0:00

Welcome. This is the New England

0:02

Journal of Medicine. I'm Dr.

0:04

Michael Bearer. This week, April

0:06

10th, 2025, we

0:08

talk about cancer-associated

0:11

venous thromboembolism, endovascular

0:13

treatment for stroke, dapaglifflosin

0:15

in patients undergoing Tavi,

0:18

screening for prostateate cancer,

0:20

and extracromosomal DNA. A

0:22

review article on Otitis

0:24

Media in Young Children.

0:26

A case report of

0:28

a woman with flank

0:31

pain, fever, and hypoxemia,

0:33

and perspectives on some

0:35

efforts toward equity and

0:37

on breaking the sacred

0:39

promise. Extended, reduced

0:42

dose, epixoban for

0:44

cancer-associated venous thromboembolism

0:48

by Isabelle May, from the

0:50

Opital Louis Morier, Colomb, France,

0:52

and co-authors. Patients with

0:55

cancer, are at higher risk

0:57

for venous thromboembalism than the

0:59

general population. Patients with

1:01

cancer-associated venous thromboembalism are

1:04

at greater risk for

1:06

recurrent events despite anti-coagulant

1:09

therapy and for bleeding

1:11

complications. Anti-coagulation with a direct

1:13

oral anti-coagulent or low molecular

1:15

weight heparin is recommended for

1:18

an initial period of six

1:20

months. Clinical Practice Guidelines

1:22

suggest that anti-coagulant therapy

1:25

be continued for as

1:27

long as the cancer

1:29

remains active or cancer

1:31

treatment is ongoing, but

1:34

clinicians need to balance

1:36

the benefits of anti-coagulant

1:38

therapy with the risk

1:41

of bleeding complications, which

1:43

persist over time. In this

1:45

trial, 1,76 patients with active

1:48

cancer and proximal deep vein

1:50

thrombosis or pulmonary embolism who

1:53

had completed at least six

1:55

months of anti-coagulant therapy

1:57

were randomly assigned to receive

1:59

oral... pixuban at a reduced

2:02

2.5 milligram or full 5

2:04

milligram dose twice daily

2:06

for 12 months. Extended

2:08

anti-coagulation with reduced dose

2:11

a pixuban was non-inferior

2:13

to full dose a pixuban

2:15

for the prevention of

2:17

recurrent venous thromboembalism in

2:20

patients with active cancer.

2:22

The reduced dose led to

2:24

a lower incidence of clinically

2:27

relevant bleeding complications than the

2:29

full dose. Simon Noble from

2:31

Cardiff University, United

2:33

Kingdom, writes in an editorial

2:36

that although the majority

2:38

of clinical studies pertaining

2:40

to anti-coagulation in patients

2:43

with cancer use major bleeding

2:45

as the primary safety outcome,

2:47

the trial by May and

2:50

co-authors used clinically relevant bleeding.

2:52

a composite of major bleeding

2:55

or clinically relevant non-major bleeding.

2:57

Furthermore, the investigators set

2:59

a very low bar for

3:02

reporting clinically relevant non-major bleeding

3:04

by using a more extensive

3:06

list of criteria than previously

3:09

recommended for clinical studies. This

3:11

factor should be regarded as a

3:13

strength because it recognizes that in

3:16

this trial population in which more

3:18

than 80% of the patients had

3:20

an incurable disease. the effect of

3:23

bleeding on overall quality of

3:25

life will often take primacy

3:27

over whether the bleeding is

3:29

classified as major or non-major.

3:31

Previous research has shown that bleeding

3:34

that has been classified as

3:36

nuisance bleeding in clinical trials

3:38

and at first glance may

3:41

appear to be of little

3:43

relevance, has a considerable effect

3:45

on patient distress, activities of

3:47

daily living, and overall emotional

3:50

health. The reduced incidence of bleeding

3:52

observed in the reduced dose

3:54

group without an increase in

3:56

the incidence of recurrent venous

3:58

thromboembolism establishes is a pixivan

4:01

administered at a 2.5 milligram

4:03

twice daily dose as an

4:06

appropriate regimen for anti-coagulation beyond

4:08

the first six months in

4:11

patients with cancer. The investigators'

4:13

decision to report patient-relevant

4:15

bleeding outcomes provides clinicians

4:17

with much needed information

4:20

for them to engage

4:22

in meaningful dialogue with

4:24

patients in order to

4:26

make anti-coagulation decisions that

4:28

are based on patients'

4:31

values and preferences.

