Episodes Of Injury Research Articles

Kidney status and events preceding death in heart failure: A real world data study on 18,456 patients with heart failure

Abstract Background Despite advancements in heart failure (HF) management, kidney dysfunction remains a significant clinical challenge, and is associated with higher mortality rates and other adverse outcomes. However, there are few studies of kidney events preceding death in patients with HF in the real world. Methods Using registry-based data, the prevalence of kidney events preceding death in patients with HF over the period 2014-2018 in Denmark. All deaths in patients with a diagnosis of HF within the previous 10 years were included. Kidney events occurring during within 1 year of death compromised of: acute kidney injury, chronic renal replacement therapy, sustained eGFR<15 mL/min/1.73 m2, or renal transplantation. The prevalence of kidney events preceding death was calculated and different subgroups were compared. Results Among the 18,586 HF patients who died, a total of 3107 (16.7%) experienced kidney events during within 1 year of death. The prevalence of HF patients with kidney events before death was 15.5% for acute kidney injury, 5.8% for chronic renal replacement therapy, 7.4% for an eGFR<15 mL/min/1.73 m2, and 0.18% for renal transplantation (see Figure 1). Acute kidney injury episodes were frequently observed in the last month before death (7.5%) (Figure 2). Age-specific analysis revealed a higher proportion of deaths associated with kidney dysfunction in patients under the age of 65 years compared to those aged 80 years and above (24.3% vs 13.4%). Furthermore, male sex, death in-hospital, reduced pre-existing kidney function, a higher degree of frailty, and lower educational status were associated with higher frequency of death associated with kidney dysfunction. Conclusion In this real-world study, a significant proportion of deaths among HF patients were associated with kidney dysfunction, particularly with acute kidney injury. Further research and awareness of renal complications are necessary to improve outcomes in this population.

Acute kidney injury results in long-term alterations of kidney lymphatics in mice.

The long-term effects of a single episode of acute kidney injury (AKI) induced by bilateral ischemia-reperfusion injury (BIRI) on kidney lymphatic dynamics are not known. The purpose of this study was to determine if alterations in kidney lymphatics are sustained in the long term and how they relate to inflammation and injury. Mice underwent BIRI as a model of AKI and were followed up to 9 mo. Although kidney function markers normalized following initial injury, histological analysis revealed sustained tissue damage and inflammation for up to 9 mo. Transcriptional analysis showed both acute and late-stage lymphangiogenesis, supported by increased expression of lymphatic markers, with unique signatures at each phase. Expression of Ccl21a was distinctly upregulated during late-stage lymphangiogenesis. Three-dimensional tissue cytometry confirmed increased lymphatic vessel abundance, particularly in the renal cortex, at early and late timepoints postinjury. In addition, the study identified the formation of tertiary lymphoid structures composed of CCR7+ lymphocytes and observed changes in immune cell composition over time, suggesting a complex and dynamic response to AKI involving tissue remodeling and immune cell involvement. This study provides new insights into the role of lymphatics in the progression of AKI to chronic kidney disease.NEW & NOTEWORTHY Here, we perform the first, comprehensive study of long-term lymphatic dynamics following a single acute kidney injury (AKI) event. Using improved three-dimensional image analysis and an expanded panel of transcriptional markers, we identify multiple stages of lymphatic responses with distinct transcriptional signatures, associations with the immune microenvironment, and collagen deposition. This research advances kidney lymphatic biology, emphasizing the significance of longitudinal studies in understanding AKI and the transition to chronic kidney disease.

Impressive weight loss induced by a very low-calorie ketogenic diet in a morbidly complex obese patient with a recent episode of acute kidney injury and advanced chronic kidney disease: a case report

The very low-calorie ketogenic diet (VLCKD), characterized by a marked energy restriction that induces rapid weight loss, has recently been proposed as a valid nutritional strategy for managing obesity. VLCKD is commonly considered dangerous for the kidneys due to the misconception that it is high in protein, beyond the risk of electrolyte imbalances and an increase in diuresis. We report a case of safe and effective weight loss induced by VLCKD in a 43-year-old Caucasian woman with a recent episode of acute kidney injury on advanced chronic kidney disease. Surprisingly, we observed that after the diet-induced weight loss, not only did renal function not worsen, but proteinuria also improved. The principal value of this case report is its singular demonstration of impressive weight loss induced by VLCKD in a complex obese patient that was apparently not accompanied by the development of serious adverse sequelae.

Clinical features and outcomes in carriers of pathogenic desmoplakin variants.

