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Welcome. This is the New

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England Journal of Medicine. I'm Dr. Michael

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Bierrer. This week, January

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4, 2024,

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we feature articles on a

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drug-eluting scaffold for infrapoplatile disease,

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a phase 2 trial

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of cyboprenlimab in IgA

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nephropathy, liquefied petroleum

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gas cooking and the effects

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on severe infant pneumonia and

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on stunting in infants, a

0:28

review article on communicating about serious

0:31

illness and end-of-life, a

0:33

clinical problem-solving describing a

0:35

swell diagnosis, and

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perspective articles on the

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journal's historical, quote, Indian

0:43

problem. We

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also feature a new clinical decisions

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on dietary protein restriction in chronic

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kidney disease. This feature

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about a man with chronic kidney

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disease offers a case vignette accompanied

0:57

by two essays, one supporting adherence

0:59

to a low protein diet and

1:02

the other recommending against it. We

1:04

want to know what you decide. Visit

1:07

nejm.org to vote.

1:12

Drug-eluting resorbable scaffold

1:14

versus angioplasty for

1:16

infrapoplatile artery disease

1:19

by Ramon Varco from the

1:21

Prince of Wales Hospital, Randwick,

1:23

New South Wales, Australia, and

1:26

colleagues. Among

1:28

patients with chronic limb-threatening

1:31

ischemia, CLTI, and

1:33

infrapoplatile artery disease, angioplasty

1:37

has been associated with

1:39

frequent reintervention and adverse

1:41

limb outcomes from restenosis.

1:43

This study evaluated the effect

1:45

of the use of drug-eluting

1:48

resorbable scaffolds on these outcomes.

1:50

261 patients with

1:52

CLTI and infrapoplatile artery disease

1:54

were randomly assigned in a

1:57

two to one ratio to

1:59

receive... treatment with an

2:01

everolomous-eluting resorbable scaffold

2:04

or angioplasty. The

2:06

composite primary efficacy endpoint of

2:08

freedom from above ankle amputation

2:11

of the target limb, occlusion

2:13

of the target vessel, clinically

2:15

driven revascularization of the target

2:18

lesion, and binary restenosis of

2:20

the target lesion at one

2:22

year was observed. That is,

2:25

no events occurred in 74%

2:28

of patients in the scaffold group and 44%

2:30

of patients in

2:32

the angioplasty group. Absolute

2:34

difference, 30 percentage points. The

2:37

primary safety endpoint of freedom from major

2:39

adverse limb events at six months and

2:41

from perioperative death was observed in 165

2:44

of 170 patients in the scaffold group

2:46

and 90

2:50

of 90 patients in the angioplasty

2:52

group. Absolute difference,

2:55

minus three percentage points. Serious

2:57

adverse events related to the index procedure occurred

3:00

in 2% of the patients in the

3:02

scaffold group and 3% of those

3:05

in the angioplasty group. Among

3:07

patients with CLTI due

3:10

to infropopliteal artery disease,

3:12

the use of an

3:14

everolomous-eluting resorbable scaffold was

3:16

superior to angioplasty with

3:18

respect to the primary

3:20

efficacy endpoint. Joshua

3:23

Beckman from the University of

3:25

Texas Southwestern Medical Center, Dallas,

3:28

writes in an editorial that

3:30

resorbable scaffolds are a newer

3:32

technology designed to provide support

3:34

to the vessel wall and

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prevent acute and subacute artery

3:39

closure. Over time,

3:41

the device is resorbed and

3:43

fosters more natural artery remodeling,

3:45

given that the device is

3:47

not permanently present, and preserved

3:50

vasomotion. In addition to

3:52

allowing for the dissolution of the

3:54

arterial support structure, these devices may

3:56

provide a platform for drug elution.

10:00

Maryland and colleagues. Pneumonia

10:03

is a leading cause of death

10:05

among children worldwide, with most deaths

10:07

occurring in infants younger than one

10:09

year of age. Approximately

10:12

83% of the 800-8,000 annual deaths from pneumonia among children occur

10:19

in Sub-Saharan Africa, South

10:21

Asia, and Latin America.

