End of life rally

When a terminal patient seems to recover briefly just before dying in the coming days. A NYT article with examples. So far unexplained. And the rest of the article won't either, so feel free to stop here.

This actually happened to my dad. He had pneumonitis, reading for 2-3 days about 65% of oxygen saturation with full supply of oxygen through a mask. Then it started improving, reading close to 80% by the time we left the hospital that night. The next day in the morning he was sitting on his bed eating his breakfast and the mask by the side of his face. The nurse later in the day saw the oxygen saturation again around 65% and made a comment "I knew there had to be something wrong, the nurse in the morning told me an unbelievable good number...". This was not a continuous monitor so we couldn't see the readings and she didn't tell us what the other nurse had read, but I believe that they saw more than 90% that morning when he was doing fine. The next day he died :_(

As the article explains, this is not particular to a given disease and actually it happens with other ones (stroke, dementia, brain cancer, heart disease, colon cancer...). The explanations seem to try to solve the mystery individually for each disease but what if the body had a powerful universal mechanism to try to fight death? Even if it was an individual one, what if we could extend it or replicate it? Hence my interest... As usual, will post as I learn...

Cheers!

PS.: I can't believe no one has done any serious research on this.

In memory of my beautiful dad

In memory of my beautiful dad, who past away two weeks ago. :_(

Today is an ironic day. It is father's day in the US. It is also the same day that we deposit his ashes in the cemetery. It may sound like cliche, but he was truly the best father anyone can have. A humble driver married to a wonderful woman, a nurse, and all what he did from there on was to care for their sons and daughter. He was warm, fun to be around, had great sense of humor and did one fine job at raising us. Not sure how he figured it out (with my mom), but that achievement alone says a lot about him.

If anything you can learn from this page, go tell your dad if he is still around how much you appreciate him. I don't think we ever told him enough. He is supposed to be that tough guy that doesn't need to hear it... but I am sure he will be happy to hear you say it.

Te quiero.

Whole body MRI scans for preventive screening

With the advances in MRI speed, it is very tempting to get a full body scan to detect stuff that may not be yet symptomatic. In my view, go for it (I plan to discuss it with my doctor**). It is not a bullet proof approach (with misses and false positives) but overall reading the 3 papers below, looks like worth the investment.

I am talking about MRI without contrast. No whole body CT scans as I really believe that no one should do those due to the high radiation levels. Don't want to get a cancer where there was none. I posted on this long ago and most of the experts/doctors will advice against them.

For MRI, except for the contrast, it is completely safe. Notice that traditionally there are real concerns with contrast (serious allergic reactions...) hence should not be used for screening. On top of those, there are new concerns. So let's investigate the other aspects, specially effectiveness without contrast:

• A paper on the topic of screening asymptomatic patients. Patients paid for the screening. They caught a small percent. So, somebody could argue it wasn't cost effective (see PS) but tell that to the two guys with malignant lesions. [Whole-Body MRI Screening in Asymptomatic Subjects - Preliminary experience and long term follow up findings]
• Similar paper with 229 patients and similar conclusions. It does explain also limitations, mostly due to the lack of contrast agent and the limitations set on scan time [An initial experience with the use of whole body MRI for cancer screening and regular health checks]
• Finally one specific to cancer detection. Goes through the different types of cancer and the MRI limitations so it is not a bullet proof approach, but still says it is a good thing, although on the context of diagnoses more than screening.

** Looks like worth getting (again without contrast), but doctor steered me away from it (even when I said I would pay). In my case we are looking to diagnose something quite specific under my rib cage so, suggested an ultrasound. So, waiting for those results but I think that I will probably still do the WB MRI.

On that sense, as usually insurance (public or private) won't pay for it, where to get it? Basically do a search on your browser. Some places nearby my location that pop up (pure examples, no recommendation):

1. Human Longevity
2. Desert Medical Imaging
3. UTSW on full skeleton scan in 7 minutes

Research/startups:

1. Erza: on  the news
2. Amra Medical: Focus on body composition

Other whole body scans:

1. ViaScan: does not talk about MRI (!). It seems to talk about EBT which I didn't realize was around and if it is what I think, it is a CT scan without movable parts (the x-ray beam is produced by an electron beam raster). Claims to be 90% of a CT scan but I don't know how that would be (the detector efficiencies, etc... are the same). That is different from photon counting CT that eventually will be out and does have the promise to reduce dose, but at the time of writing this there are only couple of systems out there.

PS.: Wilson's criteria and WHO criteria for screening. Some may make sense, like why to screen for something if it doesn't have a cure, or if the test in question is really not a good test (lots of false positives or misses). But others are purely economical (!).

