So I'm gonna get started. So the first paper is a Doppler study of portal vein and renal venous velocity and how those predict the appropriate flu response to diuresis in the ICU. So this is a prospective observational single center study in an academic center in France in 2019 and 2020. They had 81 patients and they divided them in the ones who responded to diuresis and the ones who did not. The primary outcome was to evaluate the ability of the portal pulsatility index to detect response to diuresis and the secondary outcomes to evaluate the renal venous impendence and the VIXS score to detect appropriate response to diuresis. So here I have all the formulas that they used to calculate those indexes that we talked about using the maximum velocity and the minimum velocity. And here is the VIXS score, which is a combination of the hepatic vein, portal vein, intrarenal and venous Doppler findings in conjunction with the diameter of the IVC. So those patients were above 18 years of age. They had clinical signs of volume of fluid overload and patients who had received previously diuretics or had permanent AFib, dialysis, or patients with unstable shock were excluded from the study. So for a congestion score, which was calculated based on the clinical findings and radiologic findings, above three, the patients received diuresis. So here we see the flow chart and the baseline characteristics. Most of them were status post-cardiac surgery. Here we see that by the ICU discharge, most of those patients were fluid negative and they also had decreased BNPs. So we see here that two hours after diuresis, the portal pulsating, I'm sorry, pulsatility index was improved in patients who received diuresis and the renal venous impendence was worsened and the VIXA score didn't change that much. So after that, they did create the receiver operating characteristic curve and they calculated the area under the curve to find what is the most sensitive way to calculate the appropriate response and they did found that pulsatility, as we see here, pulsatility portal venous index and the renal venous index were more sensitive than the VIXA score. So patients with appropriate response to diuresis had a high pulsatility portal index and worse renal venous impendence. We move on with this article that was published in the New England Journal of Medicine and it talks about early active mobilization during mechanical ventilation in the ICU. Again, it's an international multi-center randomized control trial, 49 hospitals, six countries from 2018 to 2021. They had two groups, patients who received early mobilization while mechanical ventilated versus a usual care group. The primary outcome was the number of days that the patients were alive and out of the hospital 180 days after randomization and secondary outcome was mortality on 180 days and number of ventilation free days and days out of the ICU from randomization day to date 28. So inclusion criteria, patients were above 18 years of age to undergo mechanical ventilation. Thank you. Okay, got it. Sorry about that. Have to go back. Okay, this is the concert study. I'll keep going. So basically the characteristics of the patients, most of them, the patients who were in the early mobilization group had like a planned ICU admission after surgery and here we see like the primary and the secondary outcome results. There was actually no statistically difference between, I'm sorry, this is it, sorry. We see here that basically the patients were in the early mobilization group had like spent more time in active seating as you see here, the yellow bars and standing than their control groups, the control group. So we see here the primary and secondary outcomes. There was actually no statistically significant difference between those two groups regarding early mobilization and basically the ones who were mobilized early had like a high risk of getting cardiac arrhythmias and oxygen desaturation. So the limitation, the level of mobilization that patients received is higher than this study, than any other study performed and there were no details regarding rehab beyond ICU. So for patients who underwent mechanical ventilation in the ICU, increased early mobilization did not affect the number of days that they were alive and out of hospital, but it was correlated with more adverse effects. So here is another article that was published in the New England Journal of Medicine. It talks about oxygen targets in comatose survivors of cardiac arrest. It's a randomized control study, two centers in Denmark, around 800 patients with out of hospital cardiac arrest that were randomly assigned to either restrictive oxygen target from 68 to 75 or liberal oxygen target to 9,805 millimeters of mercury. So the primary outcome was death from any cause or cognitive issue or vegetative coma that occurred 90 days after randomization. And secondary outcomes were neuron-specific analyzed biomarkers at 48 hours, death from any cause, cognitive scores at 90 days. So here we see the baseline characteristics which were very similar to those groups of our patients. And here we see