0:00

Welcome, this is the New England Journal

0:02

of Medicine. I'm Dr. Lisa

0:04

Johnson. This week, August 31,

0:07

2023, we feature

0:09

articles on Conquisumab

0:11

in Haemophilia A or B with

0:14

inhibitors,

0:15

the timing of primary surgery

0:17

for cleft palate, improved

0:20

mass screening for nasopharyngeal

0:22

carcinoma, gene editing

0:24

for sickle cell disease, and

0:26

on artificial sweeteners. A

0:29

review article on informative artifacts

0:32

in AI-assisted healthcare, a

0:34

case report of a woman with celiac

0:37

disease and upper gastrointestinal

0:39

bleeding, and perspective

0:42

articles on Project NextGen,

0:45

on gerineuropalliative care for

0:47

patients with dementia,

0:49

and on sexual and gender minority

0:52

refugees. Phase 3

0:55

Trial of Conquisumab

0:58

in Haemophilia with Inhibitors

1:01

by Tadashi Matsushita from

1:03

Nagoya University Hospital, Japan

1:08

Conquisumab is an anti-tissue

1:10

factor pathway inhibitor monoclonal

1:13

antibody designed to achieve hemostasis

1:16

in all haemophilia types

1:19

with subcutaneous administration.

1:22

A previous trial of Conquisumab,

1:24

the Phase 2 Explorer 4 trial,

1:27

established proof of concept in

1:30

patients with Haemophilia A or

1:32

B with inhibitors. The

1:34

Phase 3 Explorer 7 trial assessed

1:38

the safety and efficacy of

1:40

Conquisumab in 133 patients

1:43

with Haemophilia A or B

1:46

with inhibitors.

1:48

Patients were randomly assigned

1:50

in a 1-to-2 ratio to receive

1:52

no prophylaxis for at least 24

1:56

weeks, Group 1, or Conquisumab

1:59

prophylaxis. for at least 32

2:01

weeks, group 2, or were

2:04

non-randomly assigned to receive concizumab

2:07

prophylaxis for at least 24 weeks,

2:09

groups 3 and 4.

2:11

Ongoing phase 3

2:14

trials of concizumab were temporarily

2:17

paused in March 2020, owing

2:20

to non-fatal thromboembolic

2:22

events in three patients receiving

2:25

concizumab, including in one

2:27

patient from this trial. The

2:29

trials resumed after thorough investigation

2:32

of all available data and subsequent

2:35

implementation of risk mitigation

2:37

measures. The initial loading

2:40

dose of concizumab was reduced

2:43

to 1 mg per kg

2:45

of body weight. In addition, a dose

2:47

adjustment step was included.

2:50

The primary endpoint of the

2:53

estimated mean annualized

2:55

bleeding rate in group 1 was 11.8

2:57

episodes as compared with 1.7 episodes

3:00

in group 2.

3:05

The overall median annualized

3:08

bleeding rate for patients receiving

3:10

concizumab, groups 2, 3, and 4,

3:13

was zero episodes.

3:16

No thromboembolic events were

3:18

reported after concizumab therapy

3:21

was restarted.

3:22

The plasma concentrations of

3:25

concizumab remained stable

3:27

over time. Among patients

3:29

with hemophilia A or B

3:31

with inhibitors, the annualized

3:34

bleeding rate was lower with

3:36

concizumab prophylaxis than

3:39

with no prophylaxis.

3:42

In a science behind the study editorial,

3:45

H. Marika Vandenberg from the Piednett

3:48

Hemophilia Research Foundation,

3:51

Barn, The Netherlands writes

3:53

that a balance between procoagulants

3:56

and anticoagulants underpins

3:59

hemostasis.

3:59

Hemophilia, a

4:02

form of disrupted hemostasis,

4:04

is caused by dysfunctional variants

4:07

in genes encoding the procoagulant

4:10

factors 8, causing hemophilia

4:13

A, and 9, causing hemophilia

4:16

B. In their trial, Matsushita

4:19

et al. report that a first-in-class

4:21

drug restored hemostasis

4:24

in persons with hemophilia with

4:26

inhibitors.

4:27

This drug, Conchizumab, blocks

4:30

an anticoagulant protein.

4:33

In other words, it removes a powerful

4:36

break from a procoagulant

4:39

pathway.

4:40

For patients with inhibitors, there

4:42

are already several relatively

4:44

new coagulation products.

