0:00

Welcome, this is the New England

0:02

Journal of Medicine. I'm Dr.

0:04

Lisa Johnson. This week, September 28,

0:09

2023, we feature articles on anticoagulation

0:12

and atrial high-rate episodes,

0:15

tight blood glucose control in

0:17

patients in the ICU,

0:19

increasing artemisinin-resistant

0:22

malaria in Eritrea, the

0:24

death of a patient after high-dose

0:27

gene therapy, and on

0:29

anti-racist documentation practices,

0:32

a review article on where medical

0:34

statistics meets AI,

0:37

a case report of a woman with confusion,

0:40

and perspective articles on affirmative

0:43

action, population health, and

0:45

hope, on threatening the global

0:47

AIDS response, and on

0:50

swimming. Anticoagulation

0:54

with Adoxaban in Patients

0:56

with Atrial High-Rate Episodes

0:59

by Paulus Kirschhoff from

1:01

the Atrial Fibrillation Network,

1:03

Münster, Germany. Device-detected

1:07

atrial high-rate episodes, AHREs,

1:11

are atrial arrhythmias detected

1:13

by implanted cardiac devices.

1:15

AHREs

1:16

resemble atrial

1:18

fibrillation but are rare and

1:21

brief. Whether the occurrence

1:23

of AHREs in patients

1:26

without atrial fibrillation, as

1:28

documented on a conventional electrocardiogram,

1:31

justifies the initiation of anticoagulants

1:35

is not known.

1:36

In this event-driven trial, 2,536

1:38

patients 65 years of age or older who had

1:40

AHREs lasting for at

1:47

least 6 minutes and who had

1:49

at least one additional risk factor

1:51

for stroke were randomly assigned

1:54

to receive Adoxaban or

1:56

placebo.

1:58

The trial was terminated early.

3:54

there may be several reasons for

3:56

the lack of efficacy of dogs

3:59

First, the trial had inadequate

4:02

statistical power, as the incidence

4:04

of ischemic stroke was only 1%. Second,

4:08

the AHREs that had occurred

4:11

may not have been thrombogenic atrial

4:13

tachyarrhythmias, such as paroxysmal

4:16

atrial fibrillation, but may instead

4:19

have been rhythm disturbances that were

4:21

not expected to substantially impair

4:24

contraction of the left atrial

4:26

appendage. Third, the

4:28

duration and rarity of AHREs

4:31

may have been too brief or too

4:33

infrequent to provoke a left

4:35

atrial thrombus. Although

4:37

AHREs have been associated

4:40

with

4:40

stroke, the risk of stroke remains

4:43

substantially

4:43

less than the risk

4:45

associated with ECG-documented

4:48

paroxysmal or sustained

4:50

atrial fibrillation. The

4:52

lack of efficacy of anticoagulation

4:55

in reducing stroke in the current trial

4:57

may have resulted in part from the

4:59

fact that only a subset of

5:01

the AHREs were thrombogenic,

5:04

namely atrial fibrillation episodes

5:07

of sufficient duration, frequency,

5:09

or both. Future investigation

5:11

may benefit from studying the clinical

5:14

characteristics of populations

5:17

suitable for rhythm monitoring. The

5:19

threshold characteristics of AHREs

5:22

that lead to thrombus formation,

5:24

and the specific atrial tachyarrhythmias

5:27

that occurred during an AHRE

5:29

that could justify anticoagulation.

5:32

However, the device-detected AHREs

5:35

that occurred in this trial do not

5:38

adequately infer a definitive diagnosis

5:41

of paroxysmal atrial fibrillation

5:43

for all patients or a subsequent

5:46

risk of stroke.

