[Do pain therapy patients benefit from their fellow patients? : A retrospective observational study on the influence of the stage of pain management and therapy experience of fellow patients on the individual therapy success in an inpatient interdisciplinary multimodal pain therapy (IMPT)]. / Profitieren Schmerztherapiepatienten von ihren Mitpatienten? : Eine retrospektive Beobachtungsstudie zum Einfluss des Stadiums der Schmerzbewältigung und der Therapieerfahrung der Mitpatienten auf den individuellen Therapieerfolg in einer stationären interdisziplinären multimodalen Schmerztherapie (IMST).

BACKGROUND: Interdisciplinary multimodal pain therapy (IMPT) is mostly run in a group setting to encourage the exchange of experiences between patients and thus facilitate the change of pain-related attitudes and behavior. As is known from psychotherapy research, the fellow patients in a therapy group have a relevant influence on the success of the therapy for the individual patient. OBJECTIVE: We examined the extent to which therapy success in an IMST group is influenced by individual co-patient characteristics, such as cognitive behavioral pain management, the difference to their own pain management and the proportion of co-patients who repeat therapy. METHOD: In a retrospectively planned investigation of the psychometric tests of all patients in an inpatient IMST between January 2013 and February 2020, the influence of fellow patient characteristics on clinically relevant changes with respect to various parameters of the severity of chronic pain disorders was analyzed using binary logistic regression analyses. RESULTS: We examined 636 treatment cases of which 540 were first-time stays. On each day of treatment, 5 fellow patients were present, 15% of whom had repeated the therapy. We were able to show that the proportion of fellow patients who repeat the therapy (p < 0.001; odds ratio, OR = 1.032) and the cognitive behavioral pain management of the fellow patients (p < 0.001; OR = 2.885) significantly increase the probability of achieving success in at least one of the parameters examined. An influence of a specific parameter on the success of therapy could not be proven. CONCLUSION: Despite methodological limitations our results suggest that in patient groups of an IMST, patients with therapy experience and those with advanced cognitive behavioral methods for pain management should be combined with novices and patients who are still at the beginning of coping with the chronic pain disorder.

Over-expression of cFos by the Transcription Factors NFATc2 and Sp1 in Pancreatic Cancer Cells.

BACKGROUND/AIM: The transcription factors NFATc2 and Sp1 play a key role in the progression of pancreatic cancer because they interact inside the cells and exert their carcinogenic effect through transcriptional modification. Drugs can also induce a variety of oncogenic signalling cascades. The risk of tumour progression and metastasis seems to be significantly increased in the perioperative period. Our research group has previously demonstrated the function of the interaction between NFATc2 and Sp1 in pancreatic cancer and has identified the proto-oncogene cFos as a target gene. We also found that the anaesthetic drug propofol has anti-tumour properties. The aim of the present study was to investigate the effect of propofol on the expression of the transcription factors NFATc2, Sp1 and cFos in the pancreatic cancer cell lines PaTu 8988t and PANC-1 and to analyse the relevance of this effect for the cells. MATERIALS AND METHODS: Stimulation with propofol and its effects on the expression of NFATc2, Sp1 and cFos were assessed by immunoblot. Cell cycle distribution was analysed by flow cytometry, and cell proliferation was measured with the ELISA BrdU assay. Propofol and siRNA against cFos were used for stimulation. RESULTS: Propofol regulated the expression of NFATc2, Sp1 and cFos. Stimulation with 250 µM or 500 µM propofol decreased NFATc2, Sp1 and cFos signalling in the Western blot analysis. At the same time, propofol significantly inhibited proliferation and activated cell cycle. The same proliferation behaviour was observed after transient cFos inhibition. These effects were potentiated by simultaneous stimulation with propofol and transient inhibition of cFos, further inhibiting cell proliferation. Interestingly, the cell cycle activation observed after stimulation with propofol alone was reversed in both cell lines. CONCLUSION: Anaesthetists only see oncological patients in a short time window. However, the perioperative period is increasingly recognised as a very vulnerable time with a major impact on tumour progression. Further studies are needed to identify the underlying mechanisms and to verify their clinical relevance, especially in anaesthesia.