that there was actually no difference between restrictive versus liberal oxygen target in either of the primary or secondary outcomes or in adverse events. Here we see the subgroup analysis of the primary outcome, calculating hazard ratios and 95% confidence intervals, and we basically see no difference in between those groups. So the strength of this study has similar results with the HOT-ICU and ROCKS-ICU trials, and the limitations, the cardiac arrests were primarily due to coronary disease and unsure if these results would be applicable for other causes of cardiac arrest. And during COVID, follow-up was very difficult. So moving forward, this is like a similar study from the same authors, and they basically looked at into blood pressure targets in comatose survivors of cardiac arrest. Again, same cohort of patients in Denmark, around 800 patients, and they were assigned to either a map of 75 millimeters of mercury or 63. And the primary outcome was, again, death from any cause or hospital discharge with cerebral performance category three or four and 90 days, and then the secondary outcomes were similar to the ones we talked about previously. So inclusion criteria, there were patients above 18 years of age who had been resuscitated after an out-of-hospital cardiac arrest with presumed cardiac cause and had a sustained return of subcutaneous circulation, no compressions more than 20 minutes, and remained comatose on arrival at the hospital. Exclusion criteria, unwitnessed asystole, and any intracranial bleeding or stroke. So we see here the characteristics of those patients, and the patients in the low target group were more likely to have hypertension or diabetes. The ones in the high blood pressure group, they were more likely to have NMI. So here we see how the mean arterial pressure variates from baseline hours zero up to hours 48, and we see how the pressure requirements are increased during that randomization, and they kinda like come together like almost the same by 48 hours. So outcomes, so basically there was no statistically significant difference between those two groups in either the primary or secondary outcomes, and there were no significant difference in results in adverse effects. Here we see the subgroup analysis of the primary outcome, and we do see that the patients who had like high blood pressure target were more likely to have COPD, based on the thing. So the mean difference in blood pressure between those two groups was 10.5 millimeters of mercury, and therefore was lower than the expected value, which was supposed to be 14 millimeters of mercury, but however, the doses of levo and vasopressors were substantially higher in the high target group than the lower group. The strength, it was a randomized study, it was a big sample, and the results were consistent. Moving forward, this is another interesting article. It was published in the New England Journal of Medicine, and talks about aggressive or moderate fluid resuscitation in acute pancreatitis. Again, it's a multi-center control trial for 18 centers in four different countries, and they basically randomized the patients to aggressive resuscitation, defining it as 20 mL per kilo of bolus of LR, followed by three mL per kilo per hour, moderate resuscitation, bolus of 10 mL per kilo in patients with hypovolemia or no bolus, if the patient was normovolemic, followed by 1.5 mL per kilo per hour in all the patients. Those patients were assessed at 12, 24, 48, and 72 hours, and fluid resuscitation was adjusted according to the needs of the patients. So the primary outcome was the development of moderately severe or severe acute pancreatitis during hospitalization, and secondary outcomes were organ failure during the hospitalization. So those patients were above 18 years of age, diagnosed with acute pancreatitis, presented to the emergency no more than 24 hours after the pain onset, and they had received a diagnosis no more than eight hours before the enrollment. Exclusion criteria, moderate or severe disease at baseline, heart failure, hypertension, hyper, hyponatremia, hypokalemia, hypocalcemia. So here we see the baseline characteristics of those patients. They were pretty similar. Maybe the moderate flu resuscitation group had like, they were more likely to have diabetes. Here is like the resuscitation protocol that they used, and we kind of talked about it. Here we see the primary and the secondary outcomes, and we see no difference in aggressive versus moderate flu resuscitation when you come to developing severe or moderately severe pancreatitis. No difference in the secondary outcomes, but they were some differences when it came to adverse effects. And those patients who were aggressively resuscitated were more likely to become fluid overloaded, and they were more likely to show signs of pulmonary edema and pulmonary arrears on physical exam. So this is a randomized study, but it was an open label, so could be biased. It terminated at first interim to avoid fluid overload in those patients, and the resuscitation may have been too aggressive, so the authors do recommend further studies