4:47

Emochizumab is a factor 8 mimetic,

4:50

bispecific monoclonal antibody

4:53

that binds both factor 9A

4:55

and factor 10 and results in

4:58

enhanced thrombin generation.

5:00

Administered subcutaneously, it

5:03

achieves steady-state improved

5:05

hemostasis and prevents bleeding

5:08

episodes.

5:09

Matsushita et al. took a different

5:11

approach. Rather than adding a

5:13

coagulant, they sought to inhibit

5:16

a naturally occurring anticoagulant

5:19

tissue factor pathway inhibitor.

5:22

Matsushita et al. found that

5:24

tissue factor pathway inhibitor was

5:27

reduced to approximately 10% within 24

5:31

hours after a loading dose

5:33

of Conchizumab. They also found

5:36

that the median annualized bleeding

5:38

rate was zero episodes and

5:40

that approximately 60% of

5:43

the patients had no bleeding

5:45

episodes, values that meet

5:47

current benchmarks of effective hemophilia

5:50

therapy.

5:52

In the bigger picture, new treatment

5:54

options need to be weighed against

5:56

the possibility of cure of hemophilia.

5:59

through gene therapy.

6:01

Two adeno-associated virus,

6:04

AAV vector-based products

6:07

have been approved for clinical use

6:09

and more are in the pipeline.

6:12

However, the durability of

6:14

the gene therapy mediated factor

6:16

production is still being defined.

6:19

Therefore, an abundance of therapeutic

6:22

options such as Conkizumab,

6:24

other non-factor replacement products

6:27

and a multitude of clotting factor products

6:30

will play a large role in

6:32

prevention of bleeding in hemophilia

6:34

for the foreseeable future.

6:37

It is reassuring that Conkizumab

6:39

is effective in treating patients with

6:41

hemophilia A or B who

6:44

have inhibitors.

6:45

Given its reported efficacy in

6:48

both types of hemophilia without

6:50

inhibitors, Conkizumab is

6:52

now evolving as an attractive therapeutic

6:55

for all patients with hemophilia.

7:00

Timing of primary surgery

7:03

for cleft palate by Carol

7:05

Gamble

7:06

from the University of Liverpool in

7:09

the United Kingdom.

7:11

Isolated cleft palate affects

7:14

one to 25 newborns per 10,000

7:17

births worldwide, although the incidence

7:20

varies across the world.

7:23

This study evaluated whether

7:25

primary surgery at six

7:27

months of age is more beneficial

7:30

than surgery at 12 months

7:32

of age with respect to

7:34

speech outcomes, hearing outcomes,

7:37

dental facial development and safety

7:40

among infants with isolated

7:42

cleft palate.

7:44

558 infants

7:46

with non-syndromic isolated

7:48

cleft palate at 23 centers

7:51

across Europe and South America

7:54

were randomly assigned to undergo

7:56

standardized primary surgery

7:59

for closure of the

7:59

the cleft at 6 months of age

8:02

or at 12 months of age. Speech

8:05

recordings from 235 infants, 83.6%, in the 6-month group

8:08

and 226, 81.6%, in the 12-month

8:18

group were analyzable.

8:20

Insufficient velopharyngeal

8:22

function at 5 years of age

8:25

was observed in 8.9% of the infants in

8:28

the 6-month group as compared

8:31

with 15% of the infants in the 12-month group.

8:35

Post-operative complications were

8:38

infrequent and similar in the

8:40

6-month and 12-month groups.

8:43

Four serious adverse events were

8:46

reported, three in the 6-month group

8:48

and one in the 12-month group, and

8:50

had resolved at follow-up.

8:53

Adequately fit infants who underwent

8:56

primary surgery for isolated

8:58

cleft palate in adequately resourced

9:01

settings at 6 months of age

9:03

were less likely to have velopharyngeal

9:06

insufficiency at the age of 5

9:09

years than those who had surgery

9:11

at 12 months of age.

9:15

Raymond C. from Seattle Children's

9:17

Hospital, Washington writes in

9:19

an editorial that the trial by Gamble

9:21

and colleagues is remarkable because

9:24

randomized surgical trials

9:26

are rare and projects of this

9:29

magnitude, multidisciplinary,

9:31

multi-center, multinational,

9:33

and multilinguistic with a four-year

9:36

follow-up period, are unprecedented.

