Disseminated Intravascular Coagulation (DIC) is a life-threatening complication of sepsis. In surgical ICUs, DIC is frequently caused by abdominal sepsis, and the disarranged coagulation and ...complications often lead to death. The severity of sepsis is associated with a higher DIC score according to the parameters proposed by the International Society of Hemostasis and Thrombosis (ISTH) in 2001: platelet count, bleeding time (Quick), D-dimer, and fibrinogen. One problem in studying DIC is finding an adequate animal model that reflects the clinical situation of polymicrobial overwhelming infection.
We investigated whether a well-established polymicrobial sepsis model of colon ascendens stent peritonitis (CASP) is suited to investigate the complexity of DIC. For this purpose, CASP-operated mice were examined 20 h after the operation with regard to coagulation parameters using cell counts, bleeding times, rotational thromboelastometry (ROTEM), ELISAs for D-dimer and fibrinogen, and platelet accumulation in affected organs via immunohistochemistry to see if the mice develop a coagulation disorder that meets the definition of DIC proposed by the ISTH 2001 consensus conference.
Herein, we showed that the CASP model is an all-encompassing animal model to analyze the complexity of systemic DIC in murine abdominal sepsis. There is highly reproducible thrombocytopenia, a significant prolongation of the bleeding time, and a loss of fibrinogen in plasma. We also observed microvascular thrombosis due to platelet accumulation in the microcirculation of the liver.
The CASP model seems superior to other artificial models, e.g., injecting substances, for inducing DIC. CASP is one of the best true-to-life models for analyzing the complexity of disseminated intravascular coagulation in polymicrobial sepsis.
BackgroundDisseminated Intravascular Coagulation (DIC) is a life-threatening complication of sepsis. In surgical ICUs, DIC is frequently caused by abdominal sepsis, and the disarranged coagulation ...and complications often lead to death. The severity of sepsis is associated with a higher DIC score according to the parameters proposed by the International Society of Hemostasis and Thrombosis (ISTH) in 2001: platelet count, bleeding time (Quick), D-dimer, and fibrinogen. One problem in studying DIC is finding an adequate animal model that reflects the clinical situation of polymicrobial overwhelming infection.Aims and methodsWe investigated whether a well-established polymicrobial sepsis model of colon ascendens stent peritonitis (CASP) is suited to investigate the complexity of DIC. For this purpose, CASP-operated mice were examined 20 h after the operation with regard to coagulation parameters using cell counts, bleeding times, rotational thromboelastometry (ROTEM), ELISAs for D-dimer and fibrinogen, and platelet accumulation in affected organs via immunohistochemistry to see if the mice develop a coagulation disorder that meets the definition of DIC proposed by the ISTH 2001 consensus conference.ResultsHerein, we showed that the CASP model is an all-encompassing animal model to analyze the complexity of systemic DIC in murine abdominal sepsis. There is highly reproducible thrombocytopenia, a significant prolongation of the bleeding time, and a loss of fibrinogen in plasma. We also observed microvascular thrombosis due to platelet accumulation in the microcirculation of the liver.ConclusionThe CASP model seems superior to other artificial models, e.g., injecting substances, for inducing DIC. CASP is one of the best true-to-life models for analyzing the complexity of disseminated intravascular coagulation in polymicrobial sepsis.
Poor prognosis of pancreatic cancer has remained almost unchanged in recent years. Cold physical plasma was suggested as an innovative anticancer strategy, but its selective killing activity of ...malignant over non-malignant cells has only partially been explored. The present study aimed at exploring the effect of cold physical plasma on cellular viability.
Induction of cell death and apoptosis by cold physical plasma was investigated in murine PDA6606 pancreatic cancer cells and primary murine fibroblasts in vitro (2D and 3D cultures) and in ovo.
Plasma increased apoptosis in PDA6606 to a significantly higher extent compared to fibroblasts. Antioxidants abrogated these effects, suggesting a prime role of reactive oxygen species in plasma-induced apoptosis. Plasma increased apoptosis of 3D PDA6606 multicellular spheres grown in vitro and in ovo, to significantly higher rates compared to that of fibroblasts, with minimum in ovo inflammation or necrosis observed by hematoxylin and eosin staining (H&E).
These data support the future intra-operative application of cold physical plasma for the treatment of microscopic residual tumor tissue after surgical resection.
