Publications by authors named "Eva Herrmann"

292 Publications

Predictors of a successful vaginal delivery in women with type 1 diabetes: a retrospective analysis of 20 years.

Arch Gynecol Obstet 2021 Sep 24. Epub 2021 Sep 24.

Department of Obstetrics, University Hospital Jena, Am Klinikum 1, 07747, Jena, Germany.

Purpose: To evaluate the independent factors associated with the success of a trial of vaginal birth (TVB) in women with type 1 diabetes. Despite all therapeutic efforts and technological innovations, rates of caesarean sections (CS) in pregnant women with type 1 diabetes remain unchanged above 60%. Our aim was to point out influencing factors to improve the quality of antepartum counseling.

Methods: We performed a retrospective cohort study of 195 pregnancies with type 1 diabetes treated between 2000 and 2019. After exclusions, 118 women with near-term singleton pregnancies intended vaginal birth (TVB). Group differences between CS and successful vaginal delivery were analyzed. Multivariate logistic regression was performed by including clinical and metabolic variables to determine the independent effects on a successful vaginal delivery. Subgroup analysis for nulliparous women.

Results: Of 118 women with TVB, 67 (56.8%) were delivered vaginally. History of previous vaginal delivery (OR 10.29; CI 2.39; 44.30), HbA1c changes during pregnancy (per % increase; OR 0.59; CI 0.36; 0.96) and gestational weight gain (per kg; OR 0.87; CI 0.80; 0.96) were independent predictors for a successful vaginal delivery. In nulliparous women, the duration of diabetes was independently and negatively associated with vaginal delivery.

Conclusion: Provided data can help to improve antepartum counseling in type 1 diabetic patients. It seems that women with type 1 diabetes should avoid postponing pregnancy and childbirth.
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http://dx.doi.org/10.1007/s00404-021-06255-9DOI Listing
September 2021

COVID-19 among children seeking primary paediatric care with signs of an acute infection.

Acta Paediatr 2021 Sep 15. Epub 2021 Sep 15.

Institute of Medical Virology, Goethe University Frankfurt, Frankfurt am Main, Germany.

Aim: It can be challenging to distinguish COVID-19 in children from other common infections. We set out to determine the rate at which children consulting a primary care paediatrician with an acute infection are infected with SARS-CoV-2 and to compare distinct findings.

Method: In seven out-patient clinics, children aged 0-13 years with any new respiratory or gastrointestinal symptoms and presumed infection were invited to be tested for SARS-CoV-2. Factors that were correlated with testing positive were determined. Samples were collected from 25 January 2021 to 01 April 2021.

Results: Seven hundred and eighty-three children participated in the study (median age 3 years and 0 months, range 1 month to 12 years and 11 months). Three hundred and fifty-eight were female (45.7%). SARS-CoV-2 RNA was detected in 19 (2.4%). The most common symptoms in children with as well as without detectable SARS-CoV-2 RNA were rhinitis, fever and cough. Known recent exposure to a case of COVID-19 was significantly correlated with testing positive, but symptoms or clinical findings were not.

Conclusion: COVID-19 among the children with symptoms of an acute infection was uncommon, and the clinical presentation did not differ significantly between children with and without evidence of an infection with SARS-CoV-2.
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http://dx.doi.org/10.1111/apa.16101DOI Listing
September 2021

Simulation-based training improves process times in acute stroke care (STREAM).

Eur J Neurol 2021 Sep 3. Epub 2021 Sep 3.

University Hospital Frankfurt, Department of Neurology, Goethe University, Frankfurt am Main, Germany.

Background: The objective of the STREAM trial was to evaluate the effect of simulation training on process times in acute stroke care.

Methods: The multicenter prospective interventional STREAM trial was conducted between 10/2017 and 04/2019 at seven tertiary care neurocenters in Germany with a pre- and post-interventional observation phase. We recorded patient characteristics, acute stroke care process times, stroke team composition and simulation experience for consecutive direct-to-center patients receiving i.v. thrombolysis (IVT) and/or endovascular therapy (EVT). The intervention consisted of a composite intervention centered around stroke-specific in situ simulation training. Primary outcome measure was the 'door-to-needle' time (DTN) for IVT. Secondary outcome measures included process times of EVT and measures taken to streamline the preexisting treatment algorithm.

Results: The effect of the STREAM intervention on the process times of all acute stroke operations was neutral. However, secondary analyses showed a DTN reduction of 5 min from 38 min pre (interquartile range [IQR] 25 - 43 min) to 33 min (IQR 23 - 39 min), p = 0.03) post intervention achieved by simulation-experienced stroke teams. Concerning EVT, we found significantly shorter door-to-groin times in patients who were treated by teams with simulation experience as compared to simulation-naive teams in the post interventional phase (-21 min, simulation-naive: 95 min, IQR 69 - 111 vs. simulation-experienced: 74 min, IQR 51 - 92, p = 0.04).

Conclusions: An intervention combining workflow refinement and simulation-based stroke team training has the potential to improve process times in acute stroke care.
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http://dx.doi.org/10.1111/ene.15093DOI Listing
September 2021

Non-invasive assessment of fibrosis regression and portal hypertension in patients with advanced chronic hepatitis C virus (HCV)-associated liver disease and sustained virologic response (SVR): 3 year follow-up of a prospective longitudinal study.

J Viral Hepat 2021 Aug 3. Epub 2021 Aug 3.

Medizinische Klinik 1, Universitätsklinikum, Frankfurt, Germany.

Long-term effects on cirrhosis and portal hypertension of direct antiviral agent (DAA)-based eradication of hepatitis C virus (HCV) are still under debate. We analyzed dynamics of liver and spleen elastography to assess potential regression of cirrhosis and portal hypertension 3 years post-treatment. Fifty-four patients with HCV-associated cirrhosis and DAA-induced SVR were included. Liver and spleen stiffness were measured at baseline (BL), end of treatment (EOT), 24 weeks after EOT (FU24) and 1, 2 and 3 (FU144) years post-treatment by transient liver elastography (L-TE) and point shear wave elastography (pSWE) using acoustic radiation force impulse (ARFI) of the liver (L-ARFI) and spleen (S-ARFI). Biochemical, virological and clinical data were also obtained. Liver stiffness assessed by L-TE decreased between BL [median (range), 32.5(9.1-75) kPa] and EOT [21.3(6.7-73.5) kPa; p<0.0001] and EOT and FU144 [16(4.1-75) kPa; p=0.006]. L-ARFI values improved between EOT [2.5(1.2-4.1) m/s] and FU144 [1.7(0.9-4.1) m/s; p=0.001], while spleen stiffness remained unchanged. Overall, L-TE improved in 38 of 54 (70.4%) patients at EOT and 29 of 38 (76.3%) declined further until FU144, whereas L-ARFI values decreased in 30/54 (55.6%) patients at EOT and continued to decrease in 28/30 (93.3%) patients at FU144. Low bilirubin and high albumin levels at BL were associated with improved L-ARFI values (p=0.048) at EOT or regression of cirrhosis (< 12.5 kPa) by L-TE at FU144 (p=0.005), respectively. Liver stiffness, but not spleen stiffness, continued to decline in a considerable proportion of patients with advanced liver disease after HCV eradication.
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http://dx.doi.org/10.1111/jvh.13587DOI Listing
August 2021

Effects of statins after transcatheter aortic valve implantation in key patient populations.

J Cardiovasc Pharmacol 2021 Jul 19. Epub 2021 Jul 19.