4:33

Endovascular treatment for stroke

4:35

due to occlusion of

4:37

medium or distal vessels

4:39

by Marios Sicogos from

4:41

the University Hospital,

4:43

Basel Switzerland, and

4:45

co-authors. Endovascular treatment, EBT,

4:48

is known to be safe and

4:50

effective in persons with an acute

4:52

ischemic stroke caused by a

4:54

large vessel occlusion of the

4:57

internal carotid artery, the M1

4:59

segment of the middle cerebral

5:01

artery, or the bazzler artery.

5:03

However, the effect of

5:05

endovascular treatment for occclusion

5:07

of medium or distal

5:09

vessels is unclear. Current

5:11

American and European guidelines neither

5:13

recommend nor discourage EBT in

5:16

persons with occlusion of medium

5:18

or distal vessels. This trial

5:20

assessed whether EBT in addition

5:23

to best medical treatment was

5:25

more effective in reducing disability

5:28

and death than best medical

5:30

treatment alone in 543 persons

5:33

with an isolated occlusion of

5:35

medium or distal vessels treated

5:38

within 24 hours after the

5:40

person was last seen to

5:43

be well. EBT plus best

5:45

medical treatment did not result

5:47

in a lower level of

5:49

disability or a lower incidence

5:52

of death than best medical

5:54

treatment alone. Endovascular

5:57

treatment of stroke due

5:59

to medium Vessel Eclusion by

6:01

Mayank Goyle from the University

6:03

of Calgary-Coming School of Medicine,

6:05

Calgary, Alberta, Canada, and co-authors.

6:08

This study evaluated whether the

6:10

large effect size of endovascular

6:12

thrombectomy, EBT, for stroke due

6:14

to large vessel occclusion, applies

6:16

to stroke due to medium

6:19

vessel occclusion. Five hundred thirty

6:21

patients with acute ishemic stroke

6:23

due to medium vessel occclusion,

6:25

who presented within 12 hours

6:28

from the time that they

6:30

were last known to be

6:32

well and who had favorable

6:34

baseline non-invasive brain imaging were

6:36

randomly assigned to receive EBT

6:39

plus usual care or usual

6:41

care alone. Endovascular treatment for

6:43

acute ischemic stroke due to

6:45

medium vessel occclusion within 12

6:48

hours did not lead to

6:50

better outcomes at 90 days

6:52

than usual care. In

6:54

an editorial, Jay Mokow from

6:57

the Mount Sinai Health System,

6:59

New York, writes that no

7:01

matter how one considers these

7:03

data, there is no question

7:05

that these two studies represent

7:08

the current ground zero of

7:10

evidence to inform decision-making regarding

7:12

the use of thrombectomy for

7:14

stroke due to medium and

7:16

distal vessel occclusion. The data

7:19

clearly show. that thrombectomy for

7:21

distal vessel occclusions should not

7:23

be an assumed default care

7:25

pathway. Where do we go

7:28

from here? The stroke community

7:30

should not be complacent. Rather,

7:32

we must thoroughly test appropriate

7:34

questions, evaluate alternative approaches, and

7:36

not allow bias to interfere

7:39

with identifying the best treatment

7:41

strategies for patients with stroke.

