Liver cirrhosis yearly causes 1.2 million deaths worldwide, ranking as the 10th leading cause of death in the most developed countries. High susceptibility to infections along with a significant risk ...for infection-related mortality justifies the description of liver cirrhosis as the world’s most common immunodeficiency syndrome. Liver cirrhosis is an end-stage organic disease hallmarked by a multifaceted immune dysfunction due to deterioration of antimicrobial recognition and elimination mechanisms in macrophages along with an impaired antigen presentation ability in circulating monocytes. Bacterial translocation supports—and is supported by—uncontrolled activation of immune cell responses and/or loss of toll-like receptor (TLR) tolerance, which can turn exaggerated inflammatory responses to systemic inflammation. Lipopolysaccharide (LPS) or endotoxin boosts systemic inflammatory activity through activation of TLR-2- and TLR-4-dependent pathways and facilitate a massive production of cytokines. This, in turn, results into elevated secretion of reactive oxygen species (ROS), which further enhances intestinal hyperpermeability and thus sustains a vicious circle of events widely known as “leaky gut.” Albumin can be of particular benefit in cirrhotic patients with spontaneous bacterial peritonitis and/or hepatorenal syndrome type of acute kidney injury (HRS-AKI) due to anti-inflammatory and antioxidative stress as well as volume-expanding properties and endothelial-stabilizing attributes. However, presence of autoantibodies against albumin in patients with liver cirrhosis has been described. Although previous research suggested that these antibodies should be regarded as naturally occurring antibodies (NOA), the origin of the antialbumin immune response is obscure. High occurrence of NAO/albumin complexes in patients with liver disease might reflect a limited clearance capacity due to bypassing portal circulation. Moreover, high burden of oxidized albumin is associated with less favorable outcome in patients with liver cirrhosis. To date, there is no data available as to whether oxidized forms of albumin result in neoepitopes recognized by the immune system. Nevertheless, it is reasonable to hypothesize that these alterations may have the potential to induce antialbumin immune responses and thus favor systemic inflammation.
To analyze and compare the performance of the Simplified-Acute-Physiology-Score (SAPS) 2 and SAPS 3 among intermediate care patients with internal disorders.
We conducted a retrospective ...single-center analysis in patients (n = 305) admitted to an intermediate-care-unit (ImCU) for internal medicine at the University Hospital Essen, Germany. We employed and compared the SAPS 2 vs. the SAPS 3 scoring system for the assessment of disease severity and prediction of mortality rates among patients admitted to the ImCU within an 18-month period. Both scores, which utilize parameters recorded at admission to the intensive-care-unit (ICU), represent the most widely applied scoring systems in European intensive care medicine. The area-under-the-receiver-operating-characteristic-curve (AUROC) was used to evaluate the SAPS 2 and SAPS 3 discrimination performance. Ultimately, standardized-mortality-ratios (SMRs) were calculated alongside their respective 95%-confidence-intervals (95% CI) in order to determine the observed-to-expected death ratio and calibration belt plots were generated to evaluate the SAPS 2 and SAPS 3 calibration performance.
Both scores provided acceptable discrimination performance, i.e., the AUROC was 0.71 (95% CI, 0.65-0.77) for SAPS 2 and 0.77 (95% CI, 0.72-0.82) for SAPS 3. Against the observed in-hospital mortality of 30.2%, SAPS 2 showed a weak performance with a predicted mortality of 17.4% and a SMR of 1.74 (95% CI, 1.38-2.09), especially in association with liver diseases and/or sepsis. SAPS 3 performed accurately, resulting in a predicted mortality of 29.9% and a SMR of 1.01 (95% CI, 0.8-1.21). Based on Calibration belt plots, SAPS 2 showed a poor calibration-performance especially in patients with low mortality risk (P<0.001), while SAPS 3 exhibited a highly accurate calibration performance (P = 0.906) across all risk levels.
In our study, the SAPS 3 exhibited high accuracy in prediction of mortality in ImCU patients with internal disorders. In contrast, the SAPS 2 underestimated mortality particularly in patients with liver diseases and sepsis.