10:24

Observational studies suggest that

10:26

exposure to fine particulate

10:28

matter with an aerodynamic

10:30

diameter of 2.5 micrometers

10:32

or less, PM2.5, from

10:35

incomplete combustion of solid fuel

10:37

is a risk factor for

10:39

pneumonia. Nearly 30%

10:42

of the global pediatric deaths

10:44

from pneumonia are attributed to

10:46

household air pollution. This

10:48

study assessed whether cooking with

10:50

an unvented liquefied petroleum gas,

10:53

LPG stove and fuel during

10:55

pregnancy and the offspring's first

10:57

year of life would lead

10:59

to a lower incidence of

11:01

infant pneumonia and other health

11:03

outcomes than biomass, that is

11:06

wood, charcoal, animal dung and

11:08

coal cooking. The trial involved

11:10

3,200 pregnant women 18 to 34 years of age

11:12

and between 9 to less than 20

11:18

weeks gestation in India,

11:20

Guatemala, Peru and Rwanda.

11:23

From May 2018 through

11:25

September 2021, the women

11:27

were assigned to cook with

11:29

unvented LPG stoves and fuel

11:31

or to continue cooking with

11:33

biomass fuel. 3,061

11:37

infants were born and included in the

11:39

study. High uptake of

11:41

the intervention led to a reduction

11:43

in personal exposure to PM2.5 among

11:45

the children with

11:48

immediate exposure of 24.2 micrograms

11:51

per cubic meter in the intervention

11:53

group and 66 micrograms per cubic

11:55

meter in the control group. The

12:00

25 episodes of severe pneumonia were identified during

12:02

the first year of life with an incidence

12:04

of 5.67 cases per 100 child years in

12:07

the intervention group and 6.06 cases per 100

12:09

child years in the

12:16

control group. No severe

12:18

adverse events were reported to be

12:20

associated with the intervention as determined

12:23

by the trial investigators. The

12:25

incidence of severe pneumonia among

12:27

infants did not differ

12:30

significantly between those whose mothers were

12:32

assigned to cook with LPG stoves

12:34

and fuel and those whose mothers

12:36

were assigned to continue cooking with

12:39

biomass stoves. Effects

12:43

of cooking with liquefied petroleum

12:45

gas or biomass on stunting

12:47

in infants by

12:50

William Checkley from Johns Hopkins

12:52

University, Baltimore, and colleagues. Household

12:56

air pollution is associated with stunted

12:58

growth in infants. This

13:00

study evaluated whether the replacement

13:02

of biomass fuel with LPG

13:04

for cooking could reduce the

13:07

risk of stunting. Three

13:09

thousand two hundred pregnant women 18 to

13:12

34 years of age in four low

13:14

and middle income countries were included. Men

13:17

at nine to less than 20

13:19

weeks gestation were randomly assigned to

13:21

use a free LPG cookstove with

13:24

continuous free fuel delivery for 18

13:27

months or to continue using

13:29

a biomass cookstove. The

13:31

length of each infant was measured at

13:33

12 months of age. Adherence

13:36

to the intervention was high

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and the intervention resulted in

13:40

lower prenatal and postnatal 24-hour

13:42

personal exposures to fine particulate

13:45

matter than the control. Mean

13:48

prenatal exposure 35 micrograms per cubic meter

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versus 103.3 micrograms per cubic meter. Mean

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postnatal exposure 37. 1.9

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micrograms per cubic meter versus 109.2 micrograms per

14:03

cubic meter. Stunting

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occurred in 27.4% of the 1,171 infants included

14:09

in the analysis of the infants born to

14:16

women in the intervention group and

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in 25.2% of the 1,186 infants included in the analysis

14:25

of those born to women in

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the control group. An

14:30

intervention strategy starting in pregnancy

14:32

and aimed at mitigating household

14:35

air pollution by replacing biomass

14:37

fuel with LPG for cooking

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did not appear to reduce the

14:42

risk of stunting in infants. Ultrasound

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blood-brain barrier opening and

