Sepsis is the third leading cause of death worldwide and the main cause of mortality in hospitals1–3, but the best treatment strategy remains uncertain. In particular, evidence suggests that current practices in the administration of intravenous fluids and vasopressors are suboptimal and likely induce harm in a proportion of patients1,4–6. To tackle this sequential decision-making problem, we developed a reinforcement learning agent, the Artificial Intelligence (AI) Clinician, which extracted implicit knowledge from an amount of patient data that exceeds by many-fold the life-time experience of human clinicians and learned optimal treatment by analyzing a myriad of (mostly suboptimal) treatment decisions. We demonstrate that the value of the AI Clinician’s selected treatment is on average reliably higher than human clinicians. In a large validation cohort independent of the training data, mortality was lowest in patients for whom clinicians’ actual doses matched the AI decisions. Our model provides individualized and clinically interpretable treatment decisions for sepsis that could improve patient outcomes.

The Artificial Intelligence Clinician learns optimal treatment strategies for sepsis in intensive care

https://pure.bond.edu.au/ws/files/32288082/AM_Dietary_fiber_intervention_on_gut_microbiota_composition_in_healthy_adults.pdf

Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis.

One quarter of patients suffering from acute critical illness such as severe trauma, sepsis, myocardial infarction (MI) or post cardiac arrest syndrome (PCAS) develop severe hemostatic aberrations and coagulopathy, which are associated with excess mortality. Despite the different types of injurious “hit”, acutely critically ill patients share several phenotypic features that may be driven by the shock. This response, mounted by the body to various life-threatening conditions, is relatively homogenous and most likely evolutionarily adapted. We propose that shock-induced sympatho-adrenal hyperactivation is a critical driver of endothelial cell and glycocalyx damage (endotheliopathy) in acute critical illness, with the overall aim of ensuring organ perfusion through an injured microvasculature. We have investigated more than 3000 patients suffering from different types of acute critical illness (severe trauma, sepsis, MI and PCAS) and have found a potential unifying pathologic link between sympatho-adrenal hyperactivation, endotheliopathy, and poor outcome. We entitled this proposed disease entity, shock-induced endotheliopathy (SHINE). Here we review the literature and discuss the pathophysiology of SHINE.

/pdf/erratum-to-shock-induced-endotheliopathy-shine-in-acute-c2x27x4by7.pdf

Erratum to: Shock induced endotheliopathy (SHINE) in acute critical illness - a unifying pathophysiologic mechanism.

Advances in the understanding of trauma-induced coagulopathy

Less than 10% of most Western populations consume adequate levels of whole fruits and dietary fiber with typical intake being about half of the recommended levels. Evidence of the beneficial health effects of consuming adequate levels of whole fruits has been steadily growing, especially regarding their bioactive fiber prebiotic effects and role in improved weight control, wellness and healthy aging. The primary aim of this narrative review article is to examine the increasing number of health benefits which are associated with the adequate intake of whole fruits, especially fruit fiber, throughout the human lifecycle. These potential health benefits include: protecting colonic gastrointestinal health (e.g., constipation, irritable bowel syndrome, inflammatory bowel diseases, and diverticular disease); promoting long-term weight management; reducing risk of cardiovascular disease, type 2 diabetes and metabolic syndrome; defending against colorectal and lung cancers; improving odds of successful aging; reducing the severity of asthma and chronic obstructive pulmonary disease; enhancing psychological well-being and lowering the risk of depression; contributing to higher bone mineral density in children and adults; reducing risk of seborrheic dermatitis; and helping to attenuate autism spectrum disorder severity. Low whole fruit intake represents a potentially more serious global population health threat than previously recognized, especially in light of the emerging research on whole fruit and fruit fiber health benefits.

Whole Fruits and Fruit Fiber Emerging Health Effects

This study investigated the incidence of delayed norepinephrine administration following the onset of septic shock and its effect on hospital mortality. We conducted a retrospective cohort study using data from 213 adult septic shock patients treated at two general surgical intensive care units of a tertiary care hospital over a two year period. The primary outcome was 28-day mortality. The 28-day mortality was 37.6% overall. Among the 213 patients, a strong relationship between delayed initial norepinephrine administration and 28-day mortality was noted. The average time to initial norepinephrine administration was 3.1 ± 2.5 hours. Every 1-hour delay in norepinephrine initiation during the first 6 hours after septic shock onset was associated with a 5.3% increase in mortality. Twenty-eight day mortality rates were significantly higher when norepinephrine administration was started more than or equal to 2 hours after septic shock onset (Late-NE) compared to less than 2 hours (Early-NE). Mean arterial pressures at 1, 2, 4, and 6 hours after septic shock onset were significantly higher and serum lactate levels at 2, 4, 6, and 8 hours were significantly lower in the Early-NE than the Late-NE group. The duration of hypotension and norepinephrine administration was significantly shorter and the quantity of norepinephrine administered in a 24-hour period was significantly less for the Early-NE group compared to the Late-NE group. The time to initial antimicrobial treatment was not significantly different between the Early-NE and Late-NE groups. Our results show that early administration of norepinephrine in septic shock patients is associated with an increased survival rate.

/pdf/early-versus-delayed-administration-of-norepinephrine-in-3d42c6z9ln.pdf

Early versus delayed administration of norepinephrine in patients with septic shock

Acute traumatic coagulopathy (ATC) may trigger sympathoadrenal activation associated with endothelial damage and coagulation disturbances. Overexcitation of sympathetic nerve in this state would disrupt sympathetic–vagal balance, leading to autonomic nervous system dysfunction. The aim of this study

Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.

Background
Sympathetic hyperactivity occurs early in acute traumatic coagulopathy (ATC) and is closely related to its development. β-adrenoceptor antagonists are known to alleviate adverse sympathetic effects and improve outcome in various diseases. We investigated whether β-blockers have protective effects against inflammation and endothelial and hemostatic disorders in ATC.

Impact of β-Adrenoceptor Blockade on Systemic Inflammation and Coagulation Disturbances in Rats with Acute Traumatic Coagulopathy

Objective To explore the effect of pectin, a kind of soluble dietary fiber, on colonic transit time (CTT), clinical symptoms and gut microbiota in adults with slow-transit constipation. Methods A total of 80 patients with slow-transit constipation were selected between June 2011 and December 2013. For this randomized controlled trial, we evaluated the efficacy of pectin on intestinal transit time and other indices of constipation in adults with slow-transit constipation. They were randomized to receive either pectin or placebo. Treatment consisted of 4-week supplementation with 24 g/d pectin (fiber group) or maltodextrin (placebo group). Before and after 4-week treatment, CTT, constipation symptoms and fecal bacterial population were compared between groups. Results CTT of the fiber group after treatment was lower than those of fiber group before treatment and those in the placebo group ((60.2 ± 11.2) h vs (80.3 ± 9.5), (79.4 ± 11.7) h, P Conclusions Four-week soluble dietary fiber use accelerates colon transit time and alleviates clinical symptoms in patients with slow-transit constipation. Additionally, supplementary fiber offers protective effects on gut microbiota by increasing the population of healthy microflora.

Ning Li

Papers

Early versus delayed administration of norepinephrine in patients with septic shock

Chemical sympathectomy attenuates inflammation, glycocalyx shedding and coagulation disorders in rats with acute traumatic coagulopathy.

Impact of β-Adrenoceptor Blockade on Systemic Inflammation and Coagulation Disturbances in Rats with Acute Traumatic Coagulopathy

[Clinical benefits after soluble dietary fiber supplementation: a randomized clinical trial in adults with slow-transit constipation].