Monday 27 March 2017

Lungs play a key role in blood production.

Lungs play a key role in blood production



An Unexpected New Lung Function Has Been Found - They Make Blood
Bec Crew ScienceAlert | http://www.sciencealert.com/an-unexpected-new-lung-function-has-been-discovered-and-it-could-disrupt-decades-of-scientific-thought

Researchers have discovered that the lungs play a far more complex role in mammalian bodies than we thought, with new evidence revealing that they don't just facilitate respiration - they also play a key role in blood production.

In experiments involving mice, the team found that they produce more than 10 million platelets (tiny blood cells) per hour, equating to the majority of platelets in the animals' circulation. This goes against the decades-long assumption that bone marrow produces all of our blood components.

Researchers from the University of California, San Francisco also discovered a previously unknown pool of blood stem cells that makes this happen inside the lung tissue - cells that were incorrectly assumed to
mainly reside in bone marrow.

"This finding definitely suggests a more sophisticated view of the lungs - that they're not just for respiration, but also a key partner in formation of crucial aspects of the blood,"
says one of the researchers, Mark R. Looney.

"What we've observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well."

While the lungs have been known to produce a limited amount of platelets - platelet-forming cells called
megakaryocytes have been identified in the lungs before - scientists have long assumed that most of the cells responsible for blood production are kept inside the bone marrow.

Here, a
process called haematopoiesis was thought to churn out oxygen-laden red blood cells, infection-fighting white blood cells, and platelets - blood components required for the clotting that halts bleeding.

But scientists have now watched megakaryocytes functioning from within the lung tissue to produce not a few, but most of the body's platelets.

So how did we miss such a crucial biological process this whole time?

The discovery was made possible by a new type of technology based on two-photon intravital imaging - a similar technique to one used by
a separate team this week to discover a previously unidentified function of the brain's cerebellum.

The process involves inserting a substance called
green fluorescent protein (GFP) into the mouse genome - a protein that's naturally produced by bioluminescent animals such as jellyfish, and is harmless to living cells.

The mouse platelets started to emit bright green fluorescence as they circulated around the body in real time, allowing the team to trace their paths like never before.

They noticed a surprisingly large population of platelet-producing megakaryocytes inside the lung tissue, which initially didn't make much sense, seeing as they're usually associated with
bone marrow.

"When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realised we had to follow this up,"
says one of the team, Emma Lefrançais.

They found that this huge supply of megakaryocytes is actually producing more than 10 million platelets per hour in the lungs of mice, which means at least half of the body's total platelet production is occurring in the lungs.

Here's what it looks like:
Further experiments also revealed vast amounts of previously hidden blood stem cells and
megakaryocyte progenitor cells (cells that give rise to megakaryocyte and red blood cells) sitting just outside the lung tissue - about 1 million per mouse lung.

When the researchers traced the entire 'life cycle' of the megakaryocytes, they found that they likely originate in the bone marrow, then make their way to the lungs, where they start platelet production.

"It's fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,"
says one of the team, Guadalupe Ortiz-Muñoz.

"It's possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signalling we don't yet know about."

The researchers wanted to investigate if their discovery could have an effect on how we treat disorders such as lung inflammation, bleeding, and transplantation in the future, by transplanting lungs with fluorescent megakaryocyte progenitor cells into mice with low platelet counts.

The transplants produced a massive burst of platelets that quickly restored the depleted platelet counts to normal levels, and the effect lasted for several months.

Another experiment tested what would happen if the bone marrow wasn't playing a role in blood production.

The team implanted lungs with fluorescent megakaryocyte progenitor cells into mice that had been engineered to have no blood stem cells in their bone marrow.
As Michael Irving reports for New Atlas, they watched as the fluorescent cells from the transplanted lungs made their way to the bone marrow, where they not only helped to produce platelets, but also other key blood components, such as neutrophils, B cells and T cells.

