scholarly journals Extended Infusion of β-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study

2019 ◽  
Vol 69 (10) ◽  
pp. 1731-1739 ◽  
Author(s):  
Michele Bartoletti ◽  
Maddalena Giannella ◽  
Russell E Lewis ◽  
Paolo Caraceni ◽  
Sara Tedeschi ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Propensity Score ◽  
Regression Model ◽  
Bloodstream Infection ◽  
Multicenter Study ◽  
Cox Regression ◽  
Intermittent Infusion ◽  
Beta Lactams ◽  
Cirrhotic Patients ◽  
Extended Infusion

Abstract Background We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI). Methods The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching. Results Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11–0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9–32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06–0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03–0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08–0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06–2.47]). Conclusions C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.

Impact of immunosuppressive agents on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection – A propensity score matched analysis in two large, prospectively evaluated cohorts

2021 ◽  
Author(s):  
Johannes Camp ◽  
Lina Glaubitz ◽  
Tim Filla ◽  
Achim J Kaasch ◽  
Frieder Fuchs ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Propensity Score ◽  
Bloodstream Infection ◽  
Cox Regression ◽  
Immunosuppressive Agents ◽  
Late Complications ◽  
Competing Risk ◽  
Immunosuppressed Patients ◽  
Staphylococcus Aureus Bloodstream Infection ◽  
Baseline Characteristics

Abstract Background Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. Methods Data from two large prospective, international, multicenter cohort studies (INSTINCT and ISAC) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score (PS) matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroids [CSMT] and immunosuppressive agents other than steroids [IMOTS]). Results Of 3,188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 non-immunosuppressed patients. After PS matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow-up: 105/309 (33.9 %) immunosuppressed patients vs. 94/309 (30.4 %) non-immunosuppressed, hazard ratio 1.20 (95% CI 0.84–1.71). Competing risk analysis showed a cause-specific hazard ratio (CSHR) of 1.81 (95% CI 0.85–3.87) for SAB-related late-complications in patients receiving immunosuppressive agents. CSHR was higher in patients taking IMOTS (3.69; 95% CI 1.41–9.68). Conclusions Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTs warrants further investigations.

scholarly journals Treg/Th17 imbalance and its clinical significance in patients with hepatitis B-associated liver cirrhosis

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Yong-Ting Lan ◽  
Zhen-li Wang ◽  
Peng Tian ◽  
Xiao-Na Gong ◽  
Yu-Chen Fan ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Regression Model ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Decompensated Liver Cirrhosis ◽  
Cox Regression Model ◽  
Potential Marker

Abstract Background Recent studies have shown that T cell-mediated cellular immune mechanisms play important roles in the progression of hepatitis B to liver cirrhosis, but the underlying mechanisms remain unclear. This present study was aimed to determine the relationship between Treg/Th17 and hepatitis B-associated liver cirrhosis. Methods The Treg and Th17 cell frequencies in the peripheral blood of all participants, including 93 patients with hepatitis B-associated liver cirrhosis and 40 healthy subjects, were measured by flow cytometer. Cox regression model and receiver operating characteristic(ROC) curves were applied to investigate the prognostic significance of Treg/Th17 ratio in decompensated liver cirrhosis. Results We observed the Treg/Th17 imbalance was present in patients with hepatitis B-associated liver cirrhosis, with reduced Treg cells in their peripheral blood, increased Th17 cells and decreased Treg/Th17 ratio. Treg and Th17 cells were negatively correlated. Treg/Th17 imbalance was closely related to the clinical stage of hepatitis B-associated liver cirrhosis. The Virus load, Treg frequencies and the Treg/Th17 ratio were independent factors predicting decompensated liver cirrhosis from a Cox regression model. The ROC analysis showed that the Treg/Th17 ratio was the best marker for predicting decompensated liver cirrhosis. Conclusions Treg/Th17 imbalance is involved in the pathogenesis of hepatitis B-associated liver cirrhosis and the Treg/Th17 ratio can be used as a potential marker for predicting decompensated liver cirrhosis.

scholarly journals Surveillance for Hepatocellular Carcinoma Also Improves Survival of Incidentally Detected Intrahepatic Cholangiocarcinoma Arisen in Liver Cirrhosis

Liver Cancer ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 744-755
Author(s):  
Francesco Tovoli ◽  
Pietro Guerra ◽  
Massimo Iavarone ◽  
Letizia Veronese ◽  
Matteo Renzulli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Cirrhosis ◽  
Propensity Score ◽  
Intrahepatic Cholangiocarcinoma ◽  
Lead Time ◽  
Propensity Score Analysis ◽  
Lead Time Bias ◽  
Cirrhotic Patients ◽  
Surgical Treatments

