Tell Us! A survey of public opinion on how to deal with COVID-19 risks and subsequent harm.

SETTING: The COVID-19 pandemic has impacted all of us in many areas of life due to mitigation measures, delays in medical care, or the disease itself. When it concerns issues as complex and universal as COVID-19, the public should also have a say in how to deal with managing its impact. DESIGN: In a widely distributed online questionnaire, members of the Austrian public were invited to contribute experiences, ideas and opinions on the level of risk they were willing to accept regarding COVID-19. The huge variety of responses were categorised by social scientists into groups used in a workshop to draw up recommendations for responding to future challenges to the healthcare system from an interdisciplinary point of view. RESULTS: The results of the survey indicated that while members of the public are primarily afraid of illnesses caused by COVID-19, they also fear the psychological burden and effects at the societal level. CONCLUSION: Our study has shown that there is a significant public desire to have a say in issues which directly impact citizens.

CONTEXTE: La pandémie de COVID-19 a eu un impact sur chacun d'entre nous dans de nombreux domaines de la vie en raison des mesures d'atténuation, des retards dans les soins médicaux ou de la maladie elle-même. Lorsqu'il s'agit de questions aussi complexes et universelles que la COVID-19, le public devrait également avoir son mot à dire sur la façon de gérer son impact. MÉTHODE: Dans un questionnaire en ligne largement diffusé, les membres du public autrichien ont été invités à faire part de leurs expériences, idées et opinions sur le niveau de risque qu'ils étaient prêts à accepter concernant le COVID-19. La grande variété des réponses a été classée par des spécialistes en sciences sociales dans des groupes utilisés lors d'un atelier pour élaborer des recommandations visant à répondre aux futurs défis du système de santé d'un point de vue interdisciplinaire. RÉSULTATS: Les résultats de l'enquête ont indiqué que si les membres du public craignent avant tout les maladies causées par le COVID-19, ils craignent également le fardeau psychologique et les effets au niveau de la société. CONCLUSION: Notre étude a montré qu'il existe un désir significatif du public d'avoir son mot à dire sur les questions qui ont un impact direct sur les citoyens.

Low Tube Voltage Liver MDCT with Sinogram-Affirmed Iterative Reconstructions for the Detection of Hepatocellular Carcinoma.

Aim of this study was to compare low tube voltage computed tomography (80 kV) of the liver using iterative image reconstruction (SAFIRE) with standard computed tomography (120 kV) using filtered back-projection (FBP) for the detection of hepatocellular carcinoma (HCC). 46 patients (43 men) with 93 HCC confirmed by 3 T MRI with Gd-EOB-DPTA, in inconclusive cases combined with contrast-enhanced ultrasound, underwent dual-energy CT. The raw data of the 80 kV tube was reconstructed using the iterative reconstruction algorithm SAFIRE with two strengths (I3 and I5). The virtual 120 kV image data set was reconstructed using FBP. The CT images were reviewed to determine the lesion-to-liver contrast (LLC), the lesion contrast-to-noise ratio (CNR) and the sensitivity. The LLC (57.1/54.3 [I3/I5] vs. 34.9 [FBP]; p ≤ 0.01), CNR (3.67/4.45 [I3/I5] vs. 2.48 [FBP]; p < 0.01) and sensitivity (91.4%/88.2% [I3/I5] vs. 72.0% [FBP]; p ≤ 0.01) were significantly higher in the low-voltage protocol using SAFIRE. Therefore, low tube voltage CT using SAFIRE results in an increased lesion-to-liver contrast as well as an improved lesion contrast-to-noise ratio compared to FBP at 120 kV which results in a higher sensitivity for the detection of HCC.

Percutaneous Irreversible Electroporation: Long-term survival analysis of 71 patients with inoperable malignant hepatic tumors.