Effect of NFATc2- and Sp1-mediated TNFalpha Regulation on the Proliferation and Migration Behavior of Pancreatic Cancer Cells.

BACKGROUND/AIM: One in two people will develop a tumor during their lifetime. Adenocarcinoma of the pancreas is one of the most aggressive types of cancer in humans with very poor long-term survival. A central role in the carcinogenesis of pancreatic cancer has been attributed to NFAT transcription factors. Previous studies have identified the transcription factor Sp1 as a binding partner of NFATc2 in pancreatic cancer. Using expression profile analysis, our group was able to identify the tumor necrosis factor TNFalpha as a target gene of the interaction between NFATc2 and Sp1. The present study investigated the effect of TNFalpha over-expression via the transcription factors NFATc2 and Sp1 on the pancreatic cancer cell lines PaTu 8988t and PANC-1. MATERIALS AND METHODS: Transient transfection of NFATc2, Sp1, and TNFalpha siRNAs and their effects on the expression were investigated with immunoblot. Cell proliferation was measured with the ELISA BrdU assay. Cell migration was assayed with a Cell Migration Assay Kit using a Boyden chamber. RESULTS: Inhibition of the transfection factors NFATc2, Sp1, or TNFalpha by siRNA significantly inhibited proliferation, which was exacerbated when using the combination of NFATc2 and Sp1. TNFalpha was able to counterbalance this effect. In contrast to proliferation, migration of pancreatic cancer cells was increased by inhibiting these transfection factors. CONCLUSION: Tumor progression is strongly influenced by transcriptional changes in signaling cascades and oncogene mutations as well as by changes in tumor suppressor genes. Further studies are needed to understand the underlying mechanisms of these processes.

Effect of Propofol and Etomidate on the Proliferation, Cell-cycle Distribution, Apoptosis and Necrosis of Pancreatic Tumour Cells.

BACKGROUND/AIM: The influence of surgical interventions and anaesthesiological procedures on tumour progression was investigated as early as the 1920s. In current cancer management, the perioperative phase is increasingly being considered a vulnerable period with an increased risk of tumour cell dissemination due to medication, surgical manipulation, and immunosuppression. The extent to which narcotics administered in the perioperative setting influence the oncological outcomes of patients with pancreatic cancer is still unclear. MATERIALS AND METHODS: To investigate the effect of propofol and etomidate on the proliferation, cell-cycle distribution, apoptosis, and necrosis of pancreatic tumour cells in vitro, PaTu 8988t and Panc-1 pancreatic cancer cells were treated with 0-1,000 µM propofol or etomidate for 24 h each. Cell proliferation was measured with enzyme-linked immunosorbent-bromodeoxyuridine assay. The apoptosis rate was analysed with annexin V staining and the cell-cycle distribution with flow cytometry. RESULTS: Propofol at 1,000 µM induced apoptosis and inhibited cell proliferation. The cell cycle showed an increased S-phase and reduced cells in the G1-phase. At 100 µM, propofol significantly inhibited proliferation of the pancreatic cancer cell line PaTu 8988t and reduced cells in the G2-phase in the cell cycle. Etomidate had no effects on cell-cycle distribution, proliferation, apoptosis, and necrosis at the concentrations used. CONCLUSION: In this study, propofol was shown to have anticancer effects by induction of apoptosis and inhibition of cell proliferation, while etomidate did not affect pancreatic cancer cells. However, it is too early to make any recommendation for changes in clinical practice and further clinical studies are warranted to investigate the effect of anaesthetics on cancer progression.

The Effects of Analgesics on the Migration of Pancreatic Cancer Cells.

