopathology was investigated.

Method

Male KKAy mice underwent uninephrectomy (UNX). After recovery mice received high fat diet (45% LARD) and 50 mg/L LNNA in drinking water (wk0). At week 4, Lisinopril (2.5 mg/kg/day in drinking water) and at week 8 Dapagliflozin (5 and 20 mg/kg/day in diet) were started. Body weight, blood glucose, food and water intake and albuminuria were determined regularly. GFR was measured transdermally by FITC-sinistrin clearance. Mice were terminated at week 16 and renal histology was scored by a team of renal histopathologists. Non-induced and induced non-treated mice were used as controls.

Results

Treatment of KKAy mice on HFD+LNNA with Dapagliflozin reduced blood glucose immediately. Combination therapy with Lisinopril and Dapagliflozin (5 mg/kg/day) rescued the progressive GFR decline to levels seen in non-induced chow-controls (p < 0.05 vs UNX+HFD+LNNA). Pathology showed that the percentage of healthy glomeruli increased from 14% to 26% after combination therapy (Dapa 5). Interstitial fibrosis and tubular atrophy were significantly reduced by combination therapy (p < 0.05 vs UNX+HFD+LNNA).

Conclusion

Male KKAy mice on a HFD and LNNA developed DKD resulting in CKD. Combination therapy with Lisinopril and Dapagliflozin rescued GFR decline and reduced glomerular damage and interstitial fibrosis and tubular atrophy This indicates the clinical relevance of the model which can be used to study compound efficacy in both early and more advanced stages of DKD.
#2023 The role of neutrophil extracellular traps in cisplatin-induced acute kidney injury
Authors: Cao Jingyuan , Liu Haifei , Hu Xinhui , Ni Weijie , Wang Ze , Liu Hong
Published: May 2024

Background and Aims

Acute kidney injury (AKI) is a public health problem that seriously endangers human health. The exact pathogenesis of AKI has not been fully elucidated. Previous studies have shown that the immune system plays a key role in the inflammatory response of AKI in the acute phase, especially innate immunity. Recent discoveries have highlighted that neutrophils, in particular the neutrophil extracellular traps (NETs), have central roles in the occurrence and development of AKI. However, the specific role and mechanism of NETs in AKI of different etiologies are remain unclear. This study aimed to investigate the role of NETs in the development of cisplatin-induced AKI and provide potential therapeutic targets for AKI treatment.

Method

Wild-type (WT) and NETs-deficient (PAD4-/-) mouse models of AKI were constructed by intraperitoneal injection of cisplatin. Mice were weighed at 24, 48, and 72 hours after modeling, and sacrificed at 72 hours. Serum and kidney specimens were collected for renal function analysis, pathological, immunohistochemical staining, and molecular biology experiments. Mouse bone marrow neutrophils were isolated from healthy mouse. NETs were induced in vitro by adding phorbol 12 myristate 13-acetate (PMA). Primary renal tubular epithelial cells (TECs) of mouse kidney were extracted, and the cells were collected after 24 h of cisplatin and cisplatin combined with NETs intervention, respectively. The inflammatory indicators such as TNF-α, IL-1β, MCP-1, and renal injury indicators such as KIM-1 and Ngal were detected by RT-PCR.

Results

Compared with the WT-cisplatin group, the PAD4-/- -cisplatin group showed a reduced degree of weight loss after modeling, lower serum creatinine and urea nitrogen levels, and significantly improved renal function. The PAD4-/- -cisplatin group showed a significant decrease in the inflammatory indicators TNF-α, IL-1β, IL-6, and renal injury indicators KIM-1 and Ngal. Cisplatin intervention for 6 hours could induce the generation of NETs. Compared with the cisplatin intervention group, the expression of inflammatory indicators TNF-α, IL-1β, and MCP-1 were significantly higher in the cisplatin combined with NETs intervention TECs group.

Conclusion

Cisplatin directly induces neutrophils to generate NETs, which can exacerbate cisplatin-induced injury to TECs in vitro. The inhibition of NETs by PAD4-/- improves cisplatin-induced AKI. The inhibition of NETs may be a novel target for the treatment of cisplatin AKI.
#1663 Utilizing the MELD-Na score to predict renal replacement therapy and mortality among adult patients with leptospirosis-associated acute kidney injury
Authors: Soco Marc Lawrence , Ong Aaron Lemuel , Dinsay Mark Gavin , Lao Janice Jill
Published: May 2024

Background and Aims

Leptospirosis is a zoonotic disease with manifestations ranging from mild to severe. Acute kidney injury (AKI) in leptospirosis is usually a marker of poor prognosis and there remains a paucity of scoring systems utilized to predict renal replacement therapy (RRT) and mortality. The Model for End-Stage Liver Disease-Sodium (MELD-Na) was originally developed to predict survival in patients with liver cirrhosis. The components of the MELD-Na score evaluate renal and hepatic dysfunction, which are frequent complications in leptospirosis. This study aims to evaluate the prognostic significance of the admission MELD-Na score in predicting renal replacement therapy and mortality among patients with leptospirosis-associated AKI.

