Let's establish a few facts about cefepime:
🔺4th generation cephalosporin antibiotic
🔺Excretion = exclusively in the urine (mostly as unchanged drug)
🔺Readily crosses the blood-brain barrier (so it easily accesses the brain)
https://t.co/rjYG1BfGPR
1/15
Why can cefepime cause neurological toxicity?
And why is renal failure the main risk factor for this complication?
The answer requires us to learn about cefepime's structure and why it unexpectedly binds to a certain CNS receptor.
#MedTwitter #Tweetorial
Let's establish a few facts about cefepime:
🔺4th generation cephalosporin antibiotic
🔺Excretion = exclusively in the urine (mostly as unchanged drug)
🔺Readily crosses the blood-brain barrier (so it easily accesses the brain)
https://t.co/rjYG1BfGPR
The first report of cefepime neurotoxicity was in 1999.
A patient w/ renal failure received high doses of cefepime and then developed encephalopathy, tremors, myoclonic jerks, and tonic-clonic seizures.
✅All symptoms resolved after hemodialysis.
https://t.co/u7JLVitQpp
Cefepime neurotoxicity is surprisingly common, occurring in up to 15% of treated critically ill patients (w/ symptoms varying from encephalopathy to seizures).
💡The main risk factors = renal failure and lack of dose adjustment for renal function.
https://t.co/nxbnzSq8AR
What about cefepime induces neurotoxicity?
One clue is that it's not the only antibiotic that causes neurotoxicity, particularly seizures.
This actually is a class effect w/ other beta-lactam antibiotics (including penicillins and carbapenems).
https://t.co/Lf4BhON9IY
Recall that beta-lactam antibiotics all share a common structural feature: a beta-lactam ring.
https://t.co/iWXweuG4Ct
A 1971 study in cats implicated beta-lactam rings as the source of neurotoxicity.
High doses of penicillin were used to induce seizures.
🔑But pre-incubation w/ the enzyme beta-lactamase (disrupts the beta-lactam ring) blocked all seizure activity.
https://t.co/M3lDiXm88N
So why can beta-lactam antibiotics like cefepime cause neurotoxicity?
It turns that they block the binding of the inhibitory neurotransmitter gamma aminobutyric acid (GABA) to its receptor.
🔑Cephalosporins block GABA particularly effectively.
https://t.co/Eo0OlTduOE
The GABA receptor has two subtypes (A and B), and the A subtype functions as a ligand-gated Cl⁻ ion channel.
Cefepime binds to the GABA-A receptor and blocks Cl⁻ influx, which correlates with its ability to induce seizure activity.
https://t.co/l2f9QHHEEW
We've established that cefepime blocks GABA.
This induces neuro-excitation leading to seizures and other neurotoxic manifestations such as tremors and encephalopathy.
💡But why is there such a strong link with renal failure?
An obvious explanation would be that, since cefepime is renally cleared, elevated serum and CNS drug levels build up.
This is supported by the observation that cefepime and other cephalosporins block GABA in a concentration-dependent manner.
https://t.co/l2f9QHHEEW
But increased drug levels might not be the only reason that patients w/ renal failure are predisposed to neurotoxicity.
The milieu around neurons seems to matter as well.
This experiment in rat brain slices simulated a "renal" milieu by using a hyperkalemic medium around neurons.
⚡️Exposure to higher potassium levels significantly increased the ability of cefepime to induce epileptiform discharges.
https://t.co/vb3p4xXdTm
Let's ask one final question.
Why can cefepime (and other beta-lactam antibiotics) block the GABA receptor?
Exactly why hasn't been well-studied but it likely reflects sufficient structural similarity w/ GABA.
https://t.co/KN7I6ACXvb
More from Health
Before we get too far into 2021, I thought I’d write a thread recapping some of the research that came out of my lab in 2020. Most of this work was led by my talented team of graduate students, Kerrianne Morrison, @kmdebrabander, and @DesiRJones.
Back in January, a news story was published about Kerrianne’s study showing improved social interaction outcomes for autistic adults when paired with another autistic partner.
A detailed thread about the study and a link to the paper can be found here (feel free to DM me your email address if you’d like a copy of the full paper for this study or any of our studies):
Another paper published early in 2020 (it appeared a few months earlier online) showed that traditional standalone tasks of social cognition are less predictive of functional and social skills among autistic adults than commonly assumed in autism research.
Next, @kmdebrabander led and published an innovative study about how well autistic and non-autistic adults can predict their own cognitive and social cognitive performance.
Back in January, a news story was published about Kerrianne’s study showing improved social interaction outcomes for autistic adults when paired with another autistic partner.
A detailed thread about the study and a link to the paper can be found here (feel free to DM me your email address if you’d like a copy of the full paper for this study or any of our studies):
In our new paper out today, autistic adults held a \u201cget to know you\u201d conversation with an unfamiliar autistic or typically-developing (TD) person. We were curious: would social interaction outcomes differ when their partner was also autistic? THREAD https://t.co/4koqUKV9G1
— Noah Sasson (@Noahsasson) December 11, 2019
Another paper published early in 2020 (it appeared a few months earlier online) showed that traditional standalone tasks of social cognition are less predictive of functional and social skills among autistic adults than commonly assumed in autism research.
How well does social cognition predict functional and social skills in autism? Our new paper attempts to answer this question. This thread summarizes why we conducted the study, what we found, and why I think it\u2019s important. https://t.co/KB1nIpK0M2
— Noah Sasson (@Noahsasson) August 16, 2019
Next, @kmdebrabander led and published an innovative study about how well autistic and non-autistic adults can predict their own cognitive and social cognitive performance.