BACKGROUND/AIM: Adenocarcinoma of the pancreas is one of the most aggressive malignant diseases in humans. Characteristics of this tumour type are poor response to radiotherapy and chemotherapeutic agents as well as metastasis in the absence of an organ capsule. The best therapeutic option is surgical removal of the tumour followed by chemotherapy or radiotherapy. Yet, even after surgical R0-resection, the 5-year survival probability is only about 20% because of the high recurrence rate of this tumour and complications due to metastases. Furthermore, recent studies have shown that the perioperative period is a particularly vulnerable phase, during which tumour progression and metastasis may be facilitated. The effects of analgesics administered during the perioperative period are still unknown. The present work investigated the effects of analgesics on pancreatic cancer cell migration in vitro. MATERIALS AND METHODS: The migratory potential of pancreatic cancer cells was analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semi-permeable membrane under different stimuli. Cell concentration was measured by reading fluorescence (Ex/Em=530/590 nm) in a plate reader. RESULTS: Migration in PANC-1 pancreatic cancer cells was significantly decreased after 24 h stimulation with 100 µM of ropivacaine, 100 nM of sufentanil, 1,000 µM of ropivacaine and 1,000 nM of sufentanil. In the PaTu 8988t cell line, incubation with 10 µM of ropivacaine caused a slight but statistically significant increase in migration, whereas lidocaine, metamizole and paracetamol did not significantly affect migration. CONCLUSION: The risk of tumour progression and metastasis seems to be increased during major oncological surgical interventions. The recent advances in the molecular and biological understanding of pathogenesis of pancreatic cancer have not yet significantly improved patient outcome. Therefore, further studies are needed to identify the underlying mechanisms of this aggressive tumour and establish new therapeutic options for the future.

Effects of Ketamine, S-Ketamine and MK 801 on Integrin Beta-3-mediated Cell Migration in Pancreatic Carcinoma.

Introduction: Pancreatic ductal adenocarcinoma is one of the most aggressive malignancies in humans. The main reason for its unfavourable prognosis is the combination of rapid tumour growth, early-onset metastasis and currently still inadequate diagnostic and therapeutic options. Thus, only very few patients are eligible for radical resection of the primary tumour as the only curative treatment option available so far. In the perioperative period, tumour progression and metastasis are facilitated by the activation of key signalling pathways and the altered regulation of transcription factors. Various tumour entities have shown increased expression of the integrin-3 receptor subunit, which correlates with more rapid tumour progression and metastasis through advanced migration, invasion and proliferation. The influence of perioperative medication and postoperative pain management remains unclear. To investigate the effects of ketamine, s-ketamine and MK 801 on integrin beta-3-mediated cell migration in pancreatic cancer cells in vitro. Methods: The effects of ketamine, s-ketamine and MK 801 on integrin beta-3 expression were investigated with immunoblot. Cell migratory potentials were analysed using a Cell Migration Assay Kit with a Boyden chamber, in which cells migrate through a semipermeable membrane under different stimuli. Results: Stimulation with ketamine and MK 801 significantly promoted migration in pancreatic cancer cells, increasing the expression of integrin beta-3. Conclusion: Novel therapeutic approaches target the effective modulation of specific signalling and transcription pathways. The prerequisite for such 'target therapies' is comprehensive knowledge about the respective carcinogenesis. Further studies are required to identify the underlying disease mechanisms of pancreatic carcinoma.

Short-term impact of the COVID-19 pandemic on patients with a chronic pain disorder.

ABSTRACT: The current Covid-19 pandemic has already had a definite impact on the daily life of many people worldwide. It has been proposed that people with preexisting medical conditions will be harder hit by the pandemic and the subsequent measures to contain the spread of the disease. In this questionnaire-based, observational study, we aimed to assess the impact of the pandemic on patients with a chronic pain disorder, who are treated at a tertiary multidisciplinary pain center.Participants rated the impact of the pandemic on their chronic pain disorder using a self-designed questionnaire. Also, participants filled out the regular follow-up questionnaire to assess a chronic pain disorder measuring among other parameters pain intensity, symptoms of depression, anxiety, stress, and pain-related quality of life.Of 136 eligible patients who presented to our pain center between May 5th and July 17th, 112 agreed to participate in the study (82.4%). Eighty two participants (73.2%) reported a deterioration of the pain disorder using the self-designed questionnaire. The more robust parameters of the regular follow-up questionnaire showed no relevant changes compared to data collected before the pandemic. We were not able to detect any demographic and medical parameters that were clinically relevantly associated with a higher impact of the pandemic.We conclude that a chronic pain disorder is a relatively stable disease that does not change significantly due to external factors, like the Covid-19 pandemic, even if the subjective impact is perceived to be high.

