0:00

Welcome, this is the New England

0:02

Journal of Medicine. I'm Dr. Lisa

0:04

Johnson. This week, October 12,

0:08

2023, we feature articles on dexamethasone

0:11

for TB meningitis in HIV-positive

0:14

adults,

0:15

the timing of complete revascularization

0:18

after myocardial infarction, catheter

0:21

ablation for advanced heart failure

0:23

and AFib, ceftopiprol

0:26

for Staph aureus bacteremia,

0:29

and AlfaFold being recognized

0:31

through a Lasker Award, a

0:33

review article on Shiga toxin-producing

0:35

E. coli and the hemolytic uremic

0:38

syndrome, a case report of a man

0:40

with involuntary movements and

0:43

unresponsiveness, and perspective

0:45

articles on whether pandemics

0:48

ever end, on the new over-the-counter

0:51

oral contraceptive pill, and

0:53

on a reason to retire. Adjunctive

0:58

Dexamethasone for Tuberculous Meningitis

1:01

in HIV-Positive Adults,

1:04

by Joseph Donovan from the Oxford

1:07

University Clinical Research Unit,

1:10

United Kingdom, and colleagues.

1:13

Adjunctive glucocorticoids are

1:16

widely used to treat HIV-associated

1:19

tuberculous meningitis, despite

1:21

limited data supporting their safety

1:24

and efficacy. This trial

1:26

involved 520 HIV-positive adults

1:30

in Vietnam and Indonesia with

1:32

tuberculous meningitis. Participants

1:36

were randomly assigned to receive

1:38

a 6-8 week tapering course

1:40

of either dexamethasone or

1:43

placebo, in addition to 12 months

1:46

of antituberculosis chemotherapy.

1:49

The primary endpoint was

1:51

death from any cause during the 12

1:54

months after randomization.

1:56

During the 12 months of follow-up,

1:59

death occurred in 44.1% of participants in the dexamethasone

2:01

group and in 49% of participants in the placebo

2:09

group. Prespecified analyses did

2:12

not reveal a subgroup that clearly

2:14

benefited from dexamethasone.

2:17

The incidence of secondary endpoint

2:19

events, including cases of

2:21

immune reconstitution inflammatory

2:23

syndrome

2:24

during the first six

2:25

months, was similar in the two

2:27

trial groups. The numbers of

2:30

participants with at least one serious

2:32

adverse event were similar in the dexamethasone

2:35

group, 73% of participants, and the placebo group, 75.5% of participants.

2:43

Among HIV-positive adults with

2:45

tuberculosis meningitis, adjunctive

2:48

dexamethasone, as compared with

2:51

placebo, did not confer

2:53

a benefit with

2:54

respect to survival or

2:56

any secondary endpoint.

3:00

Sean Wasserman and Thomas Harrison

3:02

from St. George's London ask

3:05

in an editorial,

3:06

how should this trial influence

3:09

clinical practice?

3:11

The data show that dexamethasone

3:13

does not improve outcomes in

3:16

most patients with tuberculosis

3:18

meningitis and advanced HIV.

3:21

However, dexamethasone is not

3:23

associated with harm in this

3:25

population and in the context

3:28

of a severe disease that kills or

3:30

disables half its victims, even

3:33

a small potential reduction in mortality,

3:36

which was not excluded by this trial,

3:38

may justify continued use.

3:41

Despite the negative result, this

3:43

trial sends an unequivocal message.

3:46

A plateau has been reached with

3:48

existing therapies in tuberculosis

3:51

meningitis.

3:52

Different approaches are required in

3:55

order to improve outcomes.

3:57

Attention to low-cost non-therapists.

4:00

therapeutic interventions such as

4:02

improvements in basic supportive

4:04

management and earlier provision

4:06

of therapy through better diagnostics

4:08

and pathways to care may have

4:11

large effects. Current trials

4:14

are evaluating enhanced anti-tuberculosis

4:17

drug regimens and aspirin

4:19

which has anti-inflammatory effects

4:21

at higher

4:22

doses.

4:23

The tuberculosis community should

4:25

be open to developing and testing

4:28

even bolder interventions including

4:30

rifamycin-free drug combinations

4:33

designed specifically for tuberculosis

4:36

meningitis delivered with the most

4:38

promising novel candidates

4:40

for host directed therapy.