Pathogenic variants in the desmoplakin (DSP) gene are associated with the development of a distinct arrhythmogenic cardiomyopathy phenotype not fully captured by either dilated cardiomyopathy (DCM), non-dilated left ventricular cardiomyopathy (NDLVC), or arrhythmogenic right ventricular cardiomyopathy (ARVC). Prior studies have described baseline DSP cardiomyopathy genetic, inflammatory, and structural characteristics. However, cohort sizes have limited full clinical characterization and identification of clinical and demographic predictors of sustained ventricular arrhythmias (VAs), heart failure (HF) hospitalizations, and transplant/death. In particular, the relevance of acute myocarditis-like episodes for subsequent disease course is largely unknown. All patients with pathogenic/likely pathogenic (P/LP) DSP variants in the worldwide DSP-ERADOS Network (26 academic institutions across nine countries) were included. The primary outcomes were the development of sustained VA and HF hospitalizations during follow-up. Fine-Gray regressions were used to test association between clinical and instrumental parameters and the development of outcomes. Eight hundred patients [40.3 ± 17.5 years, 47.5% probands, left ventricular ejection fraction (LVEF) 49.5 ± 13.9%] were included. Over 3.7 [1.4-7.1] years, 139 (17.4%, 3.9%/year) and 72 (9.0%, 1.8%/year) patients experienced sustained VA and HF episodes, respectively. A total of 32.5% of individuals did not fulfil diagnostic criteria for ARVC, DCM, or NDLVC; their VA incidence was 0.5%/year. In multivariable regression, risk features associated with the development of VA were female sex [adjusted hazard ratio (aHR) 1.547; P = .025], prior non-sustained ventricular tachycardia (aHR 1.721; P = .009), prior sustained VA (aHR 1.923; P = .006), and LVEF ≤ 50% (aHR: 1.645; P = .032), while for HF, they were the presence of T-wave inversion in 3+ electrocardiogram leads (aHR 2.036, P = .007) and LVEF ≤ 50% (aHR 3.879; P < .001). Additionally, 70 (8.8%) patients experienced a myocardial injury episode at presentation or during follow-up. These episodes were associated with an increased risk of VA and HF thereafter (HR 2.394; P < .001, and HR 5.064, P < .001, respectively). Patients with P/LP DSP variants experience high rates of sustained VA and HF hospitalizations. These patients demonstrate a distinct clinical phenotype (DSP cardiomyopathy), whose most prominent risk features associated with adverse clinical outcomes are the presence of prior non-sustained ventricular tachycardia or sustained VA, T-wave inversion in 3+ leads on electrocardiogram, LVEF ≤ 50%, and myocardial injury events.

Rifaximin alone vs combination with norfloxacin for secondary prophylaxis of spontaneous bacterial peritonitis with hepatic encephalopathy: randomized controlled trial

BackgroundIn liver cirrhosis, events of spontaneous bacterial peritonitis (SBP) and hepatic encephalopathy (HE) portend a poor prognosis. Gut dysbiosis remains a common pathogenetic mechanism for both SBP and HE. Recent data suggests the role of rifaximin in gut modulation and improving intestinal dysbiosis. Due to emergence of multidrug-resistant organisms, gut-selective antibiotics with minimal systemic effects are warranted for secondary prophylaxis in patients of cirrhosis. We compared rifaximin alone vs combination with norfloxacin for secondary prophylaxis of patients of cirrhosis presenting with SBP and HE. This was a prospective, open-label, RCT which included all patients of cirrhosis with SBP and HE on admission. On discharge, in addition to standard medical treatment, patients were randomized to rifaximin 400 mg three times a day (group I) and rifaximin 400 mg three times a day with norfloxacin 400 mg once a day (group II) as a secondary prophylaxis of SBP. Primary outcomes were recurrent episodes of SBP and HE at 6 months and 28-day, 90-day, and 6-month mortalities. Secondary outcomes included number of rehospitalizations, episodes of upper gastrointestinal bleed, new acute kidney injury episodes, and change in Child–Turcotte–Pugh (CTP) and model for end-stage liver disease (MELD) scores over next 6 months.ResultsAfter screening 87 patients of cirrhosis with SBP and HE, 12 patients had in-hospital mortality and another 25 were excluded, one patient was lost to follow-up, and, finally, 49 patients were randomized into group I (n = 24) and group II (n = 25). The HE was grade 2 (18 vs 16) and grade 3 (6 vs 9) in groups I and II respectively. Primary outcomes as recurrent SBP (3 vs 2; P = 0.67); recurrent HE at 6 months (5 vs 2; P = 0.24); and 28-day (2 vs 2; P = 1.0) and 90-day mortality (4 vs 3; P = 0.72) and 6-month mortality (6 vs 8, P = 0.52) were comparable between two groups respectively. Secondary outcomes as number of rehospitalizations (3 vs 8, P = 0.07), new episodes of UGI bleed (2 vs 3, P = 0.1), new AKI episodes (4 vs 1, P = 0.06), ∆CTP (− 4 vs − 4), and ∆MELD (− 9 vs − 8) over the next 6 months were not significantly different between two groups respectively.ConclusionsRifaximin was effective in secondary prevention of both SBP and HE in patients of cirrhosis.Trial registrationThe randomized controlled trial was registered in CTRI/2021/09/036321 dated September 7, 2021.