Effects of Volatile Anesthetics on Proliferation and Viability of SW480 Colon Cancer Cells In Vitro.

BACKGROUND/AIM: For patients undergoing cancer surgery, the risk for cancer progression is enhanced during the perioperative period. To what extent the type of anesthetic can affect the metastatic process and finally the outcome of patients with cancer is under debate. For this reason, the aim of this study was to investigate the effects of the volatile anesthetics sevoflurane and desflurane on colon cancer cells in vitro. MATERIALS AND METHODS: SW480 colon carcinoma cells were exposed for 3 or 6 h to sevoflurane (1 or 2.5 vol%) or desflurane (6 or 12 vol%). Cell cycle distribution was analyzed by flow cytometry after a 24-72 h recovery and apoptosis was detected by annexin V staining after a 0-48 h recovery. Viability was tested by measuring ATP content after 0 and 24 h recovery. RESULTS: Treatment with sevoflurane or desflurane caused no or only slight changes in cell-cycle distribution and apoptosis rate. Desflurane at 12vol% significantly reduced cell viability by 17±25% and 11±22% after 3 and 6 h incubation and 24 h recovery, respectively, while 2.5 vol% sevoflurane slightly increased viability. CONCLUSION: At clinically relevant concentrations, sevoflurane and desflurane had only slight effects on SW480 colon cancer cells in vitro.

The Effects of Analgesics and Local Anesthetics on Gene Transcription Mediated by NFATc2 and Sp1 in Pancreatic Carcinoma.

BACKGROUND/AIM: Recent research has identified the transcription factors NFATc2 and Sp1 as key regulators in the carcinogenesis of pancreatic carcinoma. This study aimed to examine the effect of clinically achievable dosages of analgesics including ketamine, s-ketamine, metamizole, and paracetamol as well as that of sufentanil, ropicavaine, and lidocaine on pancreatic carcinoma cells and the expression of NFATc2 and Sp1. MATERIALS AND METHODS: The effects of analgesics on the expression of NFATc2 and Sp1 were investigated with immunoblotting. Cell proliferation was measured with the ELISA BrdU assay. RESULTS: In PaTu8988t pancreatic carcinoma cells, 48 h stimulation with ketamine and s-ketamine significantly inhibited proliferation and decreased expression of NFATc2 in the nucleus. The addition of metamizole and lidocaine reduced proliferation of PaTu8988t cells after 48 h. CONCLUSION: New treatment concepts target specific signaling and transcription pathways. The extent to which drugs influence these mechanisms in pancreatic carcinoma cells needs to be investigated in future studies.

The positive allosteric modulation of GABAA receptors mRNA in immature hippocampal rat neurons by midazolam affects receptor expression and induces apoptosis.

Background: Numerous experimental studies show that anesthetics are potentially toxic to the immature brain. Even though benzodiazepines are widely used in pediatric anesthesia and intensive care medicine, only a few studies examine the effects of these drugs on immature neurons. Methods: Hippocampal neuronal cell cultures of embryonic Wistar rats (15 days in culture) were incubated with midazolam 100 or 300 nM for either 30 min or 4 h. The time course of the mRNA expression of the glutamate receptors subunits NR1, NR2A and NR2B of the NMDA receptor, the GluA-1 and A-2 subunits of the AMPA receptor as well as the alpha 1 subunit of the GABAA receptor were examined by PCR. Apoptosis was detected using Western blot analysis for BAX, Bcl-2 and Caspase-3. Results: Midazolam at 100 and 300 nM applied for 30 min and 100 nM for 4 h affected glutamate receptor and GABAA receptor subunit expression. However, these effects were reversible within 72 h following washout. When 300 nM midazolam was applied for 4 h a significant increase in the NR 1 and NR 2A mRNA subunit expression could be detected. The increase in NR 2B receptor subunit expression as well as the GluA1 subunit expression was not reversible within 72 h following washout. This increase in mRNA glutamate receptor subunit expression was associated with a significant increase in neuronal apoptosis. Conclusion: In immature neurons midazolam altered GABA and glutamate mRNA receptor subunit expression. Prolonged increase in midazolam-induced glutamate receptor expression was associated with apoptosis.