Department of Cardiology Cardiac Surgery, Kerckhoff Heart Center, Benekestr. 2-8, 61231 Bad Nauheim, Germany Medical Clinic I (Cardiology and Angiology), University Hospital of Giessen, Klinikstr. 33, 35392 Giessen, Germany Cardioangiological Center Bethanien (CCB), Im Prüfling 23, 60389 Frankfurt, Germany Institute of Biostatistics and Mathematical Modelling, Goethe University Frankfurt, Theodor-Sterm-Kai 7, 60590 Frankfurt am Main, Germany German Centre for Cardiovascular Research (DZHK), Partner Site Rhein-Main, Frankfurt am Main, Germany.

Abstract: Statin therapy after transcatheter aortic valve replacement (TAVI) is associated with better short- and long-term outcomes. It is of interest to identify specific patient populations that might profit from statin therapy. In this retrospective, observational analysis of 2,862 patients with symptomatic aortic stenosis (AS) after successful transfemoral TAVI, survival during a three-year observation period was characterized by Kaplan-Meier analyses according to statin therapy. Hazard ratios and potential interactions for specific subgroups of patients were determined by Cox regression analyses. At hospital discharge 1,761 patients were on low- or moderate-intensity statins (LMIS), 246 patients were on high-intensity statins (HIS), and 855 patients did not take statins. Statin therapy adherence during the first three months post-TAVI was 91%. Mortality rates were 18.5%, 12.9%, and 6.9% for patients with no statin, LMIS, and HIS (p<0.001). Any statin therapy proved to be effective in patients in different classes of age, risk, and manifest cardiovascular disease and was independent of background medication. Statins were of particular benefit in high-risk patients with coronary artery disease (hazard ratio (HR)=0.57), ejection fraction < 40% (HR=0.64), or low-flow low-gradient AS (HR=0.58) and showed additional benefit even in patients taking renin-angiotensin system blockers (HR=0.74). Statins also reduced mortality in patients with malignant disease (HR=0.47). Our analysis confirmed the beneficial effect of statins on survival after TAVI and documented this phenomenon in key patient subsets. The protective effect of statins in our study is consistent with the cardioprotective mechanisms but must be explained by other, yet undetermined pleiotropic effects of statins.
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http://dx.doi.org/10.1097/FJC.0000000000001114DOI Listing
July 2021

High sedation needs of critically ill COVID-19 ARDS patients-A monocentric observational study.

PLoS One 2021 27;16(7):e0253778. Epub 2021 Jul 27.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe-University Frankfurt, Hessen, Germany.

Background: Therapy of severely affected coronavirus patient, requiring intubation and sedation is still challenging. Recently, difficulties in sedating these patients have been discussed. This study aims to describe sedation practices in patients with 2019 coronavirus disease (COVID-19)-induced acute respiratory distress syndrome (ARDS).

Methods: We performed a retrospective monocentric analysis of sedation regimens in critically ill intubated patients with respiratory failure who required sedation in our mixed 32-bed university intensive care unit. All mechanically ventilated adults with COVID-19-induced ARDS requiring continuously infused sedative therapy admitted between April 4, 2020, and June 30, 2020 were included. We recorded demographic data, sedative dosages, prone positioning, sedation levels and duration. Descriptive data analysis was performed; for additional analysis, a logistic regression with mixed effect was used.

Results: In total, 56 patients (mean age 67 (±14) years) were included. The mean observed sedation period was 224 (±139) hours. To achieve the prescribed sedation level, we observed the need for two or three sedatives in 48.7% and 12.8% of the cases, respectively. In cases with a triple sedation regimen, the combination of clonidine, esketamine and midazolam was observed in most cases (75.7%). Analgesia was achieved using sufentanil in 98.6% of the cases. The analysis showed that the majority of COVID-19 patients required an unusually high sedation dose compared to those available in the literature.

Conclusion: The global pandemic continues to affect patients severely requiring ventilation and sedation, but optimal sedation strategies are still lacking. The findings of our observation suggest unusual high dosages of sedatives in mechanically ventilated patients with COVID-19. Prescribed sedation levels appear to be achievable only with several combinations of sedatives in most critically ill patients suffering from COVID-19-induced ARDS and a potential association to the often required sophisticated critical care including prone positioning and ECMO treatment seems conceivable.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253778PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315516PMC
August 2021

Pharmacokinetics of direct oral anticoagulants in emergency situations - Results of the prospective observational RADOA-registry.

Thromb Haemost 2021 Jul 13. Epub 2021 Jul 13.

Med. Klinik III, Johann-Wolfgang-Goethe-Universitätsklinik Frankfurt, Frankfurt, Germany.

Background Direct oral anticoagulants (DOAC) are increasingly used worldwide. Little is known so far about their pharmacokinetics in emergency situations. Methods A prospective, observational registry was performed to determine the clinical course in consecutive patients with major bleeding or urgent surgery treated with DOACs. In back-up blood samples from routine care DOAC drug concentrations were measured using UPLC-MS/MS. Anticoagulant intensity at first presentation and drug half-life (t1/2), tested in repeat samples, were evaluated. Results 140 patients were prospectively included. Pharmacokinetic data were available in 94% (132/140) of patients. 67% (89/132) experienced life-threatening bleeding and 33% (43/132) needed an urgent surgery. For pharmacokinetic analysis a total of 605 blood samples was available. Median concentration on admission was 205 ng/mL for rivaroxaban and 108 ng/mL for apixaban. All treatment groups showed a high variation of drug concentrations at baseline. In rivaroxaban treated patients t½ was 17.3 hours (95% CI: 15.4 - 19.7) without significant difference in both groups (major bleeding: t½ 16.7 hours, 95% CI: 14.7 - 19.3; urgent surgery: t½ 19.7 hours, 95% CI 15.2 - 27.9; p=0.292). In apixaban treated patients t½ was 25.0 hours (95% CI: 22.9 - 27.6) with a longer t½ after urgent surgery (t1/2: 30.8 hours; 95% CI: 26.9 - 36.4) compared to severe bleeding (t1/2: 20.8 hours; 95% CI: 18.8 - 23.2; p<0.001). Conclusions Emergency patients under DOAC treatment show a high variation of anticoagulant concentrations at baseline. Compared with rivaroxaban, apixaban showed a lower median concentration on admission and a longer t½.
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http://dx.doi.org/10.1055/a-1549-6556DOI Listing
July 2021

Long-term course of bronchial inflammation and pulmonary function testing in children with postinfectious bronchiolitis obliterans.

Pediatr Pulmonol 2021 Sep 16;56(9):2966-2972. Epub 2021 Jul 16.

Department for Children and Adolescents, Division of Allergy, Pulmonology and Cystic fibrosis, University Hospital, Frankfurt, Germany.

Rationale: Postinfectious bronchiolitis obliterans (PIBO) is a rare, chronic respiratory condition, which follows an acute insult due to a severe infection of the lower airways.

Objectives: The objective of this study was to investigate the long-term course of bronchial inflammation and pulmonary function testing in children with PIBO.

Methods: Medical charts of 21 children with PIBO were analyzed retrospectively at the Children's University Hospital Frankfurt/Main Germany. Pulmonary function tests (PFTs) with an interval of at least 1 month were studied between 2002 and 2019. A total of 382 PFTs were analyzed retrospectively and per year, the two best PFTs, in total 217, were evaluated. Additionally, 56 sputum analysis were assessed and the sputum neutrophils were evaluated.

Results: The evaluation of the 217 PFTs showed a decrease in FEV1 with a loss of 1.07% and a loss in z score of -0.075 per year. FEV1/FVC decreased by 1.44 per year. FVC remained stable, showing a nonsignificant increase by 0.006 in z score per year. However, FEV1 and FVC in L increased significantly with FEV1 0.032 L per cm and FVC 0.048 L/cm in height. Sputum neutrophils showed a significant increase of 2.12% per year.

