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OBJECTIVES Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage. METHODS Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg. RESULTS Pre-clinical: human thoracic duct (n = 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P = 0.36). Plethysmography revealed similar capillary filtration coefficients (P = 0.057), but almost a doubling of the isovolumetric pressures (P = 0.005) during octreotide infusion. CONCLUSIONS Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload., OBJECTIVES: Chylothorax is a complex condition and many different pharmacological agents have been tried as treatment. Octreotide is used off-label to treat chylothorax, but the efficacy of octreotide remains unclear. A decrease in lymph production is suggested as the mechanism. In this cross-over study, we explore the direct effect of octreotide on human lymphatic drainage. METHODS: Pre-clinical: the effect of octreotide on force generation was assessed during acute and prolonged drug incubation on human lymphatic vessels mounted in a myograph. Clinical: in a double-blinded, randomized, cross-over trial including 16 healthy adults, we administered either octreotide or saline as an intravenous infusion for 2.5 h. Near-infrared fluorescence imaging was used to examine spontaneous lymphatic contractions and lymph pressure in peripheral lymphatic vessels and plethysmography was performed to assess the capillary filtration rate, capillary filtration coefficient and isovolumetric pressures of the lower leg. RESULTS: Pre-clinical: human thoracic duct (n ¼ 12) contraction rate was concentration-dependently stimulated by octreotide with a maximum effect at 10 and 100 nmol/l in the myograph chamber. Clinical: spontaneous lymphatic contractions and lymph pressure evaluated by near-infrared fluorescence did not differ between octreotide or placebo (P ¼ 0.36). Plethysmography revealed similar capillary filtration coefficients (P ¼ 0.057), but almost a doubling of the isovolumetric pressures (P ¼ 0.005) during octreotide infusion. CONCLUSIONS: Octreotide stimulated lymphatic contractility in the pre-clinical setup but did not affect the spontaneous lymphatic contractions or lymph pressure in healthy individuals. Plethysmography revealed a doubling in the isovolumetric pressure. These results suggest that octreotide increases lymphatic drainage capacity in situations with high lymphatic afterload.

Introduction and Hypothesis: Phosphodiesterase enzymes are widely distributed in female urogenital tissues. Yet, the understanding of their physiological roles and the impact of phosphodiesterase inhibitors on lower urinary tract symptoms in women remains limited. Current hypotheses are conflicting: one suggests that vasodilation might expand the periurethral vascular plexus, leading to increased urethral pressure, whereas the other proposes a relaxation of urethral musculature, resulting in decreased pressure. To further clarify this, we investigated the effect of tadalafil on the opening urethral pressure and voiding function in healthy women. Methods: We conducted a randomized, double-blind, placebo-controlled crossover trial involving 24 healthy women. Participants were randomly assigned to receive a single dose of tadalafil (40 mg) or placebo during their initial visit and then switched to the alternative treatment during their second visit. Opening urethral pressure was measured with urethral pressure reflectometry during both resting and squeezing conditions of the pelvic floor. Subsequently, voiding parameters were recorded. Results: Compared with placebo, a single dose of tadalafil significantly reduced opening urethral pressure during both resting (-6.8 cmH20; 95% confidence interval [CI], -11.8 to -1.9; p = 0.009) and squeezing conditions (-8.8 cmH20; 95% CI, -14.6 to -3.1; p = 0.005). Voiding parameters did not show significant differences (average flow rate: -0.8 ml/s [95% CI, -2.0 to 0.4; p = 0.2]; maximum flow rate: -1.7 ml/s [95% CI, -4.8 to 1.5; p = 0.3]). Conclusions: A single dose of 40 mg tadalafil moderately reduced urethral pressure in healthy women, without affecting voiding parameters. The clinical implications of this are yet to be determined.

Aims: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI. However, the literature findings are conflicting. This study aimed to evaluate citalopram's effect on opening urethral pressure (OUP) in healthy women. Methods: We conducted a randomized, double-blind, placebo- and active-controlled crossover study in 24 healthy women. On three study days, which were separated by 8 days of washout, the subjects received single doses of either 40 mg citalopram (and placeboreboxetine), 8 mg reboxetine (and placebocitalopram), or two placebos. Study drugs were administered at a 1-h interval due to a difference in estimated time to peak plasma concentration (tmax). We measured OUP with urethral pressure reflectometry under both resting and squeezing conditions of the pelvic floor at estimated tmax for both study drugs (one timepoint). Results: Compared to placebo, citalopram increased OUP by 6.6 cmH20 (95% confidence interval [CI] 0.04–13.1, p = 0.048) in resting condition. In squeezing condition, OUP increased by 7.1 cmH20 (95% CI: 1.3–12.9, p = 0.01). Reboxetine increased OUP by 30.0 cmH20 in resting condition compared to placebo (95% CI: 23.5–36.5, p < 0.001), and 27.0 cmH20 (95% CI: 21.2–32.8, p < 0.001) in squeezing condition. Conclusion: Citalopram increased OUP slightly compared to placebo suggesting that SSRI treatment does not induce or aggravate SUI.