Staurosporine induces apoptosis in pancreatic carcinoma cells PaTu 8988t and Panc-1 via the intrinsic signaling pathway.

BACKGROUND: Cancer, one of the leading causes of death worldwide, develops when the normal balance between mitosis and apoptosis is disrupted. The subsequently increased proliferation rate or decreased apoptosis rate of cells leads to uncontrolled cellular growth. Thus, the current aim of cancer research is to increase the apoptosis rate in tumor cells-while limiting the concurrent death of healthy cells-and to induce controlled apoptosis in abnormal cells. Staurosporine is a very potent inducer of apoptosis because it inhibits many different kinases. So far, many different kinase pathways of staurosporine-induced apoptosis have been discussed for various tumor entities. AIMS: To identify the effect of staurosporine in pancreatic and colorectal carcinoma cells and its apoptosis-inducing signaling pathway. METHODS: The apoptosis rate in pancreatic and colorectal carcinoma cells was analyzed by annexin V staining after staurosporine administration. Staurosporine stimulation and its effects on the expression of Bcl2, BAX, Bad, caspase-8, and caspase-9 were investigated with immunoblot. RESULTS: Staurosporine significantly increased apoptosis in pancreatic carcinoma cells. Western blot analysis showed activation of caspase-9 in PaTu 8988t and Panc-1 cells with 1 µM staurosporine. In addition, expression of Bcl2 and Bad was decreased in PaTu 8988t cells. In colorectal carcinoma cells SW 480, staurosporine stimulation did not induce apoptosis. CONCLUSION: Modern therapeutic strategies for tumor diseases target the efficient modulation of specific signaling and transcription pathways. In this respect, the therapeutic potential of protein kinase inhibitors has been repeatedly discussed. Our study showed that staurosporine induces apoptosis in pancreatic carcinoma cells via the intrinsic signaling pathway. Thus, staurosporine is a suitable positive control for in vitro apoptosis tests for the pancreatic cancer cell lines PaTu 8988t and Panc-1. Further clinical studies should analyze the impact of this finding on cancer treatment.

Acetaminophen and Metamizole Induce Apoptosis in HT 29 and SW 480 Colon Carcinoma Cell Lines In Vitro.

BACKGROUND/AIM: The perioperative phase is supposed to be a period with high vulnerability for cancer dissemination. Acetaminophen and metamizole are common analgesics administered during this phase. We investigated the effect of acetaminophen, metamizole and 4-methylaminoantipyrine (MAA) on proliferation and apoptosis of colon carcinoma cell lines (SW 480 and HT 29). MATERIALS AND METHODS: Proliferation was detected by cell proliferation ELISA BrdU, and apoptosis by Annexin V staining. Cytochrome c and caspase 3, 8 and 9 expression levels were detected by western blot. RESULTS: Acetaminophen, metamizole or MAA caused slight changes in proliferation. Acetaminophen, metamizole or the combination increased apoptosis in both cell lines. All agents decreased caspase 3 and 8 expression in SW480. Acetaminophen decreased caspase 9 expression in both cell lines. CONCLUSION: In clinically relevant doses, acetaminophen and/or metamizole induce apoptosis in both colon cancer cell lines. Both mitochondrial and death receptor pathways might be involved in acetaminophen-induced apoptosis.

Effects of metamizole, MAA, and paracetamol on proliferation, apoptosis, and necrosis in the pancreatic cancer cell lines PaTu 8988 t and Panc-1.