The findings will need to be replicated in humans before we can know for sure that the same process is occurring within our own bodies, but the study makes a strong case for this hidden function in what could be one of our most underrated organs.

It will likely also prompt scientists to investigate further how the bone marrow and lungs work together to produce our blood supply.

"It has been known for decades that the lung can be a site of platelet production, but this study amplifies this idea by demonstrating that the [mouse] lung is a major participant in the process," Traci Mondoro from the US National Heart, Lung, and Blood Institute, who was not involved in the study,
said in a press statement.

"Looney and his team have disrupted some traditional ideas about the pulmonary role in platelet-related hematopoiesis, paving the way for further scientific exploration of this integrated biology."

Sunday 5 March 2017

10 MRI Scans, 10 Different Diagnoses on same patient

10 MRI Scans, 10 Different Diagnoses on same patient

Spine J. 2016 Nov 17. pii: S1529-9430(16)31093-2. doi: 10.1016/j.spinee.2016.11.009. [Epub ahead of print]
https://www.ncbi.nlm.nih.gov/pubmed/27867079
Variability in diagnostic error rates of 10 MRI centers performing lumbar spine MRI examinations on the same patient within a 3-week period.Herzog R1, Elgort DR2, Flanders AE3, Moley PJ4.


BACKGROUND CONTEXT:

In today's health-care climate, magnetic resonance imaging (MRI) is often perceived as a commodity-a service where there are no meaningful differences in quality and thus an area in which patients can be advised to select a provider based on price and convenience alone. If this prevailing view is correct, then a patient should expect to receive the same radiological diagnosis regardless of which imaging center he or she visits, or which radiologist reviews the examination. Based on their extensive clinical experience, the authors believe that this assumption is not correct and that it can negatively impact patient care, outcomes, and costs.

PURPOSE:
This study is designed to test the authors' hypothesis that radiologists' reports from multiple imaging centers performing a lumbar MRI examination on the same patient over a short period of time will have (1) marked variability in interpretive findings and (2) a broad range of interpretive errors.

STUDY DESIGN:
This is a prospective observational study comparing the interpretive findings reported for one patient scanned at 10 different MRI centers over a period of 3 weeks to each other and to reference MRI examinations performed immediately preceding and following the 10 MRI examinations.

PATIENT SAMPLE:
The sample is a 63-year-old woman with a history of low back pain and right L5 radicular symptoms.
OUTCOME MEASURES:

Variability was quantified using percent agreement rates and Fleiss kappa statistic. Interpretive errors were quantified using true-positive counts, false-positive counts, false-negative counts, true-positive rate (sensitivity), and false-negative rate (miss rate).

METHODS:
Interpretive findings from 10 study MRI examinations were tabulated and compared for variability and errors. Two of the authors, both subspecialist spine radiologists from different institutions, independently reviewed the reference examinations and then came to a final diagnosis by consensus. Errors of interpretation in the study examinations were considered present if a finding present or not present in the study examination's report was not present in the reference examinations.

RESULTS:
Across all 10 study examinations, there were 49 distinct findings reported related to the presence of a distinct pathology at a specific motion segment. Zero interpretive findings were reported in all 10 study examinations and only one finding was reported in nine out of 10 study examinations.

Of the interpretive findings, 32.7% appeared only once across all 10 of the study examinations' reports.

A global Fleiss kappa statistic, computed across all reported findings, was 0.20±0.06, indicating poor overall agreement on interpretive findings. The average interpretive error count in the study examinations was 12.5±3.2 (both false-positives and false-negatives). The average false-negative count per examination was 10.9±2.9 out of 25 and the average false-positive count was 1.6±0.9, which correspond to an average true-positive rate (sensitivity) of 56.4%±11.7 and miss rate of 43.6%±11.7.


CONCLUSIONS:
This study found marked variability in the reported interpretive findings and a high prevalence of interpretive errors in radiologists' reports of an MRI examination of the lumbar spine performed on the same patient at 10 different MRI centers over a short time period. As a result, the authors conclude that where a patient obtains his or her MRI examination and which radiologist interprets the examination may have a direct impact on radiological diagnosis, subsequent choice of treatment, and clinical outcome.