5:57

of

6:00

KU Leuven, Belgium. Randomized

6:05

control trials have shown both

6:07

benefit and harm from tight

6:09

blood glucose control in patients

6:12

in the intensive care unit. Variation

6:14

in the use of early parenteral nutrition

6:17

and in insulin-induced severe

6:20

hypoglycemia might explain

6:22

this inconsistency. In

6:25

this study, 9,230 patients were randomly assigned

6:30

upon ICU admission to liberal

6:32

glucose control. Insulin initiated

6:35

only when the blood glucose level was

6:37

greater than 215 milligrams

6:39

per deciliter or to tight

6:42

glucose control. Blood glucose

6:44

level targeted with the use of the

6:46

logic insulin algorithm at 80

6:49

to 110 milligrams per

6:51

deciliter. Parentoral nutrition

6:54

was withheld in both groups

6:56

for the initial week. The

6:58

median morning blood glucose level

7:00

was 140 milligrams per

7:03

deciliter with liberal glucose

7:05

control and 107 milligrams

7:07

per deciliter with tight

7:09

glucose control.

7:11

Severe hypoglycemia occurred

7:13

in 0.7% of patients in

7:16

the liberal control group and in 1%

7:19

of patients in the tight control group.

7:21

The length of time that ICU care

7:24

was needed was similar in the two

7:26

groups. Hazard ratio for earlier

7:28

discharge alive with tight glucose

7:31

control, 1.00. Mortality

7:35

at 90 days was also similar, 10.1% with

7:39

liberal glucose control and 10.5% with

7:41

tight glucose control.

7:44

Analyses of eight pre-specified

7:47

secondary outcomes suggested

7:49

that the incidence of new infections,

7:51

the duration of respiratory and hemodynamics

7:54

support, the time to discharge

7:56

alive from the hospital and mortality

7:59

in the ICU.

10:00

which have acute adverse effects with

10:02

respect to inflammation and oxidative

10:04

stress, neutrophil function, kidney

10:07

function, and hemodynamics. Based

10:10

on evidence from previous randomized

10:12

control trials, the American Diabetes

10:15

Association recommends initiation

10:17

of insulin for the treatment of persistent

10:20

hyperglycemia with a targeted

10:22

glucose range of 140 mg per deciliter

10:24

to 180 mg

10:28

per deciliter for most critically

10:30

ill patients. More stringent

10:32

goals, such as a glucose level of 100

10:35

to 180 mg per

10:37

deciliter, may be appropriate

10:39

as long as they can be achieved without

10:42

clinically significant hypoglycemia.

10:47

Increasing prevalence of artemisinin-resistant

10:51

HRP2-negative malaria

10:53

in Eritrea. By Salam

10:56

Meritib from the Ministry of Health,

10:58

Asmara Eritrea. Although

11:01

the clinical efficacy of anti-malarial

11:05

artemisinin-based combination therapies

11:07

in Africa remains high,

11:10

the recent emergence of partial resistance

11:12

to artemisinin in P. falciparum

11:15

on the continent is troubling given

11:17

the lack of alternative treatments.

11:20

These authors describe the results

11:22

of therapeutic efficacy studies

11:24

conducted between 2016 and 2019 at five sites in

11:27

Eritrea, evaluating three-day

11:32

courses of artemisinin-based

11:35

combination therapy for uncomplicated

11:38

falciparum malaria. The

11:40

authors assess the percentage of patients

11:43

with day three positivity, that

11:45

is, persistent P. falciparum

11:47

parasitemia three days after

11:50

the initiation of therapy, and

11:52

assay parasites for molecular

11:55

signatures of partial resistance

11:57

to artemisinin.

11:59

The authors noted an increase in

12:02

the percentage of patients with day 3

12:04

positivity,

12:05

from 0.4% in 2016

12:07

to 1.9% in 2017 and 4.2% in 2019.

12:15

An increase was also noted in

12:17

the prevalence of the PF-CELCH13R622i

12:22

mutation in P. falciparum

12:24

parasites, which was detected in 109 of 818

12:26

isolates before treatment, from 8.6% in 2016 to 21%

12:34

in 2019. The

12:38

odds of day 3 positivity increased

12:40

by a factor of 6.2 among

12:43

the patients with PF-CELCH13622i variant

12:47

parasites. Physical

12:49

resistance to artemisinin, as

12:51

defined by the World Health Organization,

12:54

was observed in Eritrea.