BACKGROUND: Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. Recent research has shown the importance of the perioperative phase in disease progression. Particularly during this vulnerable phase, substances such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. Therefore, the effects of metamizole and paracetamol on tumor progression should be investigated in more detail because the extent to which these substances influence the carcinogenesis of pancreatic carcinoma is still unclear. This study analyzed the influence of metamizole and its active metabolites MAA (4-N-methyl-aminoantipyrine) and paracetamol on the proliferation, apoptosis, and necrosis of the pancreatic cancer cell lines PaTu 8988t and Panc-1 in vitro. METHODS: Cell proliferation was measured by means of the ELISA BrdU assay and the rate of apoptosis by flow cytometry using the Annexin V assay. RESULTS: Metamizole and paracetamol significantly inhibited cell proliferation in pancreatic cancer cells. After the addition of metamizole to PaTu 8988t cells, the rate of apoptosis was reduced after 3 h of incubation but significantly increased after 9 h of incubation. CONCLUSION: The oncogenic potential of pancreatic adenocarcinoma is mainly characterized by its extreme growth rate. Non-opioid analgesics such as metamizole and paracetamol are given as general anesthetics and postoperative analgesics. The combination of metamizole or paracetamol with cytotoxic therapeutic approaches may achieve synergistic effects. Further studies are necessary to identify the underlying mechanisms so that new therapeutic options may be developed for the treatment of this aggressive tumor.

Effects of Lidocaine on HT-29 and SW480 Colon Cancer Cells In Vitro.

BACKGROUND: Evidence is growing that the risk of cancer dissemination may be enhanced during the perioperative period. Whether particular anesthetic techniques influence oncological outcome is still under discussion. For pain management, lidocaine can be administered perioperatively by intravenous, intraperitoneal or epidural infusion. Here we investigated the effect of lidocaine on colon carcinoma cell lines (HT-29 and SW480) in vitro. MATERIALS AND METHODS: ELISA BrdU (Roche) for cell proliferation and FITC Annexin V detection kit (BD Pharming) for apoptosis analysis were applied. Cell-cycle profiles were investigated by flow cytometry. RESULTS: Cell-cycle arrest was induced in both cell lines by 1000 µM lidocaine, while no inhibition of cell proliferation was detected. Apoptosis decreased in SW480 but not in HT-29 cells. CONCLUSION: Lidocaine induces cell-cycle arrest in both colon carcinoma cell lines in vitro. The effective drug concentration can be obtained by local infiltration.

Species- and concentration-dependent differences of acetyl- and butyrylcholinesterase sensitivity to physostigmine and neostigmine.

Previous and more recent studies show that cholinesterase inhibitors (ChE-Is) are an important possibility for therapeutic intervention in Alzheimer's Disease, sepsis and other inflammatory syndromes. ChE-Is maintain high levels of acetylcholine (ACh) determining beneficial effects on the disease process. Despite numerous efforts to identify the appropriate choice of agents and dose of ChE-Is, a common protocol regarding concentration- and species-dependent differences in inhibitory potency (IC 50) of clinical relevant ChE-Is is still not available. To evaluate the in vitro sensitivity of Acetyl- and Butyrylcholinesterase (AChE, BChE), we compared the concentration-response effects of physostigmine and neostigmine on cholinesterases in whole blood from rat and human. A spectrophotometrical test system based on in vitro Ellman's reagent has been used to determine the kinetic properties of clinical relevant ChE-Is. In vitro, the enzyme activity of human AChE and BChE was inhibited in a concentration-dependent manner until a residual activity of 4-6% for AChE and 20-30% for BChE (IC 50 human AChE: 0.117 ± 0.007 µM physostigmine, 0.062 ± 0.003 µM neostigmine; IC 50 human BChE: 0.373 ± 0.089 µM neostigmine; 0.059 ± 0.012 µM physostigmine). The inhibition curve of rat BChE in contrast showed no concentration-dependency for physostigmine and neostigmine (87% residual activity even at high inhibitor concentrations). Rat AChE was inhibited in a concentration-dependent manner until a residual activity of 53%. The results suggest that cholinesterases from human and rat show marked species- and inhibitor-dependent differences in sensitivity to physostigmine and neostigmine. Knowledge of such differences may be critical in assessing the possible therapeutic effects of ChE-Is in both species and may guide researchers in the optimal design of future experiments regarding the application of ChE-Is.

The expenditure of computer-related worktime using clinical decision support systems in chronic pain therapy.

