Incidence and Risk Factors of Acute Kidney Injury in Pediatric Liver Transplant Patients: A Retrospective Study.

Background: Acute kidney injury (AKI) significantly contributes to the mortality and morbidity rates among pediatric liver transplant (LT) recipients. Objective: Our study aimed to assess the potential factors contributing to AKI in pediatric LT patients and to analyze the impact of AKI on postoperative mortality and hospitalization duration. Materials and methods: About 235 pediatric LT patients under the age of 18 between the years 2015 and 2021 were evaluated retrospectively. The relationship between preoperative and intraoperative variables of the patients and AKI developed when the early postoperative period was assessed. Results: A correlation was found between the patients' preoperative age, albumin levels, and AKI. AKI was found to be associated with the duration of surgery and intraoperative blood transfusion. Conclusion: Our findings revealed that the severity of AKI in pediatric LT patients is linked to extended surgical durations and increased blood transfusions resulting from hemodynamically compromised blood loss. Furthermore, independent risk factors for AKI were identified as prolonged warm ischemia and the overall duration of the operation. How to cite this article: Demiroz D, Colak YZ, Ozdes OO, Ucar M, Ali Erdogan M, Toprak HI, et al. Incidence and Risk Factors of Acute Kidney Injury in Pediatric Liver Transplant Patients: A Retrospective Study. Indian J Crit Care Med 2024;28(1):75-79.

Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons.

Listeria monocytogenes (L. monocytogenes) is a food-borne bacterial pathogen. Innate immunity to L. monocytogenes is profoundly affected by type I interferons (IFN-I). Here we investigated host metabolism in L. monocytogenes-infected mice and its potential control by IFN-I. Accordingly, we used animals lacking either the IFN-I receptor (IFNAR) or IRF9, a subunit of ISGF3, the master regulator of IFN-I-induced genes. Transcriptomes and metabolite profiles showed that L. monocytogenes infection induces metabolic rewiring of the liver. This affects various metabolic pathways including fatty acid (FA) metabolism and oxidative phosphorylation and is partially dependent on IFN-I signaling. Livers and macrophages from Ifnar1-/- mice employ increased glutaminolysis in an IRF9-independent manner, possibly to readjust TCA metabolite levels due to reduced FA oxidation. Moreover, FA oxidation inhibition provides protection from L. monocytogenes infection, explaining part of the protection of Irf9-/- and Ifnar1-/- mice. Our findings define a role of IFN-I in metabolic regulation during L. monocytogenes infection. Metabolic differences between Irf9-/- and Ifnar1-/- mice may underlie the different susceptibility of these mice against lethal infection with L. monocytogenes.

Does Rocuroinum Dose Adjusted Due to Lean Body Weight Provide Adequate Intubation Conditions?: A Prospective Observational Study.

Methods: This is a prospective, observational study. Patients between the ages of 18 and 65 with BMI of 18.5-34.9, who are expected to be under general anesthesia for less than 6 hours, were divided into 3 groups according to their BMI (Group 1 BMI = 18.5-24.9, Group 2 BMI = 25-29.9, Group 3 BMI = 30-34.9). These groups were randomly divided into 2 subgroups: Groups LBW; 1 LBW, 2 LBW, and 3 LBW were given rocuronium intubation dosages based on their LBW while control groups; 1K, 2K, and 3K were given 0.6 mg/kg rocuronium according to their total body weight. The data on the duration of action of rocuronium and its effects on the endotracheal intubation conditions were evaluated. Results: In Group 1, T1 time was found to be significantly longer (p=0.001). Intubation score and the use of additional rocuronium dose were found to be significantly higher in Group 1 LBW than in Group 1K (p=0.001). In Group 1, an additional rocuronium dose was needed to achieve optimal intubation conditions for subgroup 1 LBW. Rocuronium duration of action was found to be significantly longer in control groups 2 and 3, that received TBW-based dosage. Conclusion: In adult patients with a BMI of 18.5 and 24.9 BMI, we report optimal intubation conditions with the LBW-adjusted rocuronium dosage. This trial is registered with NCT05476952.

Novel NLRP3/cryopyrin mutations and pro-inflammatory cytokine profiles in Behçet's syndrome patients.