12:57

More than 5% of the patients younger

12:59

than 15 years of age with day 3

13:02

positivity also had parasites

13:04

that carried PF-CELCH13R622i. Deletions

13:09

in both HRP2 and HRP3,

13:13

which encode histidine-rich

13:15

and alanine-rich proteins, analyzed

13:18

in several cell compartments, including

13:20

the cytoplasm of P. falciparum,

13:23

were identified in 16.9%

13:26

of the parasites that carried the

13:28

PF-CELCH13R622i

13:31

mutation, which made them potentially

13:34

undetectable by HRP2-based

13:37

rapid diagnostic tests. The

13:39

emergence and spread of P. falciparum

13:42

lineages with both PF-CELCH13-mediated

13:46

partial resistance to artemisinin

13:49

and deletions in HRP2 and

13:51

HRP3 in Eritrea threatened to compromise regional

13:56

malaria control and elimination

13:58

campaigns.

14:01

Brian Greenwood from the London

14:03

School of Hygiene and Tropical Medicine

14:05

writes in a perspective article that

14:08

progress in malaria control in

14:10

some countries in sub-Saharan Africa

14:13

is now challenged by several new

14:15

threats. These include colonization

14:18

of parts of the region by the Asian

14:20

mosquito vector Anopheles Stefensi,

14:23

which, unlike the main malaria vectors

14:26

currently responsible for most malaria

14:28

transmission in sub-Saharan Africa,

14:31

thrives in urban settings, increasing

14:33

the risk of malaria in the region's

14:36

large urban centers that are currently

14:38

relatively malaria free. A

14:41

second major threat comes from the

14:43

recent emergence in East Africa

14:45

of P. falciparum parasites with

14:48

reduced susceptibility to artemisinin-based

14:51

combination drugs, the drugs that

14:53

form the mainstay of treatment of

14:55

falciparum malaria. The

14:57

results of the study by Miratib and colleagues

15:00

raise a further issue. The

15:02

investigators identified P.

15:04

falciparum parasites that were

15:07

resistant to artemisinins and

15:09

also had deletions in HRP2,

15:12

HRP3, or both, which

15:14

potentially delay the diagnosis

15:17

and effective treatment of infections

15:19

with an artemisinin-resistant parasite.

15:22

P. falciparum parasites with HRP2

15:25

or HRP3 deletions are

15:28

widely distributed in Eritrea,

15:30

and it is therefore not surprising that

15:33

some parasites with these deletions

15:35

also had the R622i

15:38

mutation associated with resistance.

15:41

It is concerning, however, that the HRP2

15:44

deletion was found three

15:46

times as frequently in parasites

15:49

carrying the R622i mutation

15:52

as in parasites without it. Given

15:55

that the HRP2 and P. falciparum-based

15:57

gene are genetically

15:59

unlinked and are on different

16:02

parasite chromosomes, it is unclear

16:05

how co-selection might operate.

16:08

To counter the threat posed to malaria

16:10

control in sub-Saharan Africa

16:12

by P. falciparum parasites with

16:15

HRP2 or HRP3

16:17

deletions and mutations

16:19

associated with resistance, countries

16:22

must rely first on enhanced

16:25

surveillance to detect these

16:27

parasites. Death

16:30

after high dose RAAV9

16:33

gene therapy in a patient with

16:35

Duchenne's muscular dystrophy by

16:38

Angela Leck from Yale School

16:40

of Medicine, New Haven, Connecticut.

16:44

Duchenne's muscular dystrophy is

16:46

a fatal X-linked myopathy

16:48

caused by mutations in DMD,

16:51

the large structural gene encoding

16:54

dystrophin.

16:56

Dystrophin plays a major role

16:58

in the function of cardiac myocytes

17:01

and skeletal myofibers as

17:03

part of the dystrophin glycoprotein

17:06

complex that anchors myofilaments

17:09

to the extracellular matrix and

17:11

prevents stress-induced damage

17:13

to the sarcolemma membrane.

17:16

Several recombinant adeno-associated

17:18

virus RAAV-based

17:21

approaches to gene therapy for this

17:23

disorder have been developed.