BACKGROUND: Estimate the expenditure of computer-related worktime resulting from the use of clinical decision support systems (CDSS) to prevent adverse drug reactions (ADR) among patients undergoing chronic pain therapy and compare the employed check systems with respect to performance and practicability. METHODS: Data were collected retrospectively from 113 medical records of patients under chronic pain therapy during 2012/2013. Patient-specific medications were checked for potential drug-drug interactions (DDI) using two publicly available CDSS, Apotheken Umschau (AU) and Medscape (MS), and a commercially available CDSS AiDKlinik® (AID). The time needed to analyze patient pharmacotherapy for DDIs was taken with a stopwatch. Measurements included the time needed for running the analysis and printing the results. CDSS were compared with respect to the expenditure of time and usability. Only patient pharmacotherapies with at least two prescribed drugs and fitting the criteria of the corresponding CDSS were analyzed. Additionally, a qualitative evaluation of the used check systems was performed, employing a questionnaire asking five pain physicians to compare and rate the performance and practicability of the three CDSSs. RESULTS: The AU tool took a total of 3:55:45 h with an average of 0:02:32 h for 93 analyzed patient regimens and led to the discovery of 261 DDIs. Using the Medscape interaction checker required a total of 1:28:35 h for 38 patients with an average of 0:01:58 h and a yield of 178 interactions. The CDSS AID required a total of 3:12:27 h for 97 patients with an average time of analysis of 0:01:59 h and the discovery of 170 DDIs. According to the pain physicians the CDSS AID was chosen as the preferred tool. CONCLUSIONS: Applying a CDSS to examine a patients drug regimen for potential DDIs causes an average extra expenditure of work time of 2:09 min, which extends patient treatment time by 25 % on average. Nevertheless, the authors believe that the extra expenditure of time employing a CDSS is outweighed by their benefits, including reduced ADR risks and safer clinical drug management.

Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and necrosis in pancreatic cancer cells.

BACKGROUND: Adenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. The oncogenic potential of this type of cancer is mainly characterized by its extreme growth rate triggered by the activation of signaling cascades. Modern oncological treatment strategies aim at efficiently modulating specific signaling and transcriptional pathways. Recently, anti-tumoral potential has been proven for several substances that are not primarily used in cancer treatment. In some tumor entities, for example, administration of glutamate antagonists inhibits cell proliferation, cell cycle arrest, and finally cell death. To attain endogenic proof of NMDA receptor type expression in the pancreatic cancer cell lines PaTu8988t and Panc-1 and to investigate the impact of ketamine, s-ketamine, and the NMDA receptor antagonist MK 801 on proliferation, apoptosis, and necrosis in pancreatic carcinoma. METHODS: Cell proliferation was measured by means of the ELISA BrdU assay, and the apoptosis rate was analyzed by annexin V staining. Immunoblotting were also used. RESULTS: The NMDA receptor type R2a was expressed in both pancreatic carcinoma cell lines. Furthermore, ketamine, s-ketamine, and MK 801 significantly inhibited proliferation and apoptosis. CONCLUSIONS: In this study, we showed the expression of the NMDA receptor type R2a in pancreatic cancer cells. The NMDA antagonists ketamine, s-ketamine, and MK 801 inhibited cell proliferation and cell death. Further clinical studies are warranted to identify the impact of these agents on the treatment of cancer patients.

Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons.

Ketamine and its stereoisomer S(+)-ketamine are widely used for sedation in pediatric anesthesia and intensive care medicine. Numerous experimental studies indicate that ketamine is potentially toxic to the developing brain. Here, we examined the long-term effects of NMDA receptor blockade on NMDA receptor subunit expression, alterations in neuronal Ca(2+)-oscillations and apoptosis. Hippocampal neurons, 15 days in culture, were exposed to either S(+)-ketamine or the NMDA receptor blocker MK801 for 24h. Cytosolic Ca(2+)-concentration was determined by fluorescence microscopy and the expression of the NMDA subunits NR1, NR2A and 2B was assessed by qRT-PCR, whereas Western blots and activated Caspase-3 served to measure the extent of apoptosis. Long-term incubation with MK801 or higher doses of S(+)-ketamine resulted in a dose-dependent decreased ability of MK801 to reduce amplitude and frequency of the Ca(2+)-oscillations 15min following washout of the drug. This was accompanied by an increase in NR1 mRNA but not the NR2A and B subunit expression at the same time point. 24h following washout of the specific drug, a significant elevation of the pro-apoptotic marker BAX, as well as activated Caspase-3 positive neurons, could be detected in cultures exposed to 100µM MK801 and 25µM S(+)-ketamine. Here, we show that long-term blockade of the NMDA receptor in developing rat hippocampal neurons significantly increased NR1 subunit expression, and that this was associated with an alteration in neuronal activity. Apoptosis was only induced 24h after withdrawal of long-term blockade for high doses of S(+)-ketamine.