Method

A retrospective, single-center, cross-sectional study was conducted at a tertiary hospital in Manila, Philippines. The study enrolled patients from January 2018 to September 2023 and collected demographic and clinical data, along with laboratory values taken on admission. The MELD-Na score was developed using these values and its distribution was visualized by histogram. Receiver operating characteristic curve analysis was used to determine the score's predictive ability and the optimum cut-off was determined by the cut-point with the highest Youden index.

Results

The study included a total of 298 patients. The median age of the participants was 39, with 88.59% being males, and 77.52% having no known comorbidities. Of the study population, 74.16% underwent RRT, while the in-hospital mortality rate was 12.08%. Univariate analysis revealed that oliguria, serum creatinine, arterial pH, serum bicarbonate, and administration of methylprednisolone pulse therapy were among the predictive factors for RRT, in line with clinical practice guidelines. Other parameters found to be predictive of RRT were serum sodium and bilirubin. An admitting MELD-Na score of >26 predicted RRT with 91.0% sensitivity [86.4, 94.4] and 87.7% specificity [76.3, 94.9], yielding an area under the curve (AUC) of 0.953 (95% CI). Conversely, an admitting MELD-Na score >31 was found to be 77.8% sensitive [60.8, 89.9] and 64.9% specific [58.8, 70.7] for predicting mortality, with an AUC of 0.748 (95% CI).

Conclusion

The MELD-Na is a good predictor of renal replacement therapy and in-hospital mortality among patients with leptospirosis-associated AKI. This scoring system holds the potential to serve as a tool for risk stratification and prognostication in moderate to severe cases of the disease. A validation cohort study is recommended for formulating a prediction scoring system based on the individual components of the MELD-Na score, such as bilirubin and sodium.
#475 Association between hospital-acquired acute kidney injury and the risk of kidney cancer
Authors: Liu Jiao , Gao Qi , Lin Yuxin , Nie Sheng , Xu Xin
Published: May 2024

Background and Aims

The effects of hospital-acquired acute kidney injury (HA-AKI) on kidney cancer remain unclear. The study aimed to investigate the association between HA-AKI and kidney cancer by a large multicenter cohort study.

Method

The real-world cohort study included Chinese adults with at least two serum creatinine (SCr) tests within 7 days during hospitalization from 24 regional central hospitals between January 2000 and December 2022. AKI was defined as a ≥26.5 μmol/l increase in serum creatinine concentration within 48 hours or a ≥50% increase over the baseline within 7 days. The primary outcome was a new diagnosis of kidney cancer, while the secondary outcomes included death attributed to kidney cancer and new diagnoses of other cancers of the urinary system. The Cox proportional hazard model was employed for analyses.

Results

Of the 342861 patients (median age, 57.06 [43.68, 68.54] yr; men, 179096 [52.2%]), 9337 patients experienced HA-AKI. During a mean follow-up of 2.03 years, 195 (0.57‰) patients with a new diagnosis of kidney cancer were detected. After multivariable adjustment, HA-AKI was significantly associated with a higher risk of kidney cancer (adjusted hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.37-4.17, P = 0.003) and kidney cancer-specific death (adjusted HR, 3.19; 95% CI, 1.90-5.37, P < 0.001). We also found that relationships between HA-AKI and cancers of the urinary system, excluding kidney cancer, such as bladder cancer, prostate cancer, were not statistically significant.

Conclusion

HA-AKI was significantly associated with increased risk of kidney cancer and death attributed to kidney cancer. Our findings highlight the importance of monitoring HA-AKI patients for early detection of kidney cancer.
#2719 Hypoalbuminemia as a mortality risk factor in acute kidney injury
Authors: Pešić Snežana , Stopić Bojan , Djuric Petar , Dimkovic Nada , Naumovic Radomir
Published: May 2024

Background and Aims

Preexisting hypoalbuminemia in many studies was an independent factor of mortality in patients with acute kidney injury (AKI). Albumin replacement in patients with AKI did not affect their survival. Each 1.0 g/l decrease in serum albumin was associated with an increased probability of developing AKI (OR 1.685). Also, it was shown that serum albumin level below 32 g/l is a significant risk factor for the occurrence of AKI. The mortality of patients with AKI is extremely high, approximately 50%, in patients with AKI who require dialysis treatment it is 50-70%, while in patients on supportive ventilation or with multisystem organ failure it is even 80-90%.

