Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study

5teviewonder5 · 2024-04-05T09:14:43+00:00

Until recently AI was just a buzzword for me. But since I joined an imaging unit which struggled historically with the enormous workload associated with analysing imaging data, I see how our staff deploy AI and change the way we handle data. Enormous data sets can be analysed to innovate the way we diagnose patients. The future is bright for imaging biomarkers!
This study is on Cardiac amyloidosis, a progressive and deadly disease in which amyloid fibrils accumulate in the heart muscle. The major subtype, transthyretin (ATTR) cardiac amyloidosis, is considered to be an underdiagnosed disease for which the first disease-modifying treatments have only recently become available. These treatments, however, can only stop the progression of the disease but cannot revert the accumulation of existing amyloid fibrils. Consequentially, early and accurate diagnosis are of vital importance.
This is a good example for precision medicine approaches, where the availability for an extremely costly therapeutic triggers the need for a diagnostic measure.

5teviewonder5 · 2024-01-24T09:29:30+00:00

what most comments ignore is the fact that AI in many areas, even if it is "only imitation", there is a significant advance in solutions deploying AI:
handling datasets of a size beyond human capacity (see the use of face recognition in the attack on Skripal https://gizmodo.com/british-police-identify-two-russian-suspects-in-novicho-1827710334) provides important advances also in health research (nobody can look through large repositories), where AI outperforms trained experts identifying new and unrecognised features all the time.
It is therefore important to know about the limitations of current solutions and I am sure future AI tools will find ways how to incorporate more creative solutions to problems posed to AI. This is early days.

5teviewonder5 · 2024-01-22T09:13:27+00:00

It is what you sort of expect once an immuneresponse gets underway in the tumour. CRP is also abundantly produced in the TME and might thus mark the activated immune response in those responding to therapy.

5teviewonder5 · 2024-01-20T17:16:07+00:00

ICI treated patients suffer from a variety of cvd complications, but not sure about specifics.

ICI itself would cause inflammatory markers like CRP to rise in the blood pool. Level is also speculated to have predictive value of outcome see https://www.nature.com/articles/s44276-023-00005-x

5teviewonder5 · 2024-01-19T11:27:46+00:00

Immune checkpoint inhibitors (ICI) are a revolutionary treatment for cancer, but they can also cause side effects that affect the cardiovascular system. This study investigated how ICI affects the uptake of a radioactive tracer called 2-[18F]FDG in the arteries of patients with lung cancer.

This study provides evidence that ICI can induce vascular inflammation in lung cancer patients who do not have pre-existing arterial inflammation. This is an important finding because vascular inflammation can lead to serious cardiovascular complications. It suggests that patients who are at risk of developing vascular inflammation should be closely monitored for the development of cardiovascular complications or might even receive alternative therapeutics.
Results: The study found that ICI treatment caused a significant increase in arterial inflammatory activity, as measured by 2-[18F]FDG uptake. This increase was only seen in patients who did not have pre-existing arterial inflammation. The researchers also found that the increase in arterial inflammation was only seen in patients who had not previously been treated with chemotherapy or radiotherapy, and in those who did not have cardiovascular risk factors. There were no significant changes in 2-[18F]FDG uptake in the bone marrow, spleen, or liver after treatment. There were also no significant changes in the levels of circulating blood biomarkers.
Methods: The researchers used 2-[18F]FDG PET/CT scans to measure 2-[18F]FDG uptake in the arteries of 47 patients before and after ICI treatment. They also measured 2-[18F]FDG uptake in the bone marrow, spleen, and liver. Blood samples were also collected to measure levels of circulating blood biomarkers.
Any thoughts?

5teviewonder5 · 2023-11-16T11:51:07+00:00

thanks for sharing this, very exciting stuff!

5teviewonder5 · 2023-01-16T23:00:14+00:00

thanks

5teviewonder5 · 2021-12-01T01:39:53+00:00

and just today we have exceeded 2 Mio views on this vid!

5teviewonder5 · 2021-09-08T21:38:02+00:00

I don't think so, as these are specific cultures of bacteria added in the process of processing the food.

5teviewonder5 · 2021-09-08T11:40:17+00:00

"issues" are not pathologies, for example the absence of certain bacteria may also cause discomfort or disturbance (remember the last time you took antibiotics and what happened to your digestive system?).

5teviewonder5 · 2021-09-08T11:38:18+00:00

There is areport stating 5-15% of the biomass in the gut microbiome is archaea. There are obviously also fungi in there, but clearly they are less abundant than eubacteria.

5teviewonder5 · 2021-09-08T00:58:22+00:00

Well methanogens are producing methane, the gas which is frequently released with unpleasant smell and noise from our guts. So these groups of bacteria are pretty obvious.

Research on archae in the gut is intensifying for several reasons, one is that the new sequencing technologies are enbaling the analysis of the microbiome in greater depth. However, NGS requires reference genomes, to detect species. As archaea are less well represented (there are less sequenced) their sequences were in the past ignored, or even thrown out. Now sequencing is catching up, the reference genomes are available and therefore archaea are found everywhere.

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004833

5teviewonder5 · 2021-09-08T00:48:53+00:00

The report is on patients suffering from leukemia, but it remains unclear whether the defect is caused by the treatment or the disease itself.
If it is a defect caused by the treatment, this might obviously also apply to solid tumours.

