Impact of initial fluid resuscitation volume on clinical outcomes in patientswith heart failure and septic shock

Background:Fluid resuscitation is a key treatment for sepsis,but limited data exists in patients with existing heartfailure(HF)and septic shock.The objective of this study was to determine the impact of initial fluid resuscitationvolume on outcomes in HF patients with reduced or mildly reduced left ventricular ejection fraction(LVEF)withseptic shock.Methods:This multicenter,retrospective,cohort study included patients with known HF(LVEF≤50%)presentingwith septic shock.Patients were divided into two groups based on the volume of fluid resuscitation in the first 6 h;<30 mL/kg or≥30 mL/kg.The primary outcome was a composite of in-hospital mortality or renal replacementtherapy(RRT)within 7 days.Secondary outcomes included acute kidney injury(AKI),initiation of mechanicalventilation,and length of stay(LOS).All related data were collected and compared between the two groups.A generalized logistic mixed model was used to assess the association between fluid groups and the primaryoutcome while adjusting for baseline LVEF,Acute Physiology and Chronic Health Evaluation(APACHE)II score,inappropriate empiric antibiotics,and receipt of corticosteroids.Results:One hundred and fifty-four patients were included(93 patients in<30 mL/kg group and 61 patientsin≥30 mL/kg group).The median weight-based volume in the first 6 h was 17.7(12.2–23.0)mL/kg in the<30 mL/kg group vs.40.5(34.2–53.1)mL/kg in the≥30 mL/kg group(P<0.01).No statistical difference was detected in the composite of in-hospital mortality or RRT between the<30 mL/kg group compared to the≥30 mL/kggroup(55.9%vs.45.9%,P=0.25),respectively.The<30 mL/kg group had a higher incidence of AKI,mechanicalventilation,and longer hospital LOS.Conclusions:In patients with known reduced or mildly reduced LVEF presenting with septic shock,no differencewas detected for in-hospital mortality or RRT in patients who received≥30 mL/kg of resuscitation fluid comparedto less fluid,although this study was underpowered to detect a difference.Importantly,≥30 mL/kg fluid did notresult in a higher need for mechanical ventilation.

Sleep and stress in the acute phase of concussion in youth

This study sought to address the complex interplay between both biological and psychological perceptions of stress and sleep in the acute stages following a mild traumatic brain injury.A secondary goal was to identify potential targets for intervention.Eleven acutely injured youth(mean age 12 years)were studied at home with overnight actigraphy,salivary cortisol and melatonin assays,and subjective ratings of stress and fatigue(injured group).Nine matched control youth also were assessed(control group).Results suggested longer sleep latencies(time to fall asleep)and higher levels of fatigue in the injured group exist(p=0.025 and p=0.004,respectively).In the injured group,stress and sleep onset were significantly related with most subjects meeting criteria for Acute Stress Disorder.Melatonin levels were lower at bedtime in the injured group.Saliva samples were collected via passive drool at three time points:~1 h before bed(“bedtime”or T1),immediately upon waking(time 2:T2),and 30 min post-waking(time 3:T3).Overnight increases in cortisol(T1 to T2)were greater for the injured group;however,post-sleep changes in cortisol(T2 to T3)were reversed with control concentrations increasing.These findings are unique in using actigraphy and salivary hormone levels in an acutely injured youth while in their homes.The differences in sleep latency and the presence of injury-related stress point to potential treatment targets in acute concussion.

An open-label multiyear study of sargramostim-treated Parkinson’s disease patients examining drug safety,tolerability,and immune biomarkers from limited case numbers

Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been evaluated.Methods As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 months.Secondary goals included numbers of CD4+T cells and monocytes and motor functions.Hematologic,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/kg.After 2 years,drug use was discon-tinued for 3 months.This was then followed by an additional 6 months of treatment.Results Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone pain.On drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment.Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased.In the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin signaling.This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.Conclusions Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment.Confirmation in larger patient populations is planned in a future phase II evaluation.