Prevalence of harassment, abuse, and mental health among current and retired senior Swedish cheerleaders

ABSTRACT This study examined the prevalence of non-accidental violence, focusing on experienced harassment and abuse (HA), and mental health among current and retired Swedish competitive cheerleaders. An online survey was distributed to current and retired athletes in the Swedish cheerleading federation. The survey assessed perceived coach–athlete relationship, sport psychological safety, resilience, mental health, and experienced HA within the cheerleading environment. A total of 284 athletes (men = 5; women = 278; gender not disclosed = 1; current athletes = 211; retired athletes = 73) completed the survey. Psychological abuse was the most frequently reported HA form (current athletes = 21.6%; retired athletes = 53.5%), followed by neglect (current athletes = 5.4%; retired athletes: 26.8%) and physical abuse (current athletes = 3.9%; retired athletes = 12.7%). A high-quality coach–athlete relationship was identified as a protective factor for HA. Additionally, 33.1% and 8.9% of participants displayed scores indicating anxiety and depression caseness, while 63.8% reported a high level of wellbeing. Anxiety/depression scores above clinical cut-off were linked to injury episodes and a high level of wellbeing to a mentally healthy environment. Resilience was found to protect mental health overall. The high occurrence of reported psychological abuse and indications of anxiety/depression related to injury episodes suggest a need of attention towards prevention and athlete protection strategies in cheerleading environments.

Hair-straightening cosmetics containing glyoxylic acid induce crystalline nephropathy

We recently reported the case of a patient who experienced three consecutive episodes of acute kidney injury, all of them following a "Brazilian" hair-straightening treatment. The cream used for the straightening procedure contained glyoxylic acid. To examine possible underlying mechanisms causing kidney injury, four groups of mice were exposed to topical application of (i) the straightening product, (ii) a cream containing 10% glyoxylic acid, (iii) a cream containing 10% glycolic acid or (iv) a control cream. Application of glycolic acid slightly increased urine oxalate excretion, while glyoxylic acid and the straightening product dramatically increased urine oxalate excretion and caused calcium oxalate nephropathy after transcutaneous absorption. Thus, glyoxylic acid was presumptively absorbed through the skin, metabolized to oxalate and promoted crystallization of calcium oxalate in urine. Hence, cosmetic products containing glyoxylic acid may induce acute kidney injury and should be discontinued. Further studies are needed to investigate the metabolism of glycolic acid and glyoxylic acid following topical application.

The Legacy Effect of Intensive versus Standard BP Control on the Incidence of Needing Dialysis or Kidney Transplantation.

The Systolic Blood Pressure Intervention Trial (SPRINT) showed that intensive lowering of systolic blood pressure (BP) increased the risk of incident chronic kidney disease and episodes of acute kidney injury. Whether intensive treatment changes the risk of kidney failure is unknown. The goal of this study was to estimate the legacy effect of intensive versus standard systolic BP lowering on the longer-term incidence of kidney failure. Secondary analysis of a randomized, open-label clinical trial with observational follow-up. Between 2010 and 2013, patients 50 years and older with hypertension and higher cardiovascular risk excluding those with diabetes mellitus, history of stroke, proteinuria >1g / day or polycystic kidney disease were recruited from 102 clinic sites in the United States and Puerto Rico. Participants were randomized to a systolic BP goal of <120 mm Hg (intensive treatment) or <140 mm Hg (standard treatment group). We linked participants with the US Renal Data System to ascertain kidney failure (initiation of dialysis therapy or transplantation) and the US National Death Index to ascertain all-cause mortality through 2020. Based on analysis of 9279 (99.1%) of 9361 randomized participants, 101 cases of kidney failure occurred over a median follow-up of 8.6 years (interquartile range 8.0 to 9.1 years), with the majority occurring in 74 (73.3%) participants with an eGFR<45 ml/min/1.73 m2 at baseline. Intensive treatment did not significantly increase the risk of kidney failure either overall (cause-specific Hazard Ratio (HR) = 1.20, 95% CI: 0.81 - 1.78) or in the subgroup of participants with baseline eGFR<45 ml/min/1.73 m2 (HR = 1.43, 95% CI: 0.89 - 2.30). Overall, and in patients with eGFR <45 ml/min/1.73 m2, there were higher rates of dialysis or transplantation among SPRINT participants randomized to intensive treatment, but the modest differences observed were not statistically significant.