4:42

Donovan and colleagues have shown

4:45

that progress can be made to

4:47

reduce suffering from tuberculosis

4:49

meningitis, but there is still

4:51

a long way to go. Timing

4:56

of complete revascularization

4:58

with multi-vessel PCI

5:01

for myocardial infarction by

5:03

Barbara Steli from the University

5:05

Hospital Zurich, Switzerland and

5:08

colleagues. In

5:10

patients with ST segment elevation

5:13

myocardial infarction STEMI

5:15

with multi-vessel coronary artery

5:18

disease the time at which complete

5:20

revascularization of non culprit

5:23

lesions should be performed remains

5:25

unknown. In this trial at 37 sites

5:29

in Europe 840 patients

5:32

in a hemodynamically stable condition

5:34

who had STEMI and multi-vessel

5:37

coronary artery disease were randomly

5:39

assigned to undergo immediate

5:42

multi-vessel percutaneous

5:44

coronary intervention PCI

5:46

or PCI of the culprit lesion

5:49

followed by stage multi-vessel

5:51

PCI of non culprit lesions

5:54

within 19 to 45 days after

5:57

the index procedure. At one

6:00

A primary endpoint event

6:02

of death from any cause, non-fatal

6:05

myocardial infarction, stroke,

6:07

unplanned ischemia-driven revascularization,

6:11

or hospitalization for heart failure

6:13

occurred in 8.5% of

6:16

patients in the immediate group as

6:18

compared with 16.3% of patients in the staged

6:22

group.

6:23

Total myocardial infarction

6:26

and unplanned ischemia-driven

6:28

revascularization occurred in 2%

6:31

and 4.1% of patients,

6:33

respectively, in the immediate group

6:36

and in 5.3% and 9.3% of

6:39

patients, respectively, in the

6:42

staged

6:42

group.

6:43

The risk of death from any cause, stroke,

6:46

and hospitalization for heart failure

6:48

appeared to be similar in the two

6:50

groups. A total of 104 patients in the immediate

6:53

group and 145 patients in the staged group

6:58

had a serious adverse event. Among

7:01

patients in hemodynamically stable

7:04

condition with STEMI and multivessel

7:06

coronary artery disease, immediate

7:09

multivessel PCI was

7:11

non-inferior to staged

7:14

multivessel PCI with respect

7:16

to the primary outcome. In

7:19

an editorial, W. Schuyler-Jones

7:22

from Duke University School of Medicine,

7:25

Durham, North Carolina writes that

7:27

in current clinical practice, the

7:29

use of primary reperfusion

7:31

therapy is widespread and

7:34

focus has shifted from quality

7:36

methods of the procedure to other

7:38

issues, such as the timing of

7:41

multivessel PCI. The

7:43

trial by Steli and colleagues improves

7:46

our evidence base and sets the stage

7:48

for a larger trial on the timing

7:51

of complete revascularization. However,

7:54

several challenges exist, including

7:57

the need to address the severity

7:59

of non-inferior infarct-related coronary

8:01

lesions, the burden of coronary

8:04

artery disease, the complexity

8:06

of anatomies

8:07

in coronary artery disease,

8:09

the size and severity of the infarcted

8:11

myocardium in the index STEMI,

8:14

and the use of guideline-directed

8:16

medical therapy in the immediate and

8:19

staged

8:19

group.

8:20

When these characteristics are factored

8:23

into the decision-making process for

8:25

patients, additional considerations,

8:28

including patient age, serum

8:30

creatinine level, if it is known

8:32

at the time of the index STEMI, patient

8:35

comfort, patient perspective, and

8:37

the appropriate and timely use of

8:39

physiological testing and intravascular

8:42

imaging will be imperative to understand.

8:46

Ultimately, a larger, more definitive

8:48

trial that incorporates all these

8:51

aspects will be necessary to determine

8:53

whether complete revascularization

8:56

should be attempted during the index

8:58

revascularization procedure or

9:00

in a staged fashion, either

9:03

during the index hospitalization or

9:05

later. As with most

9:07

clinical decisions, timing is

9:10

everything, and we owe it to our

9:12

patients to figure out how

9:14

to deliver the right care or

9:16

procedure to the right patient at

9:19

the right time. Caphater

9:22

ablation in end-stage heart

9:24

failure with atrial fibrillation

9:27

by Christian Zones from

9:29

the Rohr Universität Bohun

9:32

Bad-Unhausen, Germany, and

9:35

colleagues. The

9:37

role of catheter ablation in patients

9:39

with symptomatic atrial fibrillation

9:42

and end-stage heart failure is

9:44

unknown. This trial in Germany

9:47

involves patients with symptomatic

9:49

atrial fibrillation and end-stage

9:51

heart failure who were referred for

9:54

heart transplantation evaluation.