Method

The retrospective study included 280 patients diagnosed with AKI in the period from 2014 to 2018. Demographic, laboratory parameters and therapeutic procedures were analyzed in order to determine their influence on the treatment outcome. Binary logistic regression was used to test statistical significance to identify potential mortality factors.

Results

The incidence of AKI was 6.5%. The mean age was 67.8±13.8 years (19, 91) without statistically significant difference by gender (50.4% men) (p = 0.22). The most prevalent is prerenal AKI 57.1%, followed by renal 24.3% and postrenal 18.6%. Renal replacement therapy is required in 15.7% of patients. Intermittent HD was applied statistically significantly more often, 90.9%, and continuous renal replacement therapy (CRRT) procedures were applied in 9.1% of patients (p < 0.001). Mortality was 18.6%. With each increase in the patient's age by one year, the probability of a fatal outcome increases by 1.045 times (p = 0.000; OR: 1.045). Hypoproteinemia and hypoalbuminemia increase the probability of death. For each unit decrease in albumin by 1 g/l, the risk of death increases by 13% (p = 0.000; OR: 0.872), and each decrease in protein by 1 g/l increases the risk of death by 7% (p = 0.000 ; OR: 0.939). Among other factors that showed statistical significance are hyperphosphatemia (p = 0.001; OR: 1.990), acidosis (p = 0.007; OR: 0.002), inflammation (p = 0.029; OR: 1.003).

Conclusion

Acute kidney injury is accompanied by a high mortality rate. Low serum albumin levels at the time of diagnosis are a significant independent factor of acute kidney function impairment and death. Other risk factors that contribute to a poor outcome in patients with AOB are age, hyperphosphatemia, acidosis, and inflammation.
#976 Empagliflozin limits AKI incidence and severity following cardiac surgery: an open-label phase IV randomized pilot study
Authors: Snel Lars , Oosterom-Eijmael Marjella , Rampanelli Elena , Lankadeva Yugeesh , Plummer Mark , Preckel Benedikt , Hermanides Jeroen , van Raalte Daniël , Hulst Bram
Published: May 2024

Background and Aims

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent complication of cardiac surgery assisted by cardiopulmonary bypass (CPB). Currently, no effective preventative strategies exist to reduce the incidence of acute kidney injury (AKI). Sodium-glucose transport protein 2 (SGLT2) inhibitors are effective in reducing the incidence of AKI in studies conducted in patients with chronic kidney disease. Therefore, we hypothesized that perioperative SGLT2 inhibition could reduce the incidence of CSA-AKI.

Method

In this open-label phase IV, randomized, parallel-group, balanced (1:1), pilot study, adult patients undergoing elective cardiac surgery with CPB were randomized to receive 10 mg empagliflozin per os once daily three days before surgery until two days after surgery, or standard care. The primary outcome was AKI incidence according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Other outcomes included hypoxia-inducible factor 1 alpha (HIF1A) and urinary Kidney Injury Molecule (KIM-1), urinary neutrophil gelatinase associated lipocalin (NGAL) and metabolic parameters such as plasma ketone and glucose concentrations.

Results

Between March 2022 and April 2023, 60 patients were randomized to empagliflozin (n = 29) or control (n = 31). All patients who underwent cardiac surgery with CPB were included in the intention-to-treat analysis (n = 25; empagliflozin group, n = 30; control group). SGLT2 inhibition significantly reduced the incidence of all stages of AKI (20% vs 66.7%; absolute difference 46%, 95% CI .13 to .63, P < .001). This decline in AKI incidence was reflected in the kidney biomarkers. SGLT2 inhibition also significantly reduced the number of patients with postoperative hyperglycemia (28% vs 60%; absolute difference 32%, 95% CI −56.8 to −7.2, P  =  .029). We observed no differences in the incidence of neither ketoacidosis nor hypoglycemic events.

Conclusion

Perioperative SGLT2 inhibition, compared with standard of care, demonstrated a significant reduction in AKI incidence rates. These findings merit validation in a larger placebo-controlled trial which is currently ongoing.