Objective We aimed to evaluate the effects of combining the Simplified-Acute-Physiology-Score (SAPS) 2 or the SAPS 3 with Interleukin-6 (IL-6) or Procalcitonin (PCT) or C-Reactive Protein (CRP) ...concentrations for predicting in-hospital mortality. Material and methods This retrospective study was conducted in an interdisciplinary 22-bed intensive care unit (ICU) at a German university hospital. Within an 18-month period, SAPS 2 and SAPS 3 were calculated for 514 critically ill patients that were admitted to the internal medicine department. To evaluate discrimination performance, the area under the receiver operating characteristic curves (AUROCs) and the 95% confidence intervals (95% CIs) were calculated for each score, exclusively or in combination with IL-6 or PCT or CRP. DeLong test was used to compare different AUROCs. Results The SAPS 2 exhibited a better discrimination performance than SAPS 3 with AUROCs of 0.81 (95% CI, 0.76–0.86) and 0.72 (95% CI, 0.66–0.78), respectively. Overall, combination of the SAPS 2 with IL-6 showed the best discrimination performance (AUROC 0.82; 95% CI, 0.77–0.87), albeit not significantly different from SAPS2. IL-6 performed better than PCT and CRP with AUROCs of 0.75 (95% CI, 0.69–0.81), 0.72 (95% CI, 0.66–0.77) and 0.65 (95% CI, 0.59–0.72), respectively. Performance of the SAPS 3 improved significantly when combined with IL-6 (AUROC 0.76; 95% CI, 0.69–0.81) or PCT (AUROC 0.73; 95% CI, 0.67–0.78). Conclusions Our analysis provided evidence that the risk stratification performance of the SAPS 3 and, to a lesser degree, also of the SAPS 2 can increase when combined with IL-6. A more accurate detection of aberrant or dysregulated systemic immunological responses (by IL-6) may explain the higher performance achieved by SAPS 3 + IL-6 vs. SAPS 3. Thus, implementation of IL-6 in critical care scores can improve prediction outcomes, especially in patients experiencing acute inflammatory conditions; however, statistical results may vary across hospital types and/or patient populations with different case mix.
In patients with liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) is considered a standardized treatment of refractory ascites or variceal bleeding. TIPS thrombosis (TT) and/or ...portal vein thrombosis (PVT) are possible complications during/after TIPS placement. Previous studies suggested increased clotting activity in portal circulation (PORC). This pilot study aimed to evaluate alterations and differences of coagulation function in PORC and in peripheral circulation (PERC) via rotational thromboelastometry during TIPS.
Blood samples were collected from cirrhotic patients (
= 13; median Model of End Stage Liver Disease, MELD Score: 12; median age: 60 years) undergoing TIPS (10/13 TIPSs were elective procedures due to refractory ascites) as follows: median cubital vein (MCV; PERC)-confluence of the three hepatic veins to the inferior cava vein (HV/ICV; PORC)-portal vein (PV; PORC)-TIPS (PORC). This research utilized four variables of the extrinsic test EXTEM, i.e., clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), and maximum lysis (ML).
EXTEM results mean, M (range) ± standard deviation, SD (range) showed no significant differences for CT M (70-73) ± SD (9-13);
= 0.93 or CFT M (137-155) ± SD (75-112);
= 0.97 or MCF M (51-54) ± SD (9-10);
= 0.90 or ML M (9-10) ± SD (4-5);
= 0.89 between the compartments, i.e., MCV vs. HV/ICV vs. PV vs. TIPS. Overall, we detected no differences in coagulation function between PERC and PORC.
These results are in contrast to previous reports suggesting increased clotting activity in PORC vs. PERC in association with liver cirrhosis. Rotational thromboelastometry-based evaluation of coagulation function in PERC appears to reliably reflect coagulation function in PORC with respect to risk estimation for TT and/or PVT in cirrhotic patients undergoing TIPS.
Assessment of SARS-CoV-2 rapid antigen tests Özcürümez, Mustafa; Katsounas, Antonios; Holdenrieder, Stefan ...
Journal of laboratory medicine,
06/2021, Volume:
45, Issue:
3
Journal Article
Peer reviewed
Open access
Abstract Objectives Point-of-care antigen tests (PoC-AgTs) for the rapid detection of SARS-CoV-2 infection enable screening of additional populations with less effort, independent of laboratories and ...at a low cost. PoC-AgTs have therefore been included in national testing strategies with additional quality requirements to address limitations in specificity and sensitivity. Information given in the package inserts of the test providers should enable the user to evaluate the performance of a PoC-AgT in advance. The quality of this information has been independently assessed since the Corona Test Ordinance came into force in Germany in October 2020. Methods The completeness of analytical and diagnostic performance specifications was assessed for all package inserts publicly available via the Paul Ehrlich Institute (PEI). It was ascertained whether the minimum criteria, recommendations, and extended criteria of the PEI were comprehensibly fulfilled. The number of tests removed from the list by March 2021 was determined. Results By the closing date of the survey (17.11.2020), the PEI had listed 165 PoC-AgTs that formally fulfilled the minimum criteria and were thus reimbursed. A total of 78 identical systems were identified. Almost all providers were found to have gaps in the information on the validation results of their tests, meaning that an evaluation of performance is only possible to a limited extent. Until March 2021, 25 non-identical PoC-AgTs have been removed from the list. Conclusions Many PoC-AgTs could not be comprehensively evaluated based on the information provided by the provider. Users are therefore dependent on provider-independent sources of information.
