Effect of Remimazolam Tosilate on Respiratory Depression in Elderly Patients Undergoing Gastroscopy: A Multicentered, Prospective, and Randomized Study.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABAA) receptor agonist, having the possibility to be an ideal sedative drug for procedural sedation. At present, there are few studies on the effect of RT on respiratory depression in elderly patients. We aimed to evaluate the effect of RT on respiratory depression in elderly patients undergoing gastroscopy. Methods: This prospective, randomized, single-blinded trial recruited patients from eight centers in China between May 2022 and July 2022. A total of 346 elderly patients undergoing gastroscopy were randomly divided into RT group (0.2 mg/kg) or propofol group (1.5 mg/kg), respectively. The primary outcome was the incidence of respiratory depression. Secondary outcomes include the incidence of sedative-related adverse events, the success rate of sedation, time to fully alert, time to loss of consciousness (LOC), time to ready for discharge, as well as the the patients, endoscopists and anethetists' satisfaction. Results: The incidence of respiratory depression was significantly reduced in the RT group compared with the propofol group (9.8% vs 17.9%, P=0.042). The time of LOC and fully alert in the RT group were longer than that in the propofol group (P < 0.05). The incidences of hypotention (50.9% vs 32.4%, P=0.001) and hypotension requiring treatment (5.8% vs 1.7%, P=0.031) were significantly higher in the propofol group than that in the RT group. The incidence and severity of injection pain were more frequently recorded in the propofol group than that in the RT group (40.5% vs 12.1%, P<0.05). There were no statistically significant differences between the two groups in terms of sedation success rates, time to ready for discharge, endoscopists and anethetists' satisfaction and other sedative-related adverse events. Conclusion: RT may be a suitable alternative sedative agent for elderly patients undergoing gastroscopy due to its safety profile.

Monitoring oxidative stress in acute-on-chronic liver failure by advanced oxidation protein products.

AIM: Increased oxidative stress is important in the pathogenesis of acute-on-chronic liver failure (ACLF). This study aimed to investigate whether advanced oxidation protein products (AOPP) levels can monitor oxidative stress of ACLF patients. Furthermore, we aimed to study plasma exchange (PE) treatment and determine whether it can eliminate AOPP. METHODS: We measured AOPP levels in 50 ACLF patients, 30 patients with compensated liver cirrhosis (CR), 30 patients with chronic hepatitis B (CHB) and 50 healthy controls by spectrophotometric assay. AOPP concentrations were also measured before and after PE treatment in ACLF patients. As an apoptosis marker, serum cytokeratin 18 (CK18 M 30) levels were detected to investigate the relationship between AOPP and apoptosis in ACLF patients. RESULTS: Significantly higher AOPP levels at admission were found in patients with ACLF compared with CR, CHB and healthy controls (69.45 ± 29.04 µmol/L vs. 19.67 ± 7.02 µmol/L, 26.75 ± 5.21 µmol/L and 21.35 ± 6.15 µmol/L, respectively; P < 0.001). There was a positive relationship with total bilirubin, Child-Pugh, model for end-stage liver disease scores and CK18 M 30. In ACLF patients, AOPP levels were higher in non-survivors than survivors. An AOPP cut-off of 74.21 µmol/L was used for predicting poor prognosis. Multivariate Cox regression analysis demonstrated that AOPP were independent risk factors for prognosis. Dynamic change of AOPP levels associated with prognosis appeared earlier than total bilirubin. Following PE treatment, AOPP levels reduced to 34.65 ± 18.14 µmol/L (P < 0.001). CONCLUSIONS: Advanced oxidation protein products were suitable for monitoring the levels of oxidative stress in ACLF patients. Increased AOPP may serve as an important biological marker of worse outcome. In addition, PE therapy was effective in reducing AOPP.

[The predictive value of dynamic changes of serum thymosin b4 in liver failure patients].

Not Abstract.

[Entecavir 1.0mg monotherapy or entecavir plus adefovir dipivoxil for patients with lamivudine-resistant chronic hepatitis B had suboptimal response to lamivudine plus adefovir dipivoxil].