17:26

These authors treated a 27-year-old patient with

17:29

Duchenne's muscular dystrophy with

17:32

recombinant AAV serotype 9

17:35

containing DSA Cas9,

17:37

that is, dead Staphylococcus

17:40

aureus Cas9, in which the

17:42

Cas9 nuclease activity has

17:45

been inactivated,

17:46

fused to VP64.

17:49

This transgene was designed

17:52

to upregulate cortical dystrophin

17:55

as a custom CRISPR transactivator

17:57

therapy.

17:59

The dose of recur-

17:59

the predominant AAV used was 1

18:02

x 10 to the 14th vector

18:05

genomes per kilogram of the patient's body

18:08

weight. Mild cardiac dysfunction

18:10

and pericardial effusion developed,

18:13

followed by acute respiratory distress

18:15

syndrome, ARDS, and

18:17

a cardiac arrest six days

18:20

after transgene treatment. The

18:22

patient was initially resuscitated

18:24

but died two days later. A post-mortem

18:26

examination showed

18:29

severe diffuse alveolar damage.

18:32

Expression of transgene in the liver

18:35

was minimal, and there was no evidence

18:37

of AAV serotype 9 antibodies

18:40

or effector T-cell reactivity

18:42

in the organs. These findings

18:44

indicate that an innate immune

18:47

reaction caused ARDS

18:49

in this patient with advanced Duchenne's

18:52

muscular dystrophy, treated with

18:54

high-dose recombinant AAV

18:57

gene therapy. Where

19:00

Medical Statistics Meets Artificial

19:03

Intelligence, a review article

19:05

by David Hunter from the Nuffield

19:08

Department of Population Health in

19:10

the United Kingdom. In

19:12

the 21st century, artificial

19:15

intelligence has emerged as

19:17

a valuable approach in data

19:19

science and a growing influence

19:21

in medical research with an accelerating

19:24

pace of innovation. This

19:26

development is driven in part

19:29

by the enormous expansion in

19:31

computer power and data availability.

19:34

However, the very features

19:36

that make AI such a valuable

19:39

additional tool for data analysis

19:42

are the same ones that make it vulnerable

19:44

from a statistical perspective.

19:47

This paradox is particularly pertinent for

19:50

medical science. In this review,

19:53

the authors explore three particular

19:56

challenges at the interface of

19:58

statistics and AI. that

20:00

are of particular relevance to

20:02

medical studies, population

20:04

inference versus prediction, generalizability

20:08

and interpretation of evidence, and

20:10

stability and statistical guarantees.

20:14

The authors focus on issues of

20:16

data analysis and interpretation

20:19

of findings.

20:20

Much of the art of

20:21

applied statistics and the skills

20:23

of a trained statistician or epidemiologist

20:27

involve factors that lie outside

20:29

the data and hence cannot

20:32

be captured by data-driven

20:34

AI algorithms alone. These

20:37

factors include careful design

20:39

of experiments, an understanding

20:42

of the research question and study

20:44

objectives, and tailoring of models

20:46

to the research question in the context

20:49

of an existing knowledge base with

20:51

ascertainment and selection bias

20:54

accounted for and a healthy suspicion

20:56

of results that look too good to be true,

20:59

followed by careful model checking.

21:02

Bringing these skills to bear on

21:04

AI-enabled studies through human-in-the-loop

21:08

development in which AI supports

21:10

and assists expert human judgment

21:13

will likely enhance the effect

21:15

and uptake of AI methods

21:18

and highlight methodologic and

21:20

theoretical gaps to be addressed

21:23

for the benefit of medical science.

21:27

A 50-year-old woman with

21:28

confusion,

21:30

a case record of the Massachusetts

21:32

General Hospital by Amulya

21:34

Nagar and colleagues. A

21:38

50-year-old woman was admitted to the hospital

21:41

because of confusion. Rouen-Y

21:43

gastric bypass surgery had been performed 12

21:46

years earlier, five

21:48

months before the current presentation, dysphagia

21:51

developed and the patient began to lose

21:54

weight. Biopsy specimens

21:56

obtained during esophagogastro

21:58

duodenoscopy showed findings

22:01

consistent with lymphocytic esophagitis.