<b><i>Background:</i></b> Due to its poor survival, intrahepatic cholangiocarcinoma (ICC) is held to be a much more aggressive cancer than hepatocellular carcinoma (HCC). In most published series, patients were diagnosed when symptomatic. However, ICC is now increasingly being discovered during the surveillance for HCC in cirrhosis. Whether this earlier detection of ICC is associated with an equally dismal prognosis or not is unknown. <b><i>Methods:</i></b> This is amulticenter retrospective study of consecutive ICC patients. Patients were stratified into subgroups according to the absence/presence of cirrhosis. A propensity score matching was performed to reduce the potential biases. Cirrhotic patients were further stratified according to their surveillance status. The lead-time bias and its potential effects were also estimated. <b><i>Results:</i></b> We gathered 184 patients. Eighty-five patients (46.2%) were cirrhotic. Liver cirrhosis was not related to a worse overall survival (33.0 vs. 32.0 months, <i>p</i> = 0.800) even after the propensity score analysis (43.0 in vs. 44.0 months in 54 pairs of patients, <i>p</i> = 0.878). Among the cirrhotic population, 47 (55.3%) patients had received a diagnosis of ICC during a surveillance programme. The 2 subgroups differed in maximum tumour dimensions (30 vs. 48 mm in surveyed and non-surveyed patients, respectively). Surveyed patients were more likely to receive surgical treatments (59.8 vs. 28.9%, <i>p</i> = 0.003). Overall survival was higher in surveyed patients (51.0 vs. 21.0 months, <i>p</i> &#x3c; 0.001). These benefits were confirmed after correcting for the lead-time bias. <b><i>Conclusions:</i></b> Cirrhotic patients have different clinical presentation and outcomes of ICC according to their surveillance status. In our series, ICC in cirrhosis was not associated with worse OS. Cirrhosis itself should not discourage either surgical or non-surgical treatments.

scholarly journals Impact of Non-synchronous Diagnostic Ureteroscopy on Intravesical Recurrence in Patients Underwent Radical Nephroureterectomy for Upper Tract Urothelial Carcinoma: A Propensity-Score Matched Analysis

2019 ◽  
Author(s):  
Huamao Ye ◽  
Xiang Feng ◽  
Yang Wang ◽  
Rui Chen ◽  
Meimian Hua ◽  
...  
Keyword(s):  
Propensity Score ◽  
Regression Model ◽  
Urothelial Carcinoma ◽  
Cox Regression ◽  
Upper Tract Urothelial Carcinoma ◽  
Control Group ◽  
Radical Nephroureterectomy ◽  
Cox Regression Model ◽  
Upper Tract ◽  
The Impact

Abstract Background: The effect of diagnostic ureteroscopy (DURS) on intravesical recurrence (IVR) after radical nephroureterectomy (RNU) were controversial. To investigate the impact of DURS, we carried out this single-center retrospective study by applying propensity-score matching (PSM) and Cox regression model. Patients and Methods: The data of 160 patients with pTa-pT3 upper tract urothelial carcinoma (UTUC) were analyzed. Eighty-six patients underwent DURS (DURS group) and 74 patients without DURS (control group). The DURS group was further sub-grouped into synchronous DURS group (DURS followed by immediate RNU, n=45) and non-synchronous DURS group (DURS followed by delayed RNU, n=41). Baseline confounders were corrected by PSM. The impact of DURS on IVR was assessed by Kaplan-Meier analysis in PSM cohort and by Cox regression model in the full data set. Results: The median follow-up time was 40.4 months. No difference of the 3-year IVRFS between DURS group and control group (72.6% vs. 65.3%, p=0.263). In subgroup analysis, the 3-year IVR-free survival of non-synchronous DURS group (51.4%) was significantly lower than that of synchronous DURS (78.3%) or control group (72.6%) (p=0.027). Further Cox regression analysis showed that non-synchronous DURS (HR 1.481, 95% CI 1.031-2.127, p=0.034) was independent risk factors for postoperative IVR. Conclusions: Non-synchronous DURS was not recommended for the diagnosis and preoperative evaluation of UTUC, because it could raise the risk of IVR after RNU. For UTUC patients in need of DURS, synchronous DURS could be a safer choice than the non-synchronous DURS in terms of lowering the IVR risk.

