Abnormal liver function tests associated with severe rhabdomyolysis

Rhabdomyolysis is a syndrome of skeletal muscle injury with release of cellular constituents such as potassium,phosphate,urate and intracellular proteins such as myoglobin into the circulation,which may cause complications including acute kidney injury,electrolyte disturbance and cardiac instability.Abnormal liver function tests are frequently observed in cases of severe rhabdomyolysis.Typically,there is an increase in serum aminotransferases,namely aspartate aminotransferase and alanine aminotransferase.This raises the question of liver injury and often triggers a pathway of investigation which may lead to a liver biopsy.However,muscle can also be a source of the increased aminotransferase activity.This review discusses the dilemma of finding abnormal liver function tests in the setting of muscle injury and the potential implications of such an association.It delves into some of the clinical and experimental evidence for correlating muscle injury to raised aminotransferases,and discusses pathophysiological mechanisms such as oxidative stress which may cause actual liver injury.Serum aminotransferases lack tissue specificity to allow clinicians to distinguish primary liver injury from muscle injury.This review also explores potential approaches to improve the accuracy of our diagnostic tools,so that excessive or unnecessary liver investigations can be avoided.     

Patient preferences and predicted relative uptake for targeted therapies in metastatic colorectal cancer: a discrete choice experiment

Abstract

Objective

Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients’ preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies.     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

Concurrent removal of Cr(III), Cu(II), and Pb(II) ions from water by multifunctional TiO2/Alg/FeNPs beads

The use of multifunctional materials for water remediation is a modern approach where adsorption phenomena and heterogeneous photocatalysis can be applied for the removal of pollutants. Since the ideal remediation system should be able to remove both organic and inorganic pollutants, a crucial aspect to consider is the knowledge of operational parameters affecting the removal process, especially when heavy metal ions are present in concoction as in real systems. Given the proven efficiency of multifunctional TiO₂/Alg/FeNPs magnetic beads for the removal of model organic pollutants, this study investigated the possibility to exploit such system also for the removal of mixed heavy metals (MHM), specifically Cr(III), Cu(II), and Pb(II) ions, under ultraviolet irradiation at a wavelength of 254 nm. After a preliminary screening on the optimal catalyst loading, operating parameters such as the initial concentration of metal ions, contact and irradiation time, and pH were investigated to optimize the removal of metal ions using response surface methodology (RSM) via Box–Behnken design. Starting from a MHM solution containing 44 ppm of each metal ion, the removal of Pb(II), Cr(III), and Cu(II) ions in the aqueous solution was nearly completed (>98.4%) for all three ions within 72 min of irradiation at almost neutral pH (pH = 6.8). The stability of TiO₂/Alg/FeNPs was confirmed by retrieving and reusing the beads in three consecutive cycles of heavy metals removal without observing significant changes in catalyst efficiency.     

Comparison Between Phenylephrine and Dopamine in Maintaining Cerebral Oxygen Saturation in Thoracic Surgery: A Randomized Controlled Trial

Fluid is usually restricted during thoracic surgery, and vasoactive agents are often administered to maintain blood pressure. One-lung ventilation (OLV) decreases arterial oxygenation; thus oxygen delivery to the brain can be decreased. In this study, we compared phenylephrine and dopamine with respect to maintaining cerebral oxygenation during OLV in major thoracic surgery.Sixty-three patients undergoing lobectomies were randomly assigned to the dopamine (D) or phenylephrine (P) group. The patients’ mean arterial pressure was maintained within 20% of baseline by a continuous infusion of dopamine or phenylephrine. Maintenance fluid was kept at 5 mL/kg/h. The depth of anesthesia was maintained with desflurane 1MAC and remifentanil infusion under bispectral index guidance. Regional cerebral oxygen saturation (rScO₂) and hemodynamic variables were recorded using near-infrared spectroscopy and esophageal cardiac Doppler.The rScO₂ was higher in the D group than the P group during OLV (OLV 60 min: 71 ± 6% vs 63 ± 12%; P = 0.03). The number of patients whose rScO₂ dropped more than 20% from baseline was 0 and 6 in the D and P groups, respectively (P = 0.02). The D group showed higher cardiac output, but lower mean arterial pressure than the P group (4.7 ± 1.0 vs 3.9 ± 1.2 L/min; 76.7 ± 8.1 vs 84.5 ± 7.5 mm Hg; P = 0.02, P = 0.02). Among the variables, age, hemoglobin concentration, and cardiac output were associated with rScO₂ by correlation analysis.Dopamine was superior to phenylephrine in maintaining cerebral oxygenation during OLV in thoracic surgery.