New by @kmdebrabander and our lab: Autistic adults don\u2019t differ from non-autistic adults in the accuracy of their self-assessment on general cognitive tasks but are less accurate on social cognitive tasks. This however was unrelated to social functioning https://t.co/0MrqMKKO0r
— Noah Sasson (@Noahsasson) September 20, 2020
This is a limited point about availability of efficacy data for vaccines under development in the context of the approval for CovidShield and Covaxin in India.
There have been many so-called experts on the idiotbox opining about apparent availability of P III data which 1/n
2/n apparently the SEC had access to based on which it "supposedly" approved Covaxin. Another argument that is prevalent is other regulators (US FDA and MHRA) also approved vaccines based on P II data alone. Let me give you a few facts so that you can make your own decision.
3/n The protocols for both mRNA vaccines are publicly available. You can check. Both protocols *define* when the interim analysis will be done. This is not subjective. They clearly define how many infections need to be documented before the Data Safety Monitoring Board meets.
4/n Find the protocols for the bridging study for CovidShield and Covaxin and look for a similar milestone.
Here is one set of efficacy data post the interim analysis of a mRNA vaccine.
Source: https://t.co/BAPnP3PxEb
5/n This data was analyzed post the interim analysis where the blind was broken by the DSMB. Now ask yourself this question:
How does the SEC, or the sponsor of these studies, or the experts who are offering their opinion liberally on the idiotbox know what the efficacy is
There have been many so-called experts on the idiotbox opining about apparent availability of P III data which 1/n
2/n apparently the SEC had access to based on which it "supposedly" approved Covaxin. Another argument that is prevalent is other regulators (US FDA and MHRA) also approved vaccines based on P II data alone. Let me give you a few facts so that you can make your own decision.
3/n The protocols for both mRNA vaccines are publicly available. You can check. Both protocols *define* when the interim analysis will be done. This is not subjective. They clearly define how many infections need to be documented before the Data Safety Monitoring Board meets.
4/n Find the protocols for the bridging study for CovidShield and Covaxin and look for a similar milestone.
Here is one set of efficacy data post the interim analysis of a mRNA vaccine.
Source: https://t.co/BAPnP3PxEb
5/n This data was analyzed post the interim analysis where the blind was broken by the DSMB. Now ask yourself this question:
How does the SEC, or the sponsor of these studies, or the experts who are offering their opinion liberally on the idiotbox know what the efficacy is
Some thoughts on this: Firstly, it might be personal preference, but I am not keen on this kind of campaign as I feel like it trivialises cancer. Sometimes the serious message gets lost because people are sharing pics of cats or whatever and the important context is gone.
More importantly, the statistic being used in the campaign is misleading. It says 57% of women put off cervical screening if they can't get waxed. But on further investigation, that's not accurate.
The page here goes on to say "57% of women who regularly have their pubic hair professionally removed would put off attending their cervical screening appointment if they hadn’t been able to visit a beauty salon."
So the 57% represents a concern not across the whole population of women, but only those who regularly get waxed. So how big of an issue is this across the whole population? And what else is stopping people getting smears?
I think campaigns for cancer screening are really tricky because there is so much nuance that often doesn't fit into a catchy headline or hashtag. It's certainly not easy and is part of a bigger conversation.
It\u2019s #CervicalCancerPreventionWeek \U0001f499
— myGP (@myGPapp) January 18, 2021
Here\u2019s how you can help to raise awareness:
\U0001f431 Share an image of the cat that best reflects your undercarriage/flower/bits (technical term vulva!) current look.
#\u20e3Use the Hashtag #myCat.
\U0001f46dTell and tag your friends to let them know. pic.twitter.com/8aHf96ynjT
More importantly, the statistic being used in the campaign is misleading. It says 57% of women put off cervical screening if they can't get waxed. But on further investigation, that's not accurate.
The page here goes on to say "57% of women who regularly have their pubic hair professionally removed would put off attending their cervical screening appointment if they hadn’t been able to visit a beauty salon."
So the 57% represents a concern not across the whole population of women, but only those who regularly get waxed. So how big of an issue is this across the whole population? And what else is stopping people getting smears?
I think campaigns for cancer screening are really tricky because there is so much nuance that often doesn't fit into a catchy headline or hashtag. It's certainly not easy and is part of a bigger conversation.
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Margatha Natarajar murthi - Uthirakosamangai temple near Ramanathapuram,TN
#ArudraDarisanam
Unique Natarajar made of emerlad is abt 6 feet tall.
It is always covered with sandal paste.Only on Thriuvadhirai Star in month Margazhi-Nataraja can be worshipped without sandal paste.
After removing the sandal paste,day long rituals & various abhishekam will be https://t.co/e1Ye8DrNWb day Maragatha Nataraja sannandhi will be closed after anointing the murthi with fresh sandal paste.Maragatha Natarajar is covered with sandal paste throughout the year
as Emerald has scientific property of its molecules getting disturbed when exposed to light/water/sound.This is an ancient Shiva temple considered to be 3000 years old -believed to be where Bhagwan Shiva gave Veda gyaana to Parvati Devi.This temple has some stunning sculptures.
#ArudraDarisanam
Unique Natarajar made of emerlad is abt 6 feet tall.
It is always covered with sandal paste.Only on Thriuvadhirai Star in month Margazhi-Nataraja can be worshipped without sandal paste.
After removing the sandal paste,day long rituals & various abhishekam will be https://t.co/e1Ye8DrNWb day Maragatha Nataraja sannandhi will be closed after anointing the murthi with fresh sandal paste.Maragatha Natarajar is covered with sandal paste throughout the year
as Emerald has scientific property of its molecules getting disturbed when exposed to light/water/sound.This is an ancient Shiva temple considered to be 3000 years old -believed to be where Bhagwan Shiva gave Veda gyaana to Parvati Devi.This temple has some stunning sculptures.
