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OBJECTIVES: With SARS-CoV-2 evolving, disease severity and presentation have changed due to changes in mechanisms of entry and effector site as well as due to effects of vaccination- and/or infection-acquired immunity. We re-assessed fetal lung pathology in pregnancies with uncomplicated SARS-CoV-2 infections during the late, omicron-dominated pandemic phase to inform disease understanding and pregnancy consultation. METHODS: In this case-control study, fetal lung volumes were assessed by fetal MRI in 24 pregnancies affected by mild maternal SARS-CoV-2 infection during the omicron-dominated pandemic phase with prevailing immunity through vaccination and/or prior SARS-CoV-2 infection. RESULTS: Fetal lung volumes (normalized to estimated fetal weight) in 24 pregnancies (GA 33.3 ± 3.8, 12 female fetuses) following mild, uncomplicated SARS-CoV-2 infection did not differ significantly from both, published reference values (96.3% ± 22.5% of 50th percentile reference values, p = 0.43), or fetal lung volumes of a site-specific, non-COVID control group (n = 15, 94.2% ± 18.5%, p = 0.76). Placental assessment revealed no group differences in thrombotic changes or placental heterogeneity (p > 0.05, respectively), and fetal lung volume did not correlate with placental heterogeneity when adjusting for gestational age at scan (p > 0.05). CONCLUSION: Assessment of fetal lung volume by MRI revealed unaffected lung growth in pregnancies affected by uncomplicated SARS-CoV-2 infection in the omicron-dominated pandemic phase in the presence of prevailing hybrid immunity. This finding contrasts sharply with the observed reduction in fetal lung volume following maternal alpha-variant infection in the pre-vaccination era and might reflect tropism- as well as immunity-related effects. KEY POINTS: Question: Is fetal lung development affected by mild maternal SARS-CoV-2 infection during the omicron-dominated phase of the pandemic? FINDINGS: Fetal lung volume in 24 affected pregnancies did not differ significantly from published reference values or fetal lung volumes in 15 site-specific, non-COVID-affected control pregnancies. CLINICAL RELEVANCE: Preserved fetal lung volume following mild maternal SARS-CoV-2 infection during the omicron-dominated phase contrasts with previous findings of reduced volume in unvaccinated pregnancies during the alpha-dominated pandemic phase. These observations might reflect tropism- as well as immunity-related effects.
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BACKGROUND AND PURPOSE: To determine the potential prognostic value of proliferation and angiogenesis plasma proteins following CT-guided high dose rate brachytherapy (HDR-BT) of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: For this prospective study, HDR-BT (1 × 15 Gy) was administered to 24 HCC patients. Plasma was obtained and analyzed using an Olink proteomics Target-96 immuno-oncology-panel that included multiple markers of angiogenesis and proliferation. Fold-change (FC) ratios were calculated by comparing baseline and 48 h post HDR-BT paired samples. Patients were classified as responders (n = 12) if they had no local progression within 6 months or systemic progression within 2 years. Non-responders (n = 12) had recurrence within 6 months and/or tumor progression or extrahepatic disease within 2 years. RESULTS: Proliferation marker EGF was significantly elevated in non-responders compared to responders (p = 0.0410) while FGF-2, HGF, and PlGF showed no significant differences. Angiogenesis markers Angiopoietin-1 and PDGF-B were likewise significantly elevated in non-responders compared to responders (p = 0.0171, p = 0.0462, respectively) while Angiopoietin-2, VEGF-A, and VEGFR-2 did not differ significantly. Kaplan-Meier analyses demonstrated significantly shorter time to systemic progression in patients with increased EGF and Angiopoietin-1 (p = 0.0185, both), but not in patients with one of the remaining proteins elevated (all p > 0.1). Pooled analysis for these 9 proteins showed significantly shorter time to systemic progression for FC ≥1.3 and ≥1.5 for at least 3 proteins elevated (p = 0.0415, p = 0.0193, respectively). CONCLUSION: Increased plasma levels of EGF and Angiopoietin-1 after HDR-BT for HCC are associated with poor response and may therefore function as predictive biomarkers of outcome.
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OBJECTIVE: Minimal hepatic encephalopathy (MHE) is one of the possible complications of liver cirrhosis. In this study, a potassium-iron-phosphate-citrate complex was analyzed for its efficacy and safety in the treatment of MHE, as this complex is supposed to bind to the major pathogenic factor of MHE: intestinal ammonia. MATERIALS AND METHODS: In this placebo-controlled, double-blind clinical trial, 51 patients with MHE were randomized into two groups at a ratio of 1 : 1 and treated for 4 weeks either with a potassium-iron-phosphate-citrate complex or a placebo. The efficacy of treatment was assessed according to changes in the portosystemic encephalopathy (PSE) score. Further assessments included alterations in quality of life and safety evaluations. RESULTS: Significantly more patients showed improvements in the PSE syndrome test from pathological to nonpathological PSE scores in the potassium-iron-phosphate-citrate-treated group (72.0%) than in the placebo group (26.9%; P=0.0014). Furthermore, quality of life improved at a higher grade in the verum group (by 0.7 ± 0.6 U) compared with the placebo group (by 0.2 ± 0.6 U; P=0.0036). Adverse events occurring in 28.0% of potassium-iron-phosphate-citrate-treated patients were generally mild or moderate and affected mainly the gastrointestinal tract. CONCLUSION: Treatment with potassium-iron-phosphate-citrate significantly improved PSE scores and quality of life in patients with MHE. The potassium-iron-phosphate-citrate complex is a well-tolerated treatment option in MHE.