Supplementary figures:
#259 Predictive capacity and comparison of new biomarkers for AKI in patients undergoing non-cardiac surgery
Authors: de Cal Massimo , Virzì Grazia Maria , Ronco Claudio , Zanella Monica
Published: May 2024

Background and Aims

The diagnosis of AKI, according to the KDIGO guidelines, is still based on a tangible increase in serum creatinine which, however, cannot be detected until 24-48 hours after renal damage. Unfortunately, it has not been possible to identify among the various new biomarkers the one that is potentially able to detect AKI early, to intervene promptly to preserve renal function.

The aim of this study was to analyze, in a population of patients undergoing major non-cardiac surgery, the most recent urinary biomarkers to evaluate their predictive potential for AKI and compare them with creatinine levels.

Method

22 patients (18 males, 4 females) with an average age of 76 (67-85) years were enrolled for the study.

22 urine samples were analyzed by:

Results

Carrying out a correlation between the new biomarkers for AKI (Nephrocheck, NGALds and SEPP1) with creatinine levels at different times (pre-operative, post-operative and 24 h post-operative) shows a significant correlation only with NGALds (respectively p = 0.017, p = 0.035 and p = 0.012) (Table).

Subdividing patients based on the increase in creatinine levels from pre-operation to 24 hours post-operation, the only biomarker that showed an increase in values ​​was NGALds, while the others showed levels discordant with creatinine.

Conclusion

By analyzing the new biomarkers and comparing them with the creatinine data, it emerged that NGALds alone significantly correlated with the latter at different times. The other urinary biomarkers (Nephrocheck and SEPP1) showed no correlation with creatinine levels.

Based on this outcome, it could be assumed that NGALds is the biomarker which, due to its characteristics already stated in numerous studies and its correlation with creatinine, could be used and replace the latter as an early biomarker of AKI.
#2698 Regression of amyloid deposits after treatment with tocilizumab
Authors: Tortosa-Cabañas Marina , Acosta-Battle Jose , Perna Cristian , Andreu-Suárez África , Corral-Bote Ana , Bachiller-Corral Javier
Published: May 2024

Background and Aims

AA amyloidosis is a multisystem disease characterized by the deposition of serum amyloid A protein, which is secondary to chronic inflammation. Tocilizumab (an interleukin-6 inhibitor monoclonal antibody) is effective in suppressing inflammation, normalizing serum amyloid A protein levels and inducing remission in patients with amyloidosis. Recently, tocilizumab treatment has been associated with the disappearance of amyloid deposits.

Results

We report a case of AA amyloidosis secondary to chronic arthritis in a 61-year-old woman referred to our hospital in 2011 due to oligoarthritis of the knees and elevation of acute-phase reactants. Corticosteroids and methotrexate were prescribed, without clinical response. Two years later, the patient presented with foamy urine, nocturia, sweating and dizziness. An elevated C-reactive protein (CRP), erythrocyte sedimentation rate and nephrotic-range proteinuria were found. Rectal and oral mucosa biopsies were performed and amyloid AA deposits were detected in both (Fig. 1A, B). Magnetic resonance imaging (MRI) of the right knee showed arthropathy due to amyloid deposition (Fig. 2). Intravenous monthly tocilizumab was prescribed with rapid improvement of CRP, proteinuria (Fig. 3) and nephrotic syndrome symptoms. Arthritis also improved significantly. Two years later, a new biopsy of the rectal mucosa did not show amyloid deposits (Fig. 1C, D) and right knee MRI was normal, without evidence of amyloid synovitis (Fig. 4). Eight years later, the patient continues treatment with tocilizumab and remains clinically stable, with no evidence of recurrence.

Literature review: The efficacy of tocilizumab has been described mainly in patients with rheumatoid arthritis, but also in AA amyloidosis secondary to systemic juvenile idiopathic arthritis, familial Mediterranean fever, psoriatic arthritis, ankylosing spondylitis, Still's disease, Muckle-Wells syndrome, Behçet syndrome, polyarteritis nodosa and Takayasu arteritis. Some of the studies report long-term effectiveness of up to 9 years. In 11 case reports of patients with AA amyloidosis treated with tocilizumab, a follow-up biopsy was performed and a reduction or disappearance of the deposits was also observed. Lane et al. analyzed pre- and on-treatment serial scintigraphy scans in 20 patients with AA amyloidosis, showing that AA amyloid deposits either regressed or did not increase whilst on tocilizumab. We have not identified any study demonstrating the disappearance of amyloid arthropathy in MR images.