9:57

Patients were assigned to receive catheter

9:59

ablation and guideline-directed

10:01

medical therapy, or medical therapy

10:04

alone. 97 patients

10:07

were assigned to each group. The

10:09

trial was stopped for efficacy

10:11

by the Data and Safety Monitoring Board

10:14

one year after randomization was

10:16

completed. Casator ablation

10:19

was performed in 84% of

10:21

patients in the ablation group and in 16%

10:24

of patients in the medical

10:26

therapy group.

10:27

After a median follow-up of 18 months,

10:31

a primary endpoint event of

10:33

death from any cause, implantation

10:36

of a left ventricular assist device, or

10:38

urgent heart transplantation, had

10:40

occurred in 8% of patients in the ablation

10:43

group and in 30% of

10:46

patients in the medical therapy group. Death

10:49

from any cause occurred in 6% of

10:51

patients in the ablation group and in 20% of

10:53

patients in the medical therapy group. Procedure-related

10:59

complications occurred in 3 patients in the ablation

11:01

group and in 1 patient

11:04

in the medical

11:05

therapy group.

11:06

Among patients with atrial fibrillation

11:09

and end-stage heart failure, the combination

11:12

of catheter ablation and guideline-directed

11:15

medical therapy was associated

11:17

with a lower likelihood of

11:19

a composite of death from any cause,

11:22

implantation of a left ventricular

11:24

assist device, or urgent heart

11:26

transplantation, than medical

11:29

therapy alone. Eldrin

11:32

Lewis from Stanford University

11:34

School of Medicine, California, writes

11:37

in an editorial that patients

11:39

with heart failure often have coexisting

11:42

atrial fibrillation and the incidence

11:44

of atrial fibrillation is higher

11:46

among patients with more advanced

11:49

heart failure, ranging from 5% among

11:52

those with New York Heart Association, NYHA,

11:55

Class 1 disease to 50%

11:58

among those with NYHA. class 4

12:01

disease. The coexistence

12:03

of heart failure and atrial fibrillation

12:06

is associated with an increased

12:08

risk of hospitalization and

12:10

death. Evidence for catheter

12:13

ablation of atrial fibrillation

12:15

continues to mount with study

12:17

populations ranging from patients

12:20

with early onset atrial fibrillation

12:22

to those with symptomatic heart

12:25

failure. However, in the patient

12:27

with end-stage heart failure, clinicians

12:30

must balance safety and the potential

12:33

efficacy of restoring sinus

12:35

rhythm with an invasive procedure

12:37

given their remodeled hearts with

12:39

or without scar formation and coexisting

12:42

conditions that could make an unfavorable

12:45

risk profile more likely.

12:48

Thus, there is uncertainty regarding

12:51

the appropriate catheter-based management

12:53

of atrial fibrillation in patients

12:56

with advanced heart failure. Collectively,

12:59

the trial by Zones and colleagues

13:01

suggests that ablation in patients

13:04

with advanced heart failure can

13:06

be safely done by an experienced

13:08

electrophysiologist. However,

13:10

there are several issues that should be

13:13

considered in the interpretation of

13:15

these findings. For example,

13:17

these are highly selected patients

13:19

from a single center and the sample

13:22

is relatively small. The trial

13:24

should be expanded to include several

13:27

centers and a more diverse patient

13:29

population to determine the generalizability

13:32

of the findings. In addition,

13:35

the development of a registry to capture

13:37

longitudinal outcomes in patients

13:40

with advanced heart failure and atrial

13:42

fibrillation will be important while

13:44

the treatment pathway used in the

13:46

trial by Zones is being investigated

13:49

as a potential strategy to

13:51

delay or obviate the need

13:53

for heart transplantation or

13:56

mechanical

13:56

circulatory support.

