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Cell Death & Disease Jul 2024Damage to renal tubular epithelial cells (RTECs) signaled the onset and progression of sepsis-associated acute kidney injury (SA-AKI). Recent research on mitochondria...
Damage to renal tubular epithelial cells (RTECs) signaled the onset and progression of sepsis-associated acute kidney injury (SA-AKI). Recent research on mitochondria has revealed that mitophagy plays a crucial physiological role in alleviating injury to RTECs and it is suppressed progressively by the inflammation response in SA-AKI. However, the mechanism by which inflammation influences mitophagy remains poorly understood. We examined how macrophage migration inhibitory factor (MIF), a pro-inflammatory protein, influences the PINK1-Parkin pathway of mitophagy by studying protein-protein interactions when MIF was inhibited or overexpressed. Surprisingly, elevated levels of MIF were found to directly bind to PINK1, disrupting its interaction with Parkin. This interference hindered the recruitment of Parkin to mitochondria and impeded the initiation of mitophagy. Furthermore, this outcome led to significant apoptosis of RTECs, which could, however, be reversed by an MIF inhibitor ISO-1 and/or a new mitophagy activator T0467. These findings highlight the detrimental impact of MIF on renal damage through its disruption of the interaction between PINK1 and Parkin, and the therapeutic potential of ISO-1 and T0467 in mitigating SA-AKI. This study offers a fresh perspective on treating SA-AKI by targeting MIF and mitophagy.
Topics: Macrophage Migration-Inhibitory Factors; Mitophagy; Acute Kidney Injury; Ubiquitin-Protein Ligases; Protein Kinases; Sepsis; Animals; Humans; Mitochondria; Kidney Tubules; Epithelial Cells; Apoptosis; Protein Binding; Male; Intramolecular Oxidoreductases
PubMed: 38956064
DOI: 10.1038/s41419-024-06826-z -
International Archives of Occupational... Jul 2024The effect of heat waves on mortality is well known, but current evidence on morbidity is limited. Establishing the consequences of these events in terms of morbidity is...
PURPOSE
The effect of heat waves on mortality is well known, but current evidence on morbidity is limited. Establishing the consequences of these events in terms of morbidity is important to ensure communities and health systems can adapt to them.
METHODS
We thus collected data on total daily emergency hospital admissions, admissions to critical care units, emergency department admissions, and emergency admissions for specific diagnoses to Hospital Universitario de Son Espases from 1 January 2005 to 31 December 2021. A heat wave was defined as a period of ≥ 2 days with a maximum temperature ≥ 35 °C, including a 7 day lag effect (inclusive). We used a quasi-Poisson generalized linear model to estimate relative risks (RRs; 95%CI) for heat wave-related hospital admissions.
RESULTS
Results showed statistically significant increases in total emergency admissions (RR 1.06; 95%CI 1 - 1.12), emergency department admissions (RR 1.12; 95%CI 1.07 - 1.18), and admissions for ischemic stroke (RR 1.26; 95%CI 1.02 - 1.54), acute kidney injury (RR 1.67; 95%CI 1.16 - 2.35), and heat stroke (RR 18.73, 95%CI 6.48 - 45.83) during heat waves.
CONCLUSION
Heat waves increase hospitalization risk, primarily for thromboembolic and renal diseases and heat strokes.
PubMed: 38955849
DOI: 10.1007/s00420-024-02082-y -
Oral Oncology Jul 2024
Letter to the editor "risk prediction model for cisplatin-induced acute kidney injury in patients with head and neck cancer receiving chemoradiotherapy: A re-analysis of a phase II/III JCOG1008 trial ".
PubMed: 38955110
DOI: 10.1016/j.oraloncology.2024.106931 -
Hepatology (Baltimore, Md.) Jul 2024Hospitalized patients with cirrhosis frequently require critical care management for sepsis, hepatic encephalopathy, respiratory failure, acute variceal bleeding, acute...