scholarly journals The best solution down the line: an observational study on taurolidine- versus citrate-based lock solutions for central venous catheters in hemodialysis patients

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Sonja van Roeden ◽  
Mathijs van Oevelen ◽  
Alferso C. Abrahams ◽  
Friedo W. Dekker ◽  
Joris I. Rotmans ◽  
...  
Keyword(s):  
Observational Study ◽  
Regression Model ◽  
Multicenter Study ◽  
Cox Regression ◽  
Hemodialysis Patients ◽  
Central Venous Catheters ◽  
Central Venous ◽  
Cox Regression Model ◽  
Catheter Malfunction ◽  
Lower Hazard

Abstract Introduction To prevent infection and thrombosis of central venous catheters (CVCs) in hemodialysis patients, different CVC lock solutions are available. Taurolidine-based solutions and citrate in different concentrations are frequently used, but no definite conclusions with regard to superiority have been drawn. Methods In this retrospective, observational, multicenter study, we aimed to assess the risk for removal of CVC due to infection or catheter malfunction in hemodialysis patients with CVC access for different lock solutions: taurolidine, high-concentrated citrate (46.7%) and low-concentrated citrate (4 or 30%). A multivariable Cox-regression model was used to calculate hazard ratio’s (HR). Results We identified 1514 patients (median age 65 years, 59% male). In 96 (6%) taurolidine-based lock solutions were used. In 1418 (94%) citrate-based lock solutions were used (high-concentrated 73%, low-concentrated 20%). Taurolidine-based lock solutions were associated with a significantly lower hazard for removal of CVC due to infection or malfunction combined (HR 0.34, 95% CI 0.19–0.64), and for removal of CVC due to infection or malfunction separately (HR 0.36, 95% CI 0.15–0.88 and HR0.33, 95% CI 0.14–0.79). High-concentrated citrate lock solutions were not associated with a decreased hazard for our outcomes, compared to low-concentrated citrate lock solutions. Conclusion Removal of CVC due to infection or catheter malfunction occurred less often with taurolidine-based lock solutions. We present the largest cohort comparing taurolidine- and citrate-based lock solutions yet. However, due to the retrospective observational nature of this study, conclusions with regard to superiority should be drawn with caution.

scholarly journals Diagnostic and Prognostic Value of miR-16, miR-146a, miR-192 and miR-221 in Exosomes of Hepatocellular Carcinoma and Liver Cirrhosis Patients

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2484
Author(s):  
Thorben Fründt ◽  
Linda Krause ◽  
Elaine Hussey ◽  
Bettina Steinbach ◽  
Daniel Köhler ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Regression Model ◽  
Prognostic Value ◽  
Cox Regression ◽  
Healthy Individuals ◽  
Poor Overall Survival ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Diagnostic And Prognostic Value

We aimed to identify a specific microRNA (miRNA) pattern to determine diagnostic and prognostic value in plasma exosomes of hepatocellular carcinoma (HCC) patients. A two-stage study was carried out: exosomal miRNAs were quantified in plasma of HCC patients and healthy individuals by PCR-based microarray cards containing 45 different miRNAs (training cohort). Then, four deregulated miRNAs (miR-16, miR-146a, miR-192, and miR-221) were quantified in the validation analysis using exosomes derived from 85 HCC patients, 50 liver cirrhosis patients, and 20 healthy individuals. Exosomal miR-146a (p = 0.0001), miR-192 (p = 0.002) and miR-221 (p = 0.032) were upregulated only in HCC patients. Repeated 10-fold cross validation showed that miR-146a differentiated HCC from liver cirrhosis patients with AUC of 0.80 ± 0.14 (sensitivity: 81 ± 13%, specificity: 58 ± 22%) in a logistic regression model. High miR-192 presence is associated with poor overall survival (OS) in all HCC patients (p = 0.027) and was predictor of OS in HCC patients in an uni- and multivariate Cox regression model. Moreover, decreased miR-16 levels correlated with OS in liver cirrhosis patients (p = 0.034). Our results emphasized that exosomes secreted into the plasma carry differentially expressed miRNAs of which in particular, miR-192, miR-146, and miR-16 are promising diagnostic and prognostic markers for both HCC and liver cirrhosis patients.