14:00

Cephaloprol for treatment of

14:02

complicated Staphylococcus

14:05

aureus bacteremia

14:07

by Thomas Holland

14:08

from Duke University,

14:10

Durham, North Carolina and

14:12

colleagues. Cephaloprol

14:15

is a cephalosporin that may be

14:17

effective for treating complicated

14:20

Staphylococcus aureus bacteremia,

14:23

including methicillin-resistant

14:25

Staph aureus. In this phase 3

14:28

trial, 387 adults

14:31

with complicated Staph aureus

14:33

bacteremia were randomly assigned

14:36

to receive Cephaloprol at

14:38

a dose of 500 mg intravenously every 6 hours

14:40

for 8 days and every 8

14:45

hours thereafter, or daptomycin

14:49

at a dose of 6-10 mg

14:51

per kg of body weight intravenously

14:54

every 24 hours plus

14:57

optional as Trionam at the

14:59

discretion of the trial site investigators.

15:03

70 days after randomization, 69.8% of

15:05

patients in the Cephaloprol group and 68.7% of patients

15:12

in the daptomycin group had overall

15:15

treatment success. The findings are defined

15:17

as survival, bacteremia clearance,

15:20

symptom improvement, no new

15:22

Staph aureus-bacteremia-related

15:25

complications and no receipt of

15:27

other potentially effective antibiotics.

15:31

Findings appear to be consistent between

15:33

the Cephaloprol and daptomycin

15:36

groups in key subgroups and

15:38

with respect to secondary outcomes,

15:41

including mortality 9% and 9.1%

15:43

respectively and the percentage

15:47

of patients with microbiologic

15:49

eradication 82% and 77.3%. Adverse

15:55

events were reported in 63.4% of patients who

15:57

received

15:59

seftobiprole and 59.1% of patients

16:02

who received daptomycin. Serious

16:07

adverse events were reported in 18.8% of patients

16:09

and in 22.7% of patients, respectively. Gastrointestinal

16:17

adverse events, primarily mild nausea,

16:20

were more frequent with seftobiprole.

16:24

Seftobiprole was non-inferior to daptomycin

16:27

with respect to overall treatment

16:30

success in patients with complicated

16:33

Staph aureus bacteremia.

16:38

Shegotoxin-producing Escherichia coli

16:41

and the hemolytic uremic syndrome.

16:43

A review article by Stephen Friedman

16:46

from the Alberta Children's Hospital Research

16:48

Institute, Calgary, Alberta, Canada,

16:51

and colleagues. Shegotoxin-producing

16:55

E. coli, ESTEC, are bacteria

16:58

that carry the genes producing

17:00

shegotoxins. These pathogens

17:03

have the potential to cause diarrhea,

17:05

which is often bloody and can trigger a

17:07

thrombotic microangiopathy

17:10

that leads to the hemolytic

17:11

uremic syndrome.

17:13

The hemolytic uremic syndrome is

17:15

defined as thrombocytopenia,

17:18

platelet count less than 150,000 per

17:21

cubic millimeter, non-immune

17:23

hemolytic anemia, hematocrit

17:25

less than 30%, and azotemia,

17:28

creatinine level higher than the upper

17:31

limit of the normal range. Although

17:33

a range of microbial pathogens can

17:35

precipitate the hemolytic uremic syndrome,

17:38

ESTEC are responsible for most

17:40

cases in children worldwide.

17:43

Other notable infectious causes include

17:45

streptococcus pneumoniae and

17:47

influenza virus. ESTEC

17:50

infection causes severe illness,

17:52

particularly in children. Diagnostic

17:56

approaches that include the testing

17:58

of all children with bloody diarrhea. diarrhea

18:00

for bacterial pathogens with the use

18:02

of techniques that can identify 0157 and

18:06

non 0157 STEC. The

18:09

use of rectal swabs to obtain specimens

18:12

when stool specimens are unavailable.

18:15

And reporting toxin genotypes

18:17

when STEC are identified

18:19

are important components of care.

18:22

Close monitoring of persons infected with

18:24

high-risk STEC, avoidance

18:27

of potentially harmful interventions

18:29

and prevention of volume depletion

18:32

may avert complications. Unless

18:35

and until specific treatments emerge,

18:38

the possibility of adverse outcomes

18:40

in a patient with a high-risk STEC

18:43

infection must be considered.

18:45

Thus, it is important to monitor

18:47

the evolution of the disease and mitigate

18:50

to the extent possible

18:51

modifiable risk factors

18:54

to improve outcomes.

18:57

A 79-year-old man with

18:59

involuntary movements and unresponsiveness.

19:03

A case record of the Massachusetts General

19:05

Hospital by Albert Hung and

19:08

colleagues. A

19:10

79-year-old man was admitted to the hospital

19:12

because of involuntary left-sided

19:15

movements and transient unresponsiveness.

