BackgroundAcute kidney injury (AKI) complicating severe Plasmodium falciparum malaria occurs in up to 40% of adult patients. The case fatality rate reaches 75% in the absence of renal replacement therapy (RRT). The precise pathophysiology of AKI in falciparum malaria remains unclear. Histopathology shows acute tubular necrosis with localization of host monocytes and parasitized red blood cells in the microvasculature. This study explored the relationship of plasma soluble urokinase-type plasminogen activator receptor (suPAR), as a proxy-measure of mononuclear cell activation, and plasma P. falciparum histidine rich protein 2 (PfHRP2), as a measure of sequestered parasite burden, with AKI in severe malaria.MethodsAdmission plasma suPAR and PfHRP2 concentrations were assessed in Bangladeshi adults with severe falciparum malaria (n = 137). Patients were stratified according to AKI severity based on admission creatinine clearance.ResultsA total of 106 (77%) patients had AKI; 32 (23%), 42 (31%) and 32 (23%) were classified into ‘mild, ‘moderate’ and ‘severe’ AKI groups, respectively. Plasma suPAR and PfHRP2 concentrations increased with AKI severity (test-for-trend P <0.0001) and correlated with other markers of renal dysfunction. Admission plasma suPAR and PfHRP2 concentrations were higher in patients who later required RRT (P <0.0001 and P = 0.0004, respectively). In a multivariate analysis, both increasing suPAR and PfHRP2 were independently associated with increasing urine neutrophil gelatinase-associated lipocalin concentration, a marker of acute tubular necrosis (β = 16.54 (95% CI 6.36-26.71) and β = 0.07 (0.02-0.11), respectively).ConclusionsBoth sequestered parasite burden and immune activation contribute to the pathogenesis of AKI in severe falciparum malaria.

ObjectiveTo develop a CT-based prediction score for anastomotic leakage after esophagectomy and compare it to subjective CT interpretation.MethodsConsecutive patients who underwent a CT scan for a clinical suspicion of anastomotic leakage after esophagectomy with cervical anastomosis between 2003 and 2014 were analyzed. The CT scans were systematically re-evaluated by two radiologists for the presence of specific CT findings and presence of an anastomotic leak. Also, the original CT interpretations were acquired. These results were compared to patients with and without a clinical confirmed leak.ResultsOut of 122 patients that underwent CT for a clinical suspicion of anastomotic leakage; 54 had a confirmed leak. In multivariable analysis, anastomotic leakage was associated with mediastinal fluid (OR = 3.4), esophagogastric wall discontinuity (OR = 4.9), mediastinal air (OR = 6.6), and a fistula (OR = 7.2). Based on these criteria, a prediction score was developed resulting in an area-under-the-curve (AUC) of 0.86, sensitivity of 80%, and specificity of 84%. The original interpretation and the systematic subjective CT assessment by two radiologists resulted in AUCs of 0.68 and 0.75 with sensitivities of 52% and 69%, and specificities of 84% and 82%, respectively.ConclusionThis CT-based score may provide improved diagnostic performance for diagnosis of anastomotic leakage after esophagectomy.Key Points• A CT-based score provides improved diagnostic performance for diagnosis of anastomotic leakage.• Leakage associations include mediastinal fluid, mediastinal air, wall discontinuity, and fistula.• A scoring system yields superior diagnostic accuracy compared to subjective CT assessment.• Radiologists may suggest presence of anastomotic leakage based on a prediction score.

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