22:04

An attempt at treatment with swallowed

22:06

fluticasone did not increase

22:08

the patient's oral intake. Weight

22:11

loss occurred despite progressive

22:13

leg edema, which was suggestive

22:15

of muscle loss. Two months

22:18

before the current presentation, the

22:20

patient was admitted to the hospital because

22:22

of anasarka. The patient

22:24

had an albumin level of 1.9 grams

22:27

per deciliter. It was hypothesized

22:30

that poor oral intake from lymphocytic

22:33

esophagitis had led to protein

22:35

calorie malnutrition and hypoalbuminemia.

22:39

One week before the current

22:40

admission, the patient had rapidly

22:43

progressive encephalopathy and an

22:45

unsteady gait that resulted in

22:47

a fall. A UTI with Klebsiella

22:50

pneumoniae was diagnosed.

22:52

Hypotension abated after the

22:54

administration of vasopressors and systemic

22:57

antibiotic agents, but altered

22:59

mental status persisted.

23:02

The differential diagnosis for altered

23:04

mental status in this patient was

23:06

broad. However, there is an

23:08

increasingly recognized association

23:11

between non-sorotic hyperaminemia

23:14

and a history of Rouen Y gastric

23:17

bypass. Hyperaminemic

23:19

encephalopathy may develop

23:21

at various points after gastric

23:24

bypass surgery with hallmark

23:26

findings, including hypoalbuminemia,

23:29

nutritional deficiencies, and elevated

23:31

plasma glutamine level and a low

23:34

zinc level. Delays in

23:36

diagnosis and management may

23:38

result in a poor prognosis

23:41

with a high risk of death. In

23:43

this patient, the serum ammonia

23:45

level was 90 micromoles

23:47

per liter and remained elevated

23:50

on repeat measurements with a

23:52

maximum level of 107 micromoles per liter. documentation

24:01

practices, shaping clinical

24:03

encounters and decision-making.

24:06

A perspective by J. Corey Williams

24:09

from Georgetown University, Washington,

24:11

D.C. Clinicians

24:14

receive inconsistent instruction

24:16

on how to use patients' racial

24:18

identities in clinical documentation

24:21

and decision-making and often

24:24

document this information without

24:26

clear reasons or an understanding

24:28

of its relevance. Routine

24:30

documentation of racial categories

24:33

is rooted in the mythology of

24:35

inherent biologic differences

24:38

between racial groups, especially

24:40

between Black and non-Hispanic

24:43

white people. Such

24:45

myths founded on medical racism

24:47

and white supremacist ideology

24:49

have been used to justify historical

24:52

atrocities, including enslavement

24:55

of people of African descent and

24:57

continue to normalize disparate

24:59

treatment of Black and other racially

25:02

minoritized patients by the U.S.

25:05

healthcare system. Documentation

25:08

serves several critical functions,

25:10

recording essential data for clinical care,

25:13

communicating medical decisions, educating

25:16

trainees, and determining reimbursement.

25:19

Documentation of race in patients'

25:22

charts can trigger a cascade

25:24

of effects. Clinicians read

25:26

or copy and paste previous

25:28

notes to inform their understanding of

25:31

a patient's health and illness, and

25:33

they may carry forward any flawed

25:36

discriminatory descriptions, heuristics,

25:39

or beliefs the notes contain. These

25:42

authors recommend adopting documentation

25:44

practices that encourage anti-racism,

25:48

the active process of identifying

25:50

and dismantling racism using

25:53

measures that produce or sustain

25:55

equity among racial groups, including

25:58

changing organizational conditions. structures,

26:01

policies, practices, and

26:03

attitudes. These authors discuss

26:06

conventional medical documentation

26:08

and make recommendations for anti-racist

26:11

changes in approach. Affirmative

26:16

action, population health, and

26:18

the importance of opportunity and

26:20

hope. A perspective by

26:23

Athene Dar Venkataramani from

26:25

the University of Pennsylvania, Philadelphia.