Background Intravenous high-dose glucagon is a recommended antidote against beta-blocker poisonings, but clinical effects are unclear. We therefore investigated hemodynamic effects and safety of high-dose glucagon with and without concomitant beta-blockade. Methods and Results In a randomized crossover study, 10 healthy men received combinations of esmolol (1.25 mg/kg bolus+0.75 mg/kg/min infusion), glucagon (50 µg/kg), and identical volumes of saline placebo on 5 separate days in random order (saline+saline; esmolol+saline; esmolol+glucagon bolus; saline+glucagon infusion; saline+glucagon bolus). On individual days, esmolol/saline was infused from -15 to 30 minutes. Glucagon/saline was administered from 0 minutes as a 2-minute intravenous bolus or as a 30-minute infusion (same total glucagon dose). End points were hemodynamic and adverse effects of glucagon compared with saline. Compared with saline, glucagon bolus increased mean heart rate by 13.0 beats per minute (95% CI, 8.0-18.0; P<0.001), systolic blood pressure by 15.6 mm Hg (95% CI, 8.0-23.2; P=0.002), diastolic blood pressure by 9.4 mm Hg (95% CI, 6.3-12.6; P<0.001), and cardiac output by 18.0 % (95% CI, 9.7-26.9; P=0.003) at the 5-minute time point on days without beta-blockade. Similar effects of glucagon bolus occurred on days with beta-blockade and between 15 and 30 minutes during infusion. Hemodynamic effects of glucagon thus reflected pharmacologic glucagon plasma concentrations. Glucagon-induced nausea occurred in 80% of participants despite ondansetron pretreatment. Conclusions High-dose glucagon boluses had significant hemodynamic effects regardless of beta-blockade. A glucagon infusion had comparable and apparently longer-lasting effects compared with bolus, indicating that infusion may be preferable to bolus injections. Registration Information URL: https://www.clinicaltrials.gov; Unique identifier: NCT03533179.

AIMS: In two open-label trials, imipramine alleviated symptoms in patients with stress urinary incontinence and is therefore used off-label for this indication. However, it has never been confirmed that imipramine increases urethral pressure in a placebo-controlled setting. The purpose of this study was to investigate whether imipramine increases the opening urethral pressure compared to placebo in healthy women using urethral pressure reflectometry.METHODS: A randomized, double-blind, placebo-controlled, crossover study in 16 healthy women. Opening urethral pressure was measured predose and 1 hour after a single dose of 50 mg imipramine or placebo. The washout period was minimum of 1 week. The study was approved by the local ethics committee, conducted according to the Good Clinical Practice guidelines, and registered on ClinicalTrials.gov and EudraCT before recruitment of subjects. Funding was provided by the clinical department.RESULTS: There were no dropouts and no serious adverse events. There were 13 adverse drug reactions related to imipramine in seven subjects, one adverse event related to placebo, and two adverse events related to the measurements with urethral pressure reflectometry. Imipramine compared to placebo increased opening urethral pressure in the resting condition with 6.5 cmH2 O (95% confidence interval [CI]: -0.5, 13.5), P = 0.07, and in the squeeze condition with 7.9 cmH 2 O (95% CI: -0.3, 16.1), P = 0.06.CONCLUSIONS: In conclusion, the increase in opening urethral pressure after imipramine treatment compared to placebo was neither statistically significant nor clinically relevant, and we do therefore not recommend the off-label use of imipramine for the treatment of stress urinary incontinence.

INTRODUCTION: From January 2013, we changed the surgical strategy in our department and ceased to perform the through-knee amputation (TKA). The primary aim of this study was to investigate re-amputation rates ≤ 90 days after non-traumatic major lower-extremity amputations performed before and after this change of practice. Furthermore, we reported mortality before and after the change of practice.METHODS: All non-traumatic major lower-extremity amputations performed in a single centre in two study periods (before and after the change of practice); 2009-2012 (cohort A) and 2014-2015 (cohort B) were included. Re-amputations and all-cause mortality ≤ 90 days after the index amputations were analysed.RESULTS: Cohort A: Included 180 amputations with 27 below-knee amputations (BKA), 68 TKAs and 85 above-knee amputations (AKA). 86.7% of patients were American Society of Anesthesiologists (ASA) score 3-5. The re-amputation rate ≤ 90 days was 29.6% (95% confidence interval (CI): 12.7-47.3%) after BKA, 33.8% (95% CI: 22.7-45.3%) after TKA, 9.4% (95% CI: 2.9-15.1%) after AKA and 21.6% (95% CI: 15.6-27.6%) overall. The overall mortality ≤ 90 days was 35.2% (95% CI: 26.2-44.2%). Cohort B: Included 116 amputations with 21 BKA and 95 AKA. 92.7% of patients were ASA score 3-5. The re-amputation rate ≤ 90 days was 19.1% (95% CI: 7.7-40.0%) after BKA, 2.1% (95% CI: 0.6-7.4%) after AKA and 5.2% (95% CI: 2.4-10.8%) overall. The overall mortality ≤ 90 days was 32.8% (95% CI: 26.2-44.2%).CONCLUSIONS: The overall re-amputation rate ≤ 90 days following major lower-extremity amputation decreased significantly from 22% to 5% after cessation of the TKA procedures, but mortality remained unchanged.FUNDING: none.TRIAL REGISTRATION: not relevant.

