Efficacy and nephrotoxicity of polymyxin B in elderly patients with carbapenem resistant bacterial infection.

BACKGROUND: To study the efficacy and nephrotoxicity of polymyxin B in the treatment of elderly patients with carbapenem-resistant organism (CRO) infection. METHODS: The clinical and microbiological data of patients with CRO-infected sepsis treated with polymyxin B were retrospectively analyzed. The effective rate, bacterial clearance, incidence and recovery rate of acute renal injury (AKI) and prognosis-related indicators in AKI at different stages were compared. RESULTS: The effective rate of 215 elderly patients with CRO infection treated with polymyxin was 50.7%. The total bacterial clearance rate was 44.2%, the total incidence of AKI was 37.2%, the recovery rate of AKI was 35%, and the incidence range of polymyxin B-related AKI was 10.2-37.2%. Logistic multivariate regression analysis showed that the predictors of AKI in elderly patients were high APACHE II score, long duration of polymyxin, chronic renal insufficiency and ineffective outcome; the ROC curve showed that the cutoff value for predicting AKI was a serum creatinine concentration of 73 mmol/L before polymyxin B use, and the AUC was 0.931. CONCLUSIONS: Rational use of polymyxin B is safe and effective in elderly patients with CRO infection, and its effective outcome can improve the recovery rate of AKI.

Efficacy and safety of polymyxin B in carbapenem-resistant gram-negative organisms infections.

OBJECTIVE: To investigate how to use polymyxin B rationally in order to produce the best efficacy and safety in patients with carbapenem-resistant gram-negative organisms (CRO) infection. METHODS: The clinical characteristics and microbiological results of 181 patients caused by CRO infection treated with polymyxin B in the First Affiliated Hospital from July 2018 to May 2020 were retrospectively analyzed. The bacterial clearance rate, clinical efficacy, adverse drug reactions and 28 days mortality were evaluated. RESULTS: The overall effective rate of 181 patients was 49.72%, the total bacterial clearance rate was 42.0%, and the 28 day all-cause mortality rate was 59.1%. The effective rate and bacterial clearance rate in the group of less than 24 h from the isolation of CRO to the use of polymyxin B were significantly higher than those in the group of more than 24 h. Logistics multivariate regression analysis showed that the predictive factors for effective treatment of CRO with polymyxin B were APACHEII score, duration of polymyxin B treatment, combination of polymyxin B and other antibiotics, and bacterial clearance. 17 cases (9.36%) of acute kidney injury were considered as polymyxin B nephrotoxicity and 4 cases (23.5%) recovered after polymyxin B withdrawal. After 14 days of polymyxin B use, 3 cases of polymyxin B resistance appeared, and there were 2 cases of polymyxin B resistance in the daily dose 1.5 mg/kg/day group. CONCLUSION: For CRO infection, the treatment of polymyxin B should be early, combined, optimal dose and duration of treatment, which can achieve better clinical efficacy and microbial reactions, and reduce the adverse reactions and drug resistance.

[Clinical application of Acutegastrointestinal injury grading system assocaited with clinical severity outcome in critically ill patients: a multi-center prospective, observational study].

Objective: To investigate the feasibility of utilizing the current acute gastrointestinal injury(AGI) grading system, and explore the association of severity of AGI grade with clinical outcome in critically ill patients. Methods: The adult patients from 14 general ICUs in Zhejiang Province with an expected admission to ICU for at least 24 h were recruited, and all clinical, laboratory, and survival data were prospectively collected. The AGI grade was daily assessed based on GIsymptoms, feeding details and organ dysfunctionon the first week of admission to ICU.The intra-abdominal pressures(IAP) was measured using AbViser device. Results: Of 550 patients enrolled, mean values for age and APACHE Ⅱ score were (64.9±17.2) years and (19.5±7.4), respectively. 456 patients(82.9%) took mechanical ventilation, and 470 patients were identified for AGI. The distribution of AGI grade on the frist day of ICU admission were 50.6%(Ⅰ grade, n=238), 34.2%(Ⅱ grade, n=161), 12.4%(Ⅲ grade, n=58) and 2.8%(Ⅳ, n=13), respectively, while the distribution of the global AGI grade based on the 7-day AGI assessment of ICU admission were 24.5%(Ⅰ grade, n=115), 49.4%(Ⅱ grade, n=232), 20.6%(Ⅲ grade, n=97) and 5.5%(Ⅳ, n=26), respectively. 28- and 60-day mortality rate was 29.3%(n=161) and 32.5%(n=179), respectively. The patients with AGI had a higher 28-(31.1% vs 18.8%, P=0.025) and 60-day survival rate(34.7% vs 20.0%, P=0.01) than those with non-AGI, and also there were positive correlations between AGI grade and 28- and 60-day mortality(P<0.001). Univariate Cox regression analysis showed that age, the source of medicial admission, diabetes mellitus, coronary heart disease, the use of vasoactive drugs, serum creatinine and lactate, mechanical ventilation, APACHE Ⅱ score, the AGI grade in the first day of ICU admission and feeding intolerance within the first week of ICU stay were significantly(P≤0.02) associated with mortality. In multivariate analysis including all these variables, the source of medical admission(χ(2)=4.34, P=0.04), diabete mellitus(χ(2)=3.96, P=0.05), the use of vasoactive drugs(χ(2)=6.55, P=0.01), serum lactate(χ(2)=4.73, P=0.03), the global AGI grade in the 7-day of ICU admission(χ(2)=7.10, P=0.008), and APACHE Ⅱ score(χ(2)=12.1, P<0.001) remained independent predictors for 60-day mortality.In the further subgroup analysis including 402 patients with 7-day survival, the feeding intolerance within the first week of ICU stay could provide independent and incremental prognostic value of 60-day mortality wtih increased χ(2)value of Cox regression model(χ(2)=52.2 vs 41.9, P=0.007) . Conclusion: The AGI grading system is useful for identifying the severity of gastrointestinal dysfunction, and could be used as a strong predictor of impaired outcome. The results provide evidence to support that feeding intolerance within 7 days of admission to ICU was an independent determinant of mortality.

