Impact of Ursodeoxycholic Acid in Critically Ill Patients With Sepsis: A Retrospective Study

Background: Using ursodeoxycholic acid (UDCA) in critically ill patients as adjunctive therapy for sepsis/septic shock in neonates and children is controversial, while it has not been extensively investigated in adults. This study aims to assess the effect of UDCA use on the early resolution of sepsis/septic shock in critically ill adult patients. Method: A retrospective study of critically ill adult patients in the intensive care unit (ICU) admitted with sepsis/septic shock at King Abdulaziz Medical City. Based on their usage of UDCA, patients were categorized into two groups. A total of 88 patients were included for analysis after matching, based on severity of illness scores within 24-hours of ICU admission. The primary outcome was to assess the effect of UDCA on the severity and resolution of shock at day three of ICU admission. The secondary outcomes were 30-day in-hospital mortality, mechanical ventilation (MV) duration, and ICU length of stay (LOS). Results: Out of the 88 patients matched, 44 patients (50%) received UDCA during the study period. Using UDCA was neither associated with improvement in Sequential Organ Failure Assessment (SOFA) score ( p-value: 0.32), inotropes/vasopressors requirement ( p-value: 0.79), Glasgow Coma Scale (GCS) ( p-value: 0.59) nor total bilirubin levels ( p-value: 0.79) at day three compared with the control. There was a significant association between using UDCA and improvement in PaO2/FiO2 ratio ( p-value: 0.01) and early extubation at day three ( p-value: 0.04). Conclusion: Using UDCA in critically ill patients with sepsis/septic shock was not associated with improvement in shock severity and resolution. However, patients who received UDCA were more likely to be extubated and not require MV on day three of ICU admission.

Eff ect of ursodeoxycholic acid in postcholecystectomy cholestatic hepatopathy verified by ultrasonography

Summary: Cholestasis syndrome is accompanied by a large number of diverse liver and biliary tract diseases. Many cholestatic changes are fully reversible in the fi rst phase. However, with long-term cholestasis, extensive hepatocyte dysfunction occurs, the disease progresses, and many cholestatic syndromes result in irreversible liver damage and failure. Cholestatic liver diseases represent an important group of liver diseases that are an indication for liver transplantation. Postcholecystectomy syndrome is an imprecisely defi ned term, which includes a set of ongoing or recurrent or new diffi culties of patients after gallbladder surgery. We distinguish between early postcholecystectomy syndrome immediately in the postoperative period, or late postcholecystectomy syndrome, which occurs months or even years later. Ultrasonography is the fi rst imaging examination method for diseases of the liver and hepatobiliary system. It is a non-invasive method, available, relatively cheap, easily repeatable, and it does not represent a burden for the patient. Common bile duct dilatation after cholecystectomy is a common accidental fi nding that is inconclusive in the absence of clinical symptomatology and with normal laboratory fi ndings. Ursodeoxycholic acid forms the basis of cholestasis therapy, the only treatment whose effi cacy in cholestatic liver disease has been demonstrated in randomized and long-term studies. A further positive is that many years of ursodeoxycholic acid administration are not accompanied by more serious side eff ects. This case report supports the concept of a prompt and at the same time deepening benefi cial eff ect of ursodeoxycholic acid treatment in patients with cholestatic hepatopathy verified by ultrasonography indicated for conservative treatment or refusing invasive treatment. Key words: cholestasis – postcholecystectomy syndrome – ultrasonography – ursodeoxycholic acid

Synthesis and Exon-Skipping Properties of a 3′-Ursodeoxycholic Acid-Conjugated Oligonucleotide Targeting DMD Pre-mRNA: Pre-Synthetic versus Post-Synthetic Approach

Steric blocking antisense oligonucleotides (ASO) are promising tools for splice modulation such as exon-skipping, although their therapeutic effect may be compromised by insufficient delivery. To address this issue, we investigated the synthesis of a 20-mer 2′-OMe PS oligonucleotide conjugated at 3′-end with ursodeoxycholic acid (UDCA) involved in the targeting of human DMD exon 51, by exploiting both a pre-synthetic and a solution phase approach. The two approaches have been compared. Both strategies successfully provided the desired ASO 51 3′-UDC in good yield and purity. It should be pointed out that the pre-synthetic approach insured better yields and proved to be more cost-effective. The exon skipping efficiency of the conjugated oligonucleotide was evaluated in myogenic cell lines and compared to that of unconjugated one: a better performance was determined for ASO 51 3′-UDC with an average 9.5-fold increase with respect to ASO 51.