0:00

Welcome. This is

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the New England Journal of Medicine. I'm

0:04

Dr. Michael Bierer. This

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week, August

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24th, 2023, we feature articles on

0:11

preventing cardiovascular disease

0:14

in HIV infection, the

0:16

effect of hemodiafiltration

0:19

or hemodialysis on mortality

0:21

in kidney failure,

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a new KRAS G12C

0:25

inhibitor in solid tumors, and

0:28

on partial artemisinin resistance

0:30

in malaria parasites, a

0:32

review article on protein losing

0:35

enteropathy, a case report

0:37

of a girl with abdominal pain and

0:39

an ovarian mass, and perspective

0:41

articles on the Supreme Court and

0:44

diversity in medicine, on

0:46

outbreaks in U.S. migrant detention

0:49

centers, on turning CMS

0:51

into a health technology assessment

0:54

organization, and on the

0:56

clinic that cried, safe.

1:00

Petavastatin to prevent cardiovascular

1:03

disease in HIV infection by

1:06

Stephen Grinspoon from Massachusetts

1:08

General Hospital, Boston. The

1:11

risk of cardiovascular disease is

1:13

increased among persons with HIV infection.

1:17

This phase 3 trial assessed

1:19

whether statin use prevents atherosclerotic

1:22

cardiovascular disease events in

1:24

persons with HIV infection who are

1:26

at low to moderate risk for cardiovascular

1:29

events and who were receiving antiretroviral

1:32

therapy. Petavastatin

1:35

was chosen because it does not

1:37

interact with the drugs that are used

1:39

in antiretroviral therapy. 7,769 participants

1:42

were

1:45

randomly assigned to receive daily petavastatin

1:49

or placebo.

1:50

The median age of the participants

1:52

was 50 years. The trial

1:54

was stopped early for efficacy

1:57

after a median follow-up of 5.1 years. years.

2:00

The primary outcome of the incidence

2:02

of a major adverse cardiovascular

2:05

event was 4.81 per 1,000 person years in

2:07

the pitavastatin group and 7.32 per 1,000 person years in

2:09

the placebo

2:15

group, hazard ratio 0.65.

2:19

Muscle related symptoms occurred in 2.3%

2:21

of participants in

2:23

the pitavastatin group and in 1.4% of

2:26

those in the placebo group.

2:28

Diabetes mellitus occurred in 5.3%

2:32

and 4% of participants respectively.

2:35

Participants with HIV infection

2:38

who received pitavastatin had

2:40

a lower risk of major adverse cardiovascular

2:43

events than those who received placebo over

2:45

a median follow-up of 5.1 years.

2:50

Matthew Freiberg from Vanderbilt

2:52

University Medical Center, Nashville

2:55

writes in an editorial that the major

2:57

strengths of this trial by Grinspoon

2:59

and colleagues include the enrollment

3:02

of participants from multiple sites

3:04

globally and the inclusion of a large

3:06

number of women.

3:08

Although the underlying mechanisms that

3:10

drive the excess risk of atherosclerotic

3:13

cardiovascular disease among persons

3:15

with HIV infection

3:17

remain unclear, risk

3:19

factors that include increased levels

3:21

of LDL cholesterol and systemic

3:24

inflammation caused by HIV

3:27

probably play critical roles. Because

3:29

persons with HIV infection who are at low

3:32

to moderate risk for cardiovascular

3:34

disease are likely to have elevated

3:36

levels of systemic inflammation even

3:39

after successful viral suppression,

3:41

these results suggest that statin

3:43

therapy could reduce the risk of cardiovascular

3:46

events in this population through the

3:48

lowering of LDL cholesterol levels,

3:51

of systemic inflammation levels, or

3:54

both.

3:54

Although pitavastatin targets one

3:57

and perhaps two important risk factors

3:59

for atherosclerotic cardiovascular disease,

4:02

such as LDL cholesterol

4:04

and systemic inflammation. Other

4:06

risk factors merit attention for

4:08

this preventive approach to be transformative.