The impact of acute kidney damage in the community.

Assess incidence of Acute Kidney Diseas and Disorders (AKD) and Acute Kidney Injury (AKI) episodes and impact on progression of renal dysfunction and risk of all-cause mortality in the community. Community of 1863731 aged>23 years with at least two serum creatinine measurements. eGFR was calculated using CKD-EPI formula. CKD, AKD and AKI were defined according to the harmonized KDIGO criteria (Lameire 2021). The sCr values and RIFLE scale was used to classify episodes. Progression of renal dysfunction and mortality were evaluated. 56850 episodes of AKD in 47972 patients in 4.8 years were identified. AKD incidence of AKD was 3.51 and 12.56/1000 patients/year in non-CKD and CKD, respectively. One AKD episode was observed in 87.3% patients, two in 9.3% and three or more in 3.4%. A second episode was less common in patients without CKD (10.3%) compared to those with CKD (18.4%). Among patients without CKD a total of 43.8% progressed to CKD, and those with previous CKD 63.1% had eGFR decline of>50%. The risk of progression to CKD was higher in women, older, overweight-obesity and heart failure, as was the risk of eGFR decline>50% in CKD patients, although the number of AKD episodes was also a risk factor. AKI episodes were observed in 5646 patients with or without CKD. Of these, 12.7% progressed to CKD and of those with pre-existing CKD, 43.2% had an eGFR decline of>20%. In the toal population mortality within 3 months of detection of AKD episode occurred in 7% patients, and was even higher in patients with AKI, 30.1%. Acute elevations in serum creatinine in the community may pose a health risk and contribute to the development of CKD. Identification of therapeutic targets and provision of appropriate follow-up for those who survive an episode is warranted.

Healthcare utilization in Ghana: Insights from the 2017 Ghana Living Standard Survey.

The persistence of healthcare utilization disparities in Ghana despite several policy efforts highlights the urgency of understanding its determinants to enhance equitable health access. We sought to examine the determinants of healthcare utilization in Ghana. We used the 2017 Ghana Living Standard Survey (GLSS) data. This was a cross-sectional design, which employed a stratified two-stage random sampling technique. We analyzed data involving 8,298 respondents with information on visits to healthcare facilities for services on account of illness or injury two weeks prior to the survey. Pearson's chi-squared test was used to assess the distribution of healthcare utilization across background characteristics. Further, we used multivariable Poisson regression model with robust standard error to identify factors independently associated with healthcare utilization. Among the 8,298, the median age was 24 years (interquartile range = 7-47), 45% were males, and 45% had no education. About 42% of respondents utilized health services during an episode of illness or injury. Age, sex, educational level, marital status, wealth quintile, health insurance and severity of illness/injury were independently associated with healthcare utilization. Healthcare utilization increased significantly with wealth quintiles-those in the highest wealth quintiles had about 22% increased utilization compared to those in the lowest wealth quintiles (aPR = 1.22; 95%CI = 1.13-1.32) while it was about 77% higher among those who had valid health insurance compared to those without (aPR = 1.77; 95% CI = 1.68-1.86). Regarding severity of illness or injury, those with severe conditions were about 65% more likely to utilize healthcare services compared to those with acute conditions (aPR = 1.65; 95% CI = 1.53-1.78). Our study underscores the importance of socio-economic factors and health insurance in healthcare utilization in Ghana. Addressing these can pave the way for more equitable access to healthcare services across all segments of the population.