19:18

Episodes of involuntary movements

19:21

had started nine months earlier.

19:23

The movements were initially described

19:26

by the patient as twitching, were

19:28

not associated with a change in the level

19:30

of consciousness, and resolved after

19:32

one to two minutes. The symptoms

19:35

progressed, increasing in both duration

19:37

and frequency. The patient's family

19:40

recorded a video of one of the episodes

19:42

of involuntary movements. After

19:45

reviewing the video, the patient's neurologist

19:48

thought the episodes were consistent with chorioacetoid

19:51

movements. On the morning of admission,

19:53

an episode of involuntary movements

19:56

of the left leg and left shoulder

19:58

occurred and persisted.

19:59

for one hour.

20:01

Several hours after the symptoms abated,

20:04

the patient's wife found the patient to

20:06

be unresponsive and emergency

20:08

medical services were called. When

20:11

the emergency team arrived, the patient

20:13

was responsive. The transient

20:15

unresponsiveness that led to the patient's

20:18

admission was attributed to a combination

20:20

of sedation from clobazam and

20:22

hypovolemia and a diagnosis

20:25

of functional neurologic disorder

20:27

was considered. Two weeks

20:30

after discharge, when the patient was doing

20:32

exercises while sitting in a chair and

20:34

having a conversation with his wife, he

20:37

suddenly stopped

20:37

talking.

20:39

When emergency medical services arrived,

20:41

the patient had a facial droop on the

20:43

left side and a right gaze preference.

20:46

In this patient, the symptoms resolved

20:49

without intervention, which indicated

20:51

that he may have had an acute transient

20:54

ischemic attack, TIA. His

20:56

previous recurrent episodes of

20:58

transient chorioathetosis

21:01

on the left side that had occurred mainly

21:03

while he was sitting, standing, or exercising

21:06

were consistent with limb-shaking

21:09

TIA's from hypoperfusion

21:11

or low flow.

21:13

The patient underwent emergency

21:16

carotid endarterectomy. A holy

21:20

grail, the prediction of

21:23

protein structure.

21:25

A clinical implications of basic research

21:27

by Russ Altman

21:29

from Stanford University, California.

21:33

This year's Lasker Basic Medical

21:36

Research Award recognizes

21:38

the contributions of Demis

21:40

Hassabis and John Jumper for

21:42

their invention of the alpha-fold

21:45

artificial intelligence AI system,

21:48

which predicts the three-dimensional

21:51

3D structure of proteins from

21:53

the one-dimensional 1D sequence

21:55

of their amino acids. Their

21:58

solution of this long-standing problem

22:00

provides a path to accelerated

22:03

discoveries across biomedical

22:05

science. In the 1960s,

22:08

Anfinsen et al. showed that the 1D

22:10

sequence of amino acids can fold

22:13

spontaneously and reproducibly

22:16

into the functional 3D conformation.

22:20

Molecular chaperones can accelerate

22:22

and facilitate this process, but

22:24

these observations created a

22:26

60-year challenge for molecular biology.

22:30

Predict the 3D structure

22:32

of a protein from its 1D

22:34

sequence of

22:35

amino acids. This

22:37

challenge became more pressing

22:39

as our ability to obtain 1D

22:42

sequences exploded with the

22:44

success of the Human Genome Project.

22:47

In building AlphaFold, Hasabith

22:49

and Jumper included elements of both

22:52

physics and AI and machine

22:54

learning, but the AI and machine

22:56

learning provided most of the novelty

22:59

and leap in performance. The

23:01

two researchers creatively combined

23:04

large public data repositories

23:07

with industry-level computational

23:09

resources to build AlphaFold.

23:12

There are a multitude of potential

23:15

applications of AlphaFold, including

23:17

the design of drugs that bind tightly

23:20

to protein pockets, estimation

23:22

of the effect that genetic mutations

23:25

have on protein structure and function,

23:28

modeling of and potentially interference

23:30

with the interfaces of proteins

23:33

that create, perhaps unwanted,

23:35

protein-protein interactions, and

23:37

the design of new protein structures

23:40

for engineering purposes. Do

23:45

pandemics ever end? A

23:47

perspective by Joelle Abi-Rashead

23:50

and Alan Brandt from Harvard University,

23:53

Cambridge, Massachusetts. On

23:56

April 10, U.S. President Joe Biden

23:58

signed a resolution officially

24:01

terminating the COVID-19 national

24:03

emergency in the United States.