Conclusion: Our results demonstrated that in patients with PIBO pulmonary function decreased significantly showing persistent obstruction over an average follow-up period of 8 years. However, persistent lung growth was revealed. In addition, pulmonary inflammation persisted clearly showing an increasing amount of neutrophils in induced sputum. Patients did not present with a general susceptibility to respiratory infections.
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http://dx.doi.org/10.1002/ppul.25547DOI Listing
September 2021

Five-year outcome in 18 010 patients from the German Aortic Valve Registry.

Eur J Cardiothorac Surg 2021 May 4. Epub 2021 May 4.

Department of Cardiology, Campus Kerckhoff University of Giessen, Bad Nauheim, Germany.

Objectives: To determine the 5-year outcome in patients treated by isolated transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (sAVR)-a prospective observational cohort study.

Methods: A total of 18 010 patients were included (n = 8942 TAVI and n = 9068 sAVR) in the German Aortic Valve Registry (GARY) who were treated in 2011 and 2012 at 92 sites in central Germany. Eligible patients with TAVI and sAVR were matched using propensity scores in a nearest-neighbour approach. Patients with repeat procedures or unequivocal indication for one treatment option (e.g. frailty) were excluded (n = 4785 for TAVI and n = 2 for sAVR). This led to 13 223 patients (4157 TAVI and 9066 sAVR) as an unmatched subcohort. The main outcome measure was the 5-year all-cause mortality.

Results: TAVI patients were significantly older (80.9 ± 6.1 vs 68.5 ± 11.1 years, P < 0.001), had a higher Society of Thoracic Surgeons (STS) score (6.3 ± 4.9 vs 2.6 ± 3.0, P < 0.001) and a higher 5-year all-cause mortality (49.8% vs 16.5%, P < 0.0001). There was no major difference in in-hospital stroke, in-hospital myocardial infarction, or temporary and chronic dialysis. In the propensity score-matched group (n = 3640), there were 763 deaths (41.9%) among 1820 TAVI patients compared with 552 (30.3%) among 1820 treated with sAVR during the 5-year follow-up (hazard ratio 1.51, 95% confidence interval 1.35-1.68; P < 0.0001). New pacemaker implantation was performed in 448 patients (24.6%) after TAVI and in 201 (11.0%) after sAVR (P < 0.0001).

Conclusions: The 5-year follow-up data show that TAVI patients were significantly older and had a higher STS score than sAVR patients. After propensity score matching, TAVI with early-generation prosthesis was associated with significantly higher 5-year all-cause mortality than sAVR.
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http://dx.doi.org/10.1093/ejcts/ezab216DOI Listing
May 2021

Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality: A Systematic Review, Meta-analysis, and Meta-regression.

JAMA Surg 2021 Apr 14:e210884. Epub 2021 Apr 14.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.

Importance: Tranexamic acid (TXA) is an efficient antifibrinolytic agent; however, concerns remain about the potential adverse effects, particularly vascular occlusive events, that may be associated with its use.

Objective: To examine the association between intravenous TXA and total thromboembolic events (TEs) and mortality in patients of all ages and of any medical disciplines.

Data Source: Cochrane Central Register of Controlled Trials and MEDLINE were searched for eligible studies investigating intravenous TXA and postinterventional outcome published between 1976 and 2020.

Study Selection: Randomized clinical trials comparing intravenous TXA with placebo/no treatment. The electronic database search yielded a total of 782 studies, and 381 were considered for full-text review. Included studies were published in English, German, French, and Spanish. Studies with only oral or topical tranexamic administration were excluded.

Data Extraction And Synthesis: Meta-analysis, subgroup and sensitivity analysis, and meta-regression were performed. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Main Outcomes And Measures: Vascular occlusive events and mortality.

Results: A total of 216 eligible trials including 125 550 patients were analyzed. Total TEs were found in 1020 (2.1%) in the group receiving TXA and 900 (2.0%) in the control group. This study found no association between TXA and risk for total TEs (risk difference = 0.001; 95% CI, -0.001 to 0.002; P = .49) for venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, and cerebral infarction or ischemia. Sensitivity analysis using the risk ratio as an effect measure with (risk ratio = 1.02; 95% CI, 0.94-1.11; P = .56) and without (risk ratio = 1.03; 95% CI, 0.95-1.12; P = .52) studies with double-zero events revealed robust effect size estimates. Sensitivity analysis with studies judged at low risk for selection bias showed similar results. Administration of TXA was associated with a significant reduction in overall mortality and bleeding mortality but not with nonbleeding mortality. In addition, an increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism. Comparison of studies with sample sizes of less than or equal to 99 (risk difference = 0.004; 95% CI, -0.006 to 0.014; P = .40), 100 to 999 (risk difference = 0.004; 95% CI, -0.003 to 0.011; P = .26), and greater than or equal to 1000 (risk difference = -0.001; 95% CI, -0.003 to 0.001; P = .44) showed no association between TXA and incidence of total TEs. Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs (risk difference, -0.005; 95% CI, -0.021 to 0.011; P = .53).

Conclusions And Relevance: Findings from this systematic review and meta-analysis of 216 studies suggested that intravenous TXA, irrespective of dosing, is not associated with increased risk of any TE. These results help clarify the incidence of adverse events associated with administration of intravenous TXA and suggest that TXA is safe for use with undetermined utility for patients receiving neurological care.
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http://dx.doi.org/10.1001/jamasurg.2021.0884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047805PMC
April 2021

Reasons for Choice of Antiretroviral Regimens in HIV Patients Presenting Late for Initial Treatment in Europe.

AIDS Patient Care STDS 2021 04;35(4):110-115

Department of Infectious Diseases, HIVCENTER, University Hospital Frankfurt, Frankfurt, Germany.

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count <200/μL and/or an AIDS-defining disease (late presenters, LPs), is still a challenge, even for HIV specialists. At present, there is little information on the decision process and selection criteria that physicians must take into account when choosing the presumably optimal initial ART for LPs. This study analyzes reasons for the individual choice of first-line ART in HIV LPs. We conducted a prospective multi-center study to analyze the decision-making process of physicians treating naive HIV patients presenting with a CD4 cell count <200/μL and/or an AIDS-defining condition. Two European HIV treatment centers based in Frankfurt (Germany) and A Coruna (Spain) participated in the study. Physicians documented the reasons that led to their decision for a specific first-line ART regimen. A questionnaire was designed for the study. Decisions of the participating physicians were evaluated. A total of 52 treatment decisions were analyzed. Evaluation of the choice of antiretroviral treatment demonstrated that for the overall group of physicians, simplicity of the regimen was the most important selection criterion in 34.6% of cases. The presence of comorbidities was given as the decisive selection criterion in 26.9%, followed by experience with the chosen drugs in 21.2% of cases. In the group of physicians choosing an integrase strand transfer inhibitor (INSTI)-based regimen for first-line ART, the same selection criteria were identified as in the overall group; 33.3% of clinicians selected an INSTI-based regimen because of its simplicity. The presence of comorbidities was the second most frequent decisive criterion (31.0%), followed by personal experience with the prescribed ART (23.8%). In the protease inhibitor group, simplicity was also the most common selection criterion with 40%. Results of clinical trials were stated as the most important criterion for the selection of ART in 38% of all cases, followed by the expected adherence of the patient (22%). Among the physicians who used a non-nucleoside reverse transcriptase inhibitor-based regimen, patients' desire to have children was the most frequent criterion for selection of ART (60%). An ongoing pregnancy was the second most frequent selection criterion, followed by ART's simplicity (8%). For patients treated with a single-tablet regimen, simplicity of ART was comprehensibly the most important decisive criterion (54.5%). Experience with the chosen drugs was the decisive selection criterion in 24.2%, followed by comorbidities in 18.2% of cases. Physicians' selection of individual ART in patients presenting late for first-line treatment seems to be predominantly dependent on patient-centered factors such as adherence issues as well as the clinical experience of physicians with the prescribed drugs.
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http://dx.doi.org/10.1089/apc.2021.0011DOI Listing
April 2021

Rituximab plus leflunomide in rheumatoid arthritis: a randomized, placebo-controlled, investigator-initiated clinical trial (AMARA study).

