Challenge of intravascular volume assessment in acute ischemic stroke

Introduction

Retrospective data indicates that dehydration in acute ischemic stroke patients may be common, even though these patients frequently have elevated blood pressure. We sought to evaluate clinical and laboratory measures of intravascular volume status compared to more objective measures using ultrasound measurements of the inferior vena cava (IVC).

Respiratory oxygen uptake is associated with survival in a cohort of ventilated trauma and burn patients

Background

Little data is available in the literature about the role of end tidal oxygen in critically ill patients. We sought to identify the association between the level of respiratory oxygen and clinical outcomes in critically-ill ventilated trauma and burn patients.

Current concepts in the diagnosis,pathogenesis and management of nonarteritic anterior ischaemic optic neuropathy

Nonarteritic anterior ischaemic optic neuropathy (NAION) is the most common acute optic neuropathy in patients over the age of 50 and is the second most common cause of permanent optic nerve-related visual loss in adults after glaucoma. Patients typically present with acute, painless, unilateral loss of vision associated with a variable visual field defect, a relative afferent pupillary defect, a swollen, hyperaemic optic disc, and one or more flame-shaped peripapillary retinal haemorrhages. The pathogenesis of this condition is unknown, but it occurs primarily in patients with structurally small optic discs that have little or no cup and a variety of underlying vascular disorders that may or may not be known at the time of visual loss. There is no consistently beneficial medical or surgical treatment for the condition, but there are now animal models that allow testing of various potential therapies. About 40% of patients experience spontaneous improvement in visual acuity. Patients in whom NAION occurs in one eye have a 15–19% risk of developing a similar event in the opposite eye over the subsequent 5 years.     

Twenty Years of Active Bacterial Core Surveillance

Active Bacterial Core surveillance (ABCs) was established in 1995 as part of the Centers for Disease Control and Prevention Emerging Infections Program (EIP) network to assess the extent of invasive bacterial infections of public health importance. ABCs is distinctive among surveillance systems because of its large, population-based, geographically diverse catchment area; active laboratory-based identification of cases to ensure complete case capture; detailed collection of epidemiologic information paired with laboratory isolates; infrastructure that allows for more in-depth investigations; and sustained commitment of public health, academic, and clinical partners to maintain the system. ABCs has directly affected public health policies and practices through the development and evaluation of vaccines and other prevention strategies, the monitoring of antimicrobial drug resistance, and the response to public health emergencies and other emerging infections.     

Problems and hopes perceived by mothers,fathers and physicians of children receiving palliative care

Background

The quality of shared decision making for children with serious illness may depend on whether parents and physicians share similar perceptions of problems and hopes for the child.

Objective

(i) Describe the problems and hopes reported by mothers, fathers and physicians of children receiving palliative care; (ii) examine the observed concordance between participants; (iii) examine parental perceived agreement; and (iv) examine whether parents who identified specific problems also specified corresponding hopes, or whether the problems were left ‘hopeless’.

Method

Seventy‐one parents and 43 physicians were asked to report problems and hopes and perceived agreement for 50 children receiving palliative care. Problems and hopes were classified into eight domains. Observed concordance was calculated between parents and between each parent and the physicians.

Results

The most common problem domains were physical body (88%), quality of life (74%) and medical knowledge (48%). The most common hope domains were quality of life (88%), suffering (76%) and physical body (39%). Overall parental dyads demonstrated a high percentage of concordance (82%) regarding reported problem domains and a lower percentage of concordance on hopes (65%). Concordance between parents and physicians regarding specific children was lower on problem (65–66%) and hope domains (59–63%). Respondents who identified problems regarding a child's quality of life or suffering were likely to also report corresponding hopes in these domains (93 and 82%, respectively).

Conclusion

Asking parents and physicians to talk about problems and hopes may provide a straightforward means to improve the quality of shared decision making for critically ill children.     

The HDAC and PI3K dual inhibitor CUDC-907 synergistically enhances the antileukemic activity of venetoclax in preclinical models of acute myeloid leukemia

Venetoclax is a promising agent in the treatment of acute myeloid leukemia (AML), though its antileukemic activity is limited to combination therapies. Mcl-1 downregulation, Bim upregulation, and DNA damage have been identified as potential ways to enhance venetoclax activity. In this study, we combine venetoclax with the dual PI3K and histone deacetylase inhibitor CUDC-907, which can downregulate Mcl-1, upregulate Bim, and induce DNA damage, as well as downregulate c-Myc. We establish that CUDC-907 and venetoclax synergistically induce apoptosis in AML cell lines and primary AML patient samples ex vivo. CUDC-907 downregulates CHK1, Wee1, RRM1, and c-Myc, which were found to play a role in venetoclax-induced apoptosis. Interestingly, we find that venetoclax treatment enhances CUDC-907-induced DNA damage potentially through inhibition of DNA repair. In vivo results show that CUDC-907 enhances venetoclax efficacy in an AML cell line derived xenograft mouse model, supporting the development of CUDC-907 in combination with venetoclax for the treatment of AML.