24:06

The public health emergency ended one

24:08

month later. Last September,

24:10

Biden had stated that the pandemic

24:13

is over, when during that month

24:15

there were more than 10,000 deaths

24:18

involving COVID-19 nationwide. The

24:21

United States is, of course, not the only country

24:23

to have made such pronouncements. Several

24:26

European countries declared an

24:28

end to the emergency associated

24:30

with the pandemic in 2022, lifting

24:33

restrictions and starting to manage

24:35

COVID-19 more like influenza.

24:39

What insights can be derived from

24:41

past declarations of this sort?

24:44

Three centuries ago,

24:45

King Louis XV decreed

24:48

the end of the plague epidemic

24:50

that had been ravaging the south of France.

24:53

The plague had caused a staggering

24:55

number of deaths around the world

24:57

over multiple centuries. From 1720

24:59

to 1722, more than half the population of Marseille died. The

25:06

decree, whose main purpose was to

25:08

authorize merchants to resume their

25:10

commercial activities, invited

25:12

people to hold bonfires in

25:15

front of their houses in a public

25:17

rejoicing at the cessation of

25:19

the plague. Full of ritualized

25:22

symbolism, the decree set the

25:24

standard for the way in which the end

25:26

of an epidemic would be declared

25:29

and celebrated. It is also

25:31

a stark reminder of the economic

25:33

imperatives behind such declarations.

25:37

But

25:37

did the decree end the

25:39

plague?

25:40

Of course not.

25:41

Historical precedents make clear

25:43

that it is neither epidemiology nor

25:46

any political declaration that

25:48

determines the end of a pandemic. But

25:51

the normalization of mortality

25:53

and morbidity by means of a disease's

25:55

routinization and endemicization. What

25:58

in the context of this? context of

26:00

the COVID-19 pandemic has been

26:02

called living with the virus.

26:05

What ends a pandemic too is

26:07

government's conclusion that the associated

26:10

public health crisis is no longer

26:13

a threat to the economic productivity

26:16

of a society or to the global

26:18

economy. The

26:21

new over-the-counter oral contraceptive

26:24

pill assessing financial

26:26

barriers

26:27

to access.

26:29

A perspective by Christopher Robertson

26:31

and Anna Brahman from Boston University

26:34

School of Law. In

26:37

July, the FDA approved

26:39

OPIL, nor gestural, a progestin-only

26:43

contraceptive, the first over-the-counter

26:46

OTC daily oral contraceptive

26:48

pill in the U.S., a move

26:51

that could dramatically improve practical

26:54

access to family planning. OPIL's

26:56

price, however, hasn't been made public

26:59

and may not be revealed until the drug

27:01

enters the market in early 2024.

27:05

Although contraceptive pills generally

27:07

cost between $10 and $50

27:10

per month without insurance, there's

27:12

no indication that OPIL's price

27:14

will fall within this range. In

27:17

addition, although the manufacturer, Perigo,

27:20

has expressed interest in a consumer

27:22

assistance program, it hasn't released

27:24

details regarding eligibility

27:27

for such a program. It's

27:29

unclear whether health insurers

27:31

or federal health programs will cover

27:34

OTC versions of contraceptive

27:36

pills. The preventive care

27:39

mandate established by the Affordable Care

27:41

Act requires that insurers cover

27:43

contraceptive pills without co-payments,

27:46

though in practice prescriptions from

27:49

physicians have always served

27:51

as an indication of medical necessity,

27:54

and some components of the mandate are

27:56

facing legal challenge.

27:59

The question is whether the new OTC

28:02

pill will be widely accessible

28:04

through insurance, including Medicaid,

28:07

or available only to people who can

28:09

pay for it out of pocket. For

28:12

people who are insured, these authors believe

28:14

Congress should require coverage

28:16

so as to expand access to

28:19

reproductive health care. For

28:21

the millions of reproductive age people

28:23

who are uninsured in the U.S., OPL

28:26

may be an attractive option if

28:28

it averts the need for a physician visit,

28:31

especially for people who don't have

28:33

an existing health care relationship. Yet,

28:36

cost-related challenges could still

28:39

affect uptake. A

28:43

Reason to Retire? A perspective

28:45

by Neil Berman from Atrias Health,

28:48

Newton, Massachusetts. Why

28:51

are you retiring, Lenny? You're only 64. At

28:55

the time, Dr. Berman was in his

28:57

40s, part of a busy cardiology

28:59

practice in a community hospital just outside Boston.