Rheumatology (Oxford) 2021 Mar 19. Epub 2021 Mar 19.

Division of Rheumatology, University Hospital Frankfurt, Goethe University.

Objective: To investigate the efficacy and safety of rituximab + LEF in patients with RA.

Methods: In this investigator-initiated, randomized, double-blind, placebo-controlled phase 3 trial, patients with an inadequate response to LEF who had failed one or more DMARD were randomly assigned 2:1 to i.v. rituximab 1000 mg or placebo on day 1 and 15 plus ongoing oral LEF. The primary efficacy outcome was the difference between ≥50% improvement in ACR criteria (ACR50 response) rates at week 24 (P ≤ 0.025). Secondary endpoints included ACR20/70 responses, ACR50 responses at earlier timepoints and adverse event (AE) rates. The planned sample size was not achieved due to events beyond the investigators' control.

Results: Between 13 August 2010 and 28 January 2015, 140 patients received rituximab (n = 93) or placebo (n = 47) plus ongoing LEF. Rituximab + LEF resulted in an increase in the ACR50 response rate that was significant at week 16 (32 vs 15%; P = 0.020), but not week 24 (27 vs 15%; P = 0.081), the primary endpoint. Significant differences favouring the rituximab + LEF arm were observed in some secondary endpoints, including ACR20 rates from weeks 12 to 24. The rituximab and placebo arms had similar AE rates (71 vs 70%), but the rituximab arm had a higher rate of serious AEs (SAEs 20 vs 2%), primarily infections and musculoskeletal disorders.

Conclusion: The primary endpoint was not reached, but rituximab + LEF demonstrated clinical benefits vs LEF in secondary endpoints. Although generally well tolerated, the combination was associated with additional SAEs and requires monitoring.

Trial Registration: EudraCT: 2009-015950-39; ClinicalTrials.gov: NCT01244958.
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http://dx.doi.org/10.1093/rheumatology/keab153DOI Listing
March 2021

Evaluating a Clinical Pathway in Laparoscopic Cholecystectomy: Effective in Reducing Complications? A Propensity Score Matching Analysis.

Visc Med 2021 Feb 27;37(1):70-76. Epub 2020 Mar 27.

Department of General, Visceral, and Thoracic Surgery, Asklepios Klinik Langen, Academic Teaching Hospital Goethe University Frankfurt, Langen, Germany.

Background: Care pathways are primarily aimed at decreasing length of hospital stay (LOS) and preventing unnecessary costs while maintaining or improving the quality of care. In laparoscopic cholecystectomy, there is insufficient evidence for proving an impact upon postoperative complications.

Methods: In this retrospective study, logistic regression was used to calculate a propensity score, and, after carrying out 1:1 nearest-neighbor matching, 296 patients were analyzed in both groups with regard to postoperative complications using the Clavien-Dindo classification system as a primary aim. In addition, secondary aims were LOS, compliance to care, and deviation from the care pathway with respect to patient discharge. Relative risk of the primary outcome was calculated and compared with the e-value as sensitivity testing approach.

Results: Due to the mandatory part of the care pathway, patient record compliance was 100%. Deviation from the care pathway with respect to the planned patient discharge on postoperative day 2 was noted in 16% of the cases. After adjustment for potential factors, the relative risk when comparing Clavien-Dindo complication grades 0 versus 1-4 is 1.64 (95% CI 0.87-3.11), which did not reach significance ( = 0.127). After matching, LOS lasted 3.69 days without and 3.26 days with the care pathway, respectively.

Conclusions: Against the background of already implemented structured standard operation procedures, a care pathway is not able to reduce postoperative complications. Nevertheless, we consider our clinical pathway a highly valuable tool for the interdisciplinary management of patient hospitalization under the supervision of experienced specialized surgeons.
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http://dx.doi.org/10.1159/000506718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923876PMC
February 2021

The association between intraoperative cell salvage and red blood cell transfusion in cardiac surgery - an observational study in a patient blood management centre.

Anaesthesiol Intensive Ther 2021 ;53(1):1-9

Department of Anesthesiology, University Hospital Wuerzburg, Wuerzburg, Germany.

Introduction: Cell salvage (CS) is an integral part of patient blood management (PBM) and aims to reduce allogeneic red blood cell (RBC) transfusion.

Material And Methods: This observational study analysed patients scheduled for elective cardiac surgery requiring cardiopulmonary bypass (CPB) between November 2015 and October 2018. Patients were divided into a CS group (patients receiving CS) and a control group (no CS). Primary endpoints were the number of patients exposed to allogeneic RBC transfusions and the number of RBC units transfused per patient.

Results: A total of 704 patients undergoing cardiac surgery were analysed, of whom 338 underwent surgery with CS (CS group) and 366 were without CS (control group). Intraoperatively, 152 patients (45%) were exposed to allogeneic RBC transfusions in the CS group and 93 patients (25%) in the control group (P < 0.001). Considering the amount of intraoperative blood loss, regression analysis revealed a significant association between blood loss and increased use of RBC units in patients of the control compared to the CS group (1000 mL: 1.0 vs. 0.6 RBC units; 2000 mL: 2.2 vs. 1.1 RBC units; 3000 mL: 3.4 vs. 1.6 RBC units). Thus, CS was significantly associated with a reduced number of allogeneic RBCs by 40% for 1000 mL, 49% for 2000 mL, and 52% for 3000 mL of blood loss compared to patients without CS.

Conclusions: Cell salvage was significantly associated with a reduced number of allogeneic RBC transfusions. It supports the beneficial effect of CS in cardiac surgical patients as an individual measure in a comprehensive PBM program.
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http://dx.doi.org/10.5114/ait.2021.103735DOI Listing
January 2021

Impact of chronic kidney disease in 29 893 patients undergoing transcatheter or surgical aortic valve replacement from the German Aortic Valve Registry.

Eur J Cardiothorac Surg 2021 04;59(3):532-544

German Center for Cardiovascular Research, DZHK, Partner Site Rhine-Main, Rhine-Main, Germany.

Objectives: Chronic kidney disease (CKD) is a key risk factor in patients undergoing transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR). We analysed the impact of estimated glomerular filtration rate (eGFR) and CKD stages on their mid-term survival.

Methods: Data from 29 893 patients enrolled in the German Aortic Valve registry from January 2011 to December 2015 receiving TAVI (n = 12 834) or SAVR (n = 17 059) at 88 sites were included. The impact of renal impairment, as measured by eGFR and CKD stages, was investigated. The primary end-point was 1-year cumulative all-cause mortality.

Results: Higher CKD stages were significantly associated to lower in-hospital, 30-day- and 1-year survival rates. Both TAVI- and SAVR-treated patients in CKD 3a, 3b, 4 and 5 stages showed significant and gradually increasing HR values for 1-year all-cause mortality. The same trend persisted in multivariable analysis, although HR values for CKD 3a and 5 did not reach significance in TAVI patients, whereas CKD 4 + 5 did not reach statistical significance in SAVR. Likewise, eGFR as a continuous variable was a significant predictor for 1-year mortality, with the best cut-off points being 47.4 ml/min/1.73 m2 for TAVI and 59.8 ml/min/1.73 m2 for SAVR. Significant 8.6% and 9.0% increases in 1-year mortality were observed for every 5-ml reduction in eGFR for TAVI and SAVR, respectively.