7:43

These two trials prove that

7:45

their patient populations did not

7:47

have a benefit with thrombectomy,

7:50

and as such, performance of

7:52

thrombectomy for medium or distal

7:54

vessel occclusion in a manner

7:56

consistent with these trials is

7:59

not evidence-based. This

8:01

trial evaluated the efficacy

8:03

of the sodium glucose

8:05

co-transporter two-inplantation by Sergio

8:07

Rapoceras-Rubin from the Centro-Nacional

8:10

de investigationes cardiovascularis Carlos

8:12

Tres, Madrid, Spain, and

8:14

co-authors. This trial evaluated

8:16

the efficacy of the

8:18

sodium glucose co-transporter 2,

8:20

SGL2 inhibitor, Dapaglifflozin, as

8:22

compared with standard care

8:24

alone, in one thousand

8:26

two hundred twenty two

8:28

older adults with aortic

8:31

stenosis who are undergoing

8:33

tabby. Dapaglifflozin resulted in

8:35

a significantly lower incidence

8:37

of death from any

8:39

cause or worsening of

8:41

heart failure than standard

8:43

care alone. However genital

8:45

infection and hypotension were

8:47

significantly more common in

8:50

the Dapaglifflozin group. Oribenyauda

8:52

from the University of

8:54

California San Diego La

8:56

Jolla writes in an

8:58

editorial that the benefit

9:00

of dapagliflozin in the

9:02

Tavi population highlights the

9:04

fact that despite the

9:06

relief of the outflow

9:08

obstruction, these patients do

9:11

not have a normal

9:13

heart. Long-standing aortic stenosis

9:15

even in the absence

9:17

of symptoms leads not

9:19

only to left ventricular

9:21

hypertrophy, but also to

9:23

fibrosis and myosite degeneration.

9:25

Moreover, aortic stenosis often

9:27

does not occur in

9:30

isolation. Patients with aortic

9:32

stenosis often have co-existing

9:34

cardiometabolic illnesses. Beyond the

9:36

benefit of SGLT2 inhibition,

9:38

this trial has shown

9:40

that patients with aortic

9:42

stenosis, even after Tavi,

9:44

should receive adjunctive medical

9:46

therapy. Assessment of a

9:48

Polygenic Risk Score in

9:51

Screening for Prostate Cancer

9:53

by Johnna McHugh from

9:55

the Royal Marsden NHS

9:57

Foundation Trust, London. United

9:59

Kingdom. The incidence

10:01

of prostate cancer is

10:03

increasing. However, screening with

10:05

an assay of prostate-specific

10:07

antigen, PSA, has a

10:09

high rate for false

10:11

positive results. In this

10:13

study, the use of

10:15

a polygenic risk score

10:17

to screen for prostate

10:19

cancer was assessed. Using

10:21

germline DNA extracted from

10:23

saliva, the investigators derived

10:25

polygenic risk scores from

10:27

130 variants known to

10:29

be associated with an

10:31

increased risk of prostate

10:33

cancer. Of the 468

10:35

persons in at least

10:37

the 90th percentile of

10:39

genetic risk, who underwent

10:41

MRI and prostate biopsy,

10:43

187, 40% had prostate

10:45

cancer. In an editorial,

10:47

David Hunter from the

10:49

University of Oxford United

10:51

Kingdom writes that if

10:53

a prostate cancer screening

10:55

program started with an

10:57

assessment of a polygenic

10:59

risk score a substantial

11:01

number of clinically significant

11:03

cases would be discovered

11:05

that would have been

11:08

otherwise missed. However... starting

11:10

such a screening program

11:12

with the assessment of

11:14

a polygenic risk score

11:16

would require large-scale investment

11:18

in the management and

11:20

analysis of genome arrays,

11:22

and would raise a

11:24

host of questions about

11:26

the storage of genetic

11:28

data on populations and

11:30

the use of the

11:32

data in calculating and

11:34

potentially counseling on the

11:36

risk of many other

11:38

diseases. Critics of polygenic

11:40

risk scores are justifiably

11:42

concerned that giving people

11:44

access to risk scores

11:46

for dozens of diseases

11:48

could lead to demand

11:50

for cost ineffective screening

11:52

tests. The current study

11:54

is a first step

11:56

on a long road

11:58

to evaluating new components

12:00

of any disease screening

12:02

pathway. Otitis Media in

12:04

Young Children, a review

12:06

article by Nader-Shake, from

12:08

from the Children's Hospital

12:10

of Pittsburgh. Acute otitis

12:12

media is a bacterial

12:14

infection that occurs almost

12:16

exclusively after a viral

12:18

upper respiratory tract infection.

12:20

Common pathogens include streptococcus

12:22

pneumonia, hemophilus influenza, catarralis.

