Plasma creatine kinase indicates major amputation or limb preservation in acute lower limb ischemia

ObjectiveAcutely ischemic limbs are often of uncertain viability. To assist operative management, this study determined prospectively which indicators on admission were the best predictors of major amputation and, conversely, limb preservation.MethodsData were collected on admission. Presenting complaint, history, clinical assessment, and blood test results, including creatine kinase (CK), were recorded. Surgical procedures were noted—in particular, the presence or absence of major amputation by death or discharge. The setting was a tertiary vascular referral center in a university teaching hospital. Subjects included all patients referred as emergency cases to the vascular unit over an 18-month period who were admitted for inpatient management with acute lower limb ischemia. The main outcome measure was major amputation.ResultsA total of 97 patients with acute ischemia were studied prospectively (51 men and 46 women). Twenty-one patients (21.6%) underwent major amputation. Previous vascular surgery (P = .012), mottling (P = .001), sensory loss (P = .003), motor loss (P = .001), muscle tenderness (P < .001), absent ankle Doppler signals (P = .008), neutrophilia (P = .011), and increased CK (P < .001) were significantly associated with major amputation. If CK was normal, the risk of major amputation was 4.6% (95% confidence interval, 0.0%-9.7%). If CK was increased, the risk was 56.2% (95% CI, 39.1%-73.4%).ConclusionsSpecific clinical findings were significantly associated with major amputation. Of these, only CK had a positive predictive value greater than 50%. Plasma CK can assist operative management of acute lower limb ischemia by quantifying prospectively the risk of major amputation or limb preservation on admission

Liver Development, Regeneration, and Carcinogenesis

The identification of putative liver stem cells has brought closer the previously separate fields of liver development, regeneration, and carcinogenesis. Significant overlaps in the regulation of these processes are now being described. For example, studies in embryonic liver development have already provided the basis for directed differentiation of human embryonic stem cells and induced pluripotent stem cells into hepatocyte-like cells. As a result, the understanding of the cell biology of proliferation and differentiation in the liver has been improved. This knowledge can be used to improve the function of hepatocyte-like cells for drug testing, bioartificial livers, and transplantation. In parallel, the mechanisms regulating cancer cell biology are now clearer, providing fertile soil for novel therapeutic approaches. Recognition of the relationships between development, regeneration, and carcinogenesis, and the increasing evidence for the role of stem cells in all of these areas, has sparked fresh enthusiasm in understanding the underlying molecular mechanisms and has led to new targeted therapies for liver cirrhosis and primary liver cancers

Ketamine as the anaesthetic for electroconvulsive therapy:the KANECT randomised controlled trial

C.AS. reports grants from Vifor Pharma, outside the submitted work. I.C.R. (deceased) declared personal fees from AstraZeneca, Sanofi Aventis and Sunovion, and non-financial support from Lundbeck, between 2009 and 2014 and all outside the submitted work. Volume 212, Issue 5 May 2018 , p. 323 Ketamine as the anaesthetic for electroconvulsive therapy: the KANECT randomised controlled trial – CORRIGENDUM Gordon Fernie, James Currie, Jennifer S. Perrin, Caroline A. Stewart... https://doi.org/10.1192/bjp.2018.76 Published online: 06 April 2018 Summary: This notice describes a correction to the above mentioned paper.Peer reviewedPublisher PD

Modelling Hepatic Endoderm Development: Highly Efficient Differentiation of Human Embryonic Stem Cells to Functional Hepatic Endoderm Requires ActivinA and Wnt3a Signalling.

Human embryonic stem cells (hESCs) are a valuable source of pluripotential primary cells. However, their homogeneous cellular differentiation to specific cell types _in vitro_ has proven difficult thus far. Wnt signalling has been shown to play important roles in coordinating development and we demonstrate that Wnt3a is differentially expressed at critical stages of human liver development _in vivo_. The essential role of Wnt3a in hepatocyte differentiation from hESCs is paralleled by our _in vitro_ model, demonstrating the importance of a physiological approach to cellular differentiation. Our studies provide compelling evidence that Wnt3a signaling is important for coordinated hepato-cellular function _in vitro_ and _in vivo_. In addition, we demonstrate Wnt3a facilitates clonal plating of hESCs capable of hepatic endoderm differentiation. These studies represent an important step forward toward the use of hESC-derived hepatocytes in biomedical applications and has opened the door to high through-put metabolic analysis of human liver function

Macrophage phenotype is associated with disease severity in preterm infants with chronic lung disease.

The etiology of persistent lung inflammation in preterm infants with chronic lung disease of prematurity (CLD) is poorly characterized, hampering efforts to stratify prognosis and treatment. Airway macrophages are important innate immune cells with roles in both the induction and resolution of tissue inflammation