Conclusions: CKD ≥3b and CKD ≥3a are the independent major risk factors for mortality in patients undergoing TAVI and SAVR, respectively. In the overall population of patients with severe aortic stenosis, an appropriate stratification based on CKD substage may contribute to a better selection of patients suitable for such therapies.
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http://dx.doi.org/10.1093/ejcts/ezaa446DOI Listing
April 2021

Greater Fibrinolysis Resistance but No Greater Platelet Aggregation in Critically Ill COVID-19 Patients.

Anesthesiology 2021 03;134(3):457-467

Background: The hemostatic balance in patients with coronavirus disease 2019 (COVID-19) seems to be shifted toward a hypercoagulable state. The aim of the current study was to assess the associated coagulation alterations by point-of-care-diagnostics, focusing on details of clot formation and lysis in these severely affected patients.

Methods: The authors' prospective monocentric observational study included critically ill patients diagnosed with COVID-19. Demographics and biochemical data were recorded. To assess the comprehensive hemostatic profile of this patient population, aggregometric (Multiplate) and viscoelastometric (CloPro) measures were performed in the intensive care unit of a university hospital at a single occasion. Coagulation analysis and assessment of coagulation factors were performed. Data were compared to healthy controls.

Results: In total, 27 patients (21 male; mean age, 60 yr) were included. Impedance aggregometry displayed no greater platelet aggregability in COVID-19 in comparison with healthy controls (area under the curve [AUC] in adenosine diphosphate test, 68 ± 37 U vs. 91 ± 29 U [-27 (Hodges-Lehmann 95% CI, -48 to -1); P = 0.043]; AUC in arachidonic acid test, 102 ± 54 U vs. 115 ± 26 U [-21 (Hodges-Lehmann 95% CI, -51 to 21); P = 0.374]; AUC in thrombin receptor activating peptide 6 test, 114 ± 61 U vs. 144 ± 31 U [-31 (Hodges-Lehmann 95% CI, -69 to -7); P = 0.113]). Comparing the thromboelastometric results of COVID-19 patients to healthy controls, the authors observed significant differences in maximum clot firmness in fibrin contribution to maximum clot firmness assay (37 ± 11 mm vs. 15 ± 4 mm [21 (Hodges-Lehmann 95% CI, 17 to 26); P < 0.001]) and lysis time in extrinsic activation and activation of fibrinolysis by tissue plasminogen activator assay (530 ± 327 s vs. 211 ± 80 s [238 (Hodges-Lehmann 95% CI, 160 to 326); P < 0.001]).

Conclusions: Thromboelastometry in COVID-19 patients revealed greater fibrinolysis resistance. The authors did not find a greater platelet aggregability based on impedance aggregometric tests. These findings may contribute to our understanding of the hypercoagulable state of critically ill patients with COVID-19.

Editor’s Perspective:
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http://dx.doi.org/10.1097/ALN.0000000000003685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864605PMC
March 2021

Longitudinal testing for respiratory and gastrointestinal shedding of SARS-CoV-2 in day care centres in Hesse, Germany.

Clin Infect Dis 2021 Jan 3. Epub 2021 Jan 3.

Institute of Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Germany.

Background: With the pandemic of SARS-CoV-2 ongoing in Europe in June of 2020, day care centres were reopened in the state of Hesse, Germany, after the lockdown. The role young children play in the dynamics of the transmission was unknown.

Methods: We conducted a longitudinal study over a period of 12 weeks and two days (18 th of June 2020 to 10 th of September, 2020) to screen attendees and staff from day care centres in the state of Hesse, Germany, for both respiratory and gastrointestinal shedding of SARS-CoV-2. 859 children (age range 3 months to 8 years) and 376 staff members from 50 day care centres, which were chosen representatively from throughout the state, participated in the study. Parents were asked to perform both a buccal mucosa and an anal swab on their children once a week. Staff were asked to self-administer the swabs. RT-PCRs for SARS-CoV-2 were performed in a multiple-swab pooling protocol.

Results: 7,366 buccal mucosa swabs and 5,907 anal swabs were analysed. No respiratory or gastrointestinal shedding of SARS-CoV-2 was detected in any of the children. Shedding of SARS-CoV-2 could be detected in two staff members from distinct day care centres. One was asymptomatic at the time of testing, and one was symptomatic and did not attend the facility on that day.

Conclusion: Detection of either respiratory or gastrointestinal shedding of SARS-CoV-2 RNA in children and staff members attending day care centres was rare in the context of limited community activity and with infection prevention measures in the facilities in place.
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http://dx.doi.org/10.1093/cid/ciaa1912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799213PMC
January 2021

DIagnostic Subdural EEG electrodes And Subdural hEmatoma (DISEASE): a study protocol for a prospective nonrandomized controlled trial.

Neurol Res Pract 2020 15;2:50. Epub 2020 Dec 15.

Department of Neurosurgery, University Hospital, Goethe University Frankfurt, Schleusenweg 2-16, 60528 Frankfurt am Main, Germany.

Background: Epileptic seizures are common clinical features in patients with acute subdural hematoma (aSDH); however, diagnostic feasibility and therapeutic monitoring remain limited. Surface electroencephalography (EEG) is the major diagnostic tool for the detection of seizures but it might be not sensitive enough to detect all subclinical or nonconvulsive seizures or status epilepticus. Therefore, we have planned a clinical trial to evaluate a novel treatment modality by perioperatively implanting subdural EEG electrodes to diagnose seizures; we will then treat the seizures under therapeutic monitoring and analyze the clinical benefit.

Methods: In a prospective nonrandomized trial, we aim to include 110 patients with aSDH. Only patients undergoing surgical removal of aSDH will be included; one arm will be treated according to the guidelines of the Brain Trauma Foundation, while the other arm will additionally receive a subdural grid electrode. The study's primary outcome is the comparison of incidence of seizures and time-to-seizure between the interventional and control arms. Invasive therapeutic monitoring will guide treatment with antiseizure drugs (ASDs). The secondary outcome will be the functional outcome for both groups as assessed via the Glasgow Outcome Scale and modified Rankin Scale both at discharge and during 6 months of follow-up. The tertiary outcome will be the evaluation of chronic epilepsy within 2-4 years of follow-up.

Discussion: The implantation of a subdural EEG grid electrode in patients with aSDH is expected to be effective in diagnosing seizures in a timely manner, facilitating treatment with ASDs and monitoring of treatment success. Moreover, the occurrence of epileptiform discharges prior to the manifestation of seizure patterns could be evaluated in order to identify high-risk patients who might benefit from prophylactic treatment with ASDs.

Trial Registration: ClinicalTrials.gov identifier no. NCT04211233.
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http://dx.doi.org/10.1186/s42466-020-00096-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737265PMC
December 2020

Risk factors and outcomes associated with the carriage of tigecycline- and vancomycin-resistant Enterococcus faecium.

J Infect 2021 02 4;82(2):227-234. Epub 2020 Dec 4.

University Center for Infectious Diseases (UCI), University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany; Institute for Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany; University Center of Competence for Infection Control, State of Hesse, Germany. Electronic address:

Objectives: Vancomycin-resistant E. faecium (VRE) is a common cause of healthcare-associated infections. The emergence of VRE with tigecycline resistance (TVRE) is increasing but its impact on patient outcome is still not well defined. This study aimed to assess risk factors for the acquisition of TVRE and of patient outcomes associated with TVRE carriage/infection.

