BAMBI (bone morphogenetic protein and activin membrane-bound inhibitor) is a transmembrane pseudoreceptor structurally related to transforming growth factor (TGF)-β type 1 receptors (TGF-β1Rs). BAMBI lacks a kinase domain and functions as a TGF-β1R antagonist. Essential processes such as cell differentiation and proliferation are regulated by TGF-β1R signaling. TGF-β is the best-studied ligand of TGF-βRs and has an eminent role in inflammation and fibrogenesis. Liver fibrosis is the end stage of almost all chronic liver diseases, such as non-alcoholic fatty liver disease, and at the moment, there is no effective anti-fibrotic therapy available. Hepatic BAMBI is downregulated in rodent models of liver injury and in the fibrotic liver of patients, suggesting that low BAMBI has a role in liver fibrosis. Experimental evidence convincingly demonstrated that BAMBI overexpression is able to protect against liver fibrosis. Chronic liver diseases have a high risk of hepatocellular carcinoma (HCC), and BAMBI was shown to exert tumor-promoting as well as tumor-protective functions. This review article aims to summarize relevant studies on hepatic BAMBI expression and its role in chronic liver diseases and HCC.

Background: Out-of-hospital cardiac arrest (OHCA) is a critical health issue with survival influenced by multiple factors. This study analyzed resuscitation outcomes at the County Clinical Emergency Hospital of Sibiu, Romania, during pre-COVID-19 and pandemic periods. Methods: A retrospective analysis of 508 OHCA patients (2017–2020) assessed the return of spontaneous circulation (ROSC) as the primary endpoint. Statistical methods included decision tree analysis, logistic regression and ROC curve analysis to evaluate the predictive value of adrenaline dose and patient factors. Results: The mortality rate was 68.7%, with non-shockable rhythms predominant among fatalities. Rural patients, though younger, had lower ROSC rates than urban counterparts. Logistic regression showed that lower adrenaline doses (≤4 mg, OR 11.835 [95% CI: 6.726–20.27]; 4–6 mg, OR 2.990 [95% CI: 1.773–5.042]) were associated with better ROSC outcomes. Conclusions: A multivariable model (AUC = 0.773) incorporating demographics and pandemic status outperformed adrenaline dose alone (AUC = 0.711).

Background and Aims: Amyloidosis is a group of systemic disorders caused by extracellular deposition of misfolded serum proteins. Gastrointestinal (GI) involvement is associated with a higher risk of GI bleeding, especially if mucosal lesions are present. Our study aims to evaluate the frequency of GI manifestations in patients with amyloidosis, to clinically characterize these patients and to describe the endoscopic and histopathologic findings in GI amyloidosis. Methods: A retrospective, single-center study of all patients admitted with amyloidosis and GI manifestations was conducted at a German University Hospital between July 2003 and June 2023. Clinical, endoscopic, and histopathological data was retrieved from medical records. Results: Between July 2003 and June 2023, 63 patients with different types of amyloidosis were included into the study. Twenty-three (36,5%) were diagnosed with GI involvement of amyloidosis (60.9% male, median age 62 ± 18.28 years). The distribution of the types of amyloidosis were amyloid light chain (AL) at 52.5%, transthyretin (ATTR) at 21.7%, amyloid A (AA) at 13.0%, and unknown at 18%. Initial GI symptoms were present in 78.3% of the patients and included mainly diarrhea (34.8%), and abdominal pain (30.4%) Affected GI organs were primarily the colon (60,8%) and the stomach (39.1%). Endoscopic findings were ulcerations (47.8%), mucosal inflammation (43.5%), polyps (26.1%), erosions (13.0%), vascular malformation, polypoid protrusion, submucosal hematoma, erythema, metaplasia, and diverticulum. Histopathological findings included vascular wall thickening, (peri-)vascular and interstitial amyloid deposition. Gastrointestinal bleeding occurred in 39.1% of the patients. The mortality rate 5 years after diagnosis was 47.8%. Conclusions: Gastrointestinal amyloidosis can present with multiple symptoms and endoscopic findings, rendering diagnosis a challenge. Of clinical relevance, GI bleeding was a frequent event in our patient cohort. Therefore, clinicians must be aware of GI bleeding as a manifestation of amyloidosis and definite diagnosis should be achieved based on biopsy results.

