How Your Immune System Works & How to Improve It | Dr. Max Krummel

Core body temperature must rise by approximately 1 to 3 degrees Fahrenheit upon waking.

"And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about 1 to 3°." (said at 0:21:15)

Human core body temperature exhibits a well-documented circadian oscillation where temperature reaches a nadir (minimum) during the second half of the sleep period (typically around 04:00–05:00) and rises across the morning on its ascending limb to promote alertness and wake maintenance. However, the total peak-to-trough amplitude across an entire 24-hour day in humans is only approximately 0.5 °C to 1.0 °C (~0.9 °F to 1.8 °F). Claiming that core body temperature must rise by '1 to 3 degrees' (particularly up to 3 °F) specifically upon waking overstates both the magnitude of the immediate morning temperature change (which is a fraction of the daily amplitude) and treats a correlational circadian phase marker as a strict physiological requirement.

• context: Contribution of circadian physiology and sleep homeostasis to age-related changes in human… (Chronobiology international 2000) · cited 374x in the literature

  "Sleep of older people is particularly disrupted when scheduled on the rising limb of the temperature rhythm, indicating that the sleep of older people is more susceptible to arousal signals generated by the circadian pacemaker." (abstract, results, passage verified)

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• context: Individual differences in the phase and amplitude of the human circadian temperature rhyth… (Journal of sleep research 2000) · cited 550x in the literature

  "We found that the average Tmin occurred at 03.50 h for morning-types (M-types), 05.02 h for the neither-types and 06.01 h for evening-types (E-types)... The Tmin occurred at approximately the middle of the 8-h sleep period, but it occurred closer to wake in subjects with later Tmin values and increasing eveningness. In other words, E-types slept on an earlier part of their temperature cycle than M-types. This difference in the phase-relationship between temperature and sleep may explain why E-types are more alert at bedtime and sleepier after waking than M-types." (abstract, results)

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• context: SCN controlled circadian arousal and the afternoon "nap zone". (Sleep research online : SRO 1998) · cited 42x in the literature

  "Under normal entrained conditions for about one-third of the circadian day core body temperature, and therefore the assumed intensity of the circadian arousal system, is below the mesor with the nadir being at about 0500h; and for about two-thirds of the circadian day it is above the mesor with the acrophase on average being at about 2100h." (abstract, results, passage verified)

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Immune checkpoint blockade therapy leads to tumor disappearance in 50% of melanomas.

"I would say checkpoint blockade is one of those that you can take it and in 50% of melanomas, the tumor goes away and everything's great." (said at 2:01:33)

The claim overstates the degree of response. In advanced melanoma, dual immune checkpoint blockade (such as nivolumab plus ipilimumab in the landmark CheckMate 067 trial) achieves an objective response rate (ORR) of approximately 58% and a 5- to 6.5-year overall survival rate of around 50%. However, the overall response rate combines partial responses (tumor shrinkage >= 30%) with complete responses. Complete disappearance of tumors (complete response) occurs in only approximately 15% to 22% of treated patients, not 50%.

• context: Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. (The New England journal of medicine 2017) · cited 5431x in the literature

  "The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group." (abstract, results, passage verified)

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• context: Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in … (Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2022) · cited 1135x in the literature

  "Median OS (minimum follow-up, 6.5 years) was 72.1, 36.9, and 19.9 months in the combination, nivolumab, and ipilimumab groups, respectively. Median MSS was not reached, 58.7, and 21.9 months, respectively; 6.5-year OS rates were 57%, 43%, and 25% in patients with BRAF -mutant tumors and 46%, 42%, and 22% in those with BRAF -wild-type tumors, respectively." (abstract, results, passage verified)

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