12:24

Bulging of the tympanic

12:26

membrane is a defining

12:28

feature. Children with mild

12:30

or moderate symptoms can

12:32

be either treated with

12:34

antibiotic agents. or observed

12:36

closely. High dose amoxicillin,

12:38

80 to 90 milligrams

12:40

per kilogram of body

12:42

weight per day, divided

12:44

into two doses, remains

12:46

the first line treatment.

12:48

Amoxicillinate therapy warrants consideration

12:50

in children in whom

12:52

age influenza is likely

12:54

to predominate. That is,

12:56

those who have received

12:58

antibiotics in the previous

13:00

30 days, have conjunctivitis

13:02

otitis syndrome. or have

13:04

spontaneous rupture of the

13:06

tympanic membrane. Treatment with

13:08

antibiotics for 10 days

13:10

resulted in less treatment

13:12

failure and less use

13:14

of rescue antibiotics than

13:16

treatment for 5 days.

13:18

Timpanocentesis is indicated in

13:20

children with acute otitis

13:22

media who have had

13:24

treatment failure with multiple

13:26

rounds of antibiotic therapy.

13:28

Among children with recurrent

13:30

acute otitis media. The

13:32

incidence of acute otitis

13:34

media during a two-year

13:36

period was similar among

13:38

those who had placement

13:40

of a timpanostomy tube

13:42

and those who received

13:44

episodic antibiotic treatment. A

13:46

32-year-old woman with flank

13:48

pain, fever, and hypoxemia.

13:51

A case record of

13:53

the Massachusetts General Hospital

13:55

by Anusha Jayabolin and

13:57

colleagues. A 32-year-old woman.

13:59

was admitted with flank

14:01

pain, fever, and hypoxemia.

14:03

Two weeks earlier, sharp

14:05

intermittent pain in the

14:07

left flank developed. Two

14:09

days before the current

14:11

presentation the pain worsened

14:13

in intensity, became more

14:15

constant and was associated

14:17

with nausea. The next

14:19

day, the patient had

14:21

multiple episodes of vomiting.

14:23

On the morning of

14:25

the current presentation, she

14:27

noted a dry cough

14:29

and a subjective feeling

14:31

of warmth. She presented

14:33

to an urgent care

14:35

clinic. Physical examination revealed

14:37

abdominal tenderness on palpation

14:39

of the left lower

14:41

quadrant. The white cell

14:43

count was 19, per

14:45

microleader, with a neutrophilic

14:47

predominance. The oxygen saturation

14:49

decreased to 89% while

14:51

the patient was in

14:53

the urgent care clinic.

14:55

She was transported by

14:57

ambulance to the emergency

14:59

department. Notable laboratory findings

15:01

included lucocytosis, hematuria, heavy

15:03

proteinuria, and hypoalbiumemia. Imaging

15:05

showed multifocal pulmonary opacities,

15:07

pulmonary embolism, and renal

15:09

vein thromboses. Positive results

15:11

on testing for circulating

15:13

antiphospholipase A2 receptor antibodies

15:15

taken together with the

15:17

clinical context of the

15:19

recent onset of nephrotic

15:21

syndrome were diagnostic for

15:23

phospholipase A2 receptor associated

15:25

membranous nephropathy. Extracromissomal DNA

15:27

Amping up cancer, a

15:29

clinical implications of basic

15:31

research by Lillian Sue

15:33

and Trevor Pugh from

15:35

the University of Toronto.

15:37

Extracromosomal DNA's, EC DNA's,

15:39

are circular DNA structures

15:41

located in the nuclei

15:43

of cells outside chromosomes.

15:45

These were originally discovered

15:47

in chromosome spreads of

15:49

cells obtained from embryonic

15:51

tumors in the 1960s.

15:53

and were called double

15:55

minutes because of their

15:57

minuscule appearance. Since then,

15:59

molecular biologic and genome

16:01

technologies have shown easy

16:03

DNA is to be

16:05

a driver of carcinogenesis,

16:07

tumor heterogeneity, genome instability,

16:09

immune evasion, and therapy

16:11

resistance. In a recent

16:13

study, Bailey Eddall analyzed

16:15

the genomes of 15,682

16:17

tumor samples and detected

16:19

EC DNA in 17.1%

16:21

of the tumor samples.