Critical illness causes disturbances in lipid metabolism. Here, we investigated the levels of apolipoprotein A-IV (apoA-IV), a regulator of triglyceride and cholesterol metabolism, in human sepsis. ApoA-IV (analyzed in 156 patients with systemic inflammatory response syndrome (SIRS)/sepsis) and cholesteryl ester (CE) (analyzed in 121 of these patients) were lower in patients compared to 43 healthy controls. In contrast, triglyceride (TG) levels were elevated in patients. ApoA-IV levels in plasma of the patients did not correlate with these lipids. Patients with SIRS, sepsis or septic shock had comparable apoA-IV, TG, CE and free cholesterol (FC) levels. Patients on dialysis had significantly lower CE levels, whereas apoA-IV levels did not change much. CE levels were elevated in patients with viral sepsis due to SARS-CoV-2 infection in comparison to SIRS/sepsis patients not infected by this virus. CE levels correlated negatively with procalcitonin, interleukin-6 and bilirubin, while TGs were positively associated with bilirubin and C-reactive protein. ApoA-IV, TG, CE and FC levels were not associated with bacterial infection or survival. In conclusion, this analysis suggests that CE levels decline in sepsis-related renal failure and also shows that plasma apoA-IV and CE levels are early biomarkers of sepsis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) reduces low density lipoprotein (LDL) uptake, leading to increased plasma levels of LDL. In addition, PCSK9 has been implicated in inflammation independently of the effects on cholesterol metabolism. The current analysis showed that our 156 patients with systemic inflammatory response syndrome (SIRS) or sepsis had higher plasma PCSK9 levels in contrast with the 68 healthy controls. COVID-19 sepsis patients had increased plasma PCSK9 levels in comparison to sepsis patients not infected by SARS-CoV-2. For further analysis, patients were divided in two groups based on COVID-19. In both sub-cohorts, plasma PCSK9 levels did not correlate with C-reactive protein, leukocyte count, and procalcitonin. Plasma PCSK9 levels of both patient groups did not significantly differ among SIRS/sepsis patients with and without dialysis and patients with and without ventilation. Furthermore, vasopressor therapy was not significantly associated with altered plasma PCSK9 levels. In the non-COVID-19 SIRS/sepsis group, patients with Gram-negative and Gram-positive infections had similar plasma PCSK9 levels as patients without a detectable pathogen in their blood. In conclusion, the current study suggests PCSK9 as a possible biomarker for COVID-19, but this needs to be validated in larger cohorts.

Background/Objectives: Men are more susceptible to sepsis than women, but the underlying pathways have not been fully clarified. Lipopolysaccharide-binding protein (LBP) is an acute-phase protein that is highly elevated in sepsis. Experimental evidence shows that LBP increases to a much greater extent in male than in female mice following exposure to lipopolysaccharide. However, gender-specific studies of circulating LBP levels in sepsis patients are scarce. Methods: In the plasma of 189 patients with systemic inflammatory response syndrome (SIRS), sepsis, and septic shock, LBP levels were measured by enzyme-linked immunosorbent assay. Results: Patients with liver cirrhosis had reduced circulating LBP levels, regardless of gender. Further analysis within the non-cirrhotic patients showed no significant differences in LBP levels between sexes in patients with SIRS, sepsis, and septic shock. Ventilation, dialysis, and vasopressor therapy had no effect on LBP levels in either sex. A positive correlation between LBP and C-reactive protein was observed in the total cohort, males, and females. Infection with Gram-negative or Gram-positive bacteria had no effect on plasma LBP levels in males. However, female patients with Gram-negative infection had increased plasma LBP levels compared to females with negative and Gram-positive blood cultures, and 70 µg/mL LBP discriminates Gram-negative infections in females with a sensitivity of 88% and a specificity of 74%. Infection with SARS-CoV-2 did not change plasma LBP levels in either men or women. Female patients who did not survive had lower plasma LBP levels compared to female survivors and male non-survivors. Conclusions: This investigation highlights the influence of sex on plasma LBP levels in SIRS/sepsis patients, suggesting that LBP could be a sex-specific biomarker in critically ill patients.