Background. Previous research reported adverse clinical outcomes in association with systemic inflammation (SI) after transcatheter aortic valve replacement (TAVR). However, data characterizing the ...impact of SI, as reflected by postprocedural routine inflammatory parameters (pRIP), on clinical outcome of patients undergoing TAVR are sparse. Objectives. In light of this, the present work aimed to analyze incidence and clinical significance of pRIP after transapical (TA) and transfemoral (TF)-TAVR. Methods and Results. Data of 81 high-risk consecutive patients undergoing TAVR in our center from 2017 to 2018 were analyzed in a retrospective manner. 40 out of 81 patients (49, 4%) were treated via TF access (group A) and 41 patients via TA access (group B). Incidence, cause, and amplitude of pRIP were analyzed in relation to pre- and peri-interventional data. Assessment of outcomes was conducted according to the valve academic research consortium (VARC-2). Postprocedural C-reactive protein (pCRP) and leucocytes (pL) were significantly increased in patients undergoing TA-TAVR (group B) vs. TF-TAVR (group A; 12.1 ± 9.7 vs. 22.1 ± 7.9 mg/dl, p < 0.001 and 12.8 ± 4.0 vs. 14.2 ± 3.8/nl, p = 0.002); however, there was no significant difference regarding incidence of postprocedural fever (pF) ≥38.0°C (12.5% vs. 22%, p = 0.37). Furthermore, we observed a vast (though insignificant) trend towards a longer fever duration in group B vs. group A (9.9 ± 14.9 vs. 3.2 ± 5.9 hours, p = 0.06). Further analysis identified pCRP >30 mg/dl (hazard ratio (HR) 3.15, confidence interval (CI) 1.22–8.14, p = 0.018) and European System for Cardiac Operative Risk Evaluation (logistic EuroSCORE I (ES)) >20% (HR 2.95, CI 1.17–7.47, p = 0.02) as predictors of mortality; in this context, we also discovered a marginally significant trend for pL > 14/nl (HR 2.44, CI 0.97–6.14, p = 0.05). Multivariate analysis by use of the fisher`s exact test revealed a significant association between pCRP >30 mg/dl and ES >20% (p < 0.001). Conclusion. pRIP are significantly increased in patients undergoing TA-TAVR. pCRP >30 mg/dl, ES>20%, and pL > 14/nl are hallmark of adverse prognosis and require further investigation.
Changes in thyroid hormone levels, mostly as non-thyroidal illness syndrome (NTIS), have been described in many diseases. However, the relationship between acute liver failure (ALF) and thyroid ...hormone levels has not yet been clarified. The present study evaluates potential correlations of select thyroid functional parameters with ALF.
84 consecutively recruited ALF patients were grouped according to the outcome of ALF (spontaneous recovery: SR; transplantation or death: NSR). TSH, free thyroxine (fT4), free triiodothyronine (fT3), T4, and T3 were determined.
More than 50% of patients with ALF presented with abnormal thyroid parameters. These patients had greater risk for an adverse outcome than euthyroid patients. SR patients had significantly higher TSH, T4, and T3 concentrations than NSR patients. Albumin concentrations were significantly higher in SR than in NSR. In vitro T3 treatment was not able to rescue primary human hepatocytes from acetaminophen induced changes in mRNA expression.
In patients with ALF, TSH and total thyroid hormone levels differed significantly between SR patients and NSR patients. This might be related to diminished liver-derived transport proteins, such as albumin, in more severe forms of ALF. Thyroid parameters may serve as additional indicators of ALF severity.
Abstract Purpose The purpose was to analyze and compare the performance of Simplified Acute Physiology Score (SAPS) II and SAPS 3 (North Europe Logit) in an intensive care unit (ICU) for internal ...disorders at a German university hospital. Materials and methods This retrospective study was conducted at a single-center 12-bed ICU sector for Internal Medicine in Essen, Germany, within an 18-month period. Data for adult ICU patients (N = 548) were evaluated. SAPS II and SAPS 3 scores were assessed along with the predicted mortality rates. Discrimination was evaluated by calculating the area under the receiver operating characteristic curve, and calibration was evaluated using the Hosmer-Lemeshow goodness-of-fit C-test. The ratios of observed-to-expected deaths (standardized mortality ratio, SMR) were calculated along with the 95% confidence intervals (95% CIs). Results The in-hospital mortality rate was 22.6%, which provided an SMR of 0.91 (95% CI, 0.77-0.99) for SAPS II and 0.62 (95% CI, 0.52-0.71) for SAPS 3. Both SAPS II and SAPS 3 exhibited acceptable discrimination, with an area under the receiver operating characteristic curve of 0.84 (95% CI, 0.79-0.89) and 0.73 (95% CI, 0.67-0.79), respectively. However, SAPS II demonstrated superior SMR-based discrimination, which was closer to the observed mortality rate, compared with SAPS 3. Calibration curves exhibited similar performance based on the Hosmer-Lemeshow goodness-of-fit C-test results: χ2 = 7.10 with P = .525 for SAPS II and χ2 = 3.10 with P = .876 for SAPS 3. Interestingly, both scores overpredicted mortality. Conclusions In this study, SAPS 3 overestimated mortality and therefore appears less suitable for risk evaluation in comparison to SAPS II.
PDF