Aim of this retrospective analysis was to evaluate the survival times after percutaneous irreversible electroporation (IRE) in inoperable liver tumors not amenable to thermal ablation. 71 patients (14 females, 57 males, median age 63.5 ± 10.8 years) with 103 liver tumors were treated in 83 interventions using IRE (NanoKnife® system). The median tumor short-axis diameter was 1.9 cm (minimum 0.4 cm, maximum 4.5 cm). 35 patients had primary liver tumors and 36 patients had liver metastases. The Kaplan-Meier method was employed to calculate the survival rates, and the different groups were compared using multivariate log-rank and Wilcoxon tests. The overall median survival time was 26.3 months; the median survival of patients with primary land secondary liver cancer did not significantly differ (26.8 vs. 19.9 months; p = 0.41). Patients with a tumor diameter >3 cm (p < 0.001) or more than 2 lesions (p < 0.005) died significantly earlier than patients with smaller or fewer tumors. Patients with hepatocellular carcinoma and Child-Pugh class B or C cirrhosis died significantly earlier than patients with Child-Pugh class A (p < 0.05). Patients with very early stage HCC survived significantly longer than patients with early stage HCC with a median survival of 22.3 vs. 13.7 months (p < 0.05).

Hepatocyte-specific Smad7 deletion accelerates DEN-induced HCC via activation of STAT3 signaling in mice.

TGF-ß signaling in liver cells has variant roles in the dynamics of liver diseases, including hepatocellular carcinoma (HCC). We previously found a correlation of high levels of the important endogenous negative TGF-ß signaling regulator SMAD7 with better clinical outcome in HCC patients. However, the underlying tumor-suppressive molecular mechanisms are still unclear. Here, we show that conditional (TTR-Cre) hepatocyte-specific SMAD7 knockout (KO) mice develop more tumors than wild-type and corresponding SMAD7 transgenic mice 9 months after diethylnitrosamine (DEN) challenge, verifying SMAD7 as a tumor suppressor in HCC. In line with our findings in patients, Smad7 levels in both tumor tissue as well as surrounding tissue show a significant inverse correlation with tumor numbers. SMAD7 KO mice presented with increased pSMAD2/3 levels and decreased apoptosis in the tumor tissue. Higher tumor incidence was accompanied by reduced P21 and upregulated c-MYC expression in the tumors. Activation of signal transducer and activator of transcription factor 3 signaling was found in Smad7-deficient mouse tumors and in patients with low tumoral SMAD7 expression as compared with surrounding tissue. Together, our results provide new mechanistic insights into the tumor-suppressive functions of SMAD7 in hepatocarcinogenesis.

[Abdominal ultrasonography in patients with diabetes mellitus. Part 1: Liver]. / Abdominelle Sonografie bei Patienten mit Diabetes mellitus. Teil 1: Leber.

In patients with diabetes mellitus, abdominal ultrasonography is the appropriate diagnostic technique to detect and to follow-up secondary and accompanying diseases of the liver, the kidneys, the pancreas, the gastrointestinal tract and of abdominal vessels. Moreover, pancreatic and hepatic diseases may be realized which are of etiological importance for diabetes mellitus. Based on a systematic survey of the published literature, this review in 3 parts will describe the value of abdominal ultrasonography in patients with diabetes mellitus. Part 1 deals with the diagnostic relevance and particular findings of ultrasonographic methods in hepatic manifestations and complications of diabetes mellitus.

Multivariable analysis of clinical influence factors on liver enhancement of Gd-EOB-DTPA-enhanced 3T MRI.