Jargon

See below my list, but before that, you may want to check others out there:

1. Genomics Glossary by the NHGRI

Not all alphabetical as in some cases makes more sense to group them. Also, this is work in progress (pardon the chaos):

• ccRCC: clear cell renal cell carcinoma
• ESCM: Extramedullary spinal cord metastases
• ISCM: Intramedullary spinal cord metastases 
• TAA: tumor associated antigen (a tumor marker)
• Pathological diagnosis: aka biopsy
• FNAC: fine needle aspiration cytology. One biopsy method to collect the sample.
• Immunochemical staining: the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to antigens in biological tissues. 
• Immunogenic: able to produce an immune response.
• Immunogenic antigens:
• Neoantigens:
• Peptide:
• Neopitopes:
• Proteomics:
• Immunoproteomics:
• Autoantibodies:
• Cytosol:
• RNA:
• Exome: 
• Somatic mutation:
• MHC:
• HEV: High endothelial venues
• TIL: Tumor infiltrating lymphocyte
• in vivo
• in vitro
• FAP: fibroblast activation protein,
• Stromal cell
• CAF: cancer associated fibroblasts
• TIE: transarterial immuno embolization
• TAM: tumor-associated macrophage
• TNA: tumor-associate neutrophil
• MDSC: myeloid-derived suppressor cells.
• Tumor rechallenge
• TME: tumor micro-environment
• Glycolytic metabolism
• Hypoxia
• Upregulate
• Cytokine:
• Humoral Immunity:
• Extravasation: exit the vessel
• ROS: reactive oxygen species
• Haematopoiesis: the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately 10¹¹–10¹² new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.
• HSC: Haematopoietic stem cells: An immature cell that can develop into all types of blood cells, including white blood cells, red blood cells, and platelets. Hematopoietic stem cells are found in the peripheral blood and the bone marrow.
• Phenotype: all the observable characteristics of an organism that result from the interaction of its genotype (total genetic inheritance) with the environment. Examples of observable characteristics include behaviour, biochemical properties, colour, shape, and size.
• Homeostasis: the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes.
• CRISPR/Cas9, 
• ZFNs zinc finger nucleases 
• Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen. The mechanism of action of a mitogen is that it triggers signal transduction pathways involving mitogen-activated protein kinase (MAPK), leading to mitosis
• Stroma: the supportive tissue of an epithelial organ, tumor, gonad, etc., consisting of connective tissues and blood vessels.
• Soma: the parts of an organism other than the reproductive cells.  
• Chimera: A genetic chimerism or chimera is a single organism composed of cells with distinct genotypes.
• Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response
• Iatrogenic: doctor-caused 

• Neoplasia: the presence or formation of new, abnormal growth of tissue.
• Oligometastasis: spread to only one or two sites
• Adjuvant: (therapy) applied after initial treatment for cancer, especially to suppress secondary tumour formation.
• Systemic: full body
• Comorbidity: presence of one or more additional conditions co-occurring with a primary condition
• Angiotropism: travel along the outside of blood vessels, without entering into the bloodstream

• Median OS (overall survival): The length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that half of the patients in a group of patients diagnosed with the disease are still alive.
• Median PFS: The length of time during and after the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse. In a clinical trial, measuring the progression-free survival is one way to see how well a new treatment works.
• ORR: Objective Response Rate 
• RECIST: Response evaluation criteria in solid tumors (RECIST) is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize"), or worsen ("progress") during treatment.

• Exophytic:
• Microvascular density (MVD):
• Immune checkpoint inhibitor: A type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells. These proteins help keep immune responses in check and can keep T cells from killing cancer cells. When these proteins are blocked, the “brakes” on the immune system are released and T cells are able to kill cancer cells better. Examples of checkpoint proteins found on T cells or cancer cells include PD-1/PD-L1 and CTLA-4/B7-1/B7-2. Some immune checkpoint inhibitors are used to treat cancer.

• Hemostasis: the stopping of a flow of blood (related to coagulation)
• Homeostasis: the tendency toward a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes

Spanish:

• Patologia, Histopatologia: tissue study
• Citopatologia: analysis of free cells or tissue fragments
• Mielopatía: afección crónica de la médula espinal (generalmente se usa el término cuando la afección no es causada por inflamación o traumatismo aunque existen excepciones)

Can cancer spread through a biopsy?

The term is called "seeding" and the answer to the title question is "certainly". I feel this literature review paper does a good job explaining it: Risk of tumor cell seeding through biopsy and aspiration cytology

Notice that it is not the same risk for all type of tumors (watch with breast and liver biopsies) but somehow internet and forums play down the risk. Nevertheless that may be more ignorance or trying to calm folks on something that anyhow may have to be done no matter the concerns. Probably the advice here is to think and even get further opinions before poking. In that sense, read the first reference of the above paper for something more dramatic, from a different angle/type author (naturist, which I plan to explore on separate post). Talks also about the risks of spreading through surgery.

The review above does not mention melanoma (I think) so I searched a bit on that case and looks like it can also happen but very seldom (see here and here). Maybe because the whole thing is removed soon after?

Clinical trials

1. Find yours/contact them to join
2. What are the phases of clinical trials
3. Metrics of clinical trials: how scientists determine how worth is a given treatment.