26:29

After several states banned race-based

26:32

affirmative action in university

26:34

admissions, debates over

26:36

affirmative action culminated

26:39

in the Supreme Court's June 2023 decision

26:42

declaring affirmative action in

26:44

undergraduate, graduate, and professional

26:47

education unconstitutional.

26:50

Policy debates related to affirmative

26:53

action have typically focused on its

26:55

effects on education, employment,

26:58

and earnings. However, these debates

27:01

have generally neglected the important

27:03

role affirmative action may play

27:05

in shaping population health.

27:08

There are at least three mechanisms

27:11

by which the use of affirmative action

27:13

in admissions might affect health.

27:16

First, data from California

27:18

show that affirmative action programs

27:21

can have a positive effect on college

27:23

graduation rates and future earnings

27:26

among black, Hispanic, and American

27:28

Indian and Alaska Native students,

27:31

which underscores the value associated

27:34

with having access to selective

27:36

institutions of higher education.

27:39

Second, affirmative action programs

27:41

have important consequences for the

27:43

health care workforce. A lack

27:45

of diversity in the physician workforce

27:47

has implications for population

27:50

health and health equity. And

27:52

a third and less discussed mechanism

27:55

by which affirmative action programs may

27:57

affect health is through the messages

27:59

they have. they send to population

28:01

groups facing structural barriers.

28:04

These programs and their termination can

28:07

signal to young people about their

28:09

prospects for upward mobility, their

28:11

belonging in society, and the degree

28:14

of systemic discrimination they may

28:16

face. Such affective

28:18

consequences, namely the effects

28:20

of policies on hope and beliefs

28:23

about opportunities for upward mobility,

28:26

can meaningfully shape health-related

28:28

behaviors and

28:29

outcomes.

28:32

Threatening the Global AIDS

28:34

Response, Obstacles to

28:37

PEPFAR's Reauthorization,

28:39

a perspective by Salim

28:41

Abdul Karim from the University

28:44

of KwaZulu-Natal, Durban,

28:46

South Africa. The

28:48

U.S. President's Emergency Program

28:51

for AIDS Relief, PEPFAR, the

28:53

largest commitment in history by any

28:55

single country to address a disease,

28:58

is estimated to have averted 25 million

29:02

deaths from AIDS and enabled 5.5 million

29:05

babies to be born free from

29:08

HIV infection over the

29:10

past 20 years.

29:12

It has provided more than $100 billion

29:15

in funding for HIV prevention,

29:18

care, and treatment internationally,

29:21

supporting 55 low- and middle-income

29:23

countries that are collectively home

29:26

to 78% of all

29:28

people living with HIV.

29:31

Since its establishment, PEPFAR

29:34

has had bipartisan support in

29:36

the United States and has been reauthorized

29:39

by both chambers of the U.S.

29:41

Congress three times.

29:43

But several Republican politicians

29:46

are now demanding that reauthorization

29:49

be linked to new prohibitions

29:52

related

29:53

to abortion.

29:54

Some influential anti-abortion

29:57

organizations have

29:58

warned Republican members

29:59

of Congress that voting for the

30:02

reauthorization of PEPFAR without

30:04

abortion-related restrictions would

30:06

negatively affect the ratings these

30:09

organizations give members

30:11

each year, which

30:12

would, in turn, diminish

30:14

their prospects for re-election.

30:17

The lawmakers stalling the reauthorization

30:20

are seeking to impose on PEPFAR

30:22

a prohibition on the disbursement

30:24

of federal funding to foreign agencies

30:27

and non-governmental organizations

30:29

that provide, promote, or make

30:31

referrals to abortion services

30:34

or give information about abortions,

30:36

even if they use funding from sources

30:39

other than the U.S. government to do

30:41

so. These authors discuss

30:44

several reasons to object strenuously

30:47

to the

30:47

proposed restrictions on PEPFAR.

30:50

Its reauthorization should not be

30:52

held hostage to policies about

30:54

health care that are only distantly

30:57

related, if at all, to the primary

30:59

goals of the PEPFAR program.

31:03

Swimming, a perspective by

31:06

Margaret Isaac from the University

31:08

of Washington School of Medicine, Seattle.