PURPOSE: The purpose of this study was to identify clinical factors influencing Gd-EOB-DTPA liver uptake in patients with healthy liver parenchyma. MATERIALS AND METHODS: A total of 124 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3 T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. The relative enhancement (RE) between plain and contrast-enhanced signal intensity was calculated. Simple and multiple linear regression analyses were performed to evaluate clinical factors influencing the relative enhancement. Patients were subdivided into three groups according to their relative liver enhancement (HRE, RE ≥ 100 %; MRE, 100 % > RE > 50 %; NRE, RE ≤ 50 %) and were analyzed according to the relevant risk factors. RESULTS: Simple regression analyses revealed patient age, transaminases (AST, ALT, GGT), liver, spleen and delta-liver volume (the difference between the volumetrically measured liver volume and the estimated liver volume based on body weight) as significant factors influencing relative enhancement. In the multiple analysis the transaminase AST, spleen and delta liver volume remained significant factors influencing relative enhancement. Delta liver volume showed a significant difference between all analyzed groups. CONCLUSION: Liver enhancement in the hepatobiliary phase depends on a variety of factors. Body weight-adapted administration of Gd-EOB-DTPA may lead to inadequate liver enhancement after 20 minutes especially when the actual liver volume differs from the expected volume. KEY POINTS: • Differences between actual and expected liver volume can cause inadequate liver enhancement after 20 min. • A liver volume-adapted dose of Gd-EOB-DTPA may help to improve liver enhancement.

[Hepatocellular carcinoma: molecular pathogenesis and novel targets for therapy]. / Hepatozelluläres Karzinom - molekulare Grundlagen und Zielmoleküle für die Therapie.

Hepatocellular carcinomas rank among the most common cancers worldwide. They are characterized by phenotypic heterogeneity and poor response to treatment modalities. Although considerable progress in diagnosis and management of hepatocellular carcinomas has been made over the last decade, the exact biology of liver cancer remains poorly understood, overall hindering the development of new therapeutic strategies. The development of whole-genome analyses on different molecular levels greatly advanced our understanding of hepatocarcinogenesis by simultaneously investigating thousands of molecular targets. Although implementation of the results from these analyses in routine clinical practice is still limited, these next generation technologies offer unprecedented insights into the molecular mechanisms of the development of liver cancer. Overall, great promise rests on whole genomic approaches to improve the diagnostic testing and to identify novel targets for individualized treatment modalities in liver cancer.

[Personalised hepatology - current concepts, developments and expectations in the post-genome era]. / Personalisierte Hepatologie - Gegenwärtige Konzepte, Entwicklungen und Erwartungen im Postgenomzeitalter.

Promoted by the decoding of the human genome as part of the human genome project, individualised therapy approaches have become a realistic perspective for therapies that are more effective, less prone to side effects and economically reasonable. This also applies to chronic liver disease. With the aim not only to expand the current knowledge base through basic research on the underlying disease processes and treatment options but also to identify and characterise biomarkers, the creation of genetic fingerprints for individualised diagnosis, prognosis and treatment of patients takes its place in the centre of translational hepatology. For certain liver diseases personalised therapy approaches are already existent. Examples are the determination of viral genotypes, viral kinetics and genotyping of the IL28B polymorphism to optimise the treatment of chronic hepatitis C. The challenges of the next few years relate to the broadening of the knowledge base, the establishment of reliable and standardised technologies, and the development of intelligent bioinformatics strategies for data analysis and data integration. The following review not only summarises the current state of progress and possibilities of personalised medicine in hepatological diseases, but also explains the technical background of the limitations that currently hinder a consistent clinical implementation.

Acute renal failure and liver dysfunction after subcutaneous injection of 3-sn-phosphatidylcholine (Lipostabil®)-case report.