Impact of Extended- Versus Intermittent-Infusion Cefepime on Clinical Outcomes in Hospitalized Patients

2020 ◽  
pp. 001857871989337
Author(s):  
Reese A. Cosimi ◽  
Zachary W. Howe ◽  
Lindsay M. Saum
Keyword(s):  
Goal Attainment ◽  
Primary Outcome ◽  
Statistical Significance ◽  
Intermittent Infusion ◽  
Primary Objective ◽  
Apache Ii Score ◽  
Beta Lactams ◽  
Stay Time ◽  
Administration Method ◽  
Extended Infusion

Background: Pharmacodynamic models support potential improved antimicrobial pharmacokinetic and pharmacodynamic goal attainment in patients treated with extended-infusion (EI) versus intermittent-infusion (II) cefepime. Small clinical studies demonstrate inconsistent findings in patient outcomes, necessitating a deeper review of this administration method. Methods: This was a retrospective cohort study comparing patients receiving EI versus II cefepime between September 1, 2017, and March 31, 2018. The primary outcome was in-hospital all-cause mortality. Secondary objectives included length of hospital and ICU stay, time to defervescence, duration of therapy, duration of mechanical ventilation, and readmission rate. Subgroup analyses for the primary objective were conducted based on comorbid burden and isolate susceptibilities. Results: No statistically significant differences were noted in the 645 included patients for the primary outcome between the EI and II groups (7.8% vs 10.4%, P = .32). Median length of stay was 9 days (IQR 12) versus 11 days (IQR 14) ( P = .30), respectively. In addition, statistical significance was not seen in any of the subgroups for the primary outcome including patients with APACHE II score ≥ 20 (17.4% vs 30.6%, P = .26) and for infections caused by Pseudomonas aeruginosa (5.9% vs 20.0%, P = .23) or Enterobacteriaceae (11.1% vs 20.0%, P = .13) with minimum inhibitory concentration (MIC) ≥ 4. Conclusion: No statistically significant differences were noted between EI and II groups, although benefits in specific subpopulations may exist when these results are correlated with findings from studies examining alternative antipseudomonal beta lactams.

scholarly journals Efficacy and Safety of Antiplatelet Agents for Adult Patients With Ischemic Moyamoya Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Fei Ye ◽  
Jiaoxing Li ◽  
Tianzhu Wang ◽  
Kai Lan ◽  
Haiyan Li ◽  
...  
Keyword(s):  
Propensity Score ◽  
Conservative Treatment ◽  
Regression Model ◽  
Functional Status ◽  
Cox Regression ◽  
Antiplatelet Agents ◽  
Surgical Revascularization ◽  
History Of ◽  
Cerebral Ischemic

Background: The use of antiplatelet agents in ischemic moyamoya disease (MMD) is controversial. This study aimed to investigate the effectiveness and safety of antiplatelet therapy compared with conservative treatment and surgical revascularization in ischemic MMD patients.Methods: Ischemic MMD patients were retrospectively enrolled from eight clinical sites from January 2013 to December 2018. Follow-up was performed through clinical visits and/or telephone interviews from first discharge to December 2019. The primary outcome was the episodes of further ischemic attacks, and the secondary outcome was the individual functional status. Risk factors for future stroke were identified by the LASSO-Cox regression model. Propensity score matching was applied to assemble a cohort of patients with similar baseline characteristics using the TriMatch package.Results: Among 217 eligible patients, 159 patients were included in the analyses after a 1:1:1 propensity score matching. At a mean follow-up of 33 months, 12 patients (7.5%) developed further incident cerebral ischemic events (surgical:antiplatelet:conservative = 1:3:8; p = 0.030), 26 patients (16.4%) developed a poor functional status (surgical:antiplatelet:conservative = 7:12:7; p = 0.317), and 3 patients (1.8%) died of cerebral hemorrhage (surgical:antiplatelet:conservative = 1:2:0; p = 0.361). The survival curve showed that the risk of further cerebral ischemic attacks was lowest with surgical revascularization, while antiplatelet therapy was statistically significant for preventing recurrent risks compared with conservative treatment (χ2 = 8.987; p = 0.011). No significant difference was found in the functional status and bleeding events. The LASSO-Cox regression model revealed that a family history of MMD (HR = 6.93; 95% CI: 1.28–37.52; p = 0.025), a past history of stroke or transient ischemic attack (HR = 4.35; 95% CI: 1.09–17.33; p = 0.037), and treatment (HR = 0.05; 95% CI: 0.01–0.32; p = 0.001) were significantly related to the risk of recurrent strokes.Conclusions: Antiplatelet agents were effective and safe in preventing further cerebral ischemic attacks in adult patients with ischemic MMD. They may be a replacement therapy for patients with surgical contraindications and for patients prior to revascularization.

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