16:23

Their study shows how

16:25

extra-chromosomal DNA contributes to

16:27

tumor heterogeneity and may

16:29

drive cancer progression. Studies,

16:31

such as the one

16:34

conducted by Bailey et

16:36

al, fuel interest in

16:38

targeting extracromosomal structures as

16:40

a strategy to treat

16:42

cancer. In this issue,

16:44

we feature the next

16:46

installment of our series

16:48

of briefcase studies on

16:50

efforts toward equity. Addressing

16:52

socioeconomic barriers to residency

16:54

choice. by Deborah Weinstein

16:56

from the University of

16:58

Michigan Medical School, Ann

17:00

Arbor, and co-authors. In

17:02

a three-year pilot, applicants

17:04

to Mass General Brigham

17:06

Residency Programs, who met

17:08

specified criteria for economic

17:10

disadvantage, were guaranteed an

17:12

annual $10,000 supplement to

17:14

the standard salary for

17:16

the first three years

17:18

of residency. This represented

17:20

an increase of about

17:22

15% over the standard

17:24

first year resident salary.

17:26

In the pilot, 133

17:28

incoming residents received the

17:30

stipend. The proportion of

17:32

residents from groups underrepresented

17:34

in medicine was substantially

17:36

higher among stipend recipients

17:38

than among matriculating residents

17:40

overall. This trend has

17:42

continued in the subsequent

17:44

years. Advancing health equity

17:46

in the climate crisis.

17:48

A climate justice curriculum

17:50

for resident physicians. by

17:52

Harleen Marwa Editorial Fellow

17:54

for the NEJM. The

17:56

Longitudinal Climate Justice and

17:58

Health Equity, C.J.H. curriculum.

18:00

A four-part curriculum was

18:02

integrated into the required

18:04

longitudinal advocacy training in

18:06

the Pediatrics Residency Program

18:08

at the Children's Hospital

18:10

of Philadelphia. The goals

18:12

of the curriculum are

18:14

to increase understanding of

18:16

how climate change affects

18:18

child health and exacerbates

18:20

health inequities, to promote

18:22

climate-informed patient care. and

18:24

to equip residents with

18:26

the skills needed to

18:28

advance climate advocacy and

18:30

improve health system sustainability.

18:32

During the first year,

18:34

100 pediatrics residents participated

18:36

in CJHE sessions. Results

18:38

from pre- and post-session

18:40

surveys showed that session

18:42

participation led to improved

18:44

self-reported understanding of the

18:46

ways in which climate

18:48

change affects health and

18:50

contributes to health inequities.

18:54

Developing a primary care workforce

18:56

for underserved communities, the UC

18:59

Davis Teach program by Stephanie

19:01

Sanchez from the University of

19:03

California, Davis, Sacramento, and co-authors.

19:06

Although 37% of all resident

19:08

physicians in the United States

19:11

begin training with the intention

19:13

to pursue primary care, only

19:16

21% continue in this field

19:18

three to five years after

19:21

residency after residency. in part

19:23

because of limited exposure to

19:26

outpatient community-based care during training.

19:28

The Transforming Education and Community

19:31

Health Teach program at UC

19:33

Davis was designed to increase

19:36

that exposure. According to surveys

19:38

collected at the time of

19:41

graduation between 2010 and 2023,

19:43

54% of teach graduates practice

19:45

primary care. a rate substantially

19:48

higher than the national norm

19:50

21% and higher than the

19:53

rates among their programs other

19:55

primary care 40% and cat

19:58

categorical, 4% internal medicine graduates.

20:00

Ensuring inclusive affirmative care for

20:03

LGBTQ Plus patients, scaling up

20:05

cultural competency training by J.

20:08

Beel from Rush Medical College

20:10

of Rush University, Chicago, and

20:13

co-authors. The Rush Center for

20:15

Gender Sexuality and Reproductive Health,

20:18

Chicago. developed an internal train

20:20

the trainer curriculum, T4. T4

20:23

aims to improve access to

20:25

culturally competent relevant health care

20:28

for the LGBTQ Plus community.

