[Safety of patient care on an interprofessional training ward in visceral surgery]. / Sicherheit der Patientenversorgung auf einer viszeralchirurgischen interprofessionellen Ausbildungsstation.

BACKGROUND: Interprofessional training wards (ITW) are increasingly being integrated into teaching and training concepts in visceral surgery clinics. OBJECTIVE: How safe is patient care on an ITW in visceral surgery? MATERIAL AND METHODS: Data collection took place from November 2021 to December 2022. In this nonrandomized prospective evaluation study the frequency and severity of adverse events (AE) in 3 groups of 100 patients each in a tertiary referral center hospital for visceral surgery were investigated. The groups consisted of patients on the ITW and on the conventional ward before and after implementation of the ITW. The Global Trigger Tool (GTT) was used to search for AE. Simultaneously, a survey of the treatment was conducted according to the Picker method to measure patient reported outcome. RESULTS: Baseline characteristics and clinical outcome parameters of the patients in the three groups were comparable. The GTT analysis found 74 nonpreventable and 5 preventable AE in 63 (21%) of the patients and 12 AE occurred before the hospital stay. During the hospital stay 50 AE occurred in the operating theater and 17 on the conventional ward. None of the five preventable AE (in 1.7% of the patients) was caused by the treatment on the ITW. Patients rated the safety on the ITW better than in 90% of the hospitals included in the Picker benchmark cohort and as good as on the normal ward. CONCLUSION: The GTT-based data as well as from the patients' point of view show that patient care on a carefully implemented ITW in visceral surgery is safe.

The carcinostatic and proapoptotic potential of 4-hydroxynonenal in HeLa cells is associated with its conjugation to cellular proteins.

BACKGROUND: Previous studies have shown that the lipid peroxidation product 4-hydroxynonenal (HNE) acts as a cell growth modulator if used at low, physiological concentrations being strongly cytotoxic at higher concentrations for a number of cells. These effects of HNE also appeared to be mutually dependent on the effects of serum growth factors. The aim of this investigation was to study the concentration-dependent response of human cervical carcinoma (HeLa) cells in vitro with respect to the intracellular uptake of exogenous HNE, the cellular energy metabolism, DNA synthesis, overall gene expression and susceptibility to apoptosis. MATERIALS AND METHODS: MTT assay was applied as an index of energy metabolism and the replicative activity was quantitated by the 3H-thymidine incorporation assay. The occurence and intracellular distribution was studied with monoclonal antibodies directed against HNE-protein conjugates. Binding of HNE to serum proteins was determined with the same antibodies by Western blotting. Differential gene expression was studied by differential display RT-PCR while a novel photometric assay, denoted Titer-TACS, was used for in situ detection and quantitation of apoptosis in monolayer cell cultures. RESULTS: A physiological concentration of HNE (1 microM) had hardly any effect on the parameters of the replicative activity and the energy metabolism. No morphological changes were observed and the number of HNE-positive cells was not significantly different when compared to the untreated control cells, while most of the aldehyde appeared to be bound to serum proteins (albumin fraction). A ten-fold higher concentration (10 microM) was found to be cytostatic. Spindle-shaped cells with a picnotic nucleus were observed occasionally, as well as membrane blebs, which were HNE-positive. The number of HNE-positive cells was significantly increased compared both to the control cells and cells treated with 1 microM HNE, but in the presence of serum the effects of 10 microM HNE were negated due to its binding to the serum proteins. Finally, 100 microM HNE was cytotoxic for the HeLa cells. Most of the cells were picnotic, together with a few spindle-shaped or oval cells. The staining for HNE was diffuse and strong (90% of the cells were HNE-positive) while even binding of the aldehyde to serum proteins did not prevent its cytotoxic effects. This concentration of HNE caused acute stress response of the cells resulting in the decreased expression of several as yet unidentified genes. The altered pattern of gene expression was followed by programmed cell death, i.e. an increased number of apoptotic cells after treatment with low (1 and 10 microM) concentrations of HNE. A rebound effect was observed, i.e. a decrease of apoptotic cells after 24 hours followed by an overshooting increase after 48 hours. CONCLUSIONS: For HeLa carcinoma cells there appears to be a concentration range of HNE where it does not cause necrosis but preferentially apoptosis. At this concentration range HNE is cytochemically detectable within the cells as a protein conjugate. It is proposed that a possible differential sensitivity of cancer cells and their normal counterparts to the cytostatic activity of HNE should be explored.