14:50

aducanumab in Alzheimer's disease

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by Ali Rezai from

14:55

the Rockefeller Neuroscience Institute,

14:58

Morgantown, West Virginia and

15:00

colleagues. A

15:02

challenge of therapeutics in Alzheimer's

15:04

disease has been restriction by

15:06

the blood-brain barrier of the

15:08

delivery of therapeutic agents to

15:10

brain tissue. Low

15:12

intensity, focused ultrasound guided by

15:15

MRI has been shown to

15:17

reversibly open the blood-brain barrier

15:20

in patients with Alzheimer's disease

15:22

or other neurologic disorders. In

15:25

patients with Alzheimer's disease, anti-amyloid

15:27

antibodies have been used to

15:29

reduce cerebral amyloid beta load.

15:33

These investigators applied focused ultrasound

15:35

with each of six monthly

15:37

aducanumab infusions to temporarily open

15:40

the blood-brain barrier with the

15:42

goal of enhancing amyloid removal

15:44

in selected brain regions in

15:47

three participants over a period

15:49

of six months. The

15:52

reduction in the level of amyloid

15:54

beta was numerically greater in regions

15:56

treated with focused ultrasound than in

15:58

the home of the patients. homologous

16:00

regions in the contralateral hemisphere that

16:02

were not treated with focused ultrasound

16:05

as measured by 18F PET scan.

16:10

Cognitive tests and safety evaluations were conducted over

16:12

a period of 30 to 180 days after

16:16

treatment, but the trial was not

16:18

powered to detect clinical changes. In

16:22

a science behind the study editorial,

16:24

Kulevov Hainanen from Sunnybrook Research

16:27

Institute, Toronto, writes that the

16:29

blood-brain barrier safeguards the brain

16:32

from harmful substances while allowing

16:34

essential nutrients to pass through.

16:37

However it also impedes the delivery of

16:39

drugs to the brain. This

16:42

challenge is especially prominent when

16:44

treating Alzheimer's disease, a neurodegenerative

16:46

disorder with limited treatment options

16:48

that imposes a major burden

16:50

on healthcare due to an

16:53

aging global population. The

16:55

experimental treatment reported by Reza

16:57

and colleagues involves the creation

16:59

of an opening in this

17:01

barrier by MRI-guided focused ultrasound

17:04

to enhance drug delivery. Focused

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ultrasound generates a mechanical

17:09

wave inducing oscillations in

17:11

the medium that transitions

17:13

between compression and rarefaction.

17:15

Gas bubbles, when injected into

17:17

the bloodstream and exposed to

17:20

the ultrasound field, undergo greater

17:22

compression and expansion than surrounding

17:24

tissues and blood. These

17:26

oscillations create mechanical stress on

17:29

blood vessel walls leading to

17:31

the stretching and opening of

17:34

tight junctions between endothelial cells.

