Milrinone vs Dobutamine for the Management of Cardiogenic Shock: Implications of Renal Function and Injury.

Background: Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction. Objectives: This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function. Methods: In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Results: Baseline eGFR <60 ml/min/1.73 m2 and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m2 did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome (P interaction = 0.02) and death (P interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI. Conclusions: In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.

Safety and outcomes of performing laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy at an ambulatory site of a tertiary care hospital in Ontario.

BACKGROUND: In Ontario, bariatric surgery is publicly funded and is performed only in accredited tertiary care hospitals. The purpose of our study was to report on the safety and outcomes of performing bariatric surgery at an ambulatory site of a tertiary care hospital in southern Ontario. METHODS: We conducted a retrospective cohort study of all adult (age ≥ 18 yr) patients who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) at the ambulatory site of our tertiary care hospital between September 2016 and August 2018. The 2 sites are 1.4 km apart. Patient demographic characteristics, duration of surgery, intraoperative and 90-day postoperative complications, number of transfers and readmission to the tertiary care hospital, and emergency department visits were collected. RESULTS: A total of 314 patients (285 women [90.8%] and 29 men [9.2%] with a mean age of 41.8 yr [standard deviation (SD) 8.9 yr]) underwent surgery: LRYGB in 295 cases (93.9%) and LSG in 19 (6.0%). The mean body mass index was 45.3 (SD 5.1), the median American Society of Anesthesiologists score was 3 (range 2-4), and the median Edmonton Obesity Staging System score was 2 (range 0-4). The mean operative time was 119.8 (SD 23.1) minutes for LRYGB and 96.2 (SD 22.0) minutes for LSG, and the mean length of stay was 2.1 (SD 0.6) days and 2.1 (SD 0.2) days, respectively. Thirteen patients (4.1%) required transfer to the tertiary care hospital for a postoperative complication. Of 312 patients, 29 (9.3%) presented to emergency department within 90 days after surgery, and 8 (2.6%) required readmission to hospital; no deaths were reported. CONCLUSION: The findings suggest that LRYGB and LSG can be performed safely at an ambulatory site of a tertiary care hospital. However, caution should be exercised in performing these procedures at an ambulatory site without a tertiary care hospital affiliation, as patients may require urgent transfer for a serious postoperative complication.

Bias and sensitivity of proprioception of a passively felt hand path with and without a secondary task.

Previously, we observed changes in the scale, rotation, and location of drawn shapes when subjects simultaneously performed a secondary task, but not in the shape or proportion of the drawing. We suggested the secondary task impacted motor planning and execution or proprioception of the primary task. To isolate for proprioceptive effects, here we used the same secondary task during passive shape perception. A robotic manipulandum moved the subject's hand around the perimeter of a template shape and then a test shape differing in size, proportion, or location. Subjects also performed the same primary task while simultaneously performing a secondary task of reporting the orientation of right or left tilted arrows. We compared the performance between single and dual task, and different workspaces. In single-task conditions, subjects perceived scale, location, and proportion very close to the actual (all biases under 1 cm). A secondary task only increased the uncertainty range for judgment of scale, with no other effect. Subjects judged shapes in the centered workspace to be smaller and closer relative to the template compared with those in the peripheral workspace, although in that workspace, it was more difficult to discern changes in the proportion of the shape. The result for scale in the current passive paradigm is not different from our active study in which efference copy was available. This suggests that the scale parameters of the shape, whether actively or passively encountered, are disrupted by task interference at the level of proprioception or sensory integration rather than motor planning and execution.

Angio-adaptation in unloaded skeletal muscle: new insights into an early and muscle type-specific dynamic process.

With a remarkable plasticity, skeletal muscle adapts to an altered functional demand. Muscle angio-adaptation can either involve the growth or the regression of capillaries as respectively observed in response to endurance training or muscle unloading. Whereas the molecular mechanisms that regulate exercise-induced muscle angiogenesis have been extensively studied, understanding how muscle unloading can in contrast lead to capillary regression has received very little attention. Here we have investigated the consequences of a 9 day time course hindlimb unloading on both capillarization and expression of angio-adaptive molecules in two different rat skeletal muscles. Both soleus and plantaris muscles were atrophied similarly. In contrast, our results have shown different angio-adaptive patterns between these two muscles. Capillary regression occurred only in the soleus, a slow-twitch and oxidative postural muscle. Conversely, the level of capillarization was preserved in the plantaris, a fast-twitch and glycolytic muscle. We have also measured the time course protein expression of key pro- and anti-angiogenic signals (VEGF-A, VEGF-B, VEGF-R2, TSP-1). Our results have revealed that the angio-adaptive response to unloading was muscle-type specific, and that an integrated balance between pro- and anti-angiogenic signals plays a determinant role in regulating this process. In conclusion, we have brought new evidence that measuring the ratio between pro- and anti-angiogenic signals in order to evaluate muscle angio-adaptation was a more accurate approach than analysing the expression of molecular factors taken individually.