[Terrorist attack training exercise-What can be learned? : Baden-Württemberg counterterrorism exercise (BWTEX)]. / Terrorismusabwehrübung ­ Was können wir daraus lernen? : Baden-Württembergische Terrorismusabwehr Exercise (BWTEX).

BACKGROUND: There is a risk of terror attacks in the Federal Republic of Germany, which might increase in the future. A timely comprehensive strategy for treatment and care of a large number of casualties helps minimize chaos and improve the outcome of patients. Adequate training is vital for successful implementation of an emergency plan. Therefore, the effectiveness of training should be assessed and evaluated; however, data collection capabilities for training events are extremely limited, so that publications on the topic are almost impossible to find. OBJECTIVE: This study aimed to collect data from a simulated terrorist attack in order to draw conclusions from a clinical point of view concerning the improvement of preclinical and clinical management, taking interface problems into consideration. MATERIAL AND METHODS: On 19 October 2019 the Ministry of the Interior, Digitalization and Migration of Baden-Württemberg conducted a large-scale simulation of a terrorist attack in the city center of Constance, called the Baden-Württemberg counterterrorism exercise (BWTEX). The simulation included an explosion of a car bomb as well as the use of firearms by terrorists. The large scale of the simulation with the high number of participants in combination with close cooperation between military and civil forces was unprecedented. The police force, the armed forces, civil protection forces, air rescue teams and staff from Constance, Friedrichshafen and Sigmaringen regional hospitals in southwest Germany worked together to treat simulated injuries to victims of the attack. The following parameters were recorded when the injured patients arrived at the hospital: prehospital triage time, prehospital triage score, initial treatment and quality of documentation on site as well as triage time, triage score, injury severity scale (ISS) score based on the specified injury pattern, treatment, and quality of documentation on hospital arrival. RESULTS: Out of a total of 84 "injured patients" 55 were admitted to hospital and 80% were triaged at the scene. Injured patients of triage category 1 (TK1 red: life-threatening injury, immediate treatment) arrived at the hospital 198 ± 50 min after the attack, injured patients of triage category 2 (TK2 yellow: severely injured, urgent treatment) after 131 ± 44 min and injured patients of triage category 3 (TK3 green: slightly injured, non-urgent treatment) arrived after 157 ± 46 min. There was no significant difference in terms of arrival time at the hospital between the triage scores (r = 0.2) or between the ISS scores (r = 0.43). The authors assume that approximately 44% of TK1 patients would have died due to avoidable time delays. Prehospital medical documentation was insufficient in 78% and insufficient in 65% in the hospitals. CONCLUSION: A mass casualty incident resulting from a terrorist attack differs greatly from a conventional mass casualty incident. The scene of the attack has to be evacuated as quickly as possible, which means that a large number of patients arrive untreated at the nearest hospitals. The setting up of treatment facilities in city centers and areas close to the city seems to be counterproductive because the time delay may result in higher mortality rates of victims. The particularities of mass casualties caused by a terrorist attack have to be incorporated into terrorist attack training.

Bacterial sepsis : Diagnostics and calculated antibiotic therapy.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).

[S2k guidelines of the PEG on calculated parenteral initial treatment of bacterial diseases in adults : Focussed summary and supplementary information on antibiotic treatment of critically ill patients]. / S2k-Leitlinie der PEG zur kalkulierten parenteralen Initialtherapie bakterieller Erkrankungen bei Erwachsenen : Fokussierte Zusammenfassung und ergänzende Informationen zur Antibiotikatherapie kritisch kranker Patienten.

In January 2018 the recent revision of the S2k guidelines on calculated parenteral initial treatment of bacterial diseases in adults-update 2018 (Editor: Paul Ehrlich Society for Chemotherapy, PEG) was realized. It is a helpful tool for the complex infectious disease setting in an intensive care unit. The present summary of the guidelines focuses on the topics of anti-infective agents, including new substances, pharmacokinetics and pharmacodynamics as well as on microbiology, resistance development and recommendations for calculated drug therapy in septic patients. As in past revisions the recent resistance situation and results of new clinical studies are considered and anti-infective agents are summarized in a table.

[Adequate anti-infective treatment : Importance of individual dosing and application]. / Adäquate Antiinfektivatherapie : Bedeutung der individuellen Dosierung und Applikation.

Sepsis-induced changes in pharmacokinetic parameters are a well-known problem in intensive care medicine. Dosing of antibiotics in this setting is therefore challenging. Alterations to the substance-specific kinetics of anti-infective substances have an effect on the distribution and excretion processes in the body. Increased clearance and an increased distribution volume (Vd) and particularly compromized organ function with reduced antibiotic elimination are often encountered in patients with sepsis. Renal replacement treatment, which is frequently used in intensive care medicine, represents a substantial intervention in this system. Current international guidelines recommend individualized dosing strategies and adaptation of doses according to measured serum levels and pharmacokinetic/pharmacodynamic (PK/PD) parameters as concepts to optimize anti-infective therapy in the critically ill. Likewise, the recommendation to adjust the administration form of beta-lactam antibiotics to prolonged or continuous infusion can be found increasingly more often in the literature. This article reviews the background of the individual dosing in intensive care patients and their applicability to the clinical routine.

[Therapeutic drug monitoring and individual dosing of antibiotics during sepsis : Modern or just "trendy"?] / Therapeutisches Drug Monitoring und individualisierte Dosierung von Antibiotika bei der Sepsis : Modern oder nur "modisch"?

