Publications by authors named "J Andruszkow"

18 Publications

Increased Serum Levels of Activated Caspases in Murine and Human Biliary Atresia.

J Clin Med 2021 Jun 19;10(12). Epub 2021 Jun 19.

Department of Pediatric Surgery, Hannover Medical School, 30625 Hannover, Germany.

In biliary atresia (BA), apoptosis is part of the pathomechanism, which results in progressive liver fibrosis. There is increasing evidence suggesting that apoptotic liver injury can be non-invasively detected by measuring the caspase activity in the serum. The purpose of this study was to investigate whether serological detection of caspase activation mirrors apoptotic liver injury in the infective murine BA-model and represents a suitable biomarker for BA in humans. Analysis showed increased caspase-3 activity and apoptosis in the livers of cholestatic BALB/c mice, which correlated significantly with caspase activation in the serum. We then investigated caspase activation and apoptosis in liver tissues and sera from 26 BA patients, 23 age-matched healthy and 11 cholestatic newborns, due to other hepatopathies. Compared to healthy individuals, increased caspase activation in the liver samples of BA patients was present. Moreover, caspase-3 activity was significantly higher in sera from BA infants compared to patients with other cholestatic diseases (sensitivity 85%, specificity 91%). In conclusion, caspase activation and hepatocyte apoptosis play an important role in experimental and human BA. We demonstrated that serological detection of caspase activation represents a reliable non-invasive biomarker for monitoring disease activity in neonatal cholestatic liver diseases including BA.
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http://dx.doi.org/10.3390/jcm10122718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234421PMC
June 2021

Mouse Models of Nonalcoholic Steatohepatitis: Head-to-Head Comparison of Dietary Models and Impact on Inflammation and Animal Welfare.

Gastroenterol Res Pract 2020 13;2020:7347068. Epub 2020 Jul 13.

Department of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital, 52074 Aachen, Germany.

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3 NK1.1 cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model.
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http://dx.doi.org/10.1155/2020/7347068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374209PMC
July 2020

Evaluation of NAFLD and fibrosis in obese patients - a comparison of histological and clinical scoring systems.

BMC Gastroenterol 2020 Aug 5;20(1):254. Epub 2020 Aug 5.

Department of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital, Pauwelsstr.30, 52074, Aachen, Germany.

Background: Non-alcoholic fatty liver disease (NAFLD) is a frequent condition in obese patients and regularly progresses to non-alcoholic steatohepatitis (NASH) and subsequent cirrhosis. Histologic evaluation is the gold standard for grading and staging, but invasive biopsies are associated with obvious risks. The aim of this study was to evaluate different non-invasive tools for screening of NAFLD and fibrosis in obese patients.

Methods: In a prospective cohort study liver specimens of 141 patients were taken during bariatric surgery. Serological parameters and clinical data were collected and the following scores calculated: NASH clinical scoring system (NCS), aspartate aminotransferase to platelet ratio index (APRI), FIB-4 as well as NAFLD fibrosis score (NFS). Liver function capacity was measured preoperatively by LiMAx test (enzymatic capacity of cytochrome P450 1A2). Intraoperative liver biopsies were classified using NAFLD activity score (NAS) and steatosis, activity and fibrosis (SAF) score.

Results: APRI was able to differentiate between not NASH and definite NASH with a sensitivity of 74% and specificity of 67% (AUROC 0.76). LiMAx and NCS also showed significant differences between not NASH and definite NASH. No significant differences were found for NFS and Fib-4. APRI had a high sensitivity (83%) and specificity (76%) in distinguishing fibrosis from no fibrosis (AUROC = 0.81). NCS and Fib-4 also revealed high AUROCs (0.85 and 0.67), whereas LiMAx and NFS did not show statistically significant differences between fibrosis stages. Out of the patients with borderline NASH in the histologic NAS score, 48% were classified as NASH by SAF score.

Conclusions: APRI allows screening of NAFLD as well as fibrosis in obese patients. This score is easy to calculate and affordable, while conveniently only using routine clinical parameters. Using the NAS histologic scoring system bears the risk of underdiagnosing NASH in comparison to SAF score.
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http://dx.doi.org/10.1186/s12876-020-01400-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405451PMC
August 2020

Adenosquamous Carcinoma of the Pancreas Comprise a Heterogeneous Group of Tumors With the Worst Outcome: A Clinicopathological Analysis of 25 Cases Identified in 562 Pancreatic Carcinomas Resected With Curative Intent.

Pancreas 2020 May/Jun;49(5):683-691

From the Department of Surgery and Transplantation, University Hospital RWTH Aachen, Aachen.

Objectives: Information of the clinicopathological characteristics and outcome data of patients with adenosquamous carcinoma of the pancreas (ASCAP) remains limited. This study's aim is to describe the clinical, pathological, and molecular characteristics of 25 resected ASCAPs.

Methods: Of all 25 cases, patient characteristics, follow-up data, and pathological/immunohistological features were reviewed and analyzed.

Results: In this 3-institutional retrospective analysis of 562 pancreatic cancer patients, we identified 25 cases with histologically confirmed ASCAP (4.4%). Follow-up was available in 21 ASCAP and 50 pancreatic ductal adenocarcinoma control patients with a median overall survival of 8.2 and 21 months, respectively. Age, tumor size, localization in the tail, lymph node status, and resection margin seem to be the most significant factors of survival in our ASCAP cohort. In contrast to pancreatic ductal adenocarcinoma, positive expression of p63, keratins K5/14, and the epidermal growth factor receptor are a robust marker profile of these tumors.

Conclusions: Adenosquamous carcinoma of the pancreas comprises a group of neoplasms in which stage and adverse morphological features contribute to its bad prognosis. Further work must be pursued to improve detection and treatment options to reduce mortality. Specifically, differences in biology might become a target for the development of possible therapies.
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http://dx.doi.org/10.1097/MPA.0000000000001548DOI Listing
May 2021

Effect of neurokinin-1-receptor blockage on fracture healing in rats.

Sci Rep 2019 07 5;9(1):9744. Epub 2019 Jul 5.

Department of Orthopedic Trauma and Reconstructive Surgery, University of Aachen Medical Center, Aachen, Germany.

Neurologic injury and selective blockage of sensory nerve endings is associated with impaired fracture healing, however, the role of specific neurotransmitters has not been sufficiently investigated. Our aim was to investigate the impact of specific Substance P-receptor blockage on fracture healing, since the neuropeptide Substance P has both neurogenic and osteogenic activity. After intramedullary stabilization, an isolated femur fracture was induced in 72 Sprague-Dawley rats. In the NK1-R group, the neurokinin-1-tachykinin receptor for substance P was blocked by a specific antagonist (SR140333) for the first two weeks after fracture induction. The control group only received vehicle. Gene-expression, histology, micro-computed tomography, and biomechanical tests were performed. NK1-receptor blocking suppressed osteocalcin expression at one week, collagen 1A2 expression at one and two weeks and collagen 2A1 expression at 2 weeks after fracture induction. Biomechanical testing revealed a significant reduction in maximal load to failure in the NK1-R group at 6 weeks (69.78 vs. 155.45 N, p = 0.029) and at 3 months (72.50 vs.176.33 N, p = 0.01) of fracture healing. Blocking the NK1-receptor suppresses gene expression in and reduces biomechanical strength of healing bone. Therefore, we assume a potential therapeutic relevance of Substance P in cases of disturbed fracture healing.
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http://dx.doi.org/10.1038/s41598-019-46278-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611911PMC
July 2019
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