4:11

Hypertension and diabetes are

4:14

often routinely addressed in clinical

4:16

care, although behavioral risk factors

4:18

such as cigarette smoking, unhealthy

4:21

alcohol consumption, drug use, obesity,

4:24

and mental health conditions are often

4:26

under assessed,

4:27

under addressed, or both,

4:30

in part because these risk factors can

4:32

be challenging to modify.

4:35

Moreover, alcohol consumption

4:37

at relatively low doses can

4:39

result in a higher risk of physiological

4:42

injury among persons with HIV

4:44

infection. Thus, targeting

4:46

these less traditional risk factors

4:49

in this population could result in

4:51

beneficial effects, either directly

4:53

on the cardiovascular system or indirectly

4:56

by reducing systemic inflammation.

4:58

As part of this overall effort,

5:01

this trial represents a necessary

5:03

first step toward a comprehensive

5:06

preventive approach to reducing the risk

5:08

of cardiovascular disease among persons

5:10

with HIV infection.

5:13

Effect of Hemodiofiltration

5:16

or Hemodialysis on Mortality

5:18

in Kidney Failure. By Peter

5:20

Blankestein from the University

5:22

Medical Center, Utrecht, The Netherlands.

5:26

Several studies have suggested that patients

5:29

with kidney failure may benefit from

5:31

high-dose hemodiofiltration

5:34

as compared with standard hemodialysis.

5:36

However, given the limitations of the various

5:38

published studies, additional data

5:41

are needed.

5:42

This trial involved 1,360

5:45

patients with kidney failure who had received

5:47

high-flux hemodialysis for at least

5:50

three months.

5:51

The patients were randomly assigned

5:53

to receive high-dose hemodialfiltration

5:56

or continuation of conventional high-flux

5:59

hemodialysis.

6:00

The primary outcome was death

6:02

from any cause. The median

6:04

follow-up was 30 months. The

6:07

mean convection volume during the

6:09

trial in the hemodial filtration group

6:11

was 25.3 liters per

6:14

session.

6:15

Death from any cause occurred

6:18

in 17.3% of

6:20

patients in the hemodial filtration

6:22

group and in 21.9% of

6:25

patients in the hemodialysis group.

6:27

In patients with kidney failure resulting

6:30

in kidney replacement therapy, the

6:32

use of high-dose hemodial filtration

6:35

resulted in a lower risk of death

6:37

from any cause than conventional

6:40

high-flux hemodialysis.

6:43

Thomas Golper from the University

6:46

of Vermont, Burlington writes in

6:48

an editorial that in the trial by Blanca

6:50

Stain and colleagues, the incidence of

6:52

death from any cause, the primary outcome

6:55

was lower among the patients with kidney

6:57

failure who underwent hemodial filtration

7:00

than among those who underwent high-flux hemodialysis

7:03

at a median follow-up of 30 months.

7:05

The trial was specifically designed

7:07

to explore the outcomes of a large

7:10

convective volume during hemodial

7:12

filtration because of conflicting

7:14

results when lesser volumes

7:17

were applied. Ideally, the trial

7:19

should have included patients who were just beginning

7:21

dialysis, but the duration of recruitment

7:24

would have been impracticably long.

7:26

The investigators' finding of the most

7:29

notable benefit among the least ill patients

7:32

is not a surprise.

7:33

Kidney replacement therapies do

7:36

not reverse all the ravages

7:38

of uremia.

7:40

As compared with high-flux hemodialysis,

7:42

hemodial filtration at a high

7:45

convective volume may more effectively

7:47

slow deterioration and improve

7:50

survival. Uremia removal

7:52

was slightly superior in the hemodial

7:55

filtration group, but that is generally

7:57

considered to be an unlikely explanation.

7:59

for the outcome.

8:01

For maximum benefit, it appears

8:03

that hemodial filtration should be

8:05

performed as early as is

8:08

reasonable in patients with kidney failure.