INTRODUCTION: Orthogeriatric service has been shown to improve outcomes in patients with hip fracture. The purpose of this study is to evaluate the effect of orthogeriatrics at Bispebjerg University Hospital, Denmark. The primary outcome is mortality inhospital and after 1, 3, and 12 months for patients with hip fracture. The secondary outcome is mortality for home dwellers and nursing home inhabitants.MATERIALS AND METHODS: This is a retrospective clinical cohort study with an historic control group including all patients with hip fracture admitted from 2007 to 2011. Patients with hip fracture are registered in a local database, and data are retrieved retrospectively using the Danish Civil Registration Number.RESULTS: We included 993 patients in the intervention group and 989 patients in the control group. A univariate analysis showed only significantly decreased mortality inhospital 6.3% vs 3.1% (P = .009) after orthogeriatrics. However, when adjusting for age, gender, and American Society of Anaesthesiologists (ASA) score in a multivariate analysis, including all patients with hip fracture, we find significantly reduced mortality inhospital (odds ratio [OR] 0.35), after 30 [OR 0.66] and 90 days [OR 0.72] and 1 year [OR 0.79]). When using a univariate analysis for home-dwelling patients, we found significantly reduced mortality inhospital (8.3-2.0%, P < .0001), after 30 days (12.2-6.8%, P = .004) and 90 days (20.5-13.0%, P = .002). One-year mortality was not significant. Patients from nursing homes had no significant decreasing mortality at any point of time in the univariate analysis.CONCLUSION: We have shown significant decreases for inhospital, 30 day, 90 day, and 1-year mortality after implementation of orthogeriatric service at Bispebjerg Hospital when adjusting for age, gender, and ASA score. Future trials should include frail patients with other fracture types who can benefit from orthogeriatrics.

There is a 5- to 8-fold increased risk of mortality during the first 3 months after a hip fracture. Several risk factors are known. We studied the predictive value (for mortality) of routine blood tests taken on admission.

Hip fractures are associated with high mortality, but the cause of this is still not entirely clear. We investigated the effect of surgical delay, weekends, holidays, and time of day admission on mortality in hip fracture patients.

A part of the payload of the second Ariane 5 prototype vehicle to be launched by Arianespace, was a small technology demonstration satellite. On October 30th, 1997, this test satellite, dubbed Teamsat, was launched into Geostationary Transfer Orbit and would as such pass the Van Allen radiation belts twice per orbit. One of the experiments onboard Teamsat was the so-called Autonomous Vision System (AVS). The AVS instrument is a fully autonomous star tracker with several advanced features for non-stellar object detection and tracking, real-time image compression and transmission. The objectives for the AVS in Teamsat were to test these functions, to validate their autonomous operation in space, and to assess the operational constraints of a high radiation environment on such processes. This paper describes the AVS experiment, and the radiation flux experienced onboard TEAMSAT. This overview is followed by examples of the radiation impact on the AVS instrument flown onboard the TEAMSAT, and finally the operations of the various countermeasures are discussed.

The second qualification flight of Ariane 5 blasted off-the European Space Port in French Guiana on October 30, 1997, carrying on board a small technology demonstration satellite called TeamSat. Several experiments were proposed by various universities and research institutions in Europe and five of them were finally selected and integrated into TeamSat, namely FIPEX, VTS, YES, ODD and the Autonomous Vision System, AVS, a fully autonomous star tracker and vision system. This paper gives short overview of the TeamSat satellite; design, implementation and mission objectives. AVS is described in more details. The main science objectives of the AVS were to verify, in space, multiple autonomous processes intended for spacecraft applications such as autonomous star identification and attitude determination, identification and tracking of non-stellar objects, imaging and real-time compression of image and science data for further ground analysis. AVS successfully determined the attitude and attitude dynamics of TeamSat.

The ability to detect and track non-stellar objects by utilizing a star tracker may seem rather straight forward, as any bright object, not recognized as a star by the system is a non stellar object. However, several pitfalls and errors exist, if a reliable and robust detection is required. To test the operation, performance and robustness of such a function, the Autonomous Vision System (AVS), a fully autonomous star tracker that has flown onboard the Teamsat was equipped with several advanced features. These features included a non-stellar object detection and tracking module and an image and science data compression module. This paper describes the AVS, sensitivity, and possible detection ranges for various objects. The general description is followed by examples of images and tracking series obtained by the AVS on Teamsat.