29:03

Lenny was an old-time internist,

29:06

an avuncular solo practitioner

29:08

beloved by the community. Lenny's

29:10

decision to retire puzzled Dr. Berman. He

29:14

knew Lenny had had some medical issues,

29:16

but he was still running a busy solo practice.

29:19

Lenny's answer had puzzled Dr. Berman

29:22

even more. My patients'

29:24

illnesses are starting to get to me, Lenny

29:26

said. Dr.

29:29

Berman didn't really appreciate what Lenny

29:31

meant, but Lenny's answer stayed with him. Now,

29:34

having just retired himself at 71,

29:37

Dr. Berman understands exactly

29:40

what Lenny meant. Part of Dr.

29:42

Berman's professional effectiveness depends

29:45

on maintaining a certain distance from

29:47

his patients. He must be able

29:49

to concentrate on the situation evolving

29:52

before him. The symptoms, the signs,

29:54

the lab tests, all the hard data

29:57

that will inform the therapeutic decisions

29:59

associated with him.

30:00

Some conditions are eminently

30:03

predictable, but others are just

30:05

sheer bad luck. Many are

30:07

degenerative, and their frequency increases

30:10

with age. As a young physician,

30:13

Dr. Berman was able to compartmentalize

30:15

illness. It was something that happened to his

30:17

patients, not to him. He

30:20

could understand their illnesses, but he

30:22

never saw himself in their place. Dr.

30:25

Berman would try to alleviate their suffering, but

30:28

his primary task was to diagnose

30:30

and treat their condition. Objectivity

30:33

helped Dr. Berman cope with the

30:35

stress of dealing with his patients, life-threatening

30:38

and life-changing situations.

30:41

It enabled Dr. Berman to see his

30:43

work in a more intellectual and

30:45

less emotional light. But

30:48

as he grew older, this distinction

30:51

became harder to maintain. The

30:54

typical description he'd write in the chart

30:56

of a 70-year-old elderly

30:58

gentleman could suddenly be

31:00

him. His patients and their problems

31:03

became more difficult to compartmentalize

31:05

as separate from himself.

31:08

Dr. Berman started to feel the

31:10

extra-medical aspects of their

31:13

illnesses much more acutely

31:15

than he had when he was younger. The

31:18

unfairness of disease, the inevitability

31:21

of age and the breakdown of the body.

31:26

In our images in Clinical Medicine, a

31:28

72-year-old man presented with a two-day history

31:31

of an itchy linear rash across

31:34

his back.

31:35

Two days before symptom

31:36

onset, he had prepared

31:38

and eaten a meal containing shiitake

31:41

mushrooms. A diagnosis

31:43

of shiitake dermatitis was

31:45

made. Shiitake dermatitis

31:47

occurs after consumption of

31:50

raw or undercooked shiitake

31:52

mushrooms. The streaky rash,

31:55

known as flagellate erythema,

31:57

is characteristic of the self-limited

31:59

condition. condition. A dietary history

32:02

clinches the diagnosis. The patient

32:04

was advised to fully cook shiitake

32:07

mushrooms in the future. Topical

32:09

glucocorticoids and oral antihistamines

32:12

were also given for treatment of the

32:14

symptoms. In

32:16

another image, a 53-year-old

32:18

woman with a history of lung cancer presented

32:21

with three months of progressive

32:23

shortness of breath and cough. CT

32:26

revealed a calcified lymph node

32:28

that had migrated into the left main

32:31

stem bronchus. A diagnosis

32:33

of broncholithiasis was made.

32:36

Broncholithiasis occurs when

32:38

calcified material, typically

32:40

a mediastinal lymph node, erodes

32:43

into a bronchus, causing cough,

32:45

dyspnea, hemoptysis, or even

32:48

expectoration of broncholith fragments.

32:52

During bronchoscopy, the broncholith

32:54

was visualized in the left main

32:56

stem bronchus. A holmium

32:59

laser and rigid forceps were used

33:01

to fracture the broncholith into multiple

33:03

pieces and remove it.

33:06

Immediately after the procedure, the patient's

33:08

dyspnea and cough resolved.

33:12

This concludes our summary. Let

33:14

us know what you think about our podcast.

33:17

Any comments or suggestions may

33:19

be sent to audio at NEJM.org.

33:23

Thank you for

33:24

listening.