A comparison of fiberoptical guided tracheal intubation via laryngeal mask and laryngeal tube.

BACKGROUND: Fiberoptical assisted intubation via a placed laryngeal mask airway (LMA) has been described as save and easy procedure to manage a difficult airway. The laryngeal tube (LT) is a promising alternative to the LMA as supraglottic airway device. Fiberoptical assisted intubation via LT is possible, however considered more difficult. The aim of this study was to compare the fiberoptical assisted intubation via LT and LMA. MATERIALS AND METHODS: A total of 22 anesthesiologists with different levels of experience participated in the study performed on an adult airway model. Primarily the supraglottic device was placed and correct position was confirmed by successful ventilation. A 5 mm internal diameter tracheal tube was loaded onto a flexible 3.6 mm fiberscope and the so prepared device was inserted into the proximal lumen of the LMA or the LT. The glottis was passed under visual control and the tube advanced into the trachea. After removal of the fiberscope, ventilation was examined clinically by inspection. Success rates, procedure time and observed complications of LMA versus LT were compared (U-test; P < 0.05). RESULTS: Placement of the endotracheal tube was successful in all attempts using both the LMA and LT. There was no difference in the time needed for the placement procedure (33 [26-38] s LMA; 35 [32-38] s LT). Only minor technical complications were observed in both groups. CONCLUSION: A fiberoptical assisted intubation via LT can be considered as a relevant alternative in advanced airway management.

The possible impact of the German DRGs reimbursement system on end-of-life decision making in a surgical intensive care unit.

BACKGROUND: More than 70 % of critically ill patients die in intensive care units (ICUs) after treatment is reduced. End-of-life decision making in the ICU is a grey area that varies in practice, and there are potential economic consequences of over- and under-treatment. The aim of this study was to describe the end-of-life decisions of critically ill patients in a surgical ICU in Germany and to identify how financial incentives may influence decision making. METHODS: Data on the admission diagnosis, end-of-life decision making and cause of death were obtained for 69 critically ill patients who died in the ICU (Hospital of Bayreuth, Germany) in 2009. A cost-revenue analysis was conducted on the 46 patients who did not die within 3 days of ICU admission. Because we lacked real data on costs, our analysis was based on the average cost for each diagnosis-related group (DRG) from the Institute for the Hospital Remuneration System (InEK). Hospital revenues based on the DRG were considered. Subsequently, we compared the estimated financial impact of earlier and later decisions to withdraw or withhold futile therapy. RESULTS: In this study, we found that end-of-life decision making was poorly documented. Only 11 % of patients had a valid power of attorney and advanced directives, and therapy with presumed consent was performed in 43 % of all cases. From long-stay patients, therapy was withdrawn for 37 % of patients and withheld from 26 % of patients, and 37 % of the patients died receiving maximal therapy. Almost 72 % of DRG-related reimbursements were dependent on ventilation hours. The average total cost estimate (according to InEK) for the 46 long-stay patients was 1,201,000 . The revenues without additional remuneration were 1,358,000 , and the total estimated profit was approximately 157,000 . Only 10 cases were assumed to be non-profitable. In cases where the decision to withdraw or withhold therapy could have occurred 3 days earlier, the estimated profit shrank to 72,000 (46 % of estimated ICU profit). In situations where the decision to withdraw or withhold therapy from patients could have occurred 3 days later, the hypothetical profit rose to 217,000 (138 % of estimated ICU profit). CONCLUSION: There are still few patients with clear self-determination, and almost half of therapies are performed only according to presumed consent. The strong nonlinear dependence of DRG revenues on ventilation hours could influence ethical decision making of medical professionals. The decision-making process and appropriate therapy in the ICU setting need to be defined more clearly and better documented, focusing on the benefits to the patient while respecting patient consent.