The Bernese Hypothermia Algorithm: a consensus paper on in-hospital decision-making and treatment of patients in hypothermic cardiac arrest at an alpine level 1 trauma centre

INTRODUCTION: Guidelines for the treatment of patients in severe hypothermia and mainly in hypothermic cardiac arrest recommend the rewarming using the extracorporeal circulation (ECC). However,guidelines for the further in-hospital diagnostic and therapeutic approach of these patients, who often suffer from additional injuries—especially in avalanche casualties, are lacking. Lack of such algorithms may relevantly delay treatment and put patients at further risk. Together with a multidisciplinary team, the Emergency Department at the University Hospital in Bern, a level I trauma centre, created an algorithm for the in-hospital treatment of patients with hypothermic cardiac arrest. This algorithm primarily focuses on the decision-making process for the administration of ECC. THE BERNESE HYPOTHERMIA ALGORITHM: The major difference between the traditional approach, where all hypothermic patients are primarily admitted to the emergency centre, and our new algorithm is that hypothermic cardiac arrest patients without obvious signs of severe trauma are taken to the operating theatre without delay. Subsequently, the interdisciplinary team decides whether to rewarm the patient using ECC based on a standard clinical trauma assessment, serum potassium levels, core body temperature, sonographic examinations of the abdomen, pleural space, and pericardium, as well as a pelvic X-ray, if needed. During ECC, sonography is repeated and haemodynamic function as well as haemoglobin levels are regularly monitored. Standard radiological investigations according to the local multiple trauma protocol are performed only after ECC. Transfer to the intensive care unit, where mild therapeutic hypothermia is maintained for another 12 h, should not be delayed by additional X-rays for minor injuries. DISCUSSION: The presented algorithm is intended to facilitate in-hospital decision-making and shorten the door-to-reperfusion time for patients with hypothermic cardiac arrest. It was the result of intensive collaboration between different specialties and highlights the importance of high-quality teamwork for rare cases of severe accidental hypothermia. Information derived from the new International Hypothermia Registry will help to answer open questions and further optimize the algorithm.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h.

Randomised trial of a clinical dosing algorithm to start anticoagulation with phenprocoumon

Prospective validation of two algorithms for the initiation of phenprocoumon treatment.

Differential roles of Rho-kinase and myosin light chain kinase in regulating shape, adhesion, and migration of HT1080 fibrosarcoma cells

We present evidence for differential roles of Rho-kinase and myosin light chain kinase (MLCK) in regulating shape, adhesion, migration, and chemotaxis of human fibrosarcoma HT1080 cells on laminin-coated surfaces. Pharmacological inhibition of Rho-kinase by Y-27632 or inhibition of MLCK by W-7 or ML-7 resulted in significant attenuation of constitutive myosin light chain phosphorylation. Rho-kinase inhibition resulted in sickle-shaped cells featuring long, thin F-actin-rich protrusions. These cells adhered more strongly to laminin and migrated faster. Inhibition of MLCK in contrast resulted in spherical cells and marked impairment of adhesion and migration. Inhibition of myosin II activation with blebbistatin resulted in a morphology similar to that induced by Y-27632 and enhanced migration and adhesion. Cells treated first with blebbistatin and then with ML-7 also rounded up, suggesting that effects of MLCK inhibition on HT1080 cell shape and motility are independent of inhibition of myosin activity.

[Acute lower gastrointestinal bleeding--an evidence-based algorithm for diagnosis and treatment]

Novel means to locate and treat lower gastrointestinal bleeding (lGB) allow to reduce the rate of required surgical interventions and help to limit the extend of resection. The risk stratification of patients with lGB is the primary step of our recommended treatment algorithm. Accordingly, risk stratifying instruments, which are only partly validated up to now, are gaining significance in lGB. Whereas, gastro-duodenoscopy and colonoscopy prior to angiography or scintigraphy are established diagnostic tools, capsule enteroscopy offers a novel approach to hemodynamic stable patients with lGB that are difficult to localize. With its every increasing sensitivity, Angio-Computer Tomography is likely to replace scintigraphy and diagnostic angiography in the very near future. In addition, recent advances in superselective microembolisation have been shown to have the potential rendering surgical interventions in a majority of patients with acute lGB unnecessary. The extend of required surgical resection is largely dependent on the success to localize the bleeding source of prior diagnostics. Only if the source is identified, a limited segmental resection should be performed. Should surgery be required, we suggest to maintain the effort to localize the bleeding, either by prior laparoscopy and/or by intraoperative entero-colonoscopy. Eventually, if the source of bleeding remains unclear total colectomy with ileorectal anastomosis represents the procedure of choice in patients with acute lGB.

Different migration of vascular smooth muscle cells from human coronary artery bypass vessels. Role of Rho/ROCK pathway

BACKGROUND: We examined whether vascular smooth muscle (VSMC) or endothelial cell (EC) migration from internal mammary artery (MA) differed from VSMC or EC migration from saphenous vein (SV). METHODS AND RESULTS: Migration to PDGF-BB (1-10 ng/ml) was lower in VSMC from MA than SV; however, attachment, movement without chemokine, and chemokinesis were identical. Unlike VSMC, migration of EC was similar in response to several mediators. Expression of PDGF receptor-beta was lower in VSMC from MA than SV, while alpha-receptor expression was higher. PDGF-BB-induced RhoA activity was lower in MA than SV, while basal activity was identical. Rosuvastatin and hydroxyfasudil impaired PDGF-BB-induced migration of VSMC from MA and SV. Mevalonate and geranylgeranylpyrophosphate rescued inhibition by rosuvastatin. PDGF-BB induced less stress fiber formation in VSMC from MA than SV. A dominant negative RhoA mutant inhibited stress fiber formation to PDGF-BB, while a constitutively active mutant resulted in maximal stress fiber formation in MA and SV. Rosuvastatin and hydroxyfasudil impaired PDGF-BB-induced stress fiber formation in MA and SV. CONCLUSIONS: VSMC migration to PDGF-BB is lower in MA than SV, which is at least in part related to lower activity of the Rho/ROCK pathway.

Collapsed cone convolution and analytical anisotropic algorithm dose calculations compared to VMC++ Monte Carlo simulations in clinical cases

The purpose of this work was to study and quantify the differences in dose distributions computed with some of the newest dose calculation algorithms available in commercial planning systems. The study was done for clinical cases originally calculated with pencil beam convolution (PBC) where large density inhomogeneities were present. Three other dose algorithms were used: a pencil beam like algorithm, the anisotropic analytic algorithm (AAA), a convolution superposition algorithm, collapsed cone convolution (CCC), and a Monte Carlo program, voxel Monte Carlo (VMC++). The dose calculation algorithms were compared under static field irradiations at 6 MV and 15 MV using multileaf collimators and hard wedges where necessary. Five clinical cases were studied: three lung and two breast cases. We found that, in terms of accuracy, the CCC algorithm performed better overall than AAA compared to VMC++, but AAA remains an attractive option for routine use in the clinic due to its short computation times. Dose differences between the different algorithms and VMC++ for the median value of the planning target volume (PTV) were typically 0.4% (range: 0.0 to 1.4%) in the lung and -1.3% (range: -2.1 to -0.6%) in the breast for the few cases we analysed. As expected, PTV coverage and dose homogeneity turned out to be more critical in the lung than in the breast cases with respect to the accuracy of the dose calculation. This was observed in the dose volume histograms obtained from the Monte Carlo simulations.