Acute Kidney Disease following Acute Kidney Injury in Children-A Retrospective Observational Cohort Study on Risk Factors and Outcomes.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding AKD in children are scarce. The purpose of our study was to explore the risk factors for developing AKD based on exposures and susceptibilities in children with AKI doubled by the biological parameters from the first day of identified AKI. In addition, we followed the trajectory of AKD following an acute kidney injury (AKI) episode in children during hospital admission and after discharge with special considerations towards mortality and progression to new-onset CKD. Methods: We retrospectively evaluated 736 children, ages between 2 and 18 years old, with identified AKI during hospital admission in a tertiary care hospital from west Romania over a 9-year period. Results: AKD incidence following an AKI episode was 17%. Patients who developed AKD were older, with higher baseline serum creatinine, urea, C reactive protein and lower proteins, haemoglobin and sodium levels. In the adjusted model, no biological parameters influenced AKD development. Regarding certain exposures and personal susceptibilities in children with AKI, only anaemia independently increased the risk of AKD development by 2.47 times. However, out of the AKI causes, only the intrinsic causes of AKI independently increased the risk of progressing to AKD (glomerulonephritis by 4.94 and acute tubule-interstitial nephritis by 2.76 times). AKD increased the overall mortality by 2.6 times. The factors that independently increased the risk of CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: Only anaemia, glomerulonephritis and acute tubule-interstitial nephritis increased the risk of AKD development in children with AKI. AKD was an independent risk factor for mortality and new-onset CKD in children.

#2705 Hypertension as a risk factor for mortality and the development of chronic kidney disease after an episode of acute kidney injury in the elderly

Abstract Background and Aims Acute kidney injury (AKI) is a real public health problem due to its severity and its consequences in the short, medium and long term. Hypertension is a very common disease in our country. The association between hypertension and acute and chronic renal failure is not well studied in our country, and given the lack of data, we proposed to carry out this study and even more so the elderly, who are fragile subjects with multiple illnesses. Method We undergone a retrospective study which was carried out in the nephrology department of Fattouma Bourguiba hospital in Monastir. We included patients aged &amp;gt; 65 years, who had an AKI with full recovery who had been hospitalized between January 2002 and December 2015. Our study aimed to assess the impact of hypertension on mortality and the development of chronic kidney disease (CKD) after an episode of AKI. Results Our population was made up of 67 men and 60 women, 30.1% had multiple comorbidities. Pre renal Aki represented the predominant mechanism of AKI which was retained in our study with a rate of 40% and dehydration as the main aetiology in 70 patients. In the short term, 15 patients had progressed to CKD. The mean overall survival in our study was 159 months with a high risk of mortality in elderly (patients aged &amp;gt;65 years), who had multiple comorbidities, hypertensive, diabetics, with vascular disease, Charlson Comorbidity index &amp;gt;5, who presented with hyperkalaemia &amp;gt;5.5 and pre renal mechanism of the AKI episode. In the medium term and the long term, 4 and 2 patients developed CKD respectively. Hypertension was a factor in poor prognosis and mortality in elderly subjects after an episode of acute kidney injury (p=0.005). Conclusion Hypertension is a real public health problem impacting the short, medium and long term prognosis of patients who have had an episode of AKI with full recovery.

#594 Long-term risk of incident/progressive chronic kidney disease, or end-stage kidney disease post-acute kidney injury: systematic review, meta-analysis

Abstract Background and Aims Little is known about which patients to follow-up after an episode of acute kidney injury (AKI) for future risks. The aim of this review is to assess the association between AKI and the incidence or progression of chronic kidney disease (CKD) or end-stage kidney disease (ESKD), stratified by subcategories of AKI-stages, -durations, and clinical settings. Method A systematic search of the literature in PubMed and Embase was performed by two reviewers to identify studies that examined CKD incidence (development of CKD stage ≥3), CKD progression (worsening of kidney function in patients with CKD stage ≥3), or ESKD, in patients with AKI versus patients without AKI. The risk of bias was assessed using the Newcastle-Ottawa Scale. Relative effect estimates (odds and hazard ratios) were pooled using a random effects model. Results In total, 48 retrospective and 13 prospective studies, encompassing 140.985 patients with AKI, were included in this review. All the studies were of moderate or high quality. The pooled effect ratio was 3.36 (95% confidence interval (CI) 2.68-4.03) for CKD incidence (n = 31 studies). This remained 3.40 (95% CI 1.79-5.00) in a sub analysis including patients with a recovered kidney function post-AKI, and 1.49 (95% CI 1.44-1.55) in a sub analysis including patients with an AKI lasting less than 3 days (Fig. 1). Overall, the effect ratio for CKD progression (n = 11 studies) was 1.70 (95% CI 1.38-2.01) and 3.81 (95% CI 2.58-5.04) for ESKD (n = 24 studies). The increased risk of these two outcomes were not seen in the sub analyses only including patients with AKI lasting less than 3 days. Overall, there is an observable higher risk for CKD incidence, CKD progression, and ESKD with increased AKI staging, although not always statistically significant. Minimal variations were observed across clinical settings. Conclusion In our review, including over 60 studies, we found that AKI was associated with an increased risk of CKD incidence, CKD progression, and ESKD. Patients with higher AKI-stages had even larger risks. Notably, even brief episodes of AKI (lasting less than 3 days) were associated with a higher risk of CKD incidence compared to patients without AKI. In contrary, the risk for ESKD is not enlarged in a sub analysis including patients with recovered kidney function compared to patients without AKI. These result warrant close monitoring of the kidney function post-AKI, specifically in patients with AKI lasting 3 days or longer. Future research should focus more on the risk of CKD progression in order to tailor follow-up care in these more vulnerable patients.