The prevention of nosocomial infections requires participation from the patients themselves. In the past, however, patients have been apprehensive to point out hygiene-relevant behaviour to the ...personnel.In the project AHOI, the possibilities of active patient involvement in infection prevention are identified, tested and realized. The goal is a prevention strategy based upon three dimensions: "adherence", "empowerment" and "acceptance". "AHOI" stands for the "
ctivation of patients, persons in need of care and care givers for a
ygiene-conscious participati
n in
nfection control". Results from the AHOI pilot study on the implementation of a multimodal intervention bundle are reported.
In 2017, a two-stage patient survey was conducted on two surgical wards for 14 weeks. In addition to the intervention bundle, acceptance, adherence and empowerment regarding individual hygiene behaviour and perception were evaluated. The bundle included an AHOI-welcome-box with an informational and entertaining brochure and supportive incentives. Furthermore, multiple visual materials like video presentations for patients' bedside TV, posters and visual reminders in the patients' bedrooms and sanitary facilities were installed.
179 respondents were surveyed at admission, 139 at discharge and 133 at both time points. Almost all respondents wanted to contribute to infection control. The AHOI project was well accepted by patients. Two-thirds wanted to be more involved. More than a third expected a negative response from staff after pointing out hygiene deficiencies. Four respondents observed a deficiency in hygiene with healthcare personnel and reported a very positive reaction once this was communicated to the personnel. More than four-fifths of the respondents felt well integrated and adequately informed post intervention. The feeling of active involvement correlated significantly with subjective participation and adherence to hygienic measures, especially self-reported hand disinfection.
The results demonstrated that the required inclusion of patients in infection control is possible with AHOI. Active involvement of patients and relatives is associated with improvements in adherence to infection prevention measures.
Highlights • In clinical practice routine, the use of ethanol-based hand rubs generates measurable amounts of ethanol and its metabolites in urine. • This indicates the absorption of ethanol and its ...subsequent degradation. • Compared to the daily oral intake of alcoholic beverages, fruit juices or using consumer products containing ethanol, the amount of ethanol absorption resulting from repeated applications of ethanol-based hand rubs is negligible. • Use of ethanol-based hand rubs in clinical practice is not comparable with the oral consumption of alcoholic beverages.
Background
The aim of this study was to evaluate the feasibility, morbidity, and cost-effectiveness of the closure of the appendicular stump with a single non-absorbable polymeric clip compared with ...the closure of the appendicular stump with a stapler.
Methods
From January 2009 to December 2009, 82 patients, 31 males and 51 females (mean age of 35.4 years; range of 17 to 79 years), were included in this prospective, non-randomized trial. In 56 patients, the appendicular stump was closed by staplers, and in 26 patients, a single Hem-o-lok MLX polymeric clip was applied. The data collected included age, sex, time of surgery, costs, time of hospitalization, day-time of surgery, complications, and preoperative white blood count (WBC) and c-reactive protein (CRP).
Results
There were no differences between the two groups regarding age, sex, WBC, CRP, and time of hospitalization. Time of surgery was longer in the clip group due to the introductory phase. Morbidity did not differ significantly and was highly acceptable in both groups. The costs of one set of Hem-o-lock clips were negligible compared to staplers (19.94 € versus 356.43 €).
Conclusions
The use of a single non-absorbable polymeric clip is easy to use even for surgical trainees; it is safe and cost-effective. We suggest the use of a single clip for the closure of the appendicular stump as the standard procedure in laparoscopic appendectomy whenever possible.
Pancreatic cancer is the fourth leading cause of tumour death in the western world. However, appropriate tumour models are scarce. Here we present a syngeneic murine pancreatic cancer model using 7 ...Tesla MRI and evaluate its clinical relevance and applicability.
6606PDA murine pancreatic cancer cells were orthotopically injected into the pancreatic head. Liver metastases were induced through splenic injection. Animals were analyzed by MRI three and five weeks following injection. Tumours were detected using T2-weighted high resolution sequences. Tumour volumes were determined by callipers and MRI. Liver metastases were analyzed using gadolinium-EOB-DTPA and T1-weighted 3D-Flash sequences. Tumour blood flow was measured using low molecular gadobutrol and high molecular gadolinium-DTPA.
MRI handling and applicability was similar to human systems, resolution as low as 0.1 mm. After 5 weeks tumour volumes differed significantly (p < 0.01) when comparing calliper measurments (n = 5, mean 1065 mm3+/-243 mm3) with MRI (mean 918 mm3+/-193 mm3) with MRI being more precise. Histology (n = 5) confirmed MRI tumour measurements (mean size MRI 38.5 mm2+/-22.8 mm2 versus 32.6 mm2+/-22.6 mm2 (histology), p < 0,0004) with differences due to fixation and processing of specimens. After splenic injection all mice developed liver metastases with a mean of 8 metastases and a mean volume of 173.8 mm3+/-56.7 mm3 after 5 weeks. Lymphnodes were also easily identified. Tumour accumulation of gadobutrol was significantly (p < 0.05) higher than gadolinium-DTPA. All imaging experiments could be done repeatedly to comply with the 3R-principle thus reducing the number of experimental animals.