Copyright © 2016 Elsevier Inc. All rights reserved.

More time walking means less time in hospital

New study shows more time walking means less time in hospital

https://theconversation.com/new-study-shows-more-time-walking-means-less-time-in-hospital-71554


In my practice as a GP, I have been impressed by a few energetic and active 80 year olds who remain in good health while many their age have succumbed to various chronic diseases. So in 2005, when the University of Newcastle established a
large community based health study of people aged 55 to 80, I made sure we recorded the participants’ physical activity in detail.

A decade later, we can report the influence of physical activity on the need for hospital care as published in the
Medical Journal of Australia today.

We used pedometers to record daily step counts, giving a much more precise measure of activity than the usual self-report questionnaires. Median daily step counts ranged from 8,600 in the youngest to 3,800 in those over 80 years, and weekend days had on average 620 fewer steps than weekdays.

The inactive people (taking 4,500 steps per day) averaged 0.97 days of hospital care per year. The more active people (taking 8,800 steps per day) needed only 0.68 days of care per year. In our analysis we adjusted for the effects of age, sex, the number of illnesses people had when they started, smoking, alcohol intake and education.

We wondered if the causation might be running the opposite direction. That is, that sick people walk less rather than activity preventing illness. To test this idea, we repeated the analysis ignoring all hospital admissions in the first two years of follow up to remove the immediate effects of serious illness. The difference is shown in the graph below.

The association extends right across the range of activity levels, showing any activity is good for health, and the more the better. The participants in our study wore the pedometers from morning until night, so a lot of what we recorded as steps was general activity around the house or the workplace, not necessarily continuous walking.
Recent research shows any that activity is better than sitting down, so even light activity is protective of health. Pedometers don’t capture swimming or cycling accurately, but these things make up a small part of daily activity.

Looking at why these patients were in hospital, more active people had fewer admissions for cancer and diabetes, but surprisingly, there was no difference for heart disease. We suspect that might be due to a gap in the data for heart admissions to private hospitals for a few of the years.
What if everyone got walking?

The difference of 0.29 hospital days per year between the inactive and active people is about a 30% reduction. Does this mean if we could get everyone in the population taking 8,800 steps per day we could shut a third of all hospital beds, and send a third of all doctors and nurses off to practice their golf swing? Unfortunately not.

It turns out our study sample is a rather healthy lot, requiring less hospital care than the average for their age. Compared to our average value of less than one day per year of hospital care, figures from the
Australian Institute of Health and Welfare for 2014-15 show Australians between 55 and 85 years required 14.2 million days of hospital care, or 2.65 bed days per person.
Getting in 40 minutes of walking a day would reap big rewards in overall health.

Whether increasing activity would be of more or less benefit across the whole of the Australian population is unclear. It may be that the general population would have even more to gain from physical activity than our study participants, or it may be that they have serious chronic diseases that make increased activity impossible.

Let’s imagine for a moment that something changes the walking habits of all Australians, so everyone is walking at least 8,800 steps per day – maybe a combination of a Fitbit craze and an oil shortage that sends petrol to A$10 a litre. What effect would this have on health services?

Considering only the people aged over 55, at a minimum it would reduce the need for hospitalisation by 975,000 bed days per year, for a saving of $1.7 billion dollars. Given there are health benefits at other ages, and the less healthy Australians not represented in our study could benefit more, the actual benefit is likely to be even greater.

An extra 4300 steps per day is not much.
It’s just 40 minutes walking, which might include going to the shops, picking up kids, or taking the stairs at work. It doesn’t have to be “exercise”, although higher intensity activity for those who enjoy it has greater health benefits.
With governments searching for ways to reduce spending, and
16% of the federal budget being spent on health, tackling physical inactivity of individual patients, as well as ensuring our urban centres are walking- and cycling-friendly would make a major difference.