8:10

If the FDA approves the use of hemodial

8:13

filtration in the United States, American

8:15

nephrologists are likely to use

8:17

the technology more as

8:19

dialysis machines are gradually

8:22

replaced.

8:23

Meanwhile, both nephrologists and

8:25

patients could gain experience with

8:27

expanded hemodialysis as an

8:30

intermediate therapy

8:31

between high-flux hemodialysis

8:34

and hemodial filtration. Each

8:36

of these steps will move us closer

8:38

toward improving outcomes in patients

8:41

with kidney failure.

8:44

Single Agent Dvarasib

8:47

in Solid Tumors with KRAS

8:49

G12C Mutation

8:51

by Adrian Sacher from the Princess

8:53

Margaret Cancer Center, Toronto, Canada.

8:57

Mutations in the KRAS gene

8:59

are the most common oncogenic driver

9:02

mutations found in human cancer.

9:04

Dvarasib is a covalent

9:07

KRAS G12C inhibitor

9:09

that was designed to have high potency

9:12

and selectivity. It binds to

9:14

the cysteine residue and irreversibly

9:16

locks the protein into its inactive

9:19

state, turning off its oncogenic

9:22

signaling.

9:23

This Phase 1 study evaluated

9:26

Dvarasib administered orally

9:28

once daily in 137 patients

9:31

who had advanced or metastatic

9:33

solid tumors that harbor a

9:35

KRAS G12C mutation,

9:38

including 60 patients with

9:40

non-small cell lung cancer, 55 with

9:43

colorectal cancer, and 22

9:45

with other solid tumors.

9:47

No dose-limiting toxic effects

9:50

or treatment-related deaths were reported.

9:53

Treatment-related adverse events occurred

9:55

in 93% of patients. Grade 3 events occurred

9:58

in 11% of patients.

9:59

and a grade four event in

10:02

one patient, 1%.

10:04

Treatment related adverse events resulted

10:06

in a dose reduction in 14% of

10:08

patients and discontinuation of treatment

10:11

in 3%.

10:13

Among patients with non-small cell

10:15

lung cancer, a confirmed response

10:17

was observed in 53.4% of patients and

10:21

the median progression-free survival

10:23

was 13.1 months.

10:26

Among patients with colorectal cancer,

10:28

a confirmed response was observed

10:31

in 29.1% of patients and

10:34

the median progression-free survival was 5.6 months.

10:37

Responses were also observed in patients

10:40

with other solid tumors. Serial

10:42

assessment of circulating tumor

10:44

DNA showed declines

10:47

in KRASG12C variant

10:49

allele frequency associated with

10:51

response and identified genomic

10:54

alterations that may confer

10:56

resistance to Dvarisib.

10:58

Treatment with Dvarisib resulted

11:01

in durable clinical responses across

11:03

KRASG12C positive

11:05

tumors with mostly low grade

11:08

adverse events.

11:11

Evolution of partial resistance to

11:14

artemisinins in malaria parasites

11:16

in Uganda by Melissa

11:19

Conrad from the University of California,

11:21

San Francisco. Partial

11:24

resistance of Plasmodium falciparum

11:27

to artemisinin-based therapies, the

11:29

most important malaria drugs, emerged

11:32

in Southeast Asia and now

11:34

threatens East Africa.

11:37

Partial resistance, which manifests

11:39

as delayed clearance after therapy,

11:42

is mediated principally by mutations

11:45

in the KELCH protein K13, PFK13.

11:50

Limited longitudinal data are

11:52

available on the emergence and spread

11:54

of artemisinin resistance in Africa.

11:57

These investigators performed annual.

13:59

the intestine, indicated by elevated

14:02

alpha-1 antitrypsin levels in

14:04

the stool, which leads to

14:06

panhypoprotonemia in

14:09

the absence of liver or kidney

14:11

disease.

14:12

Protein losing enteropathy

14:14

is a syndrome, not a disease. Therefore,

14:17

it is important to identify the underlying

14:20

cause in each patient. Many

14:22

acquired and congenital diseases

14:24

are manifested as protein losing enteropathy.