31:13

2002, they were standing in the ocean on the Pacific

31:15

coast of Costa Rica. Dr. Isaac

31:18

and her brother, water waist-high,

31:21

hot sun on their faces, sand

31:23

and salt water swirling eddies between

31:25

their toes. Around them,

31:28

the indistinct sound of surf and

31:30

laughter. They were warm, relaxed,

31:33

content. But every so

31:35

often, a moment occurs in which everything

31:38

changes. A point of inflection.

31:41

Eyes blink, a breath is taken, a

31:44

gust ruffles the hair, the landscape

31:46

shifts, and danger makes

31:49

its presence known. In

31:51

this moment in 2002, this

31:53

blink of an eye, they found themselves

31:56

carried beyond the breakers, pulled

31:58

out by a muscular

31:59

riptide for which that beach was

32:02

apparently known.

32:04

The fact that Dr. Isaac barely

32:06

knew how to swim was something she

32:08

was aware of only in a vague sort of way,

32:10

the need for this skill in her daily

32:12

life being virtually non-existent.

32:15

But on that day she found

32:17

herself flailing against a rip

32:19

current, trying her best to paddle

32:22

to shore as the ocean, insistent

32:24

and resolute, pulled her back.

32:27

Her brother, a foot taller and seventy

32:29

pounds heavier, tried to pull her up,

32:32

but the two of them were more than he could

32:34

manage. When she looks back,

32:36

Dr. Isaac is surprised by how

32:39

quickly she gave in to fatigue

32:41

and helplessness, recognizing

32:43

that she was severely outmatched,

32:46

figuring that it was the end. And

32:49

out of nowhere, a lifeguard

32:51

swam nimbly around the current and

32:54

pulled their exhausted, shaking,

32:56

humbled bodies to shore. There

32:59

have been moments in these past three years

33:02

when Dr. Isaac has felt like she

33:04

was drowning again. She

33:06

has visceral memories of the early

33:08

spring of 2020, when the

33:10

first patient with COVID pneumonia she

33:12

had cared for on the palliative care service

33:15

died in the ICU. Dr.

33:17

Isaac stood with the patient's family

33:20

outside the window of his room as

33:22

they said goodbye to him through

33:25

a speakerphone and felt the

33:27

tugging feeling of

33:28

being pulled under again.

33:31

Last winter,

33:33

Dr. Isaac took swimming lessons.

33:35

Her coach started gently, helping

33:38

Dr. Isaac gain comfort just being

33:40

in the water. Soon, the coach

33:43

coaxed Dr. Isaac to jump

33:45

in a deep water pool and notice

33:47

how little movement was truly

33:49

required to keep her head above

33:52

water. Head down, legs

33:54

strong, breath steady,

33:56

small adjustments to keep afloat.

34:01

In our images in clinical medicine, a

34:04

54-year-old woman with asthma and allergic

34:06

rhinitis presented to the emergency

34:08

department with a three-month history

34:10

of productive cough, dyspnea,

34:13

and constitutional symptoms. Peripheral

34:16

eosinophilia was noted.

34:18

CT of the chest showed upper

34:20

lobe predominant peripheral and

34:23

subpleural consolidations that

34:25

spared the perihilar region.

34:28

The radiographic pattern was described

34:31

as a photographic negative of

34:33

pulmonary edema, a finding

34:35

suggestive of chronic eosinophilic

34:38

pneumonia. In another

34:41

image, a 38-year-old man

34:43

with a history of corneal transplantation

34:46

presented with tearing, photophobia,

34:48

and reduced visual acuity in

34:51

his left eye. On slit-lamp

34:53

examination, a dendritic

34:55

ulcer was seen. A diagnosis

34:58

of herpes simplex dendritic keratitis

35:01

was made. Keratitis

35:04

is the most common form of ocular

35:06

herpes simplex infection. This

35:10

concludes our summary. Let us know

35:12

what you think about our podcast. Any

35:14

comments or suggestions may be sent

35:17

to audio at NEJM.org.

35:21

Thank you for listening.