17:37

They also stimulate active vacuole

17:39

transport through these cells. Thus

17:41

the integrity of the blood-brain

17:44

barrier is compromised allowing molecules

17:46

to diffuse into the brain. The

17:49

barrier reseals itself within approximately

17:51

6 hours with less time

17:53

for mild exposures or larger

17:55

molecules and more time after

17:57

higher exposure levels. by

18:00

Reza and colleagues involved small tissue

18:02

volumes which were not systematically chosen

18:04

in one side of the brain

18:07

of three patients only. Expanding

18:09

treatment to clinically significant volumes

18:11

on both sides of the

18:13

brain is crucial for assessing

18:16

its efficacy in slowing disease

18:18

progression. Moreover, additional studies

18:20

are needed to establish long-term

18:23

safety and efficacy and cost-effective

18:25

treatment devices that are not

18:28

reliant on online MRI guidance

18:30

must be developed for broader

18:33

accessibility. That all being

18:35

said, the results spark optimism

18:37

that this approach to treatment

18:39

together with agents that remove

18:41

amyloid beta might eventually

18:43

slow the progression of Alzheimer's

18:46

disease. Navigating

18:49

and communicating about serious illness

18:51

and end-of-life. A review article

18:54

by Vicki Jackson from Massachusetts

18:56

General Hospital Boston and Linda

18:58

Emanuel from the Feinberg School

19:01

of Medicine Chicago. Conversations

19:04

about prognosis can be difficult

19:06

and confusing for both patients

19:08

and clinicians. It is

19:10

not uncommon that patients who

19:12

have a serious illness such

19:14

as cancer or heart failure

19:17

continue to express seemingly unrealistic

19:19

hopefulness despite conversations in which

19:21

accurate prognostic information has been

19:23

well communicated and tailored to

19:25

the patient's preferences. This

19:28

reaction is disconcerting for clinicians who

19:30

want to understand what is most

19:32

important to the patient and are

19:34

rightly concerned that a patient may

19:36

not be prepared for the end

19:38

of life. Such concerns

19:40

that lack of preparation can

19:42

lead to poor quality end-of-life

19:44

care are supported by evidence

19:47

of late referrals to hospice

19:49

and unwanted in-hospital deaths. Partnering

19:52

With patients as they

19:54

navigate serious illness requires

19:56

effectively communicating prognostic information

19:58

while responding. The

22:00

on numerous occasions with the

22:02

same symptom complex routine laboratory

22:05

tests were repeatedly negative. After.

22:07

Extensive evaluation that ruled out

22:10

infectious, inflammatory and structural causes

22:12

of pain. a C T

22:14

Scan that showed bow wall

22:17

sickening considered in the context

22:19

of a family history of

22:21

episodic abdominal pain in an

22:24

uncle generated concern for hereditary

22:26

angioedema as the cause of

22:28

his symptom complex. Hereditary angioedema

22:31

is a rare auto so

22:33

most dominant genetic disorder that

22:35

typically develops in childhood. Diseases.

22:38

Characterized by recurrent episodes of swelling

22:40

in various parts of the body

22:43

and can be severely debilitating. Laboratory.

22:46

Testing that documented a low

22:48

level of see one estrus

22:50

activity confirm the diagnosis. Indigenous

22:55

Americans, The. Journal's

22:57

Historical Quote Indian

22:59

Problem. A perspective

23:01

by David Jones from Harvard

23:04

University, Cambridge, Massachusetts and colleagues.

23:07

By. The time the journal was

23:10

launched in eighteen twelve. Boston.

23:12

Had witnessed two centuries

23:14

of destructive confrontations between

23:17

Europeans and Indigenous Americans.

23:19

Although. Some indigenous communities persisted

23:22

in New England, most conspicuously

23:24

and wailing few indigenous people

23:26

would have been visible on

23:29

Boston Streets. But. Away

23:31

from the Atlantic coast, North

23:33

America remained and indigenous continent.

23:35

Over. The ensuing years, the

23:38

journal published thousands of articles

23:40

that mentioned indigenous people, but

23:42

far fewer that focused on

23:45

them. The. Journal like

23:47

American Society more broadly

23:49

had a quotes Indian

23:51

problem. Racism. Against

23:54

Indigenous Americans and Settler

23:56

colonial strategies shaped centuries

23:59

of dispossession, war, subjugation,

24:01

and impoverishment. These.

24:03

Attitudes persist today.

24:06

The. Journal's authors theorized about

24:09

the merits of savagery

24:11

and civilization, decried indigenous

24:14

medicines, speculated about susceptibility

24:16

to epidemics or prophesized

24:19

indigenous extinction, The.

24:21

Disdain was often

24:23

gratuitous. An eighty

24:25

Ninety Five article about syphilis

24:28

slandered indigenous women who had

24:30

been sent to assimilationist industrial

24:33

schools. Quotes. A

24:35

prevalent opinion, especially among philanthropists,

24:38

is that the Indian S.

24:40

is a model of chastity.

24:43

God. Spare the model. Even.

24:45

Some of the girls who have been

24:48

to the schools on the Atlantic coast

24:50

are common property for white men. What?