Methods: At the University Hospital Frankfurt, we conducted a matched pair TVRE-VRE analysis to identify risk factors for TVRE carriage. Bed-to-bed contacts and potential transmission routes were reconstructed. TVRE were whole-genome sequenced to confirm suspected transmission events and to identify tigecycline resistance mechanisms.

Results: 76 TVRE cases were identified between 02/2014-04/2017 and compared to VRE colonized or infected controls. TVRE carriage was associated with exposure to tigecycline, an increased rate of bloodstream infections (BSI) with VRE or Candida spp., and higher mortality. Whole-genome sequencing-based analysis of 24 TVRE provided evidence for transmissions of TVRE, also across different wards.

Conclusions: Tigecycline exposure is the main risk factor for TVRE carriage. VRE/TVRE- and Candida-BSI are associated with worse clinical outcome. Hospital transmission of TVRE may occur despite strict contact precautions, whereas both antimicrobial stewardship and infection control interventions are of high importance to prevent emergence and spread of TVRE.
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http://dx.doi.org/10.1016/j.jinf.2020.12.003DOI Listing
February 2021

Clonal haematopoiesis in chronic ischaemic heart failure: prognostic role of clone size for DNMT3A- and TET2-driver gene mutations.

Eur Heart J 2021 01;42(3):257-265

Department of Medicine, Cardiology, Goethe University Hospital, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.

Aims: Somatic mutations of the epigenetic regulators DNMT3A and TET2 causing clonal expansion of haematopoietic cells (clonal haematopoiesis; CH) were shown to be associated with poor prognosis in chronic ischaemic heart failure (CHF). The aim of our analysis was to define a threshold of variant allele frequency (VAF) for the prognostic significance of CH in CHF.

Methods And Results: We analysed bone marrow and peripheral blood-derived cells from 419 patients with CHF by error-corrected amplicon sequencing. Cut-off VAFs were optimized by maximizing sensitivity plus specificity from a time-dependent receiver operating characteristic (ROC) curve analysis from censored data. 56.2% of patients were carriers of a DNMT3A- (N = 173) or a TET2- (N = 113) mutation with a VAF >0.5%, with 59 patients harbouring mutations in both genes. Survival ROC analyses revealed an optimized cut-off value of 0.73% for TET2- and 1.15% for DNMT3A-CH-driver mutations. Five-year-mortality was 18% in patients without any detected DNMT3A- or TET2 mutation (VAF < 0.5%), 29% with only one DNMT3A- or TET2-CH-driver mutations above the respective cut-off level and 42% in patients harbouring both DNMT3A- and TET2-CH-driver mutations above the respective cut-off levels. In carriers of a DNMT3A mutation with VAF ≥ 1.15%, 5-year mortality was 31%, compared with 18% mortality in those with VAF < 1.15% (P = 0.048). Likewise, in patients with TET2 mutations, 5-year mortality was 32% with VAF ≥ 0.73%, compared with 19% mortality with VAF < 0.73% (P = 0.029).

Conclusion: The present study defines novel threshold levels for clone size caused by acquired somatic mutations in the CH-driver genes DNMT3A and TET2 that are associated with worse outcome in patients with CHF.
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http://dx.doi.org/10.1093/eurheartj/ehaa845DOI Listing
January 2021

Transcatheter Versus Rapid-Deployment Aortic Valve Replacement: A Propensity-Matched Analysis From the German Aortic Valve Registry.

JACC Cardiovasc Interv 2020 11;13(22):2642-2654

Department of Cardiac Surgery, University Hospital Lübeck, Lübeck, Germany.

Objectives: This study sought to compare patient characteristics, procedural outcomes, and valve hemodynamics of surgical aortic valve replacement (SAVR) with current-generation rapid-deployment valves (RDVs) versus transcatheter aortic valve replacement (TAVR) with current-generation transcatheter heart valves (THVs).

Background: The patient population currently treated with RDVs may have potential similarities with the current TAVR population, but comparative studies in a large patient population remain scarce.

Methods: A total of 16,473 patients who underwent isolated SAVR using current-generation RDVs or isolated transfemoral TAVR with current-generation THVs between 2011 and 2017 were enrolled into the German Aortic Valve Registry. Baseline, procedural, and in-hospital outcome parameters were analyzed for RDVs and THVs before and after 1:1 propensity score matching. Furthermore, RDVs and THVs with similar design characteristics were compared with each other.

Results: A total of 1,743 patients received SAVR with an RDV, whereas 14,730 patients were treated with transfemoral TAVR. Patients treated with TAVR were significantly older and had higher surgical risk scores. Following valve replacement, patients treated with an RDV had a significantly higher rate of disabling stroke (1.7% vs. 1.1%; p = 0.03), need for transfusion of >4 red blood cell units (8.5% vs. 1.4%; p < 0.001), and new onset renal replacement therapy (1.9% vs. 1.2%; p = 0.01), whereas the need for a new permanent pacemaker was lower (8.4% vs. 14.9%; p < 0.001). In-hospital mortality was similar (1.6% vs. 1.8%; p = 0.62). These findings persisted after 1:1 propensity score matching, but in-hospital mortality was significantly higher after RDVs (1.7% vs. 0.6%; p = 0.003). Balloon-expandable (BE) RDVs had significantly lower residual gradients compared with BE-THVs, while self-expanding (SE)-RDVs had significantly higher residual gradients compared with SE-THVs.

Conclusions: In a large all-comers' registry, TAVR with current-generation THVs was associated with improved in-hospital outcomes compared with SAVR with current-generation RDVs. The pacemaker rate is significantly higher with TAVR. Post-procedural hemodynamic function varied between individual RDVs and THVs.
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http://dx.doi.org/10.1016/j.jcin.2020.09.018DOI Listing
November 2020

Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers.

JCI Insight 2020 11 19;5(22). Epub 2020 Nov 19.

Paul Ehrlich Institute, Division of Virology, Langen, Germany.

Many mutation analyses of the HBV genome have been performed in the search for new prognostic markers. However, the Kozak sequence preceding precore was covered only infrequently in these analyses. In this study, the HBV core promoter/precore region was sequenced in serum samples from European inactive HBV carriers. Quadruple mutation GCAC1809-1812TTCT was found with a high prevalence of 42% in the Kozak sequence preceding precore among all HBV genotypes. GCAC1809-1812TTCT was strongly associated with coexistence of basal core promoter (BCP) double mutation A1762T/G1764A and lower HBV DNA levels. In vitro GCAC1809-1812TTCT lead to drastically diminished synthesis of pregenomic RNA (pgRNA), precore mRNA, core, HBsAg, and HBeAg. Calculation of the pgRNA secondary structure suggests a destabilization of the pgRNA structure by A1762T/G1764A that was compensated by GCAC1809-1812TTCT. In 125 patients with HBV-related cirrhosis, GCAC1809-1812TTCT was not detected. While a strong association of GCAC1809-1812TTCT with inactive carrier status was observed, BCP double mutation was strongly correlated with cirrhosis, but this was only observed in absence of GCAC1809-1812TTCT. In conclusion, our data reveal that GCAC1809-1812TTCT is highly prevalent in inactive carriers and acts as a compensatory mutation for BCP double mutation. GCAC1809-1812TTCT seems to be a biomarker of good prognosis in HBV infection.
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http://dx.doi.org/10.1172/jci.insight.135833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710305PMC
November 2020

Transcatheter or surgical aortic valve implantation in chronic dialysis patients: a German Aortic Valve Registry analysis.

Clin Res Cardiol 2021 Mar 23;110(3):357-367. Epub 2020 Sep 23.

Department of Cardiology, University Hospital Frankfurt am Main, Frankfurt, Germany.

Objectives: The aim of this study was to compare outcomes of transcatheter and surgical aortic valve implantation in chronic dialysis patients with aortic valve stenosis (AS).

