BC HEALTH
Saved by @WebbDarrrel

It's Monday AM post-@ASCO #GU21 & clinic starts in a couple of hours! Lots to process - I'll try to tackle optimal 1L tx for #kidneycancer. I'll make a case for cabo/nivo, leaning on the beautiful (& timely) tables below from @lalaniMD, @SoaresAndrey & @brian_rini (1/15)

 What about IO/IO? We have long f/u w #CM214 data w nivo/ipi, no doubt (@AlbigesL et al in @myESMO Open). And treatment-free interval discussed by McDermott @BIDMChealth is no doubt impt. But we've known data not as impressive for favorable risk (2/15)
And furthermore, as @ERPlimackMD points out in another tweet, impt to look at primary PD rates (seen in @lalaniMD's table) - nivo/ipi at 19%!!! CR rate used to be something we highlighted w nivo/ipi, but now comparable across studies (3/15)
Okay now to the really tough stuff - comparing TKI/IO regimens. Something interesting I will add to @brian_rini @uromigos table above is the HR for PFS by INVESTIGATOR review. If the diff in HR for PFS by IND review caught your eye, this is even more striking (4/15)
I think INV-assessed PFS is impt, but if you're a skeptic, forget that argument. Turn instead to #QOL with axi/pembro. Kudos to @brian_rini @tompowles1 @ERPlimackMD et al for advocating for QOL in KN-426. @crisbergerot et al have taughts us the importance of these metrics. (5/15)
Unfortunately, we're not seeing any improvement in QOL w axi/pembro. This is a bit concerning - if balanced between arms, are we prolonging PFS at the expense of the patient's overall well-being? Inc tumor regression should be accompanied by some symptomatic improvement. (6/15)
Okay, now on to one of the headliners at @ASCO #GU21 this past weekend. The CLEAR study presented by @motzermd @DrChoueiri @DrTHut @tompowles1 @CPRT65 et al. Simultaneously published in @NEJM - congrats friends! (7/15)
Just one point on the curves, which I heard @tompowles1 bring up on a @Uromigos podcast w @DrChoueiri (of note, I also saw @manuelmaiamd bring this up during @motzermd's presentation in the @ASCO #GU21 pres). Why do the OS curves merge? Not so in #CheckMate9ER! (8/15)
Regardless, some may be swayed by the 16% CR rate with len/pembro. Now HERE is where we need to dive into baseline characteristics. Nearly 10% more fav risk in CLEAR, and also, more pts with prior neph. So, the odds of getting CR (or even PR) stacked against #CheckMate9ER (9/15)
I'll next make the point that LEN IS HARD TO TOLERATE. I'm glad @SoaresAndrey highlights the rate of discontinuation in #CLEAR, which appears much higher than in #CheckMate9ER. I've seen 7al versions of the data, but no matter how you slice it, d/c rate⬆️with len/pembro. (10/15)
What's my experience with len? I ran a RP2 study w @DrDanielHeng @hipsytips @docjavip et al. We tried to lower dose from 18 to 14 mg & preserve efficacy, but with the caveat of this being a small non-inferiority study, it didn't appear feasible. 👀rates of d/c due to AEs! (11/15)
Remember, I was comparing 18 and 14 mg. The dose in #CLEAR even HIGHER at 20 mg! This is one of those settings where QOL data ESSENTIAL. Remember, our pts are thankfully doing better & will be on drug longer - we need to look out for their GLOBAL well-being! (12/15)
Now THIS is what we need to see. Improved QOL with cabo/nivo, as @DrChoueiri presented at #ESMO20. Remember, the dose of 40 mg is used in #CheckMate9ER - LOWER than the dose of 60 mg used in #METEOR, with cabo as 2L/3L tx. (13/15).
Confession: I was skeptical when @DrChoueiri @motzermd @tompowles1 @apolo_andrea & the brilliant team for #CheckMate9ER chose 40. But @neerajaiims & I have since reported data from #COSMIC021 (cabo/atezo across multiple settings). Efficacy at both doses seems quite good (14/15)
SUMMARY: In 2021, we are blessed w gr8 data from mult 1L trials in #kidneycancer. I feel that cabo/nivo is the way to go; the goalpost is shifted beyond just PFS/RR/OS, we now need QOL! Thx to the amazing data summaries that facilitated this thread. Open to all comments. (15/15)

