Lessons learned during implementation of MR-guided High-Intensity Focused Ultrasound treatment of uterine fibroids.

BACKGROUND: Although promising results have been reported for Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, this treatment is not yet widely implemented in clinical practice. During the implementation of a new technology, lessons are learned and an institutional learning-curve often has to be completed. The primary aim of our prospective cohort study was to characterize our learning-curve based on our clinical outcomes. Secondary aims included identifying our lessons learned during implementation of MR-HIFU on a technical, patient selection, patient counseling, medical specialists and organizational level. RESULTS: Our first seventy patients showed significant symptom reduction and improvement of quality of life at 3, 6 and 12 months after MR-HIFU treatment compared to baseline. After the first 25 cases, a clear plateau phase was reached in terms of failed treatments. The median non-perfused volume percentage of these first 25 treatments was 44.6% (range: 0-99.7), compared to a median of 74.7% (range: 0-120.6) for the subsequent treatments. CONCLUSIONS: Our findings describe the learning-curve during the implementation of MR-HIFU and include straightforward suggestions to shorten learning-curves for future users. Moreover, the lessons we learned on technique, patient selection, patient counseling, medical specialists and organization, together with the provided supplements, may be of benefit to other institutions aiming to implement MR-HIFU treatment of uterine fibroids. Trial registration ISRCTN14634593. Registered January 12, 2021-Retrospectively registered, https://www.isrctn.com/ISRCTN14634593 .

Role of TGF-beta in the tumor stroma.

Recent findings have demonstrated that the tumor stroma actively contributes to tumorigenesis. The communication of malignant cells and tumor stromal components is orchestrated in part by a network of growth factors. One of these growth factors is transforming growth factor-beta (TGF-beta), a secreted multifunctional protein that acts in a highly cellular contextual manner. TGF-beta can either stimulate or inhibit the tumor-promoting effects of the different components of the tumor stroma. In this review, we discuss our current understanding on how TGF-beta influences different stromal compartments.

Long-term sedation with propofol 60 mg ml(-1) vs. propofol 10 mg(-1) ml in critically ill, mechanically ventilated patients.

BACKGROUND: Hypertriglyceridaemia is the main cause of therapeutic failure during propofol use in long-term sedated mechanically ventilated patients. Propofol 60 mg ml(-1) has been developed to reduce fat and volume load for the critically ill patient. The purpose of the study was to compare the effectiveness of sedation, achievability of effective concentrations and the effects on serum lipid concentrations of propofol 60 mg ml(-1) vs. propofol 10 mg ml(-1) for long-term sedation in critically ill patients. METHODS: In this randomized, open, prospective study, 20 critically ill, mechanically ventilated patients who required sedation for a minimum of 48 h received propofol 60 mg ml(-1) or propofol 10 mg ml(-1) in doses as required during 2-5 days. RESULTS: No differences between propofol 60 mg ml(-1) and propofol 10 mg ml(-1) were observed in the effectiveness of sedation using the Ramsay Sedation score and the Subjective Sedation score, nor in relation to the propofol concentrations. Between the two groups, there were no significant differences in the daily propofol dose, number of daily infusion rate adjustments or need for additional sedatives. Mean serum triglyceride concentrations were higher in the propofol 10 mg ml(-1) group compared with the propofol 60 mg ml(-1) group [5.26 (3.19) vs. 3.22 (2.05) mmol l(-1), P > 0.05][mean (SD)]. Patients in the propofol 10 mg ml(-1) group received more fat from the propofol infusion than from the propofol 60 mg ml(-1) group [53.2 (29.6) vs. 10.0 (4.7) % compared with fat from nutrition, respectively]. A significant relationship was observed between the daily total fat dose and the serum triglyceride concentration (r2 = 0.32, P < 0.001), whereas there was no significant correlation between the daily propofol dose and the serum triglyceride concentration. CONCLUSION: Propofol 60 mg ml(-1) is a useful alternative to propofol 10 mg ml(-1) for the long-term sedation of critically ill patients. Sedation with propofol 60 mg ml(-1) reduces fat and volume load by 83%, which reduces the risk of hypertriglyceridaemia.

No benefit of intraoperative whole blood sequestration and autotransfusion during coronary artery bypass grafting: results of a randomized clinical trial.

OBJECTIVES: In a randomized clinical trial of patients undergoing elective coronary artery bypass grafting, we evaluated the effect of intraoperative whole blood sequestration and autotransfusion on postoperative blood loss and the use of allogeneic blood products. METHODS: Male patients were included if it was possible to obtain at least 500 mL of autologous blood. For patients in group H (heparin autotransfusion, 50 patients; mean age 59 +/- 8 years), an average of 670 +/- 160 mL heparinized blood was drawn before bypass and reinfused after the period of the extracorporeal circulation. For patients in group C (citrate autotransfusion, 48 patients; mean age 60 +/- 10 years), 450 +/- 109 mL of citrate blood, drawn before administration of heparin, was used. Controls (N-group) consisted of 46 patients aged 62 +/- 8 years. Strict transfusion criteria were used, and blood loss and use of allogeneic blood products during the hospital stays of all patients were recorded. Mean differences with their 95% confidence intervals adjusted for potential confounders were obtained by multiple linear regression. RESULTS: The mean difference (95% confidence interval) of blood loss of group H minus N was -93 mL (-307 to 139) and for C minus N was -66 mL (-186 to 179). The mean number of allogeneic blood transfusions for group H was 0.85 +/- 1.74. Group C and group N used 0.94 +/- 1.56 and 0.84 +/- 1.24. CONCLUSION: In coronary artery bypass grafting there is no effect of heparin or citrate intraoperative whole blood sequestration with regard to blood loss or use of allogeneic blood.

Two alternative models for spontaneous flagellar motor switching in Halobacterium salinarium.

Halobacteria are light-sensitive microorganisms which swim by means of rotating flagella. Under constant environmental conditions, they reverse their swimming direction about every 10-30 s. This is due to spontaneous switchings of the flagellar motors from clockwise to counterclockwise rotation or vice versa. However, it is unknown how the direction of rotation is regulated. In this paper, two stochastic models which could explain the characteristics of sequences of spontaneous switching events are discussed. The process is described in terms of a "motor switch" cyclically running through a sequence of states and triggering a reversal whenever a cycle is complete. Referring to previously stated hypotheses, modelling is based on the assumption that transitions between the states of the switch either occur with constant probability per unit time or are actively regulated by an endogenous biochemical oscillator. It is shown that both models yield a good description of the experimental data, though they are mutually exclusive.