AXL and its corresponding ligand growth arrest-specific 6 (GAS-6) are critically involved in hepatic immunomodulation and regenerative processes. Pleiotropic inhibitory effects on innate inflammatory responses might essentially involve the shift of macrophage phenotype from a pro-inflammatory M1 to an anti-inflammatory M2. We aimed to assess the relevance of the AXL/GAS-6-pathway in human liver regeneration and, consequently, its association with clinical outcome after hepatic resection. Soluble AXL (sAXL) and GAS-6 levels were analyzed at preoperative and postoperative stages in 154 patients undergoing partial hepatectomy and correlated with clinical outcome. Perioperative dynamics of interleukin (IL)-6, soluble tyrosine-protein kinase MER (sMerTK), soluble CD163 (sCD163), and cytokeratin (CK) 18 were assessed to reflect pathophysiological processes. Preoperatively elevated sAXL and GAS-6 levels predicted postoperative liver dysfunction (area under the curve = 0.721 and 0.722; P < 0.005) and worse clinical outcome. These patients failed to respond with an immediate increase of sAXL and GAS-6 upon induction of liver regeneration. Abolished AXL pathway response resulted in a restricted increase of sCD163, suggesting a disrupted phenotypical switch to regeneratory M2 macrophages. No association with sMerTK was observed. Concomitantly, a distinct association of IL-6 levels with an absent increase of AXL/GAS-6 signaling indicated pronounced postoperative inflammation. This was further supported by increased intrahepatic secondary necrosis as reflected by CK18M65. sAXL and GAS-6 represent not only potent and easily accessible preoperative biomarkers for the postoperative outcome but also AXL/GAS-6 signaling might be of critical relevance in human liver regeneration. Refractory AXL/GAS-6 signaling, due to chronic overactivation/stimulation in the context of underlying liver disease, appears to abolish their immediate release following induction of liver regeneration, causing overwhelming immune activation, presumably via intrahepatic immune regulation. (Hepatology Communications 2022;6:576-592).

Graphical abstract

Aims Left ventricular hypertrabeculation/non-compaction (LVHT) is a cardiac abnormality of unknown pathogenesis and frequently associated with neuromuscular disorders. The N-terminal fragment of the pro brain natriuretic peptide (NT-pro-BNP) is a prognostic marker in heart failure whose relevance in LVHT patients is largely unknown. The aim of the study was to assess the role of NT-pro-BNP levels as prognostic markers in LVHT. Methods and results Data of LVHT patients were collected in a database from one echocardiographic laboratory since 1996. The hospital information system was screened for measurements of NT-pro-BNP levels, and their association with clinical and echocardiographic baseline parameters was retrospectively assessed. During follow-up, the endpoints were death and heart transplantation. In 113 patients (median age 57 years, 24% women), data about NT-pro-BNP measurements were found, ranging from 8 to 121 152 (median 2029) ng/L. High NT-pro-BNP levels were associated with heart failure, valvular abnormalities, diabetes mellitus, hypertension, angina pectoris, number of LVHT-affected segments, end-diastolic diameter, and systolic dysfunction. During a follow-up of 73 (±64; 0-237) months, 35% of the patients reached an endpoint. High NT-pro-BNP levels were associated with the occurrence of an endpoint (P < 0.001). By multivariate analysis, predictors for endpoints were increased age (P = 0.0025), atrial fibrillation (P = 0.0023), natural logarithm of NT-pro-BNP levels (P = 0.0073), diabetes mellitus (P = 0.014), and thromboembolic events before diagnosis (P = 0.0347). Conclusions Also in LVHT patients, high NT-pro-BNP levels are indicators for death and heart transplantation.

Introduction. The gold standard for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection is real-time reverse transcription PCR (rRT-PCR), which is expensive, has a long turnaround time and requires special equipment and trained personnel. Nasopharyngeal swabs are uncomfortable, not suitable for certain patient groups and do not allow self-testing. Convenient, well-tolerated rapid antigen tests (RATs) for SARS-CoV-2 detection are called for. Gap statement. More real-life performance data on anterior nasal RATs are required. Aim. We set out to evaluate the anterior nasal AMP RAT in comparison with rRT-PCR in a hospital cohort. Methodology. The study included 175 patients, either hospitalized in a coronavirus disease 2019 (COVID-19) ward or screened in a preadmittance outpatient clinic. Two swabs were collected per patient: an anterior nasal one for the RAT and a combined naso-/oropharyngeal one for the rRT-PCR. Sixty-five patients (37%) were rRT-PCR-positive [cycle threshold (C t) <40]. Results. The anterior nasal AMP RAT showed an overall sensitivity and specificity of 29.2 % (18.6–41.8, 95 % CI) and 100.0 % (96.7–100.0, 95 % CI) respectively. In patients with a C t value <25, <30 and <33, higher sensitivities were observed. Time since symptom onset was significantly higher in patients with a false-negative RAT (P=0.02). Conclusion. The anterior nasal AMP RAT showed low sensitivities in this cohort, especially in patients with a longer time since symptom onset. Further knowledge concerning the viral load and antigen expression over time and in different swabbing locations is needed to outline the usage time frame for SARS-CoV-2 RAT.

No abstract