Background: Chronic dialysis patients undergoing heart valve surgery are at higher risk for morbidity and mortality. Whether interventional techniques can reduce this risk is unclear because dialysis patients have thus far been excluded from randomized trials.

Methods: Chronic dialysis patients with AS enrolled in the German Aortic Valve Registry (GARY) between 2012 and 2015 were analyzed to compare transcatheter aortic valve implantation (TAVI n = 661) with surgical aortic valve replacement (SAVR n = 457). Propensity scores for inverse probability of treatment weighting (IPTW) were used to adjust the comparison of the two treatment groups for potential confounders.

Results: TAVI patients were older (78 ± 7.3 vs. 69 ± 10.2 years, p < 0.01, unadjusted) and had more comorbidities. Mortality at 1 year was the same (TAVI: 33.4% vs. SAVR 35.0%, p = 0.72, IPTW-adjusted) while it was lower with TAVI at 30 days (8.6% vs. 15.0%, p = 0.02, IPTW-adjusted). TAVI patients required more pacemaker implantation and showed more aortic regurgitation. SAVR patients required more blood transfusions and had longer hospital stay. Diabetes mellitus, atrial fibrillation, previous PCI, urgent procedure and EuroSCORE were associated with elevated 30-day mortality. Atrial fibrillation and older age were independent risk factor of 1-year mortality in both groups.

Conclusions: Chronic dialysis patients with AS undergoing TAVI or SAVR had the same 1-year mortality, although survival at 30 days was better with TAVI. These results suggest that TAVI may improve peri-procedural outcomes.
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http://dx.doi.org/10.1007/s00392-020-01717-7DOI Listing
March 2021

Efficacy of Norfloxacin Prophylaxis to Prevent Spontaneous Bacterial Peritonitis: A Systematic Review and Meta-Analysis.

Clin Transl Gastroenterol 2020 08;11(8):e00223

Institute of Biostatistics and Mathematical Modeling, Goethe University, Frankfurt am Main, Germany.

Introduction: With the emergence of multidrug-resistant organisms, the efficacy of antibiotic prophylaxis to prevent spontaneous bacterial peritonitis (SBP) has been debated. The aim of this study was to assess factors impacting effectiveness of SBP prophylaxis.

Methods: We searched PubMed, Embase, and the Cochrane Registry from inception to May 2019 to identify randomized controlled trials of patients with liver cirrhosis that assessed SBP occurrence/recurrence during antibiotic prophylaxis with the common antibiotic agents. Network meta-analysis was performed, pooling data with regard to incidence rate ratios (IRRs) of SBP, death, or extraperitoneal infections.

Results: Overall, 1,626 patients in 12 randomized controlled trials were included. During primary prophylaxis, the incidence rate of SBP and death in the norfloxacin-treated patients was 0.117 and 0.438 per patient-year, respectively, and IRRs of placebo vs norfloxacin were significantly higher (IRR 5.35, 95% confidence interval 1.99-14.38, P = 0.0009 for SBP and IRR 2.04, 95% confidence interval 1.20-3.44, P = 0.008 for death). The efficacy of norfloxacin to prevent SBP, but not death, decreased over time (annual percent change from 1992 to 2015 8.2%, P = 0.019), The positive treatment effect was lower in studies including patients with increased ascites protein (P = 0.021) or exceedingly high serum bilirubin (P = 0.012) levels. Norfloxacin was not superior to other antibiotics. The incidence rate of SBP was 2.5-fold higher in patients treated with norfloxacin as secondary compared with primary prophylaxis. No significant differences between treatment designs were observed in secondary prophylaxis.

Discussion: Norfloxacin remained superior to placebo in preventing SBP, yet the efficacy to prevent SBP, not death, decreased over time. Further studies to understand this phenomenon are urgently needed.
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http://dx.doi.org/10.14309/ctg.0000000000000223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431273PMC
August 2020

Hepatitis C Clearance by Direct-Acting Antivirals Impacts Glucose and Lipid Homeostasis.

J Clin Med 2020 Aug 21;9(9). Epub 2020 Aug 21.

Department of Internal Medicine, University Hospital Frankfurt, 60596 Frankfurt, Germany.

Background: Chronic hepatitis C virus (HCV) infections are causally linked with metabolic comorbidities such as insulin resistance, hepatic steatosis, and dyslipidemia. However, the clinical impact of HCV eradication achieved by direct-acting antivirals (DAAs) on glucose and lipid homeostasis is still controversial. The study aimed to prospectively investigate whether antiviral therapy of HCV with DAAs alters glucose and lipid parameters.

Methods: 50 patients with chronic HCV who were treated with DAAs were screened, and 49 were enrolled in the study. Biochemical and virological data, as well as noninvasive liver fibrosis parameters, were prospectively collected at baseline, at the end of treatment (EOT) and 12 and 24 weeks post-treatment.

Results: 45 of 46 patients achieved sustained virologic response (SVR). The prevalence of insulin resistance (HOMA-IR) after HCV clearance was significantly lower, compared to baseline (5.3 ± 6.1 to 2.5 ± 1.9, < 0.001), which is primarily attributable to a significant decrease of fasting insulin levels (18.9 ± 17.3 to 11.7 ± 8.7; = 0.002). In contrast to that, HCV eradication resulted in a significant increase in cholesterol levels (total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein (HDL-C) levels) and Controlled Attenuated Score (CAP), although BMI did not significantly change over time ( = 0.95). Moreover, HOMA-IR correlated significantly with noninvasive liver fibrosis measurements at baseline und during follow-up (TE: = 0.45; = 0.003, pSWE: = 0.35; = 0.02, APRI: = 0.44; = 0.003, FIB-4: = 0.41; < 0.001).

Conclusion: Viral eradication following DAA therapy may have beneficial effects on glucose homeostasis, whereas lipid profile seems to be worsened.
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http://dx.doi.org/10.3390/jcm9092702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564474PMC
August 2020

Comparison of common perioperative blood loss estimation techniques: a systematic review and meta-analysis.

J Clin Monit Comput 2021 Apr 19;35(2):245-258. Epub 2020 Aug 19.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Germany.

Estimating intraoperative blood loss is one of the daily challenges for clinicians. Despite the knowledge of the inaccuracy of visual estimation by anaesthetists and surgeons, this is still the mainstay to estimate surgical blood loss. This review aims at highlighting the strengths and weaknesses of currently used measurement methods. A systematic review of studies on estimation of blood loss was carried out. Studies were included investigating the accuracy of techniques for quantifying blood loss in vivo and in vitro. We excluded nonhuman trials and studies using only monitoring parameters to estimate blood loss. A meta-analysis was performed to evaluate systematic measurement errors of the different methods. Only studies that were compared with a validated reference e.g. Haemoglobin extraction assay were included. 90 studies met the inclusion criteria for systematic review and were analyzed. Six studies were included in the meta-analysis, as only these were conducted with a validated reference. The mixed effect meta-analysis showed the highest correlation to the reference for colorimetric methods (0.93 95% CI 0.91-0.96), followed by gravimetric (0.77 95% CI 0.61-0.93) and finally visual methods (0.61 95% CI 0.40-0.82). The bias for estimated blood loss (ml) was lowest for colorimetric methods (57.59 95% CI 23.88-91.3) compared to the reference, followed by gravimetric (326.36 95% CI 201.65-450.86) and visual methods (456.51 95% CI 395.19-517.83). Of the many studies included, only a few were compared with a validated reference. The majority of the studies chose known imprecise procedures as the method of comparison. Colorimetric methods offer the highest degree of accuracy in blood loss estimation. Systems that use colorimetric techniques have a significant advantage in the real-time assessment of blood loss.
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http://dx.doi.org/10.1007/s10877-020-00579-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943515PMC
April 2021

Evaluation of the Integrated Pulmonary Index® during non-anesthesiologist sedation for percutaneous endoscopic gastrostomy.