Hospitalized patients with cirrhosis frequently require critical care management for sepsis, hepatic encephalopathy, respiratory failure, acute variceal bleeding, acute kidney injury (AKI), shock and optimization for liver transplantation (LT), while outpatients have unique care considerations. Point-of-care ultrasonography (POCUS) enhances bedside examination of the hepatobiliary system and relevant extrahepatic sites. POCUS includes cardiac ultrasound and is used to assess volume status and hemodynamic parameters like cardiac output, systemic vascular resistance, cardiac contractility, and pulmonary artery pressure, which aid in the early and accurate diagnosis of heart failure, cirrhotic cardiomyopathy, porto-pulmonary hypertension, hepatopulmonary syndrome, arrhythmia, and pulmonary embolism. This also helps in fluid management and vasopressor use in resuscitation of patients with cirrhosis. Lung ultrasound can help in differentiating pneumonia, effusion, and edema. Further, ultrasonography guides interventions such as line placement, drainage of abdominal collections/abscesses, relief of tension pneumothorax, drainage of pleural and pericardial effusions, and biliary drainage in cholangitis. Additionally, its role is essential to assess liver masses, foci of sepsis, for appropriate sites for paracentesis, and to assess for vascular disorders such as portal vein or hepatic vein thrombosis. Renal ultrasound can identify renal and post-renal causes of AKI and aid in diagnosis of pre-renal AKI through volume assessment. In this review, we address the principles and methods of POCUS in hospitalized patients and in outpatients with cirrhosis and discuss the application of this diverse modality in clinical hepatology.
PubMed: 38954829
DOI: 10.1097/HEP.0000000000000990 -
PloS One 2024[This corrects the article DOI: 10.1371/journal.pone.0252419.].
[This corrects the article DOI: 10.1371/journal.pone.0252419.].
PubMed: 38954700
DOI: 10.1371/journal.pone.0306663 -
International Journal of Surgery... Jul 2024Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options...
Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.
BACKGROUND
Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies.
MATERIAL AND METHODS
This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates.
RESULTS
A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses.
CONCLUSION
Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.
PubMed: 38954672
DOI: 10.1097/JS9.0000000000001861 -
European Heart Journal. Acute... Jul 2024Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T...
BACKGROUND
Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations.
METHODS
Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2).
RESULTS
The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86) and 75% (95% CI 58-88).
CONCLUSION
Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.
PubMed: 38954535
DOI: 10.1093/ehjacc/zuae079 -
Inflammation primes the murine kidney for recovery by activating AZIN1 adenosine-to-inosine editing.The Journal of Clinical Investigation Jul 2024The progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of...
The progression of kidney disease varies among individuals, but a general methodology to quantify disease timelines is lacking. Particularly challenging is the task of determining the potential for recovery from acute kidney injury following various insults. Here, we report that quantitation of post-transcriptional adenosine-to-inosine (A-to-I) RNA editing offers a distinct genome-wide signature, enabling the delineation of disease trajectories in the kidney. A well-defined murine model of endotoxemia permitted the identification of the origin and extent of A-to-I editing, along with temporally discrete signatures of double-stranded RNA stress and Adenosine Deaminase isoform switching. We found that A-to-I editing of Antizyme Inhibitor 1 (AZIN1), a positive regulator of polyamine biosynthesis, serves as a particularly useful temporal landmark during endotoxemia. Our data indicate that AZIN1 A-to-I editing, triggered by preceding inflammation, primes the kidney and activates endogenous recovery mechanisms. By comparing genetically modified human cell lines and mice locked in either A-to-I edited or uneditable states, we uncovered that AZIN1 A-to-I editing not only enhances polyamine biosynthesis but also engages glycolysis and nicotinamide biosynthesis to drive the recovery phenotype. Our findings implicate that quantifying AZIN1 A-to-I editing could potentially identify individuals who have transitioned to an endogenous recovery phase. This phase would reflect their past inflammation and indicate their potential for future recovery.
PubMed: 38954486
DOI: 10.1172/JCI180117 -
JAMA Network Open Jul 2024Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
IMPORTANCE
Current evidence is conflicting for associations of extended-infusion β-lactam (EI-BL) therapy with clinical outcomes.
OBJECTIVE
To investigate the association of EI-BL therapy with survival, adverse events, and emergence of antibiotic resistance in adults with gram-negative bloodstream infections (GN-BSI).
DESIGN, SETTING, AND PARTICIPANTS
This cohort study of consecutive adults with GN-BSI admitted to 24 United States hospitals between January 1, 2019, and December 31, 2019, receiving EI-BL were compared with adults with GN-BSI receiving the same agents as intermittent infusion β-lactam (II-BL; ≤1-hour infusions). Statistical analysis was performed from January to October 2023.