#2379 Acute kidney injury as a key predictor of major adverse cardiovascular events in chronic kidney disease patients

Abstract Background and Aims Chronic kidney disease (CKD) significantly raises cardiovascular event risks. The influence of acute-on-chronic kidney incidents is less understood. This study examines the link between acute kidney injury (AKI) episodes and subsequent Major Adverse Cardiovascular Events (MACE) in CKD patients. Method From 2013 to 2016, the CKD-REIN cohort enrolled 3033 adults with CKD stages 3-5 (average age 67; 66% male; mean eGFR 33 mL/min/1.73m²) from 40 French outpatient nephrology clinics, reflecting national geographic and legal diversity. During a 5-year follow-up, all AKI episodes, whether inpatient or outpatient, were identified, confirmed, and categorized per KDIGO-AKI standards by an expert panel. Cardiovascular events were evaluated using clinical trial Cardiovascular and Stroke Endpoint Definitions. MACE cumulative incidences (myocardial infarction, stroke, heart failure hospitalization, cardiovascular death) post-AKI were calculated using Aalen-Johansen methods, accounting for kidney failure and death risks. The impact of the first AKI episode on MACE risk was analyzed using a multivariable Cox model, treating AKI as a time-variable and stratifying by characteristics (in/outpatient status, AKI stage, pre-renal causes, renal recovery at discharge). Factors like demographics, cardiovascular risks, CKD severity, and treatments were considered. Interaction and sensitivity analyses were performed, excluding those with prior AKI or cardiovascular disease. Results During a median follow-up of 5.2 years, 530 patients experienced an incident AKI episode. The cumulative incidence of MACE at 1 year following this initial episode of AKI was 8.1% [95% confidence interval, 6.1; 10.8], with a median time to occurrence of 6.7 months after AKI. After adjustment for multiple confounders, we observed a substantial increased hazard of MACE associated with a first episode of AKI (HR = 5.99 [4.63; 7.76], p &amp;lt; 0.001), and this association remained significant for each MACE component (Fig. 1A). A dose-response relationship was observed, with higher risks in more severe AKI cases (KDIGO grades 2-3) and among hospitalized versus non-hospitalized patients (Fig. 1B). This association was also observed across all subgroups, without any interaction with age, sex, nor major comorbidities (diabetes, history of AKI, or cardiovascular events), as well as in various sensitivity analyses. Overall, we estimated an attributable risk fraction of 18.1% [13.6; 22.4] for MACE associated with AKI episodes within this population. Conclusion Our study highlights a strong dose-response relationship between incident AKI events and the risk of subsequent major cardiovascular events in CKD patients. These findings suggest that AKI may not only be a marker of increased cardiovascular risk but also a potential mediator of this risk. From a clinical perspective, these results underscore the importance of close monitoring and management of AKI in CKD patients to reduce the risk of MACE. This study improves our understanding of the interplay between renal and cardiovascular health, emphasizing the need for integrated care approaches in this high-risk population.

Extreme elevations of donor-derived cell-free DNA increases the risk of chronic lung allograft dysfunction and death, even without clinical manifestations of disease