with more restrictive fluid resuscitation. So this is another article, intravenous vitamin C in adults with sepsis in the intensive care unit. Again, it's a randomized controlled trial, 35 ICUs in four different countries, around 900 patients with ICU stay of less than 24 hours with proven or suspected infection as the main diagnosis that were on vasopressor to receive infusion or vitamin C, placebo infusion of vitamin C every six hours for up to 96 hours. The primary outcome was composite of death or persistent organ dysfunction on day 28. And secondary outcomes, a number of days without organ dysfunction in the ICU up to date 28, mortality at 28 days in six months, and quality of life in six months. So here we see the baseline characteristics of those patients, they were very similar. And here we see the outcomes, and we see that patients who received vitamin C were more likely to die or to present, to have like a persistent organ dysfunction in 28 days. There were no other statistically significant parameters in the secondary outcomes or the safety outcomes. Here we see that that's a Kaplan-Meier analysis of survival at six months, so at six months there was no like difference in patients who received placebo or vitamin C when it came to mortality. Here we see the subgroup analysis of the primary outcome, and we do see that the patients who received vitamin C were more likely to be female, have like a fairly scale score that was like higher, and they were more likely to die. Strength and limitation, that's a large sample, blinding study, and there was high protocol adherence. Limitations, there was no information regarding pathogens and the appropriateness of antimicrobial therapy during that study, so that's something that was unclear. So in adults with sepsis who were receiving vasopressor therapy in the ICU, the receipt of intravenous vitamin C resulted in a higher risk of death for persistent organ dysfunction at 28 days when compared to placebo. Now we have the final article, and it talks about fluid balance and renal replacement therapy, initiation strategy, early versus later RRT in patients who did not need it urgently. So again, randomized controlled trial, 3,000 patients, very ill, critically ill, with severe AKI in 15 countries in multiple centers. They compared, as we talked about, accelerated versus standard initiation of RRT without urgent need. They evaluated the difference in cumulative, I'm sorry, fluid balance by randomized group from the day of randomization through the entire stay or up to day 14 in the ICU. They divided the trials, intention to treat cohort into quartiles based on the participant's fluid balance at the time of randomization. That was something that was done first time in literature. Evaluated whether baseline fluid balance modified the effect of RRT initiation on all-cause 90-day mortality, and that was the primary outcome of the trial. Then secondary outcomes were RRT-dependent in surviving patients, composite outcome of death, RRT-dependent in 90 days, and mortality in the ICU. So here we see, like all the patients who received dialysis and we see that the accelerated RRT initiation patient group ended up with having like less fluid balance than the other one. Here we see the characteristics of the patients. It's a long table, so I would encourage you to look at it when you read the paper. And here we see the outcomes, and we see that patients who, there was no statistically difference between patients received early in, oh, I'm sorry. There was no statistically difference in patients received dialysis early versus late, but however, the patients received early dialysis, they were more likely to have like free ventilator days in the ICU. And here is, it's a table that shows the effect of accelerated RRT initiation across the quartiles based on the fluid balance, and they categorized it by the presence or absence of sepsis, and there was like no statistical significance in all-cause mortality. And again, this is a primary outcome. Here we have like the quartiles based on the fluid balance baseline, and we see no statistical significance in mortality. So this is assessment of fluid balance on the relationship between RRT and initiation strategies and clinical outcomes. It's, the generalizability is pretty good as it includes so many different countries and centers. The limitations, the physicians did administer diuretics during the study, and those data were not recorded. And the fluid balance measures did not include insensible losses, did not account to fluid intake or losses prior to the ICU admissions. So an accelerated strategy of RRT initiation conferred a modest reduction in cumulative fluid balance during the two weeks following enrollment. The fluid balance at the time of randomization was associated with several markers of illness severity. However, earlier initiation of RRT did not confer improved mortality, but did lead to greater number of hospital-free days in patients with the highest degree of fluid overload. Thank you.

doppler studies

fluid response

ICU patients

early mobilization

oxygen targets