INTRODUCTION: Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often caused by drugs especially antibiotics or non-steroidal anti-inflammatory drugs. Drug-induced liver dysfunction and renal failure after subcutaneous injection of phosphatidylcholine was not reported so far. 3-sn-Phosphatidylcholine has been described as a cell lysis reaction-inducing drug. Its in vitro data indicated a relevant toxicity potential. In particular human cell types such as fibroblast-like preadipocytes, vascular and skeletal muscle cells, or renal epithelial cells react more sensitive than other human cell types. CASE REPORT: We present a 28-year-old woman who received 3.5 g (70 mL) of 3-sn-phosphatidylcholine (Lipostabil®) at once subcutaneously (s. c.) in both gluteal regions. The drug was originally introduced to prevent fat embolism. Nevertheless, its off-label use in aesthetic therapy for treatment of localized fat deposits through subcutaneous administration is becoming increasingly common. Three hours after injection the patient suffered from severe nausea and emesis. Within 24 hours a dramatic increase of liver enzymes and a beginning liver dysfunction were observed. Subsequently, renal function deteriorated two days later making a temporary haemodialysis necessary. Hepatic improvement was observed after three days of treatment. Renal function was fully recovered after two weeks. CONCLUSION: To the best of our knowledge, this is the first reported patient presenting with acute liver dysfunction and renal failure after subcutaneous injection of 3-sn-phosphatidyl-choline (Lipostabil®) indicating the risk of an off-label use of this drug.

BlotBase: a northern blot database.

With the availability of high-throughput gene expression analysis, multiple public expression databases emerged, mostly based on microarray expression data. Although these databases are of significant biomedical value, they do hold significant drawbacks, especially concerning the reliability of single gene expression profiles obtained by microarray data. Simultaneously, reliable data on an individual gene's expression are often published as single northern blots in individual publications. These data were not yet available for high-throughput screening. To reduce the gap between high-throughput expression data and individual highly reliable expression data, we designed a novel database "BlotBase", a freely and easily accessible database, currently containing approximately 700 published northern blots of human or mouse origin (http://www.medicalgenomics.org/Databases/BlotBase). As the database is open for public data submission, we expect this database to quickly become a large expression profiling resource, eventually providing higher reliability in high-throughput gene expression analysis. Realizing BlotBase, Pubmed was searched manually and by computer based text mining methods to obtain publications containing northern blot results. Subsequently, northern blots were extracted and expression values of different tissues calculated utilizing Image J. All data were made available through a user friendly web front end. The data may be searched by either full text search or list of available northern blots of a specific tissue. Northern blot expression profiles were displayed by three expression states as well as a bar chart, allowing for automated evaluation. Furthermore, we integrated additional features, e.g. instant access to the corresponding RNA sequence or primer design tools making further expression analysis more convenient. Finally, through a semiautomatic submission system this database was opened to the bioinformatics community.

[The solid pseudopapillary tumor (SPT)--a rare neoplasm of the pancreas]. / Der solid pseudopapilläre Pankreastumor (SPT)--eine seltene Raumforderung der Bauchspeicheldrüse.

BACKGROUND: In general, the rare SPT is a tumour of low malignancy predominantly affecting young women. The outcome after radical resection is favourable. In exceptional cases the tumour presents as solid pseudopapillary carcinoma (SPC) with typical malignant features and even metastases. Unresectable liver metastases can be treated with RFA, TACE or chemotherapy. METHODS: We retrospectively reviewed the surgical approach, immunohistochemistry and clinical outcome in five female patients (1998--2007). RESULTS: The mean age was 16 years (range: 13-47 years). For radical tumour removal a pancreato-duodenectomy (n = 3), a distal pancreatectomy (n = 1) and an enucleation (n = 1) were performed. We encountered a mean tumour diameter of 8 cm (range: 6-15 cm), an angioinvasion (3/5) and a lymphatic infiltration (1/5). After 30 to 101 months follow-up four patients were free of recurrence. Chemotherapy has resulted in a survival of over 98 months in a case of SPC with liver metastases. CONCLUSION: SPT is a tumour of low malignancy. Radical resection is recommended for long-term recurrence-free survival. Chemotherapy may prolong survival in SPC with unresectable metastases.

[Liver function test to predict hepatic failure after liver resection--expensive and without clinical relevance?]. / Funktionsdiagnostik vor Leberresektion--teuer und ohne klinische Relevanz?