20:30

Since the launch of T4

20:32

in February 2022, the program

20:35

has recruited and trained 52

20:37

trainers in three cohorts. This

20:40

initiative has supported the delivery

20:42

of 178 sessions throughout the

20:45

health system between March 2022

20:47

and June 2024, reaching more

20:50

than 4,000 employees and students.

20:52

A post-training survey of the

20:55

cohorts, a year after the

20:57

initial training, confirmed that the

21:00

curriculum prepared them well for

21:02

the task. Breaking the Sacred

21:05

Promise. A perspective by Asita

21:07

Jayawardina from Children's Minnesota, Minneapolis.

21:10

As Dr. Jayawardina sees it,

21:12

his role as a doctor

21:14

can be distilled down to

21:17

a simple and sacred promise.

21:19

He will use his knowledge

21:22

and skills to solve previously

21:24

unsolvable problems and improve the

21:27

life of the patient sitting

21:29

in front of him. The

21:32

unique and unequivocal fulfillment that

21:34

comes from delivering on this

21:37

promise is the single biggest

21:39

reason most doctors become and

21:42

remain doctors. But this is

21:44

the story of a broken

21:47

promise. Dr. Jayawardina met Bodie

21:49

when he was just a

21:52

few weeks old as Bodie's

21:54

parents sat in Dr. Jayawardina's

21:56

office digesting Bodys' just discovered

21:59

diagnosis of bilateral profound sensory

22:01

neural hearing loss. Together, they

22:04

investigated the reasons why their

22:06

little bundle of joy wasn't

22:09

able to respond to the

22:11

sound of their voices. Then,

22:14

together, they navigated through Bodys'

22:16

diagnosis of a GJB2 mutation,

22:19

the most common genetic cause

22:21

of sensory neural hearing loss.

22:24

Like many parents of children

22:26

with his autosomal recessive mutation,

22:29

Bodie's parents had been born

22:31

with normal hearing and wanted

22:34

to give their child the

22:36

same ability they had to

22:39

communicate with the world. If

22:41

they were going to achieve

22:43

this goal, Bodie had one

22:46

option. Cochlear implantation. But a

22:48

few weeks after Dr. Jayawardina

22:51

met with Bodie's family, they

22:53

heard from his insurance company

22:56

that coverage for his implant...

22:58

had been denied. Trust me,

23:01

I've got this, Dr. Jayawardina

23:03

told Bodi's parents, as he

23:06

asked his team to set

23:08

up a peer-to-peer discussion for

23:11

him with an insurance representative.

23:13

Once again, coverage was denied.

23:16

The weeks of distress caused

23:18

by these repeated, prolonged, and

23:21

unnecessary denials felt like a

23:23

strategically designed insurmountable wall and

23:25

nearly defeated them. In

23:29

our images in clinical

23:31

medicine, a 22-year-old man

23:33

presented with a one-year

23:35

history of a red

23:37

scaly rash on his

23:39

face and body. Direct

23:41

immunofluorescence of a skin

23:43

biopsy specimen showed intercellular

23:46

IGG antibodies against Desmogline

23:48

1. A diagnosis of

23:50

Pemphagus fallacious, thought perhaps

23:52

to be an endemic

23:54

subtype seen in South

23:56

America, was made. in

23:58

another a 54-year-old man -old man

24:01

presented with a a

24:03

-month history of of weakness.

24:05

Examination showed proximal

24:07

muscle weakness weakness and absent

24:09

reflexes that briefly reappeared

24:11

after voluntary muscle

24:13

contraction, shown in a

24:16

video at at .org.

24:18

A diagnosis of the

24:20

Lambert -Eten Myesthenic Syndrome, an

24:22

autoimmune disorder of the

24:24

presynaptic neuromuscular junction,

24:26

was made. made. This

24:29

concludes our summary. Let us

24:31

know what you think

24:33

about our podcast. our Any

24:35

comments or suggestions or be

24:37

sent to may be sent to audio at

24:40

nejm.org. Thank you for listening.