EXPOSURES
EI-BL (ie, ≥3-hour infusion).
MAIN OUTCOMES AND MEASURES
EI-BL and II-BL groups underwent 1:3 nearest-neighbor propensity score matching (PSM) without replacement. Multivariable regression was applied to the PSM cohort to investigate outcomes, all censored at day 90. The primary outcome was mortality; secondary outcomes included antibiotic adverse events and emergence of resistance (≥4-fold increase in the minimum inhibitory concentration of the β-lactam used to treat the index GN-BSI).
RESULTS
Among the 4861 patients included, 2547 (52.4%) were male; and the median (IQR) age was 67 (55-77) years. There were 352 patients in the EI-BL 1:3 PSM group, and 1056 patients in the II-BL 1:3 PSM group. Among 1408 PSM patients, 373 (26.5%) died by day 90. The odds of mortality were lower in the EI-BL group (adjusted odds ratio [aOR], 0.71 [95% CI, 0.52-0.97]). In a stratified analysis, a survival benefit was only identified in patients with severe illness or elevated minimum inhibitory concentrations (ie, in the intermediate range for the antibiotic administered). There were increased odds of catheter complications (aOR, 3.14 [95% CI, 1.66-5.96]) and antibiotic discontinuation because of adverse events (eg, acute kidney injury, cytopenias, seizures) in the EI-BL group (aOR, 3.66 [95% CI, 1.68-7.95]). Emergence of resistance was similar in the EI-BL and II-BL groups at 2.9% vs 7.2%, respectively (P = .35).
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with GN-BSI, EI-BL therapy was associated with reduced mortality for patients with severe illness or those infected with nonsusceptible organisms; potential advantages in other groups remain unclear and need to be balanced with potential adverse events. The subsequent emergence of resistance warrants investigation in a larger cohort.
Topics: Humans; Male; Female; Middle Aged; Gram-Negative Bacterial Infections; Anti-Bacterial Agents; beta-Lactams; Aged; Bacteremia; Infusions, Intravenous; Cohort Studies; United States; Adult; Retrospective Studies
PubMed: 38954416
DOI: 10.1001/jamanetworkopen.2024.18234 -
Knee Surgery, Sports Traumatology,... Jul 2024This study compares postoperative outcomes of robotic-assisted total knee arthroplasty (RA-TKA) versus navigation-guided total knee arthroplasty (NG-TKA). Using...
Robotic-assisted total knee arthroplasty reduces postoperative complications and length of stay without increased cost compared to navigation-guided techniques: A national analysis.
INTRODUCTION
This study compares postoperative outcomes of robotic-assisted total knee arthroplasty (RA-TKA) versus navigation-guided total knee arthroplasty (NG-TKA). Using Nationwide Inpatient Sample (NIS) data, it provides an analysis of postoperative complications, mortality, hospital costs and duration of stay.
METHODS
The study analysed 217,715 patients (81,830 RA-TKA; 135,885 NG-TKA) using NIS data from 2016 to 2019. Elective TKA patients were identified through the International Classification of Diseases, 10th Revision codes. Statistical analyses, including logistic regression modelling, were performed using Statistical Package for the Social Sciences and MATLAB.
RESULTS
RA-TKA patients were younger (66.1 vs. 67.1 years, p < 0.0001) and had similar mortality rates (0.024% vs. 0.018%, p = 0.342) but shorter length of stay (LOS) (1.89 vs. 2.1 days, p < 0.0001). Mean total charges were comparable between RA-TKA ($66,180) and NG-TKA ($66,251, p = 0.669). RA-TKA demonstrated lower incidences of blood-related complications (11.67% vs. 14.19%, p < 0.0001), pulmonary oedema (0.0306% vs. 0.066%, p < 0.0001), deep vein thrombosis (0.196% vs. 0.254%, p = 0.006) and acute kidney injury (AKI) (1.356% vs. 1.483%, p = 0.016).
CONCLUSION
RA-TKA reduces postoperative complications and LOS without increasing costs, highlighting the relevance of this technology in patient care.
LEVEL OF EVIDENCE
Level III.
PubMed: 38953206
DOI: 10.1002/ksa.12348