This model permits monitoring of tumour growth and metastasis formation in longitudinal non-invasive high-resolution MR studies including using contrast agents comparable to human pancreatic cancer. This multidisciplinary environment enables radiologists, surgeons and physicians to further improve translational research and therapies of pancreatic cancer.
To investigate the role of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in postoperative polymicrobial abdominal sepsis.Sepsis is the leading cause of death among critically ...ill surgical patients. TRAIL is commonly known as an apoptosis-inducing agent in cancer cells. It also plays an important role in the regulation of inflammatory reactions. The role of TRAIL in polymicrobial sepsis is still unclear.
Experimental animal model.
University laboratory.
C57BL/6 mice.
Colon ascendens stent peritonitis (CASP) was induced in female mice. One hour, 24 hrs, and 48 hrs after induction of CASP, murine recombinant TRAIL was given intravenously.
This study demonstrates a protective effect of TRAIL in CASP, an experimental model of murine polymicrobial sepsis. Intravenous administration of recombinant TRAIL to mice after CASP induction led to highly significantly prolonged survival. The migration of effector cells into the peritoneal cavity was strongly enhanced. Consequently, TRAIL-treated mice eliminated bacteria significantly better from the peritoneal cavity, the source of infection. Systemic spread of gut bacteria was also reduced by several orders of magnitude. As a result of the reduced systemic spread of bacteria, the accumulation of neutrophils within the spleen and mesenteric lymph nodes was strongly decreased.
TRAIL-treated mice are highly protected from abdominal sepsis. Because diagnosis and therapy are frequently delayed in human sepsis, it is remarkable that TRAIL is effective when given via a therapeutic approach. Therefore, this study suggests a therapeutic potential for TRAIL in human sepsis. This should be addressed in future trials.
The particular importance of the vagus nerve for the pathophysiology of peritonitis becomes more and more apparent. In this work we provide evidence for the vagal modulation of inflammation in the ...murine model of colon ascendens stent peritonitis (CASP). Vagotomy significantly increases mortality in polymicrobial sepsis. This effect is not accounted for by the dilatation of gastric volume following vagotomy. As the stimulation of cholinergic receptors by nicotine has no therapeutic effect, the lack of nicotine is also not the reason for the reduced survival rate. In fact, increased septic mortality is a consequence of the absent modulating influence of the vagus nerve on the immune system: we detected significantly elevated serum corticosterone levels in vagotomised mice 24 h following CASP and a decreased ex vivo TNF-alpha secretion of Kupffer cells upon stimulation with LPS. In conclusion, the vagus nerve has a modulating influence in polymicrobial sepsis by attenuating the immune dysregulation.
Disseminated Intravascular Coagulation (DIC) is a life-threatening complication of sepsis. In surgical ICUs, DIC is frequently caused by abdominal sepsis, and the disarranged coagulation and ...complications often lead to death. The severity of sepsis is associated with a higher DIC score according to the parameters proposed by the International Society of Hemostasis and Thrombosis (ISTH) in 2001: platelet count, bleeding time (Quick), D-dimer, and fibrinogen. One problem in studying DIC is finding an adequate animal model that reflects the clinical situation of polymicrobial overwhelming infection. We investigated whether a well-established polymicrobial sepsis model of colon ascendens stent peritonitis (CASP) is suited to investigate the complexity of DIC. For this purpose, CASP-operated mice were examined 20 h after the operation with regard to coagulation parameters using cell counts, bleeding times, rotational thromboelastometry (ROTEM), ELISAs for D-dimer and fibrinogen, and platelet accumulation in affected organs via immunohistochemistry to see if the mice develop a coagulation disorder that meets the definition of DIC proposed by the ISTH 2001 consensus conference. Herein, we showed that the CASP model is an all-encompassing animal model to analyze the complexity of systemic DIC in murine abdominal sepsis. There is highly reproducible thrombocytopenia, a significant prolongation of the bleeding time, and a loss of fibrinogen in plasma. We also observed microvascular thrombosis due to platelet accumulation in the microcirculation of the liver. The CASP model seems superior to other artificial models, e.g., injecting substances, for inducing DIC. CASP is one of the best true-to-life models for analyzing the complexity of disseminated intravascular coagulation in polymicrobial sepsis.