Pharmacokinetic variability of anti-infective drugs due to pathophysiological changes by severe sepsis and septic shock is a well-known problem for critically ill patients resulting in suboptimal serum and most likely tissue concentrations of these agents.To cover a wide range of potential pathogens, high concentrations of broad spectrum anti-infectives have to reach the site of infection. Microbiological susceptibility testing (susceptible, intermediate, resistant) don't take the pharmacokinetic variability into account and are based on data generated by non-critically ill patients. But inter-patient variability in distribution and elimination of anti-infective drugs in ICU patients is extremely high and also highly unpredictable. Drug clearance of mainly renally eliminated drugs and thus the required dose can differ up to 10-fold due to the variability in renal function in patients with severe infections. To assure a timely and adequate anti-infective regime, individual dosing and therapeutic drug monitoring (TDM) seem to be appropriate tools in the setting of pathophysiological changes in pharmacokinetics (PK) and pharmakodynamics (PD) due to severe sepsis. In the case of known minimal inhibitory concentration, PK/PD indices (time or peak concentration dependent activity) and measured serum level can provide an optimal target concentration for the individual drug and patient.Modern anti-infective management for ICU patients includes more than the choice of drug and prompt application. Individual dosing, optimized prolonged infusion time and TDM give way to new and promising opportunities in infection control.

[Bacterial sepsis : Diagnostics and calculated antibiotic therapy]. / Bakterielle Sepsis : Diagnostik und kalkulierte Antibiotikatherapie.

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).

γ-Secretase inhibition promotes fibrotic effects of albumin in proximal tubular epithelial cells.

BACKGROUND AND PURPOSE: Albuminuria is an important biomarker of renal dysfunction and is a major mediator of renal damage and fibrosis during kidney disease. The mechanisms underlying albumin-induced renal fibrosis remain unclear. There has been significant interest in γ-secretase activity in tubular epithelial cells in recent times; however, its potential role in albumin-induced fibrosis has not been investigated. EXPERIMENTAL APPROACH: The primary aim of this study was to examine the role of γ-secretase in albumin-induced fibrotic effects in proximal tubular cells. The effects of increasing albumin concentrations on fibrosis indicators and mediators in the human HK-2 cell line were examined in the presence and absence of a γ-secretase inhibitor, compound E. KEY RESULTS: Treatment with albumin resulted in a number of pro-fibrotic effects, including up-regulation of fibronectin, TGF-ß1 and the EGF-R. Interestingly, similar effects were observed in response to treatment with the γ-secretase inhibitor, compound E. Co-treatment of cells with albumin and an EGF-R inhibitor, AG-1478, resulted in significant inhibition of the observed pro-fibrotic effects, suggesting a major role for the EGF-R in albumin-induced fibrotic events. Albumin-induced effects on the EGF-R appeared to be mediated through inhibition of γ-secretase activity and were dependent on ERK-MAPK signalling. CONCLUSIONS AND IMPLICATIONS: These results provide novel insights into the mechanisms of albumin-induced fibrotic effects in tubular epithelial cells, suggesting important roles for the γ-secretase and the EGF-R. These results suggest that the proposed use of γ-secretase inhibitors as anti-fibrotic agents requires further investigation.

[Reasonable and unreasonable hygiene measures in anesthesia in the intensive care unit]. / Sinnvolle und nicht sinnvolle Hygienemassnahmen in der Anästhesie und auf Intensivstationen.

The objective of this review is to describe which hygiene measures are appropriate and necessary in anaesthesia and the ICU and which are not, whereby unnecessary hygiene measures are those which are not substantiated by scientific data. The most effective single infection control measure is still hand disinfection between patient contacts. Unnecessary measures include routine sampling of environmental surfaces, disinfecting the floor in the ICU, protective gowns for visitors, so called in-line filters in the infusion system etc. Ventilator tubes only need to be exchanged once a week, even when no HMEs are used.

Investigation of suspected nosocomial clusters of Staphylococcus haemolyticus infections.

OBJECTIVE: To determine whether typing methods can discriminate among Staphylococcus haemolyticus isolates. DESIGN: Molecular epidemiological evaluation of S. haemolyticus isolates obtained from patients hospitalized on a hematology service and in a surgical intensive-care unit (SICU). SETTING: A large Midwestern teaching hospital. INTERVENTIONS: None. RESULTS: Over 22 days, S. haemolyticus was isolated from five patients on the hematology service. Isolates from four patients had the same unusual antibiogram and biotype. Ribotyping, restriction endonuclease digestion of plasmid DNA (REAP), and whole chromosomal DNA analysis by pulsed-field gel electrophoresis (PFGE) confirmed that these isolates were identical and different from the fifth patient's isolate and from 6 control isolates. In a second cluster, 11 S. haemolyticus isolates obtained from eight patients in the SICU had similar antibiograms and biotypes. By REAP and ribotype analysis, isolates from four patients were identical. However, PFGE indicated that only two of these patients shared a common strain. CONCLUSIONS: Antibiograms or biotyping may discriminate among isolates of S. haemolyticus if the results of these tests are unusual. Many clinical isolates can be differentiated by REAP analysis, ribotyping, or PFGE. However, some isolates are identical by all of these methods, suggesting that they may have been transmitted nosocomially.