Invasive mechanical ventilation in patients with acute respiratory distress syndrome receiving extracorporeal support: a narrative review of strategies to mitigate lung injury.

Veno-venous extracorporeal membrane oxygenation is indicated in patients with acute respiratory distress syndrome and severely impaired gas exchange despite evidence-based lung protective ventilation, prone positioning and other parts of the standard algorithm for treating such patients. Extracorporeal support can facilitate ultra-lung-protective ventilation, meaning even lower volumes and pressures than standard lung-protective ventilation, by directly removing carbon dioxide in patients needing injurious ventilator settings to maintain sufficient gas exchange. Injurious ventilation results in ventilator-induced lung injury, which is one of the main determinants of mortality in acute respiratory distress syndrome. Marked reductions in the intensity of ventilation to the lowest tolerable levels under extracorporeal support may be achieved and could thereby potentially mitigate ventilator-induced lung injury and theoretically patient self-inflicted lung injury in spontaneously breathing patients with high respiratory drive. However, the benefits of this strategy may be counterbalanced by the use of continuous deep sedation and even neuromuscular blocking drugs, which may impair physical rehabilitation and impact long-term outcomes. There are currently a lack of large-scale prospective data to inform optimal invasive ventilation practices and how to best apply a holistic approach to patients receiving veno-venous extracorporeal membrane oxygenation, while minimising ventilator-induced and patient self-inflicted lung injury. We aimed to review the literature relating to invasive ventilation strategies in patients with acute respiratory distress syndrome receiving extracorporeal support and discuss personalised ventilation approaches and the potential role of adjunctive therapies in facilitating lung protection.

Thyroid storm following suicide attempt by hanging.

Summary A 19-year-old woman with asphyxiation complicated by cardiac arrest, following an unsuccessful suicide attempt by hanging, developed an uncommon complication of trauma-induced thyroid storm. She was initially admitted to the intensive care unit intubated and mechanically ventilated for postcardiac arrest management. Investigation of thyroid storm was pursued after the patient was noted to be persistently hypertensive, tachycardic and agitated despite high levels of sedation. Thyroid function tests confirmed the clinical suspicion of progressive thyrotoxicosis, with associated imaging consistent with thyroid inflammation secondary to band-like traumatic pressure to the lower half of the thyroid gland. Treatment with ß-blockers and a thionamide resulted in the eventual resolution of her thyroid storm state and normalisation of her thyroid function. We conclude that traumatically induced thyroid storm should be considered in all hypermetabolic patients following blunt neck injuries including hanging, and that traditional treatment of hyperthyroidism can be successfully applied.

Posterior reversible encephalopathy syndrome resulting from repeat bortezomib usage.

Bortezomib is a chemotherapeutic agent that acts via proteasome inhibition resulting in cellular apoptosis and inhibition of angiogenesis. Although widely accepted as treatment of multiple myeloma and non-Hodgkin's lymphoma, it has also been shown to be efficacious in a variety of solid tumours such as pancreatic and colonic. Posterior reversible encephalopathy syndrome (PRES) is a neuroradiological syndrome characterised by vasogenic oedema involving the postero-occipital cortical and subcortical white matter resulting in visual disturbances, seizures and altered mental status. Although in most cases PRES is reversible with removal of the provoking condition or drug, if not appropriately recognised and treated it may lead to permanent and life-threatening sequelae such as intracerebral haemorrhage and ischaemic infarction. We report a case of PRES associated with bortezomib therapy and contrast it with four other previously reported cases. Recognition of this potentially severe neurological complication is important with the increasingly widespread use of bortezomib.

Characterisation of integrin-linked kinase signalling in sporadic human colon cancer.

The putative oncogene, integrin-linked kinase (ILK) is a protein serine/threonine kinase that has been reported to regulate a number of biological properties including anchorage-independent cell cycle progression, tumour cell invasion and apoptosis. Overexpression of ILK has been documented in a wide variety of human malignancies including Ewing's sarcoma (ES), primitive neural ectodermal tumours (PNETs) and prostate tumours (PT). We recently reported that ILK signalling was also dysregulated in patients with the genetic condition familial adenomatous polyposis (FAP), a precursor to colon cancer. In this study, we extended our previous work by investigating the ILK-signalling pathway in sporadic human colon cancer and representative lymph node metastases. The data indicate that the ILK protein is significantly hyperexpressed in malignant acini in relation to normal crypts. Moreover, overexpression of ILK not only coincided with increased MBP phosphotransferase activity but as well with effects on downstream targets like GSK3beta. Based upon the presented data, we propose that ILK signalling is dysregulated early during the development of human colon cancer, and that selective inhibition of this molecule alone or in combination with the standard therapeutic modality might be a more effective means of treating colon cancer.

Curcumin attenuates DNB-induced murine colitis.

Numerous therapies used for inflammatory bowel disease (IBD) target the transcription factor NF-kappaB, which is involved in the production of cytokines and chemokines integral for inflammation. Here we show that curcumin, a component of the spice turmeric, is able to attenuate colitis in the dinitrobenzene sulfonic acid (DNB)-induced murine model of colitis. When given before the induction of colitis it reduced macroscopic damage scores and NF-kappaB activation. This was accompanied by a reduction in myeloperoxidase activity, and using semiquantitative RT-PCR, an attenuation of the DNB-induced message for IL-1beta was detected. Western blotting analysis revealed that there was a reproducible DNB-induced activation of p38 MAPK detected in intestinal lysates by using a phosphospecific antibody. This signal was significantly attenuated by curcumin. Furthermore, we show that the immunohistochemical signal is dramatically attenuated at the level of the mucosa by curcumin. We conclude that the widely used food additive curcumin is able to attenuate experimental colitis through a mechanism correlated with the inhibition of the activation of NF-kappaB and effects a reduction in the activity of p38 MAPK. We propose that this agent may have therapeutic implications for human IBD.