14:27

Generally, such disorders either

14:30

damage the intestinal mucosa

14:32

or block gastrointestinal

14:34

lymphatic flow through obstruction

14:37

and lymphangiectasia.

14:39

Improved diagnostic approaches,

14:41

especially genomic testing, have revealed

14:44

disease entities that cause protein

14:46

losing enteropathy, and this has

14:48

led to the development of effective therapies.

14:51

The presenting features of protein

14:54

losing enteropathy are hypoprotonemia,

14:57

edema, nutritional deficiencies,

15:00

both generalized and localized

15:02

infections, and gastrointestinal

15:05

symptoms, including diarrhea,

15:07

steatoria, abdominal pain,

15:10

and vomiting.

15:11

Hypoprotonemia is non-selective

15:13

with reduced albumin and immunoglobulin

15:16

levels, edema, of

15:18

the face and arms and legs,

15:21

and effusions, peritoneal,

15:23

pleural, and pericardial, are caused

15:25

by reduced oncotic pressure in

15:27

blood.

15:28

Infections can result from hypogamaglobulinemia

15:32

and lymphopenia. In children,

15:35

malabsorption and malnutrition

15:37

may be severe, resulting in retarded

15:39

growth and development.

15:41

The approach to care involves

15:43

diagnosing and correcting the underlying

15:46

condition while managing the manifestations

15:48

of protein losing enteropathy, principally

15:51

with treatments that mitigate gastrointestinal

15:54

protein loss and its sequelae,

15:56

as well as providing emotional and

15:59

family support.

16:02

A 15-year-old girl with abdominal

16:04

pain and an ovarian mass, a

16:07

case record of the Massachusetts General

16:09

Hospital by Andrea Zuckerman and

16:11

colleagues. A

16:14

15-year-old girl was evaluated for abdominal

16:16

pain.

16:17

Six weeks earlier, lower abdominal

16:19

pain developed along the midline. The

16:22

pain was sharp and crampy, increased

16:24

with movement, and decreased with lying

16:27

down.

16:28

The patient was taken to an emergency department.

16:31

Ultrasonography revealed a complex,

16:33

thick-walled cyst in the right ovary.

16:36

A

16:36

diagnosis of ruptured ovarian

16:39

cyst was considered,

16:41

and the patient was discharged home with

16:43

plans to undergo repeat transabdominal

16:46

ultrasonography six weeks later.

16:48

After discharge, the abdominal pain

16:51

slowly resolved.

16:52

Three days after discharge, the patient

16:54

resumed competitive long-distance

16:56

running.

16:57

Five weeks later, she participated

17:00

in a running competition.

17:02

The next day, abdominal

17:04

pain recurred, and the patient was unable

17:06

to go to school. She was brought to the emergency

17:08

department. On examination, the

17:11

right lower abdomen was firm and distended

17:14

with mild tenderness.

17:16

Imaging studies revealed the

17:18

development of a large heterogeneously

17:20

attenuating mass that displaced

17:23

the bowel and pelvic viscera.

17:26

In this case, the differential diagnosis

17:28

was focused on ovarian neoplasms.

17:32

Juvenile granulosa cell tumors

17:34

account for only 2 to 5% of all ovarian

17:36

tumors,

17:39

but they are the most common malignant

17:41

sex-cord stromal tumors of the

17:43

ovary in adolescence, occurring

17:46

at a mean age of 13 years.

17:49

Granulosa cell tumors are typically

17:51

unilateral and appear as echogenic,

17:54

septated, cystic, or solid

17:56

masses on imaging.

17:57

They are frequently associated with ascites

17:59

and

17:59

and intra-tumor hemorrhage.

18:02

Patients typically present with abdominal

18:04

pain.

18:05

Juvenile granulosis cell tumor

18:07

was the most likely diagnosis in

18:10

this patient. The

18:13

Supreme Court and the importance of

18:15

diversity in medicine, a perspective

18:18

by Clyde Yancey from Northwestern

18:20

University, Chicago.

