Cell death used to be easy

I was recently happy to be asked to write a chapter about cell death in the new version of the Swedish textbook on intensive care medicine (You'll find the previous edition here we expect the new one to be published in 2019). Touching up on cell death i found this paper where the leaders everyone in the field spell out the latest understanding about different forms of regulated cell death.

When I last read about cell death it was recognised that there were two basic types, necrosis, that is normal cell death, and apoptosis or programmed cell death. I had heard a little about necroptosis, as it was recently shown to be important in the kidney. I also recognised the name autophagy, but rather thought it was something liver cells did in starvation. It still does, but now it is also a general term for a kind of cell death machinery as well.

It turns out there are now twelve types of regulated cell death (RCD), and even the morphology is no longer any indication of the type of cell death involved. Because, as they write,

"Moreover, each type of RCD can manifest with an entire spectrum of morphological features ranging from fully necrotic to fully apoptotic, and an immunomodulatory profile ranging from anti-inflammatory and tolerogenic to pro-inflammatory and immunogenic."

This plethora of mechanisms does rather complicate the understanding of cell death. Especially so as most of the mechanisms can be activated a little bit and then regress, as long as the death threshold has not been reached. And, even more so as they may switch mechanism if you try to intervene against one of the pathways. This is actually one of the major take-home messages of the paper. We have tried a number of different cell death inhibitors that seem to work in experimental systems where the trigger is controlled. However, when we try them out in patients we find that the cells die anyway.

On the other hand, the great number of different mechanisms opens the possibility of an equally great number of new and shiny papers.

Monitoring in anaesthesia and intensive care - 8th Hedenstierna symposium

Activity has not been the highest as of late, but now I am back (perhaps anyway). Today I attended the Hedenstierna symposium in Uppsala on the actual 77th birthday of Göran Hedenstierna himself. He attended, as he always does, and he was suitably embarrassed when the whole meeting sang happy birthday to him.

The good thing with having a famous scientist to name your seminar after is that you can attract real top-names from around the world. This means there are ample opportunities to expand your network both in your field and in associated fields. There were the brilliant Göran Stemme, group leader from KTH who developed the microneedles me and his former student Niclas Roxhed wrote about some years ago. Then Michell Chew chewed on about the very current area of using point-of-care ultrasound in intensive care, and Fernando Sipmann simpered (not really) on monitoring the respiration. After lunch, Declan Bates declared a sermon on mathematical modelling that none of us really understood, but it was very impressive. Finally, Marlies Ostermann orated about the actually important organs, the kidneys. She had a hard time convincing the mostly respiratory scientists in the audience that kidneys are quite simple and just the most fun to be had in physiology.

It wasn't really the final talk, there were Johanna Hästbacka from Helsinki who talked on monitoring inflammation, and Emory Brown from America on neuromonitoring, but I had to pick up my dog from daycare and missed out.