Hepatic failure after liver resection is a complication that is dreaded by surgeons and has a poor outcome. Inadequate functional reserve of the remaining liver parenchyma leads to the inability to regenerate and finally to the progression of liver failure. In order to predict the functional reserve of the remaining liver parenchyma, many different liver function tests have been established. Basis for most liver function assessments are metabolic liver functions such as cytochrome p450 dependent pathways or the extraction and biliary excretion of dye. Nuclear imaging of the liver parenchyma does not only allow visualisation of the liver but also accumulation of information on hepatocyte volume that might be a better predictor for the hepatic reserve and the regenerative capacity compared to the liver volume alone. However, to date no single method has been proven to be able to predict safe limits of resectability. If an underlying liver disease is excluded the resectability is mostly limited by volumetric analysis and technical feasibility of liver resection. In patients with underlying liver disease cirrhosis should be excluded. In case of liver cirrhosis, only Child-Pugh-Turcott A patients with normal bilirubin levels and without portal hypertension should be considered for liver resection.

Dissemination of hepatocellular carcinoma is mediated via chemokine receptor CXCR4.

In different tumour entities, expression of the chemokine receptor 4 (CXCR4) has been linked to tumour dissemination and poor prognosis. Therefore, we evaluated, if the expression of CXCR4 exerts similar effects in human hepatocellular carcinoma (HCC). Expression analysis and functional assays were performed in vitro to elucidate the impact of CXCL12 on human hepatoma cells lines. In addition, expression of CXCR4 was evaluated in 39 patients with HCC semiquantitatively and correlated with both, tumour and patients characteristics. Human HCC and hepatoma cell lines displayed variable intensities of CXCR4 expression. Loss of p53 function did not impact on CXCR4 expression. Exposure to CXCL12 mediated a perinuclear translocation of CXCR4 in Huh7/Hep3B cells and increased the invasive potential of Huh7 cells. In HCC patients, CXCR4 expression significantly correlated with progressed local tumours (T-status; P=0.006), lymphatic metastasis (N-status; P=0.005) and distant dissemination (M-status; P=0.009), as well as with a decreased 3-year-survival rate (P=0.01). In summary, strong expression of CXCR4 is significantly associated with progressed hepatocellular cancer.

Histone deacetylase inhibition by valproic acid down-regulates c-FLIP/CASH and sensitizes hepatoma cells towards CD95- and TRAIL receptor-mediated apoptosis and chemotherapy.

Hepatocellular carcinoma (HCC) is highly resistant to chemotherapy, leading to a poor prognosis of advanced disease. Inhibitors of histone deacetylase (HDACi) induce re-differentiation in tumor cells and thereby re-establish sensitivity towards apoptotic stimuli. HDACi are entering the clinical stage of tumor treatment, and several substances are currently being tested in clinical trials to prove their efficacy in the treatment of leukemias and solid tumors. In this study, we investigated the impact of the HDACi valproic acid (VA) on TRAIL- and CD95-mediated apoptosis in hepatoma cells, as well as its sensitizing effect on a chemotherapeutic agent. Treatment of HepG2 cells with VA increased sensitivity to CD95-mediated apoptosis (4% apoptosis vs. 42%), and treatment with epirubicin (74% vs. 90% viability). Caspase-3 activity was significantly enhanced in cells treated with VA plus anti-CD95 antibodies compared to cells treated with antibodies alone. In parallel, VA strongly augmented the effect of TNF-related apoptosis-inducing ligand (TRAIL or Apo2 ligand) on HepG2 cells (10% vs. 58% apoptosis). VA induced down-regulation of cellular FLICE-inhibitory protein (c-FLIP/CASH, also known as Casper/iFLICE/FLAME-1/CLARP/MRIT/usurpin), providing a possible molecular mechanism underlying the increased sensitivity towards cell death-mediated apoptosis. HDAC inhibitors are a promising class for the treatment of leukemias. In addition, among other class members, VA deserves further evaluation as a treatment option for patients with advanced HCC.

Nitritoid reactions: case reports, review, and recommendations for management.