J Clin Monit Comput 2020 Jul 30. Epub 2020 Jul 30.

Department of Internal Medicine 1, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.

Standard monitoring of heart rate, blood pressure and arterial oxygen saturation during endoscopy is recommended by current guidelines on procedural sedation. A number of studies indicated a reduction of hypoxic (art. oxygenation < 90% for > 15 s) and severe hypoxic events (art. oxygenation < 85%) by additional use of capnography. Therefore, U.S. and the European guidelines comment that additional capnography monitoring can be considered in long or deep sedation. Integrated Pulmonary Index® (IPI) is an algorithm-based monitoring parameter that combines oxygenation measured by pulse oximetry (art. oxygenation, heart rate) and ventilation measured by capnography (respiratory rate, apnea > 10 s, partial pressure of end-tidal carbon dioxide [PetCO]). The aim of this paper was to analyze the value of IPI as parameter to monitor the respiratory status in patients receiving propofol sedation during PEG-procedure. Patients reporting for PEG-placement under sedation were randomized 1:1 in either standard monitoring group (SM) or capnography monitoring group including IPI (IM). Heart rate, blood pressure and arterial oxygen saturation were monitored in SM. In IM additional monitoring was performed measuring PetCO, respiratory rate and IPI. Capnography and IPI values were recorded for all patients but were only visible to the endoscopic team for the IM-group. IPI values range between 1 and 10 (10 = normal; 8-9 = within normal range; 7 = close to normal range, requires attention; 5-6 = requires attention and may require intervention; 3-4 = requires intervention; 1-2 requires immediate intervention). Results on capnography versus standard monitoring of the same study population was published previously. A total of 147 patients (74 in SM and 73 in IM) were included in the present study. Hypoxic events occurred in 62 patients (42%) and severe hypoxic events in 44 patients (29%), respectively. Baseline characteristics were equally distributed in both groups. IPI = 1, IPI < 7 as well as the parameters PetCO = 0 mmHg and apnea > 10 s had a high sensitivity for hypoxic and severe hypoxic events, respectively (IPI = 1: 81%/81% [hypoxic/severe hypoxic event], IPI < 7: 82%/88%, PetCO: 69%/68%, apnea > 10 s: 84%/84%). All four parameters had a low specificity for both hypoxic and severe hypoxic events (IPI = 1: 13%/12%, IPI < 7: 7%/7%, PetCO: 29%/27%, apnea > 10 s: 7%/7%). In multivariate analysis, only SM and PetCO = 0 mmHg were independent risk factors for hypoxia. IPI (IPI = 1 and IPI < 7) as well as the individual parameters PetCO = 0 mmHg and apnea > 10 s allow a fast and convenient conclusion on patients' respiratory status in a morbid patient population. Sensitivity is good for most parameters, but specificity is poor. In conclusion, IPI can be a useful metric to assess respiratory status during propofol-sedation in PEG-placement. However, IPI was not superior to PetCO and apnea > 10 s.
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http://dx.doi.org/10.1007/s10877-020-00563-2DOI Listing
July 2020

Graduated compression stockings in the prevention of postoperative pulmonary embolism. A propensity-matched retrospective case-control study of 24 273 patients.

Ann Med Surg (Lond) 2020 Aug 30;56:203-210. Epub 2020 Jun 30.

Clinic for General, Visceral and Thoracic-Surgery, Asklepios Klinik Langen, Academic Teaching Hospital Goethe-Universität Frankfurt, Röntgenstr 20, Langen, 63225, Germany.

Introduction: Recommendations for venous thromboembolism and deep venous thrombosis (DVT) prophylaxis using graduated compression stockings (GCS) is historically based and has been critically examined in current publications. Existing guidelines are inconclusive as to recommend the general use of GCS.Patients/Methods: 24 273 in-patients (general surgery and orthopedic patients) undergoing surgery between 2006 and 2016 were included in a retrospectively analysis from a single center. From January 2006 to January 2011 perioperative GCS was employed additionally to drug prophylaxis and from February 2011 to March 2016 patients received drug prophylaxis alone. According to german guidelines all patients received venous thromboembolism prophylaxis with weight-adapted LMWH. Risk stratification (low risk, moderate risk, high risk) was based on the guideline of the American College of Chest Physicians. Data analysis was performed before and after propensity matching (PM). The defined primary endpoint was the incidence of symptomatic or fatal pulmonary embolism (PE). A secondary endpoint was the incidence of deep venous thromboembolism (DVT).

Results: After risk stratification (low risk n = 16 483; moderate risk n = 4464; high risk n = 3326) a total of 24 273 patient were analyzed. Before to PM the relative risk for the occurrence of a PE or DVT was not increased by abstaining from GCS. After PM two groups of 11 312 patients each, one with and one without GCS application, were formed. When comparing the two groups, the relative risk (RR) for the occurrence of a pulmonary embolism was: Low Risk 0.99 [CI95% 0.998-1.000]; Moderate Risk 0.999 [CI95% 0.95-1.003]; High Risk 0.996 [CI95% 0.992-1.000] (p > 0.05). The incidence of PE in the total group LMWH alone was 0.1% (n = 16). In the total group using LMWH + GCS, the incidence was 0.3% (n = 29). RR after PM was 0.999 [CI95% 0.998-1.00].

Conclusion: In comparison to prior studies with only small numbers of patients our trial shows in a large group of patients with moderate and high risk developing VTE we can support the view that abstaining from GCS-use does not increase the incidence of symptomatic or fatal PE and symptomatic DVT.
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http://dx.doi.org/10.1016/j.amsu.2020.06.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7338863PMC
August 2020

AFP ratio predicts HCC recurrence after liver transplantation.

PLoS One 2020 2;15(7):e0235576. Epub 2020 Jul 2.

Medizinische Klinik 1, Universitätsklinikum Frankfurt, Frankfurt, Germany.

Background/aims: Hepatocellular carcinoma (HCC) is a leading indication for liver transplantation (LT) worldwide. Early identification of patients at risk for HCC recurrence is of paramount importance since early treatment of recurrent HCC after LT may be associated with increased survival. We evaluated incidence of and predictors for HCC recurrence, with a focus on the course of AFP levels.

Methods: We performed a retrospective, single-center study of 99 HCC patients who underwent LT between January 28th, 1997 and May 11th, 2016. A multi-stage proportional hazards model with three stages was used to evaluate potential predictive markers, both by univariate and multivariable analysis, for influences on 1) recurrence after transplantation, 2) mortality without HCC recurrence, and 3) mortality after recurrence.

Results: 19/99 HCC patients showed recurrence after LT. Waiting time was not associated with overall HCC recurrence (HR = 1, p = 0.979). Similarly, waiting time did not affect mortality in LT recipients both with (HR = 0.97, p = 0.282) or without (HR = 0.99, p = 0.685) HCC recurrence. Log10-transformed AFP values at the time of LT (HR 1.75, p = 0.023) as well as after LT (HR 2.07, p = 0.037) were significantly associated with recurrence. Median survival in patients with a ratio (AFP at recurrence divided by AFP 3 months before recurrence) of 0.5 was greater than 70 months, as compared to a median of only 8 months in patients with a ratio of 5.

Conclusion: A rise in AFP levels rather than an absolute threshold could help to identify patients at short-term risk for HCC recurrence post LT, which may allow intensification of the surveillance strategy on an individualized basis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235576PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332004PMC
September 2020
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