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Welcome, this is the New England Journal

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of Medicine. I'm Dr. Lisa

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Johnson. This week, November

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30, 2023,

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we feature articles on

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levothyroxine for unstable brain-dead

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heart donors, amivantamab

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in lung cancer

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with EGFR-exon-20 insertions,

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amikacin to prevent

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ventilator-associated pneumonia, and

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tarlatamab in small-cell lung

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cancer, a new

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series on wearable digital health

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technology with a review article

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on digital technology for diabetes,

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a case report of a man with sickle

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cell disease and right hip pain, and

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perspectives on coverage for

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emerging technologies, on

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methadone clinic engagement and cancer

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care, and on learning

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from the bomb. A

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new clinical decisions addresses the

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approach to menstrual migraine with

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aura. A woman who

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has chronic migraines with aura comes

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to the clinic to discuss her

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headaches. The headaches usually occur around

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the time of her menses. This

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clinical decisions offers a case

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vignette accompanied by two essays,

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one supporting prescription of oral

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combined contraceptive pills and the

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other recommending against it. We

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want to know what you decide.

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Visit nejm.org to

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vote. Intravenous

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Levothyroxine for Unstable

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Brain-Dead Heart Donors

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by Rajat Dar, from

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Washington University School of Medicine,

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St. Louis, Missouri. Hemodynamic

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instability and myocardial dysfunction

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are major factors preventing

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the transplantation of hearts

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from organ donors after

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brain death. Intravenous

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Levothyroxine is widely used

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in donor care. On

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the basis of observational

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data suggesting that more

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organs may be transplanted

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from donors who receive

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hormonal supplementation. In this

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trial involving 15 organ

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procurement organizations in the United

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States, 838 hemodynamically

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unstable potential heart donors

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were randomly assigned within

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24 hours after

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declaration of death according

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to neurologic criteria to

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open label infusion of

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intravenous levothyroxine or saline

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placebo. Hearts were transplanted

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from 230 donors 54.9% in the levothyroxine group

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and 223 53.2% in

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the saline group. Graft survival

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at 30 days occurred in 97.4%

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of hearts transplanted

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from donors assigned to receive

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levothyroxine and 95.5% of hearts

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transplanted from donors assigned

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to receive saline. There

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were no substantial between-group

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differences in weaning from

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vasopressor therapy, ejection fraction

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on echocardiography or organs

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transplanted per donor but

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more cases of severe hypertension

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and tachycardia occurred in the

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levothyroxine group than in the

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saline group. In

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hemodynamically unstable brain dead

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potential heart donors intravenous

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levothyroxine infusion did not

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result in significantly more

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hearts being transplanted than

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saline infusion. Karen

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Koush from Stanford University School

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of Medicine, California writes

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in an editorial that this

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trial had several limitations including

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no blinding of the trial

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personnel with respect to trial

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group assignments, a lack of

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centralized interpretation of donor

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echocardiograms and a lack

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of standardization of concomitant

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donor medical therapies. Even

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so, this study provides the

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most definitive data to date

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about donor thyroid hormone replacement

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therapy. The results

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have major clinical implications

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for organ procurement organizations,

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OPOs, around the country.

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Data from the United Network for Organ Sharing

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show that 48% of

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all potential organ donors and 55%

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of donors with left ventricular

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dysfunction were treated with levothyroxine

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from 2015 to

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2022. Overall,

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almost half the OPOs in

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the United States routinely administer

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thyroid hormone during donor care.

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Perhaps the most remarkable aspect of

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this trial is that it was

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performed at all. Conducting

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research that involves organ

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donors, particularly randomized controlled

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trials, is fraught with

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challenges. These include

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recruitment of participating OPOs,

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which often do not have

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dedicated staff or resources for

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conducting research. Logistic challenges

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inherent in performing trial procedures

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at the large number of

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donor hospitals and organ recovery

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facilities, lack of

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trial oversight, difficulties with

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obtaining authorization for donor

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research, and lack of

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dedicated funding mechanisms. Indeed,

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this trial was largely

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unfunded, relying on internal

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support within each participating

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OPO. These obstacles,

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among others, have resulted in

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a paucity of randomized controlled

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trials, which provide definitive data

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to inform donor care and

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to increase the yield and

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utilization of donor organs.

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After these hurdles are overcome,

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will the organ donation and

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transplantation community be able

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to meet the goal

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of increasing the availability

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of donor organs for

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life-saving transplantation? Amavantimab

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plus chemotherapy in

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NSCLC with EGFR

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exon 20 insertions

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by Kaikun Zhou from

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Shanghai Pulmonary Hospital, China.

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Amavantimab has been approved

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for the treatment of

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patients with advanced non-small

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cell lung cancer, NSCLC,

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with epidermal growth factor

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receptor, EGFR exon 20

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insertions, who have had

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disease progression during or

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after platinum-based chemotherapy. Phase

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one data showed the

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safety and anti-tumor activity

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of Amavantimab plus carboplatin

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pematrexet chemotherapy. Additional

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data on this combination therapy

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are needed. In this

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phase three trial, 308

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patients with advanced NSCLC

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with EGFR exon 20

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insertions, who had not

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received previous systemic therapy,

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were randomly assigned to

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receive intravenous Amavantimab plus

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chemotherapy or chemotherapy alone.

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The primary outcome of progression-free

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survival was significantly longer in

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the Amavantimab chemotherapy group as

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compared with the chemotherapy group,

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median 11.4 months and 6.7

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months respectively. At

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18 months, progression-free survival

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was reported in 31% of the

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patients in

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the Amavantimab chemotherapy group and in

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3% in the

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chemotherapy group. A complete

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or partial response at data cutoff

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was reported in 73% and 47% respectively. The

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predominant adverse events

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associated with amavantimab

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chemotherapy were reversible

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hematologic and EGFR-related

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toxic effects. 7%

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of patients discontinued amavantimab

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owing to adverse reactions.

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The use of amavantimab

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with chemotherapy resulted in

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superior efficacy as compared

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with chemotherapy alone as

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first-line treatment of patients

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with advanced NSCLC with

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EGFR exon 20 insertions.

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Inhaled amacasin to

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prevent ventilator-associated pneumonia.

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By Stefan Ermann from

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the St. Trops-Bitalier-Regional Universitaire

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du Tour, France.