4-Hydroxynonenal modifies the effects of serum growth factors on the expression of the c-fos proto-oncogene and the proliferation of HeLa carcinoma cells.

In this study, the effect of 4-hydroxynonenal (HNE), a peroxidation product of omega-6-poly-unsaturated fatty acids, on the expression of the c-fos proto-oncogene and growth factor-induced proliferation of HeLa carcinoma cells in vitro was investigated. The Fos protein forms the heterodimer AP-1 with the Jun protein and regulates the cell cycle by inducing cyclin D1. Agents that are able to induce c-fos include serum, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF), all of which were used in this study. The proliferation rate was determined by cell counting (viable and dead cells according to trypan blue exclusion) and the BrdU assay. The c-fos mRNA level was monitored by the reverse transcriptase/polymerase chain reaction. In the absence of HNE, serum-deprived cells responded to serum stimulation with a more than 10-fold increase of the c-fos mRNA level as well as with an increased rate of DNA synthesis and cell multiplication. Both EGF and PDGF (applied in combination with insulin) were able to substitute for FCS and induced rapid growth of the tumor cells preincubated in serum-deprived medium. In the absence of growth factors a negative correlation between the HNE concentration (range: 1-250 microM) and the c-fos mRNA level was observed. We suppose that HNE interferes in this case with the basal activity of the c-fos promoter. EGF, when applied after the HNE treatment, induced rapid growth of the tumor cells preincubated in serum-free medium, if HNE was used in a physiological concentration (1 microM). No difference was observed compared to the HNE-free control. c-fos mRNA level was nearly unchanged. In contrast, a cytotoxic concentration of the aldehyde (100 microM) caused a complete inhibition of proliferation, although a twofold increase of the c-fos mRNA level immediately after the aldehyde treatment was observed. A similar effect of HNE in cytotoxic concentration on c-fos expression was observed when cells were grown in presence of PDGF instead of EGF. Hence, in both cases HNE possibly interferes with the signal transduction pathway, which is initiated by external growth factors. The increased c-fos expression might be part of an abortive attempt to overcome the stressful condition raised by a cytotoxic concentration of HNE.

Inhibition of HeLa cell proliferation by 4-hydroxynonenal is associated with enhanced expression of the c-fos oncogene.

Previous studies have shown that the highly reactive aldehyde 4-hydroxynonenal (HNE), a mediator of oxidative stress, can either stimulate or inhibit cell proliferation, depending on the concentration of the aldehyde and the presence of serum. HNE can also induce differentiation of tumour cells in vitro and inhibit the tumour development in vivo. The aim of the study presented was to find out more details about the basic mechanisms by which HNE influences cell growth behaviour. Therefore we analysed the effect of HNE on the transcription of the c-fos gene in HeLa cells, to clarify the pathway by which the aldehyde modulates gene transcription and growth behaviour of the cells. At a supraphysiological concentration (50 microM) the aldehyde caused an enhanced c-fos transcription (as measured by the reverse transcriptase/polymerase chain reaction assay), while it inhibited cell proliferation markedly. Therefore, we assume that among the "early" effects of HNE on cellular growth regulation might be an altered expression of the "early response" genes (c-fos), while a "late" effect might be an altered autocrine/paracrine growth regulation of the cells. This finding on the possible basic mechanisms of the biological effects of HNE together with the already described high toxicity of the aldehyde for cancer cells give support for the further evaluation of the possible use of HNE in cancer biotherapy.