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@br0oklynzo0 @KatyMontgomerie @ElPolloDiabloX @AbigailShrier @chadfelixg Okay, so you haven't read the study in the British Journal of Sports Medicine, you've read a Guardian story about it.

I have now read the study, and I teach critical appraisal as part of my job, so let's dive into it a bit.

@KatyMontgomerie @ElPolloDiabloX @AbigailShrier @chadfelixg First things first, the sample size in this study is tiny. 46 people. Plus, the point of comparison was "all women and men under the age of 30 in the Air Force between 2004 and 2014" rather than a longitudinal group.

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During a normal pregnancy, oxidative stress enhances antioxidant mechanisms that are capable of reacting by way of enzyme activity and non-enzyme free radical deactivators. However, pregnancy is also a state in which this adaptation and balance may be easily disrupted.

There is strong evidence that a chronicin flammatory reaction combined with the presence of a local oxidizing environment may play a vital role in the etiology and development of complications during pregnancy.

In late pregnancy, damage to DNA (especially when it is caused by oxidative stress) is associated with pre-eclampsia(PE), intrauterine growth restriction (IUGR), and the death of mothers in developing countries; it largely determines pregnancy – related susceptibility to diseases

The referential values of ROS and NOS and their minimal and safe concentrations or physiologically beneficial concentrations are yet to be determined.

The measurement of oxidative stress in vivo is perceived as controversial,

as the sen-sitivity and specificity of various oxidative stress markers is unknown.. .
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The importance of T-cell immunity!
A recent study has found that after one dose of Pfizer’s vaccine, patients had a strong T-cell response, and a boosted antibody response after their second dose. This is good news for many reasons so let’s read up.

This study found that people’s antibodies were moderately effective against the original strain after their first dose of Pfizer’s vaccine, less effective against the B.1.1.7 variant, and were unable to neutralize the B.1.351 variant. Read what I said, that’s only after ONE dose.

However, they had strong T-cell responses against ALL known variants after the first dose. So why is this important? To recap, T-cells stimulate B-cells to make antibodies. Antibodies are just your first line of defense which is what is initiated when you get a vaccine.

It’s our T-cells that are responsible for long-term immunity. When antibodies diminish after your initial inoculation, your T-cells-will tell your B-cells it’s time to produce more antibodies. As long as your T-cells still recognize this virus and inform your B-cells they need

to produce antibodies, the vaccine is still doing its job. Your antibodies will get built up over and over again. Just FYI your TCRs and your BCRs target different parts of the Coronavirus’ spike protein. Antibodies can prevent infection, your T cell-responses ensure that those
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Thread on how atheism leads to mental retardation (backed with medical citations🧵💉)

To start with, atheism is an unnatural self-contradicting doctrine.

Medical terminology proves that human beings are naturally pre-disposed to believe in God. Oxford scientists assert that people are "born believers".

https://t.co/kE0Fi588yn
https://t.co/OqyXcGIMJn


It should be known that atheism could never produce an intelligently-functioning society and neither ever will.

Contrastingly, Islam produced several intellectuals & polymaths, was on the forefront of scientific development, boasting 100% literacy


It is also scientifically proven that atheism led to lesser scientific curiosity and scientific frauds, which is also why atheists incline to pseudo-science.

Whereas, religion in general and Islam in particular boosted education.

https://t.co/19Onc84u3g


Atheists are also likely to affected by pervasive mental and developmental disorders like high-functioning autism.

Cognitive Scientists and renowned Neurologists found that more atheism is leads to greater autism.

https://t.co/zRjEyFoX3P
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