Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who defervesce spontaneously are not clear. In this study, we analysed patients with KD diagnosed between 1994 and 2024 at our centre who had defervesced spontaneously, had normal acute-phase reactants, and underwent echocardiographic examination, and in whom IVIg had not been administered. We reviewed the records of patients with KD from January 1994 - December 2024. The diagnosis of KD was based on standard guidelines. Patients with KD were said to be in spontaneous defervescence when they remained afebrile for ≥ 48 h, had normal acute-phase reactants [C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR)] and no coronary artery abnormalities (CAAs) on echocardiography at presentation, and when IVIg was not administered. Patients with spontaneous defervescence were subdivided into (i) early defervescence (Ed-KD), if the interval between onset of symptoms and defervescence was < 10 days, and (ii) late defervescence (Ld-KD), if the duration between onset of symptoms and defervescence was ≥ 10 days, respectively. Details of the clinical profile, laboratory investigations, and echocardiography findings were obtained from the records. Of the 1499 patients with KD enrolled during the study period, 115 patients (7.7%; 86 boys) defervesced spontaneously. The median age at disease onset was 6 years (mean, 5.6 years; range, 0.8-15 years). The median duration of fever, defined as the total duration of the febrile episode before spontaneous defervescence, was 5 days (range, 1-21 days). The median interval between illness onset (defined as fever onset) and diagnosis of KD was 15 days (range, 4-40 days), indicating that diagnosis was often made after fever had already subsided. The most common clinical feature was periungual desquamation, followed by rash, oral-mucosal changes, cervical lymphadenopathy, and conjunctival injection. Incomplete presentation was noted in 73.9% (n = 85/115) of patients. No patient has developed CAAs or other cardiac sequelae over a median follow-up of 9 months (range 2 months-156 months). The cumulative follow-up for the cohort was 235 patient-years. The 'low-risk' subgroup of patients with KD who defervesce spontaneously, and have normal acute phase reactants with no CAAs at presentation, have good clinical and coronary outcomes.

Acute kidney injury (AKI) involves abrupt loss of kidney function driven in part by proximal tubule metabolic stress, yet the role of glycolytic regulation in tubular injury susceptibility remains unclear. Lactate dehydrogenase A (LDHA) is a key regulator of glycolytic flux and redox balance, but its function in proximal tubules during AKI is poorly defined. In this work, we use a cisplatin-induced AKI model to investigate the role of proximal tubule LDHA in regulating metabolic responses and injury severity. Proximal tubule-specific LDHA knockout mice (PEPCK[Cre]LDHA[Δ/Δ]) and LDHA[flox/flox] controls were subjected to cisplatin-induced AKI. Untargeted metabolomics of kidney cortex and single-nucleus RNA sequencing (snRNA-seq) were performed to define metabolic and cell-specific transcriptional responses. Loss of proximal tubular LDHA exacerbated cisplatin-induced AKI, as evidenced by worsened kidney function and tubular injury, accompanied by increased expression of inflammatory markers following injury. The analysis also showed a distinct metabolic profile at baseline in LDHA-deficient kidneys, which became more pronounced after cisplatin exposure, with coordinated changes in purine and nucleotide metabolism, energy-related metabolites, and pathways linked to redox balance and mitochondrial function. snRNA-seq revealed intrinsic transcriptional changes within proximal tubule cells at baseline and after injury, reflecting cellular stress and metabolic remodeling without strong activation of classic inflammatory gene programs. Together, these findings identify proximal tubular LDHA as a key regulator of metabolic flexibility and injury tolerance in cisplatin-induced AKI, and suggest that disrupted coordination of glycolytic and nucleotide metabolism increases tubular vulnerability, highlighting metabolic regulation as a potential therapeutic target.

BackgroundProlonged mechanical ventilation (PMV) is associated with poor long-term outcomes. The ProVent14 score was developed to estimate one-year mortality among patients receiving mechanical ventilation for at least 14 days. However, contemporary validation of the model and its performance earlier during mechanical ventilation remain uncertain. We aimed to evaluate the validity of the ProVent14 score in a modern ICU cohort and assess its predictive performance when applied earlier during mechanical ventilation.MethodsWe conducted a retrospective cohort study using the Medical Information Mart for Intensive Care (MIMIC-IV) database (2008-2022). Adult ICU admissions receiving at least seven days of mechanical ventilation were included. Patients with chronic neuromuscular disease, extensive burns, or chronic mechanical ventilation were excluded. Three non-mutually exclusive cohorts were constructed based on duration of ventilation (≥7,≥10, and ≥14 days). Predictors from the original ProVent14 model (age, platelet count, vasopressor use, hemodialysis requirement, and trauma admission status) were assessed at each time point. The primary outcome was one-year mortality from the onset of prolonged ventilation. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using the Hosmer-Lemeshow test. Results: A total of 1344, 634, and 249 patients comprised the day-7, day-10, and day-14 cohorts, respectively. One-year mortality ranged from 64% to 67% across cohorts. The ProVent model demonstrated consistent discrimination at day 7, day 10, and day 14 (AUC 0.74, 0.72, and 0.71, respectively) with acceptable calibration (Hosmer-Lemeshow P-values 0.50, 0.18, and 0.21). Model performance remained stable across different study periods. Conclusions: The ProVent score maintains stable predictive performance in a contemporary ICU population. Similar discrimination and calibration at days 7 and 10 suggest that prognostic assessment may be feasible earlier during mechanical ventilation.