18:23

In a landmark ruling on June 29th,

18:26

the U.S. Supreme Court decided

18:29

in favor of students for fair

18:31

admissions in parallel cases

18:33

against the University of North Carolina

18:35

and Harvard College. The decision

18:38

effectively ends the legal consideration

18:40

of race in university admissions, especially

18:43

for selective institutions.

18:46

It no doubt extends to

18:48

medical school admissions.

18:50

But these authors recognize the importance

18:53

of diversity and have identified potential

18:55

strategies for supporting diversity

18:58

in medicine

18:59

while complying with the court's ruling.

19:02

First,

19:03

admissions committees could

19:05

emphasize comprehensive review,

19:07

particularly review of applicants'

19:10

life journeys, recognizing that

19:12

although scholarly accomplishment and

19:15

raw intellect are prerequisites

19:17

for medical school admission, many additional

19:20

attributes including empathy,

19:23

perseverance in the face of uncertainty,

19:25

a learning-oriented mindset,

19:28

deft powers of observation, good

19:31

listening skills, a focus on

19:33

teamwork, and collegiality

19:35

are valuable if students are to become

19:38

successful physicians. None

19:40

of these qualities are evident in test

19:42

results or grade point averages.

19:45

Second, committees could consider

19:48

how applicants in essays or interviews

19:50

articulate the effects of racialized

19:53

acculturation on their personal journeys

19:55

and highlight particular contributions

19:58

they could make to an institution or...

19:59

profession that can't be captured

20:02

by traditional metrics.

20:03

Third,

20:04

committees could stress character

20:07

assessment, reflecting on applicants'

20:09

life histories and resilience and

20:11

the challenges they've faced, and incorporate

20:14

metrics such as adversity

20:16

scores, which are often especially relevant

20:18

to students from economically challenged backgrounds

20:21

that have required early life sacrifices

20:24

and work experiences.

20:28

Outbreaks in US migrant

20:30

detention centers, a vaccine

20:32

preventable cause of health inequity.

20:35

A perspective by Nathan Lowe from

20:37

Stanford University, Stanford, California.

20:41

Rates of vaccine preventable infectious

20:44

diseases are high among

20:46

detained migrants in the United States.

20:49

In 2022, US Immigration

20:51

and Customs Enforcement, ICE, detained

20:54

more than 300,000 migrants, housing

20:56

them in detention centers in which environmental

20:59

conditions, including crowding, poor

21:01

ventilation, and lack of sanitation,

21:03

increase the risk of infectious disease

21:06

transmission and outbreaks.

21:08

Moreover, detained migrants often

21:10

have poor access to health care,

21:13

including vaccination.

21:15

Amid pressure on ICE in the initial

21:17

months of the COVID-19 pandemic, the

21:20

agency started publicly reporting

21:22

COVID-19 case numbers and

21:24

deaths.

21:25

Early in the pandemic, the incidence

21:27

of COVID-19 was 13 times

21:30

as high among the detained migrant

21:32

population as among the general

21:35

US population, which put ICE

21:37

under major scrutiny from members of Congress,

21:40

the courts, and human rights organizations.

21:43

Even before the COVID-19 pandemic, there

21:45

were well-documented infectious disease

21:48

outbreaks in ICE detention centers. These

21:51

authors previously documented the

21:53

intense transmission of influenza,

21:56

varicella, and mumps in 17

21:58

centers over the past year.

21:59

approximately three years.

22:02

Moving forward, these authors propose

22:05

that the U.S. government consider requiring

22:07

systematic and complete data collection

22:10

and public reporting for all

22:12

vaccine-preventable infectious diseases

22:15

in U.S. migrant detention centers

22:17

tied to greater oversight, monitoring,

22:20

and enforcement of surveillance practices.

22:23

The authors believe

22:24

this would be a first step toward improving

22:27

the health of members of this vulnerable

22:29

population, people who work at

22:31

detention centers and surrounding

22:34

communities.