24:53

Their habits with the bucks

24:55

are is not known by

24:57

many white devils contract venereal

25:00

diseases from the blankets. Or

25:03

nineteen Thirteen essay by

25:05

Earnest Hardman about appendicitis

25:07

included a striking caption.

25:10

Quote. There. Is no

25:12

good Indian, but a dead

25:14

Indian. And there is no

25:16

safe appendix but a completely

25:18

obliterated one. This. Adage:

25:21

A relic of frontier wars

25:23

endured for decades. Equally

25:26

striking, or the Erasers

25:28

decades could pass without

25:30

the journal seriously engaging

25:32

with problems of indigenous

25:34

health. For. Centuries European

25:37

colonists and American settlers

25:39

self entitled to seize

25:42

indigenous lands and devastate

25:44

indigenous communities. These. Processes

25:46

where cataclysmic indigenous communities

25:49

contend with pronounced health

25:51

inequities to this day.

25:54

And. Yet writings in the Journal. For.

25:56

Many influential health experts

25:58

routinely it. The Breast:

26:01

Euro American fantasies of

26:03

superiority and conquest. What?

26:05

Can American Medicine offer

26:08

in service of apology,

26:10

reconciliation and repair to

26:13

resurgent indigenous communities? Although.

26:16

It's simple enough to mind

26:18

the journal's archived for slanderous

26:20

commentaries. The. Challenge is

26:22

to strike a balance

26:24

among documenting what authors

26:26

said, conveying empathy and

26:29

outrage and suggesting productive

26:31

interpretation. The. Journal's historical

26:33

commentaries about Indigenous Americans

26:35

reveal more about authors

26:37

and editor's values and

26:39

priorities then about indigenous

26:42

communities themselves. Such racist

26:44

discourse reflected perpetuated and

26:46

legitimated settler colonists faith

26:48

in the righteousness of

26:50

their mission. It's

26:53

essential that readers understand

26:55

these dynamics is they

26:57

are to recognize and

26:59

repudiate similar process he's

27:01

at work. Today. In.

27:05

Our images in Clinical Medicine. A.

27:08

Forty three year old woman

27:10

presented to the dermatology clinic

27:12

with an eight year history

27:14

of a trophic t land

27:17

check Tadic yellow brown plaques

27:19

with irregular vile laces borders

27:21

on both since analysis of

27:23

skyn biopsy have the right

27:26

shin showed several layers of

27:28

Niekro bio says within the

27:30

dermis perry vascular inflammatory sell

27:33

infiltrates, college and degeneration and

27:35

findings consistent with granule Ahmadis

27:37

dermatitis. A diagnosis of Niekro

27:39

Bios is the point a car was

27:41

made. Niekro. Biosystem Appoint a

27:44

Cat is a chronic granule Ahmadis

27:46

Skyn disorder that is frequently associated

27:48

with diabetes and may proceed the

27:51

development of impaired glucose control. However,

27:53

the condition is also seen in

27:56

person's without diabetes has occurred in

27:58

this patient who had. Normal

28:00

results on glycemic testing there

28:02

are no evidence based guidelines

28:04

for treatment and the lesions

28:06

often abate on their. In.

28:09

Another image say fifty four

28:11

year old woman presented with

28:14

a crooked painful singer after

28:16

falling onto her outstretched hand.

28:18

Radio. Graphs have the right

28:20

hand showed dorsal dislocation of the

28:23

proximal and distal inter full angel

28:25

joints of the see singer which

28:27

created a stepladder shape. A

28:30

diagnosis of simultaneous dislocation of

28:32

the proximal and distal interpol

28:34

angel joints of the singer

28:36

was made, Although dislocation of

28:38

an inter phalanges joint is

28:40

commonly seen, simultaneous dislocations within

28:43

the same finger or rare.

28:45

Treatment. With closed reduction and splintering

28:47

of the singer was provided. This.

28:50

Concludes our summary: Let us

28:52

know what you think about

28:54

our podcast. Any comments or

28:56

suggestions may be sent to

28:58

audio at nejm.org. Thank

29:01

you for listening.