[Prognostic analysis of acute-on-chronic liver failure after withdrawal of nucleos(t)ide analogues for antiviral treatment of chronic hepatitis B].

OBJECTIVE: To investigate the prognostic factors for acute-on-chronic liver failure (ACLF) after the withdrawal of nucleos(t)ide analogues (NAs) for the antiviral treatment of chronic hepatitis B (CHB). METHODS: The clinical data of 67 hospitalized patients with ACLF after withdrawal of NAs for the antiviral treatment of CHB were analyzed retrospectively. RESULTS: The HBeAg status before initial treatment and after recurrence, course of the antiviral treatment, duration from the withdrawal of NAs to recurrence, and type of NAs before and after withdrawal were not associated with the prognosis of ACLF. The Cox univariate regression analysis showed that serum bilirubin, international normalization ratio, serum creatinine, model of end-stage of liver disease (MELD) score, hepatic encephalopathy, and concurrent infection were associated with the 12-week death. The Cox multivariate regression analysis showed that MELD score and hepatic encephalopathy were independent predictors for 12-week death. The area under the receiver operating characteristic curve for the MELD score to predict 12-week death was 0.906, with an optimal cutoff value of 32, a sensitivity of 82.9%, a specificity of 88.5%, a positive predictive value of 91.9%, and a negative predictive value of 76.7%. CONCLUSION: MELD score and hepatic encephalopathy are closely associated with the prognosis of patients with ACLF after withdrawal of NAs for the antiviral treatment of CHB.

A prospective study of transfusion-transmitted virus transmission by blood transfusion.

Recently, a new single-stranded DNA virus (TT virus, TTV) has been isolated and related to post-transfusion hepatitis. The aim of this study was to investigate the prevalence of TTV in blood donors and blood recipients, and the incidence of TTV transmission by blood transfusion. TTV DNA and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV), were examined in 130 blood recipients, and the presence of TTV was studied in their 340 corresponding blood donors. The prevalence of TTV infection was 10.6% (36/340) in donors and 8.5% (11/130) in blood recipients, before transfusion. Eighteen subjects (15.1%) were found to be TTV positive, after transfusion, in the 119 blood recipients without TTV before transfusion; at least one of the corresponding donors was TTV positive. There were 46 subjects with post-transfusion hepatitis virus infection, 45 with HCV infection (including seven co-infected with TTV) and two with HBV infection (including one co-infected with HCV and one co-infected with TTV). The recipient with TTV and HBV co-infection and three of the seven patients with TTV and HCV infection had alanine aminotransferase (ALT) levels higher than 90 Ul-1, but only two of the 10 isolated TTV infections had a mild ALT elevation. These results show that prevalence of TTV was high in blood donors and hospitalized patients, and isolated TTV infection is not related to significant ALT elevation.

Purification and structural characterization of progastrin-derived peptides from a human gastrinoma.

Several peptides derived from the gastrin-predicted preprohormone sequence were isolated from a human gastrinoma by gel permeation, anion exchange, and reverse phase chromatography. The peptides were identified and characterized structurally by a combination of radioimmunoassays, mass spectral analysis, and microsequence analysis. The largest peptide, progastrin-(1-35) (cryptagastrin), extends from the putative processing site for the signal peptidase to the double basic residues adjacent to the amino terminus of gastrin 34. A shorter form of this peptide, progastrin-(6-35) (cryptagastrin-(6-35), was also isolated in smaller amounts. In addition, sulfated and nonsulfated gastrin 17 amides (progastrin-(55-71)) and the glycine-extended nonsulfated gastrin 17 (progastrin-(55-72)) were identified by radioimmunoassay, and their structures were confirmed by mass spectral analysis. Isolation of cryptagastrin indicates that the signal peptide of human preprogastrin contains 21 amino acid residues, and progastrin, therefore, contains 80 amino acids. There is minimal processing of the cryptic peptide preceding the sequence of gastrin 34. An amidated gastrin form larger than gastrin 34 could contain 71 amino acids. No evidence was obtained for processing that would produce gastrins containing more than 34 but less than 71 amino acid residues.

Mitotic reversion in prophase of PTK1 cells induced by argon laser microirradiation.

In this paper, we report the effects of laser microirradiation of prophase nucleoli and mitotic chromosomes in cells of female rat kangaroo kidney epithelial cell line PTK1. When the laser power delivered to sample surface was 90-190 mW, irradiation of one of the two nucleoli in the prophase cell did not inhibit the mitotic progress, but resulted in the loss of the irradiated nucleolus in daughter cells. When the laser power was increased to 360-420 mW, either irradiation of the nucleolus or chromosome in midprophase caused a blockage of mitosis at terminal midprophase. The irradiated cells returned morphologically to early prophase. No mitotic reversion occurred in the case of irradiation of chromosomes at late prophase, prometaphase, metaphase, and anaphase. Irradiation of the cytoplasm in prophase cells caused a 50-70 min mitotic delay at prophase. However, the irradiated cells underwent successive mitotic divisions. The mechanism of laser-induced mitotic prophase reversion is discussed.