Lung transplant recipients are traditionally monitored with pulmonary function testing (PFT) and lung biopsy to detect post-transplant complications and guide treatment. Plasma donor-derived cell free DNA (dd-cfDNA) is a novel molecular approach of assessing allograft injury, including subclinical allograft dysfunction. The aim of this study was to determine if episodes of extreme molecular injury (EMI) in lung transplant recipients increases the risk of chronic lung allograft dysfunction (CLAD) or death. This multicenter prospective cohort study included 238 lung transplant recipients. Serial plasma samples were collected for dd-cfDNA measurement by shotgun sequencing. EMI was defined as a dd-cfDNA above the third quartile of levels observed for acute rejection (dd-cfDNA level of ≥5% occurring after 45 days post-transplant). EMI was categorized as Secondary if associated with co-existing acute rejection, infection or PFT decline; or Primary if not associated with these conditions. EMI developed in 16% of patients at a median 343.5 (IQR: 177.3-535.5) days post-transplant. Over 50% of EMI episodes were classified as Primary. EMI was associated with an increased risk of severe CLAD or death (HR: 2.78, 95% CI: 1.26-6.22,p = 0.012). The risk remained consistent for the Primary EMI subgroup (HR: 2.34, 95% CI 1.18-4.85, p=0.015). Time to first EMI episode was a significant predictor of the likelihood of developing CLAD or death (AUC=0.856, 95% CI=0.805-0.908, p<0.001). Episodes of EMI in lung transplant recipients are often isolated and may not be detectable with traditional clinical monitoring approaches. EMI is associated with an increased risk of severe CLAD or death, independent of concomitant transplant complications.

INCIDENCE AND MORTALITY RISK OF AKD AND AKI IN THE PRIMARY CARE

Objective: Objective: The aim of the present study was to assess the impact of hypertension in the incidence of Acute Kidney Damage and Acute Kidney Injury episodes in the community, defined by changes in serum creatinine and temporal window. Design and method: The study analyzed the EHR of a community of 1,863,731 adult subjects &gt;23 years of age with serum creatinine before, during and after the AKD episode for a variable period of time. eGFR was calculated using the CKD-EPI formula. AKD and AKI were defined according to the harmonized KDIGO criteria (Lameire 2021). The acute event was defined as having occurred when the blood creatinine was at least 150% of the mean of the previous creatinine measurement. AKD is considered to have ended when the creatinine falls to at least the threshold created by the pre-event mean plus half the increment produced during the episode within three months. AKI was defined as a sudden drop in creatinine within seven days. The RIFLE scale was used to classify episodes. HTN was considered when it was recorded in the EHR (CIE9 and 10). Results: During a mean follow-up of 4.8 years, 56,850 episodes of AKD were identified in 47,670 patients. The incidence was 4.49 and 19.0/1000 patients/year in non-CKD and CKD subjects, respectively. Overall, HTN was present in 62.8% of patients, 49,9% among those without CKD before the event and in 92.6% in CKD patients. In patients without CKD, HTN increases the risk of more severe RIFLE class of AKD (Risk 47.4%, Injury 64.1% and Failure 66.0%). The prevalence of HTN in patients with AKI was 76.6% without differences in the RIFLE class (Risk 76.3%, Injury 77.2% and Failure 76.9%). A higher mortality was recorded among the AKI patients. Conclusions: The data from this study reinforce the concept that acute elevations in serum creatinine occurring and managed in the community may pose a health risk and HTN is an important risk factor. Future work should consider how best eAlerts can be utilized, targeted and implemented.

Seeing and Sensing the Hepatorenal Syndrome (HRS): The Growing Role of Ultrasound-Based Techniques as Non-Invasive Tools for the Diagnosis of HRS.

More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome.

Care seeking behavior of the victims of unintentional injuries: A community-based study in a community development block of Purba Bardhaman District, West Bengal.

Care-seeking after injury episodes is generally associated with major uncertainties concerning its incidence, care, and cure/disappearance, and the price of care. Though the utilization pattern of the population is shaped by social, economic, cultural and political factors, it varies widely for the rich and the poor. With this background, a community-based epidemiological study was conducted to determine the care-seeking behavior of victims of unintentional injuries. A cross-sectional study was conducted from May 2023-September 2023 in the Bhatar block of Purba Bardhaman district, West Bengal. Cluster random sampling was applied to select a required sample of 555 individuals from 24 villages. Study tools used were predesigned and pretested schedules developed by the researchers with the help of guidelines for conducting community surveys on injuries provided by the World Health Organization (WHO). The study had approval from the Institutional Ethics Committee. Descriptive statistics were performed using SPSS V16. Out of 49 injury episodes, 51.0% had received first aid. Out of 39 injury episodes seeking medical attention, a traditional practitioner, healer or bone setter was the type of first medical contact in the case of the majority of injury episodes (38.5%), followed by a hospital (35.9%). Low utilization of government healthcare facilities is a cause for concern. Reliance on unqualified informal healthcare providers is also a cause for concern. Our findings will help design community interventions to increase the provision of appropriate first aid in unintentional injuries.

Intervention treatment reducing cellular senescence inhibits tubulointerstitial fibrosis in diabetic mice following acute kidney injury.