22:36

Turning CMS into a

22:39

Health Technology Assessment

22:41

Organization,

22:42

a perspective by Peter Newman from

22:45

Tufts Medical Center, Boston.

22:48

Recent developments have compelled the Centers

22:50

for Medicare and Medicaid Services, CMS,

22:53

to expand its role in conducting

22:55

health technology assessment.

22:58

This is especially notable given the relative

23:00

absence of health technology assessment elsewhere

23:03

in the federal government and historical

23:05

opposition to the idea.

23:07

But it is reasonable for Medicare to

23:09

consider careful in the evidence underlying

23:12

the technologies it pays for.

23:14

These authors believe the CMS

23:16

should embrace the role and expand

23:18

its capabilities to appropriately

23:21

reflect the importance and magnitude

23:23

of these responsibilities.

23:25

Several steps could improve the agency's

23:27

prospects for success.

23:29

First, CMS can develop a

23:32

workforce that is commensurate with

23:34

its growing responsibilities.

23:36

Congress can appropriate resources

23:38

for the agency to add staff with expertise

23:40

in clinical research, trial design,

23:43

epidemiology, and biostatistics.

23:45

Second, CMS can improve

23:48

coordination with the FDA,

23:50

including by participating in earlier

23:53

interagency discussions and interacting

23:56

with product manufacturers about

23:58

their clinical development programs.

23:59

programs to identify potential discrepancies

24:03

between the agency's requirements

24:05

related to endpoints and post-marketing

24:07

commitments.

24:08

Third,

24:10

Medicare has already created

24:12

a Coverage with Evidence

24:14

Development, CED, option

24:17

to pay for promising technologies

24:19

while requiring additional study to

24:22

strengthen the available evidence.

24:24

However, CMS could strengthen

24:26

its CED program. Data collection

24:29

periods are often lengthy, and the process

24:31

costly, and coverage policy

24:33

seldom changes as a consequence of

24:36

the additional evidence obtained.

24:38

Advances in databases and

24:41

analytic techniques could improve

24:43

the CED framework.

24:46

The Clinic That Cried Safe,

24:49

a perspective by Leighton Shrier from

24:52

the University of Toronto, Canada.

24:55

How did you find the clinic? Mom

24:57

asks. I Googled every fertility

25:00

clinic in the region, Leighton explains

25:02

matter-of-factly,

25:04

found which ones offered fertility

25:06

preservation, and took the one with the

25:08

shortest wait time. That's it.

25:10

Three simple steps. Well, four,

25:13

actually. There was one other,

25:15

rather crucial thing they'd done. They

25:17

looked for rainbow flags.

25:20

Websites with pages dedicated

25:22

to LGBTQ plus family

25:25

planning. Clinics trumpeting, gender-affirming

25:28

care. Slogans, suggesting

25:30

that their space was a safe one.

25:33

Can I help you? The receptionist

25:36

asks, jolting Leighton out of their

25:38

trance.

25:39

Yeah, they stutter. I have

25:41

an appointment.

25:42

And your name? Leighton.

25:45

She nods and clicks away at her keyboard.

25:48

Health card?

25:50

Leighton hesitates. Their health card

25:52

still has their birth name on it.

25:54

Their legal name. Umm,

25:57

they fumble for their card and hand

25:59

it to her. I go by Layton,

26:01

they reiterate. Oh, that's not a

26:04

problem at all. I'll make a note on your file.

26:06

Her easiness reassures them. They

26:09

take it as evidence that she knows what

26:11

she's doing, that she sees stuff like

26:13

this all the time.

26:15

They said they were a gender-affirming clinic,

26:17

after all.

26:18

If you could just fill out these forms for

26:21

me, she says, handing Layton a clipboard.

26:24

The forms are supposed to be straightforward,

26:26

but they're not. The first question

26:29

asks for their name. Legal

26:32

or preferred, Layton wonders. They

26:34

write Layton and move on. Gender,

26:38

two options, male or

26:40

female. None of the above,

26:42

they think, or all of the above. They're

26:45

asking about gender, but Layton knows

26:47

they mean sex. Layton haruffs,

26:50

disgruntled, and checks female.