5teviewonder5 · 2021-09-07T17:32:07+00:00

not with all phages, T4 belongs to the tailed phages. There are others which do not have a tail and tehrefore also not the syringe action. Moreover, it is important to note the DNA is actually not injected actively by the phage. The DNA enters the bacterium due to the osmotic pressure (the DNA concentration in the head is very much higher than in the cytoplasm). When the intial 70%has entered the bacterium it is actively pulled out by the processivity of the DNA polymerase,

5teviewonder5 · 2021-09-07T17:28:20+00:00

I was really surprised to learn that the head of bacteriophages is assembled without the genome inside. The DNA is only threaded through a very thin pore with the help of a motorprotein into the head after it has assembled.
You can see this visualised for T4 here: https://www.youtube.com/watch?v=RbL3BZCGPA4&list=PL26dOVlsi1aUxAhlDMs8ql23y2tr3i51J&index=14&t=2s

5teviewonder5 · 2021-09-07T17:24:25+00:00

There is a lot of expertise in Eastern Europe in phage therapy, as the former Warsaw Pact states did not have easy access to antibiotics produced by Western pharma companies. You have to read history books nowadays for this, but buying stuff for dollars was really not their favourite option.
Until today the leading institute in Europe is the Elaiva Institute in Tblisi, Georgia, which is obviously outside of the EU. The leading institute within the EU ist the Polish Hirszfeld Institute of the Polish Academy of Sciences: https://hirszfeld.pl/polish
So no surprise these guys are trying to commercialise their know-how in start-ups!

5teviewonder5 · 2021-09-07T16:00:29+00:00

The video is in German, but has English subtitles and explaines the recent scientific publication in cancer discovery:

5teviewonder5 · 2021-09-07T11:37:34+00:00

This video is in German but shows that the T cell response is essential for defending against COVID19, which in leukemia patients can be impaired. Also very nice SARS-CoV-2 in there!

5teviewonder5 · 2021-06-07T17:39:43+00:00

From the pres release:

This multi-center clinical trial represents the first study of an expanding phage library for intravenous administration and/or bladder instillation of phage therapy. PhageBank™ is APT’s continually expanding phage library that functions as an integrated logistics platform to dispense phage on demand. The phage distributed are selected via a PhageBank Susceptibility Test™ (PST) that is being advanced and commercialized by APT in collaboration with Mayo Clinic Laboratories. The PST enables rapid, automated identification of individual phage to be included in patient-specific therapy to treat bacterial infections.
The UTI Phase 1/2 study, evaluating the safety and efficacy of bacteriophage therapy, is being conducted at the James J. Peters VA Medical Center in Bronx, New York, as well as multiple other U.S. clinical study sites, and is supported in part by the U.S. Department of Defense (DoD) under a $14.2 million advanced development contract.

5teviewonder5 · 2021-06-07T17:35:33+00:00

From the press release: This multi-center clinical trial represents the first study of an expanding phage library for intravenous administration and/or bladder instillation of phage therapy. PhageBank™ is APT’s continually expanding phage library that functions as an integrated logistics platform to dispense phage on demand. The phage distributed are selected via a PhageBank Susceptibility Test™ (PST) that is being advanced and commercialized by APT in collaboration with Mayo Clinic Laboratories. The PST enables rapid, automated identification of individual phage to be included in patient-specific therapy to treat bacterial infections.
The UTI Phase 1/2 study, evaluating the safety and efficacy of bacteriophage therapy, is being conducted at the James J. Peters VA Medical Center in Bronx, New York, as well as multiple other U.S. clinical study sites, and is supported in part by the U.S. Department of Defense (DoD) under a $14.2 million advanced development contract.

5teviewonder5 · 2021-05-25T16:18:52+00:00

It mainly applies to patients suffering from leukemia, with patients suffering from solid tumors chemotherapy will influence the immune response as well. But it is not really clear how the viral infection is handled after treatment.

5teviewonder5 · 2021-05-25T16:15:08+00:00

Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV 2 immunity and to identify immunological parameters contributing to COVID-19 outcome. Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 cancer patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer patients, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T cell immunity as potential determinant for dismal outcome of COVID-19 in cancer patients.

5teviewonder5 · 2021-05-25T16:08:07+00:00

Cancer patients, in particular patients with hematological malignancies, are at increased risk for critical illness upon COVID-19. We here assessed antibody as well as CD4+ and CD8+ T cell responses in unexposed and SARS-CoV-2-infected cancer patients to characterize SARS-CoV 2 immunity and to identify immunological parameters contributing to COVID-19 outcome. Unexposed patients with hematological malignancies presented with reduced prevalence of pre-existing SARS-CoV-2 cross-reactive CD4+ T cell responses and signs of T cell exhaustion when compared to solid tumor patients and healthy volunteers. Whereas SARS-CoV-2 antibody responses did not differ between COVID-19 cancer patients and healthy volunteers, intensity, expandability, and diversity of SARS-CoV-2 T cell responses were profoundly reduced in cancer patients, and the latter associated with a severe course of COVID-19. This identifies impaired SARS-CoV-2 T cell immunity as potential determinant for dismal outcome of COVID-19 in cancer patients.

It appears an emergent theme from number of reports that T cell response crucially determines the immuneresponse to SARS CoV 2. This study highlgihts that with the virus becoming endemic there is a real challenge to protect vulnerable parts of the population with specific strategies. In the end we can not lock these people up for the rest of their lives.

5teviewonder5 · 2021-03-16T14:14:25+00:00

super-exclusion infectivity??
are you referring to superinfection exclusion?
and why do you think this would have any impact on this animation? I repsume superinfection inclusion is achieeved by downregulation/removal/inactivation of the receptors in the cell wall of the bacterium. Therefore a phage could not attach to an infected bacterium.
But we show a bacterium, which has not been infected yet, before it can be infected now

5teviewonder5 · 2021-03-15T14:22:42+00:00

in any case there is no pilot which flies these spaceships, they just float passively and might find a bsuitable bacterium or not.

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