Senescence of kidney tubules leads to tubulointerstitial fibrosis (TIF). Proximal tubular epithelial cells undergo stress-induced senescence during diabetes and episodes of acute kidney injury (AKI), and combining these injuries promotes the progression of diabetic kidney disease (DKD). Since TIF is crucial to progression of DKD, we examined the therapeutic potential of targeting senescence with a senolytic drug (HSP90 inhibitor) and/or a senostatic drug (ASK1 inhibitor) in a model of TIF in which AKI is superimposed on diabetes. After 8 weeks of streptozotocin-induced diabetes, mice underwent bilateral clamping of renal pedicles to induce mild AKI, followed by 28 days of reperfusion. Groups of mice (n=10-12) received either vehicle, HSP90 inhibitor (alvespimycin), ASK1 inhibitor (GS-444217), or both treatments. Vehicle-treated mice displayed tubular injury at day 3 and extensive tubular cell senescence at day 10, which remained unresolved at day 28. Markers of senescence (Cdkn1a and Cdkn2a), inflammation (Cd68, Tnf, and Ccl2), and TIF (Col1a1, Col4a3, α-Sma/Acta2, and Tgfb1) were elevated at day 28, coinciding with renal function impairment. Treatment with alvespimycin alone reduced kidney senescence and levels of Col1a1, Acta2, Tgfb1, and Cd68; however, further treatment with GS-444217 also reduced Col4a3, Tnf, Ccl2, and renal function impairment. Senolytic therapy can inhibit TIF during DKD, but its effectiveness can be improved by follow-up treatment with a senostatic inhibitor, which has important implications for treating progressive DKD.

HOSPITAL READMISSION AND MORTALITY RATES IN PATIENTS WITH CONCURRENT DEPRESSION AND INFLAMMATORY BOWEL DISEASE: INSIGHTS FROM THE NATIONAL READMISSIONS DATABASE, 2016–2019

Abstract BACKGROUND Inflammatory Bowel Disease (IBD) is a proinflammatory condition that is known to be associated with depression. Research examining causality suggests that Crohn's disease (CD) or ulcerative colitis (UC) patients are vulnerable to triggering pre-existing mental health conditions and that conversely, a pre-existing disorder such as depression may have an effect on the disease process and course of IBD. There is a paucity of comprehensive studies examining the downstream effects of depression on patients with IBD such as readmission rates and mortality. The complexity of the interaction between depression and IBD remains a fertile ground for further investigations in terms of pathological reciprocity and downstream consequences. METHODS In this retrospective observational study, patients were queried from the National Readmissions Database from 2016 to 2019. ICD-10 codes were used to identify patients with Crohn’s disease, ulcerative colitis, and depression. Primary outcomes were mortality and readmission rates at 30 days and 90 days. Secondary outcomes were index admission mortality, hospital length of stay (LOS), and total hospitalization charges (TOTHC) at 30 and 90 days respectively. The top 10 readmission diagnoses in each subgroup were also identified. RESULTS For patients with CD and depression, the mean age at readmission was 51.6 years with a high readmission and mortality rate at 30 days (readmission rate 5.2%, p&amp;lt;0.01; mortality rate 2.8%, p&amp;lt;0.01) which increased significantly at 90 days (readmission rate 8.4%, p&amp;lt;0.01). Hospital LOS and TOTHC remained relatively the same compared to the index admission for both 30-day and 90-day readmissions (Table 1,2). A similar trend was seen for UC and depression as well: mean age at readmission was 51.4 years with a high readmission rate and mortality at 30 days (readmission rate 5.0%, p&amp;lt;0.01; mortality rate 2.6%, p&amp;lt;0.01) which increased significantly at 90 days (readmission rate 8.4%, p&amp;lt;0.01; mortality rate 2.9%, p&amp;lt;0.01). Sepsis, hypertensive heart disease accompanied by heart failure and/or chronic kidney disease, acute kidney injury, hypoxia, and acute depressive episodes were the top primary associated readmission etiologies at 30 days and 90 days when correlated with a diagnosis of UC or CD. (Table 1, 2). CONCLUSION Our investigation revealed that patients affected by both depression and either UC or Crohn’s disease exhibited elevated readmission rates and a notably amplified mortality risk at 30 days post-readmission, with a more substantial increase observed at the 90-day mark. These findings underscore the significance of healthcare providers routinely screening for depression, addressing the management of mental health, and acknowledging the considerable impact it has on patients with co-occurring chronic diseases like UC or CD as an integral facet of comprehensive care. Table 1 Table 2