OBJECTIVE: We assessed nitritoid reactions, which are a well recognized side effect of chrysotherapy that occur in roughly 5% of patients taking gold sodium thiomalate (GST). METHODS: Between January 1996 and January 2000, 8 patients followed in our gold monitoring program at Mary Pack Arthritis Centre experienced nitritoid reactions observed by the clinic nurse. We undertook a chart review to determine the risk factors, timing, course, and outcome of nitritoid reactions. RESULTS: Patients' ages ranged from 36 to 69 years, and 7 of 8 were women. Duration of gold therapy prior to nitritoid reactions ranged from 13 months to 13 years. Seven had previously had mucocutaneous reactions, and one experienced gold dermatitis following a nitritoid reaction. Two of 8 patients were taking angiotensin converting enzyme inhibitor agents. Seven reactions were classified as mild, and one was a severe reaction with hypotension, syncope, and angina. CONCLUSIONS: Management includes a high index of suspicion in patients experiencing nausea, flushing, or dizziness following gold injections, switching from GST to gold sodium aurothioglucose, injection in the recumbent position, and observation for 20 minutes after injections in individual patients.

Chemotherapy with gemcitabine in patients with advanced gallbladder carcinoma.

BACKGROUND: Advanced or metastatic gallbladder carcinoma is regarded not much sensitive to chemotherapy. Standard chemotherapy regimens have not been established up to now. PATIENTS: We report on 5 patients with advanced gallbladder carcinoma who received chemotherapy with gemcitabine. RESULTS: Of these 5 patients, 3 demonstrated a partial remission and stable disease was achieved in another patient. Only one patient had no benefit from treatment with gemcitabine. CONCLUSION: We conclude that gemcitabine may be an effective drug in the palliative treatment of gallbladder cancer, and thus its efficiency warrants evaluation in further studies.

Long-Term Clinical Remission in a Patient with Metastatic Gastric Cancer after Palliative Chemotherapy.

BACKGROUND: More than 50% of patients with gastric cancer initially present with locally advanced or metastatic disease. In general, gastric cancer in an advanced or metastatic stage is regarded as incurable. Despite treatment with palliative chemotherapy, the median survival time is still limited and does not exceed 12 months. CASE REPORT: We report on a patient with advanced and metastatic gastric cancer who received palliative surgery and subsequent palliative chemotherapy. RESULTS: Complete remission occurred after R2 resection and palliative chemotherapy. The patient is now disease-free for 10 years after the end of chemotherapy. CONCLUSIONS: Palliative chemotherapy for metastatic gastric cancer may seldom lead to long-term clinical remission. Copyright 2000 S. Karger GmbH, Freiburg

Safety of self-injection of gold and methotrexate.

OBJECTIVE: We review our experience with safety, efficacy, and practicality of self-administration of gold and methotrexate (MTX) in 40 patients. METHODS: Between 1992 and 1995, 40 patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) followed in the drug monitoring clinics of the Mary Pack Arthritis Centre were taught to self-administer parenteral gold or MTX. Self-injection education was recommended to patients who were stable and improved taking parenteral gold or MTX, and who had not experienced serious side effects. Charts were reviewed to extract and analyze prospectively collected data regarding safety, efficacy, and compliance. RESULTS: Sixty-five percent of patients performed self-injection and 35% received injections at home from a partner. Side effects in the self-injection patients are similar to those observed in clinic patients receiving drug by nurse administration. One MTX treated patient required treatment for interstitial pneumonitis, which developed after 22 weeks on self-injection. Side effects of self-injection included superficial irritation at the injection site in 2 patients and dosing error in 2 patients with no adverse effects. Seventy percent of gold and MTX treated patients continued self-injection after a mean of 34 months. Patients surveyed for satisfaction identified time saving and convenience as major benefits. CONCLUSION: With basic instruction and close supervision, self-injection of antirheumatic drugs is safe in selected patients. Self-injection reduces utilization of health care services, and is convenient and time and cost-saving to the patient.