🚨BIG NEWS: In January, the unpublished VICTAS trial of vitamin C in #sepsis was stopped after enrolling just 501 of a planned 2000
Now data on clinicaltrials.gov shows why, and it doesn’t look good for #vitaminC. Is this the last🔩in⚰️of the ‘metabolic cure’?
A short🧵
1/
I’ve been hopeful but more than a little skeptical about the 🍹🍋 metabolic cocktail for sepsis (vitamin C + hydrocortisone + thiamine) since the original before/after case series.
I’ve followed this literature closely & have been waiting eagerly for the results of the RCTs.
2/
Thats’s why I was excited to see that VICTAS had posted results. bit.ly/3j3Iatl
The VICTAS trial is the largest (& arguably best) of the vitamin C RCTs: a placebo-controlled, Double-blind RCT done at 43 sites across the US. The 1° endpoint was vasopressor free days.
3/
The results are incomplete & we will need to wait for the actual publication to get the full picture.
But what we can see doesn’t look good:
* similar mortality rate in both arms
* more vasopressor free days in the control group
* some adverse events in the vitamin C arm 4/
Even with this limited data and some simple stats, we can see that there is no significant difference in all cause mortality:
- HAT 22.2% vs Placebo 24.1% (RR 0.92 95% CI 0.67 - 1.27; p = 0.67)
There also isn’t a difference in vasopressor free days:
- HAT 25 vs Placebo 26 5/
When we think about these results in the context of the other published studies it 🎨a consistent🖼:
- *not one* study has replicated the effect seen by Marik et al
See my updated Forrest Plot (full blog post soon): The more studies we do the smaller the overall effect. 6/
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Shortly before 3am on June 4, 1993, a mechanic at Miami airport looked in the wheel well of a DC-8 cargo jet from Bogotá. He saw the body of a teenager, curled in a ball, wearing only a t-shirt and shorts and frozen like an "ice cube."
The first paramedic pronounced him dead. The second found a weak pulse.
Somehow he had just survived 5 hours at 35,000 feet without heat or air pressure.
This should have killed him three different ways.
A🧵& blog post on how he survived.
1/
At 35,000 ft, there are three simultaneous killers:
🫁 Hypoxia: PO₂ is ~37 mmHg, well below the consciousness threshold of ~60 mmHg. Most peopple lose consciousness is 15-30 seconds. Even fully acclimatized Everest summiteers (at 29,000) survive only by driving PaCO₂ to ~8 mmHg through maximal hyperventilation.
🥶 Hypothermia: Ambient temp is –55°C. Accidental hypothermia causes fatal arrhythmia below ~28°C core temp. The coldest recorded accidental hypothermia survivor (13.7°C) lived only because of ECMO.
💥 DCS: Barometric pressure 179 mmHg (23% of sea level). The risk of decompression sickness and nitrogen gas embolism approaches 100% above 30,000 ft without a pressure suit.
No reasonable physiologist, handed these parameters, would predict survival. Yet somehow a 17 year old stow-away survived all three.
2/
The key is that hypothermia and hypoxia are mutually protective. The mechanism:
1️⃣ Hypoxia disables the thermostat
The preoptic anterior hypothalamus is exquisitely sensitive to hypoxia. As PaO₂ falls during ascent, it loses the ability to defend core temperature. The body becomes poikilothermic: temperature tracks the environment and the stow-away gets cold without shivering.
2️⃣ Hypothermia suppresses VO₂
The Q10 for brain CMRO₂ is 2.2. By the time core temp hits ~27°C (threshold for unconsciousness), brain O₂ consumption is ~45% of baseline. Demand meets the catastrophically low supply.
Cardiac surgeons exploit this in deep hypothermic circulatory arrest (DHCA), cooling the brain to 15-18°C to permit operating on a bloodless field.
The stowaway essentially did this to himself!
Lots of news articles reporting "Smartphone use on the toilet increases risk of hemorrhoids" citing a small single center study.
Great headlines but also a textbook example of *reverse causation* - a common methodological flaw in observational studies
A 🧵
Reverse causation occurs when we flip the arrow of cause→effect.
Protopathic bias is a subtype: An exposure (often a treatment/behavior) is started because early symptoms are already present, making it look like the exposure caused the outcome.
2/
A common example of reverse causation/protopathic bias is increased inhaler use --> increased risk of asthma hospitalization.
Did the inhaler use cause the hospitalization?
No! The person was developing symptoms which is why they were using the inhaler...
Well designed RCT shows patients randomized to an exercise program had substantially improved survival after adjuvant chemotherapy for colon cancer.
- 5 yr disease-free survival 80.3% vs
73.9% (HR 0.72)
- 8 yr overall survival 90.3% vs 83.2% (HR 0.63)
This is groundbreaking! 1/
Some deets on the CHALLENGE trial
A 55 center trial done over 15 years (2009-2024) that randomized n=889 people with resected colon cancer after adjuvant chemotherapy to either:
- participate in a structured exercise program
- or to receive health-education materials alone
2/
The intervention was pretty comprehensive:
Personal activity consultant (PACs) - essentially trainers - got to know the participant 1:1, introduced them to the gym and came up with personalized activity goals
Regular every 2 week sessions helped participants reach the goals
Tragic news today about former president Biden's prostate cancer diagnosis. I wish him well.
As someone who follows presidential health reporting, I noticed something odd: unlike his predecessors, Biden's physician's never reported PSA.
How to interpret this absence? A🧵 1/
There are two possibilities:
1️⃣ Biden’s PSA was never checked
2️⃣ Biden’s PSA was checked but it wasn't reported
Strictly speaking, not checking PSA could be a medically correct option. Whether or not to test PSA is a complex question and is not the topic of this thread.
2/
Like many VIPs, presidents tend to have excessive testing that is not always strictly evidence-based.
For example, Bush 43 had an exercise treadmill test and a TB test for no apparent reason.
In honor of #MayThe4thBeWithYou let's consider the most difficult airways in the Star Wars universe:
1. Darth Vader
Species: human
Vader presents several challenges: Vent dependent at baseline, airway burns from Mustafar, limited neck mobility.
Discuss GOC before saving him
2. Fodesinbeed Annodue
Species: Trog
All airways require teamwork, but intubating Fodesinbeed Annodue's two heads really will require two operators.
Consider double simultaneous awake fiberoptic intubation
Be sure to consent both heads.
You will never find a more wretched hive of scum & challenging airways than Mos Eisley (except maybe at Jabba's)
3.Greedo
Species: Rodian
Micrognathia, posterior airway, no nasal intubation, green skin so no pulse ox
Approach: VL + bronchoscope. Intubate quickly (shoot first)