26:53

Then they hear it, their name, their

26:56

legal name, being called,

26:58

two syllables like slaps across

27:00

their face. It's Layton,

27:03

actually, they mumble as they stand up. Right,

27:06

sorry, the nurse says, barely acknowledging

27:09

her mistake. Follow me, please. Layton

27:12

waits for the doctor. Slap,

27:14

slap, a voice asks, not waiting

27:17

for a response. Hi, I'm Dr.

27:19

D. The doctor introduces herself as

27:21

she walks into the room.

27:22

I understand you're here to talk about

27:25

fertility preservation. Is that right?

27:27

The appointment passes in a blur.

27:30

Only fragments of conversation

27:32

reach Layton's ears.

27:34

During puberty, you, when

27:36

women menstruate, we, since

27:39

you're choosing to change, will

27:41

inject female hormones. All

27:44

things considered, she concludes, you're

27:46

the perfect candidate. I'll have the

27:48

nurse drop by to explain the procedure

27:50

in more detail.

27:52

And with that, she's out the door. In

27:55

the hallway,

27:56

Layton hears the doctor issuing

27:59

orders to the nurse.

28:00

Let's get her started on full-a-stim

28:03

right away and book a follow-up for Thursday.

28:06

She can get blood work then as well.

28:09

Her, Leighton shudders. A

28:11

punch in the gut. She a

28:13

kick to the curb. Leighton leaves

28:16

the clinic thirty minutes later, battered

28:18

and bruised. The rainbow flag

28:20

on the door, the one that smiled at

28:23

them on the way in, bids them

28:25

farewell. But they don't acknowledge

28:27

it anymore. They know better

28:29

now. Like the boy who cried

28:32

wolf, the rainbow flags

28:34

cry safe. And

28:36

they can't trust them anymore.

28:41

In our images in Clinical Medicine,

28:43

a thirty-year-old man with aplastic

28:46

anemia presented with fever, non-parodic

28:48

rash and ankle and knee pain.

28:51

Ten days before presentation, he

28:53

had completed a course of horse anti-thymocyte

28:56

globulin.

28:57

Physical examination was notable for

28:59

a morbiliform rash across his torso

29:02

and arms and a perpuric rash

29:04

on the legs.

29:05

Laboratory studies were notable for worsening

29:08

neutropenia, low C3 and

29:10

C4 levels and a C-reactive

29:12

protein level of 114 milligrams per liter. A

29:17

clinical diagnosis of serum

29:19

sickness was made.

29:21

Serum sickness is a type 3

29:23

hypersensitivity reaction due to

29:25

the formation of antigen, antibody

29:27

or immune complexes. The condition

29:30

classically occurs after the

29:32

therapeutic administration of non-human

29:36

protein and manifests as

29:38

a triad of fever, rash and arthralgia,

29:41

as in this case.

29:42

Horse anti-thymocyte globulin

29:44

was added to the patient's list of drug

29:47

allergies and not used again.

29:50

In another image, a man presented

29:53

with a painless enlargement of the

29:55

left testicle, MRI of

29:57

the pelvis showed a lobulated left

29:59

testicular

29:59

mass with heterogeneous enhancement.

30:02

Owing to concern about testicular

30:04

cancer, an orchiectomy was performed.

30:08

Histopathological examination showed

30:10

granulomatous inflammation with

30:12

caseous necrosis, a real-time

30:15

PCR assay identified M-tuberculosis.

30:19

CT of the chest was normal.

30:21

A diagnosis of testicular

30:23

tuberculosis was made.

30:25

A nine-month course of antituberculosis

30:27

therapy was prescribed.

30:31

This concludes our summary. Let us

30:33

know what you think about our audio summaries.

30:36

Any comments or suggestions may be

30:38

sent to

30:39

audio at nejm.org.

30:43

Thank you for listening.