OBJECTIVE: To evaluate the efficacy of entecavir (ETV) 1.0 mg/d or ETV plus adefovir dipivoxil (ADV) in adults with chronic hepatitis B virus (HBV) infection who had previously resisted lamivudine (LAM) and failed with rescue treatment of LAM + ADV. METHODS: 40 patients were enrolled. 14 patients were treated with ETV 1.0 mg/d monotherapy while 26 patients were treated with ETV 1.0 mg/d + ADV 10 mg/d. The HBV DNA level, liver function, HBV serology and renal function were observed. RESULTS: There was no statistically significant difference with baseline situation between group ETV 1.0 mg and group ETV + ADV. HBV DNA level in group ETV 1.0 mg was (5.768 ± 0.709) log10 copies/ml on baseline, and it declined to (4.712 ± 0.846) log10 copies/ml, (3.914 ± 0.996) log10 copies/ml, (3.702 ± 0.934) log10 copies/ml, (3.879 ± 0.913) log10 copies/ml and (3.855 ± 1.070) log10 copies/ml at 4, 8, 12, 24 and 48 weeks. HBV DNA level in group ETV + ADV was (5.703 ± 0.845) log10 copies/ml on baseline, and it declined to (4.476 ± 0.905) log10 copies/ml, (3.590 ± 0.884) log10 copies/ml, (2.987 ± 0.673) log10 copies/ml and (2.933 ± 0.535) log10 copies/ml at 4, 8, 12 and 24 weeks. At 24 weeks, there were 28.6% patients achieved HBV DNA < 500 copies/ml in group ETV 1.0 mg, but there were 80.8% patients in group ETV + ADV achieved this level. Statistically significant difference existed between (x(2) = 8.469, P = 0.004 ). At 48 weeks, there were still 4 patients achieved HBV DNA < 500 copies/ml in group ETV 1.0 mg, but patients in group ETV + ADV all achieved it. At 24 weeks, ALT levels of 42.9% patients in group ETV 1.0 mg were back to normal, but there were 92.3% patients' ALT levels back to normal in group ETV + ADV. There was statistically significant difference (x(2) = 9.337, P = 0.002). At 48 weeks, ALT levels of 57.1% patients in group ETV 1.0 mg were back to normal, but all patients' ALT levels were back to normal in group ETV + ADV. At 48 weeks, there was 1 patient with HBeAg seroconversion in group ETV 1.0 mg while there were 4 patients in group ETV + ADV. CONCLUSION: As rescue treatment for patients with chronic hepatitis B who had previously resisted LAM and failed with treatment of LAM + ADV, ETV + ADV was more efficient than ETV 1.0 mg monotherapy, and it can achieve better virological and biochemical response.

Serum thymosin beta4 levels in patients with hepatitis B virus-related liver failure.

AIM: To investigate whether serum thymosin beta4 can provide diagnostic or prognostic information in liver failure patients caused by chronic hepatitis B virus (HBV) infection. METHODS: Serum thymosin beta4 levels were measured in 30 patients with acute-on-chronic liver failure (ACLF), 31 patients with chronic liver failure (CLF), 30 patients with compensated liver cirrhosis (CR) and 32 patients with chronic hepatitis B and 30 healthy controls. Serum thymosin beta4 levels were measured by enzyme-linked immunosorbent assay and Child-Pugh and model for end-stage liver disease (MELD) scores were calculated for each patient on admission. RESULTS: Compared with healthy controls, serum thymosin beta4 levels in ACLF, CLF, CR and chronic hepatitis B patients were significantly lower, 6.5047 (4.7879-10.5314) microg/mL vs 0.4632 (0.2759-0.8768) microg/mL, 0.6981 (0.5209-1.2008) microg/mL, 1.8053 (0.8110-2.3397) microg/mL, 3.7803 (1.8570-6.4722) microg/mL, respectively (P < 0.001). The levels of thymosin beta4 in liver failure (ACLF or CLF) patients were markedly lower than that in CR (P < 0.001), and a difference was also found between CLF and ACLF patients (P = 0.038). In patients with chronic liver disease, there was a positive relationship between thymosin beta4 levels and albumin, choline esterase, and platelet (P < 0.001), and negative relationship with alanine aminotransferase (P = 0.020), aspartate aminotransferase, total bilirubin, international normalized ratio of prothrombin time, and Child-Pugh and MELD scores (P < 0.001). Of the 61 liver failure patients, the thymosin beta4 levels of non-survivors were significantly lower than that of survivors (P = 0.007). Receiver operating characteristics analysis identified a thymosin beta4 cutoff level of 0.5708 microg/mL for predicting poor prognosis in all liver failure patients. The serial thymosin beta4 values were observed in 13 liver failure inpatients. Lower initial values were observed in the death. While greater improvement in thymosin beta4 value was found in those who recovered from the disease. CONCLUSION: Serum thymosin beta4 can be used as an important potential predictor for liver failure caused by chronic HBV infection.

[Telbivudine treatment on cirrhosis resulting from chronic hepatitis B].

OBJECTIVE: To study the therapeutic efficacy of 48-week telbivudine treatment on cirrhosis resulting from chronic hepatitis B. METHODS: 80 patients were equally divided into two groups, and treated with telbivudine 600 mg or lamivudine 100mg once daily for 48 weeks, respectively. The changes of virological and biochemical markers, PTA, Child-Pugh score, and viral resistance were observed at the different time points after antiviral treatment. RESULTS: The mean of serum HBV DNA level in telbivudine group before treatment was (6.52+/-1.33) log10 copies/ml, and the mean reduction of serum HBV DNA was (2.09+/-1.30), (2.83+/-1.22), (3.23+/-1.27), (3.42+/-1.32), (3.65+/-1.30), (3.67+/-1.43) log10 copies/ml at 2, 4, 8, 12, 24, 48 weeks, respectively. The proportion of patients with serum HBV DNA undetectable was 92.5% (37/40) at 24, 48 weeks. At week 24 and 48, the rates of HBeAg/anti-HBe seroconversion were 30.0% (6/20), 35.0% (7/20), respectively. ALT, AST, albumin, total bilirubin, PTA, and Child-Pugh score were improved (P less than 0.05). Mutation of YMDD observed in telbivudine group was 5.0%. The mean reduction of serum HBV-DNA and the proportion of patients with undetectable serum HBV-DNA were greater in telbivudine group than in lamivudine group (P less than 0.05). CONCLUSIONS: Telbivudine can rapidly and effectively inhibit the replication of HBV in patients with cirrhosis resulting from chronic hepatitis B, and the resistance mutation rate was low. In addition, telbivudine treatment can improve the liver function.