Conclusion

Tocilizumab treatment controls chronic inflammatory disease and improves symptoms of AA amyloidosis. Long-term treatment with tocilizumab may remove amyloid deposits from tissues, leading to a definitive cure of this disease.
#2358 Impact of COVID-19 on the clinical course of nephrotic syndrome in children: a single-center study
Authors: Park Min Ji , Cho Min Hyun
Published: May 2024

Background and Aims

Children with nephrotic syndrome may experience disease relapse or aggravation triggered by various viral infections. Limited studies on the clinical implications of the coronavirus disease 2019 (COVID-19) pandemic in children with nephrotic syndrome have been published worldwide. Therefore, this study aimed to investigate the effects of COVID-19 on the clinical course of nephrotic syndrome in children.

Method

The medical records of pediatric patients with idiopathic nephrotic syndrome who visited our hospital between February and June 2022 were retrospectively analyzed. Patients aged <1 year and >19 years and those with inadequate medical records were excluded. Finally, total 59 patients (20 pediatric patients diagnosed with COVID-19 and 39 pediatric patients who did not have COVID-19) were included in the study.

Results

Twenty of the total 59 patients with nephrotic syndrome were diagnosed with COVID-19 during the study period. The mean age at the time of the diagnosis of nephrotic syndrome and COVID-19 in all 20 patients was 4.6 ± 3.5 and 8.9 ± 3.9 years, respectively. Three patients (15%) were diagnosed with nephrotic syndrome relapse during COVID-19 and the relapse rate was similar to them without COVID-19 (20.5%, 8/39 patients). At the time of the COVID-19 diagnosis, fever (85%) and cough (40%) were the most common symptoms. After the diagnosis of COVID-19, all patients showed improvement with symptomatic treatment, including antipyretic analgesics and cold medicine. None of the critical patients required hospitalization or oral antiviral medications.

Conclusion

Despite the use of immunosuppressants, the clinical manifestations of COVID-19 in children with nephrotic syndrome were not severe and are expected to be similar to that in the general population. The relapse rate of nephrotic syndrome in children with COVID-19 was also not different from them without COVID-19.
#340 Time dependent changes in the treatment of relapsing Minimal Change Disease – a multicenter cohort study
Authors: Kristensen Tilde , Maas Rutger , Birn Henrik , Ivarsen Per
Published: May 2024

Background and Aims

Prednisolone monotherapy is the most used initial immunosuppressive treatment for nephrotic syndrome in adults with Minimal Change Disease (MCD) but choice of treatment in relapsing MCD is not as well described. With the introduction of new drugs and increased concern relating to the adverse events of prednisolone, treatment might have changed over time. The aim of this study is to describe changes in daily clinical practice of relapsing MCD within the last 35 years.

Method

A multicenter, retrospective analysis of adult patients with biopsy proven MCD from 13 hospitals from 1987-2022 in Denmark and the Netherlands. Patients were identified from the pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Relapse is defined when the nephrologist found indication to restart an immunosuppressive treatment or increase the ongoing immunosuppression in patients in partial or complete remission.

Results

We included 167 Dutch and 72 Danish patients (n = 239) with MCD. Most patients (n = 205, 86%) were initially treated with prednisolone monotherapy. Overall, 93% (n = 220) gained remission and 56% (n = 123) of those who went into remission had one or more relapse with 68% of these occurring in the first year after remission. At the time of relapse, 89% were in complete remission and 11% were in partial remission. At first relapse, prednisolone monotherapy was the most prescribed treatment both before and after 2010 (69% and 45%, respectively), while the use of CNI tripled after 2010 (p = 0.002) (10% to 32%). At second relapse, prescription of CNI after 2010 showed a five-fold increase compared with before 2010 (49% vs 10%, respectively) while the use of prednisolone monotherapy was halved (50% to 24%). The use of cyclophosphamide decreased by two-thirds (32% to 10%) after 2010.

Before 2010, 54% of patients received prednisolone monotherapy for their third to 14th relapse, but after 2010 this decreased to 26%. The use of rituximab and CNI both increased and after 2010 these were both prescribed to about one third of patients at third to 14th relapse. The use of cyclophosphamide decreased from 30% to 2% comparing before and after 2010.

Rituximab was only used after 2010, and more frequently with the number of relapses (6% at first relapse and 36% at third to 14th relapse). Regardless of the choice of treatment the rates of remission were high.

Conclusion

The treatment of relapses has changed over time with a reduced use of prednisolone monotherapy and cyclophosphamide and increased use of CNI and rituximab.