Behçet's syndrome (BS) is a systemic inflammatory disorder with unknown etiology. Features of both innate and adaptive immunity have been claimed in the pathogenesis of BS. To test the possible dysregulation of the NLRP3/cryopyrin (Nod-like receptor with a pyrin domain 3) inflammasome, as a result of mutation(s), we performed single-strand conformation polymorphism analyses and/or sequencing of all the coding regions and intron-exon boundaries of NLRP3/cryopyrin and ASC (apoptosis-associated speck-like protein containing CARD) genes from Turkish BS patients and healthy controls. At the same time, we determined pro-inflammatory cytokine secretion profiles of peripheral blood cells in response to LPS treatment using ELISA. BS patients with vascular involvement showed significantly increased levels of TNF-α release at 2-, 4- and 8-h post-treatment and significantly increased IL-1ß levels were detected at 2h (P = 0.005) and 4h (P = 0.025) (n = 10). We identified four mutations in the NLRP3/cryopyrin gene, V200M (n = 3/104) and T195M (n = 1/104), in BS patients but none in control samples. No mutations were detected in the ASC gene. The effect of these NLRP3/cryopyrin mutants on ASC speck assembly and IL-1ß secretion was tested and the V200M mutant was shown to induce IL-1ß secretion. Thus, it is likely that certain mutations in NLRP3/cryopyrin in combination with yet unknown other factors may contribute to the pro-inflammatory cytokine profiles in BS patients.

A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription.

Cells maintain the balance between homeostasis and inflammation by adapting and integrating the activity of intracellular signaling cascades, including the JAK-STAT pathway. Our understanding of how a tailored switch from homeostasis to a strong receptor-dependent response is coordinated remains limited. Here, we use an integrated transcriptomic and proteomic approach to analyze transcription-factor binding, gene expression and in vivo proximity-dependent labelling of proteins in living cells under homeostatic and interferon (IFN)-induced conditions. We show that interferons (IFN) switch murine macrophages from resting-state to induced gene expression by alternating subunits of transcription factor ISGF3. Whereas preformed STAT2-IRF9 complexes control basal expression of IFN-induced genes (ISG), both type I IFN and IFN-γ cause promoter binding of a complete ISGF3 complex containing STAT1, STAT2 and IRF9. In contrast to the dogmatic view of ISGF3 formation in the cytoplasm, our results suggest a model wherein the assembly of the ISGF3 complex occurs on DNA.

Regional Anaesthesia Management in a Patient with Leprosy: Rare Case with Rare Application.

Leprosy is a chronic infectious disease that is caused by Mycobacterium leprae and affects the skin and nerves. Patients with leprosy having related peripheral neuropathy and involvement of other organs may have cardiac, respiratory dysautonomia and autonomic dysfunctions. There are very few studies regarding anaesthetic management of patients suffering from leprosy. Moreover, very few studies concerning regional anaesthesia in patients with lepromatous leprosy have been reported. In this study, we aim to assess regional anaesthesia management with combined spinal epidural anaesthesia in a patient who had been followed up with a diagnosis of leprosy for a long time and was scheduled for operation because of a femoral neck fracture.

The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate.

The HECT domain E3 ligase HACE1 has been identified as a tumor suppressor in multiple cancers. Here, we report that HACE1 is a central gatekeeper of TNFR1-induced cell fate. Genetic inactivation of HACE1 inhibits TNF-stimulated NF-κB activation and TNFR1-NF-κB-dependent pathogen clearance in vivo. Moreover, TNF-induced apoptosis was impaired in hace1 mutant cells and knockout mice in vivo. Mechanistically, HACE1 is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic caspase-8 effector complex. Intriguingly, loss of HACE1 does not impair TNFR1-mediated necroptotic cell fate via RIP1 and RIP3 kinases. Loss of HACE1 predisposes animals to colonic inflammation and carcinogenesis in vivo, which is markedly alleviated by genetic inactivation of RIP3 kinase and TNFR1. Thus, HACE1 controls TNF-elicited cell fate decisions and exerts tumor suppressor and anti-inflammatory activities via a TNFR1-RIP3 kinase-necroptosis pathway.