9:39

However, although the authors concluded

9:42

that early surgery was associated

9:45

with better speech at 5 years

9:47

of age than later surgery, this

9:50

editorialist believes that results

9:52

should be interpreted in the context

9:55

of the overall design of the trial.

9:59

surgery to treat villopharyngeal

10:02

insufficiency was greater in

10:04

the six-month group than in the

10:06

12-month group, 30 procedures

10:09

in 27 children versus 17 procedures

10:13

in 16 children, and speech

10:15

assessments performed after the

10:18

secondary procedures were used

10:20

in the analysis.

10:22

Thus, the trial evaluated the

10:24

mixed effects of primary

10:26

surgery and secondary surgery

10:29

in some patients.

10:30

The considerations with regard to early

10:33

surgery include the greater technical

10:36

complexity of the procedure and

10:38

the greater risks associated with anesthesia,

10:41

airway complications, and potential

10:44

neurodevelopmental sequelae.

10:46

Early surgery may also contribute

10:48

to mid-facial growth restriction,

10:51

which becomes apparent only later in

10:53

adolescence and may require

10:55

complex corrective jaw surgery.

10:58

The conclusions of the present trial

11:01

should be regarded within the context

11:04

of the specific trial population,

11:07

in which over two-thirds of infants

11:09

who were screened were excluded because

11:12

their cleft was part of a syndrome, they

11:14

were deemed to be medically unfit for

11:16

early surgery, or they had a cleft

11:19

that was too wide, and with

11:21

the goal of optimizing function

11:24

while reducing the burden of care.

11:26

Although families and health care providers

11:29

could be anxious to address a birth

11:31

difference early in life, whether

11:34

early surgery is associated

11:36

with a clinically meaningful long-term

11:38

benefit

11:39

is unclear.

11:41

Given that uncertainty, this editorialist

11:44

believes it may be preferable

11:46

to defer surgery to a time

11:49

when it is easier to perform and

11:51

involves less risk.

11:55

Anti-epstein bar virus

11:57

BNLF2B for Mass

12:00

Screening for Nasopharyngeal

12:02

Cancer by Tingdong Li

12:05

from the State Key Laboratory of

12:07

Vaccines for Infectious Diseases,

12:09

Xiamen, China.

12:12

Nasopharyngeal carcinoma is

12:14

common in China, Southeast

12:17

Asia, and North Africa, and

12:19

it is ubiquitously associated

12:21

with Epstein-Barr virus, EBV

12:24

infection.

12:25

Screening with either EBV-specific

12:28

antibodies or EBV DNA

12:31

can increase the percentage of

12:33

patients in whom nasopharyngeal carcinoma

12:36

is diagnosed at an early stage

12:38

from approximately 20% to more than 70%. However,

12:43

the use of nasopharyngeal carcinoma

12:46

screening in clinical practice

12:48

has been hampered by the low positive

12:51

predictive value, which was only 4.8%, even in areas

12:53

where EBV is endemic

12:57

in China.

12:58

These authors report on the identification

13:01

and validation of an anti-BNLF2B

13:05

total antibody, P85AB,

13:08

as a novel serologic biomarker

13:11

for nasopharyngeal carcinoma

13:14

screening. After a retrospective

13:16

case control study, the performance

13:19

of the novel biomarker was validated

13:22

through a large-scale prospective

13:24

screening program and compared

13:26

with that of the standard two antibody-based

13:29

screening method. P85AB

13:32

was the most promising biomarker

13:35

for nasopharyngeal carcinoma

13:37

screening with high sensitivity, 94.4%,

13:39

and specificity, 99.6%.

13:46

Among the 24,852 eligible participants in the

13:48

prospective cohort, 47 cases of nasopharyngeal carcinoma, 38

13:56

at an early stage, were identified.

14:01

P85AB showed

14:03

higher sensitivity than the two

14:05

antibody method, 97.9% vs. 72.3%, higher specificity, 98.3%

14:07

vs. 97%, and

14:17

a higher positive predictive value, 10%

14:20

vs. 4.3%.

14:24

The combination of P85AB

14:27

and the two antibody method markedly

14:30

increase the positive predictive value

14:33

to 44.6%, with

14:35

sensitivity of 70.2%. These

14:39

results suggest that P85AB

14:42

is a promising novel biomarker

14:45

for nasopharyngeal carcinoma screening

14:48

with higher sensitivity, specificity,

14:51

and positive predictive value

14:53

than the standard two antibody

14:56

method.

14:58

CRISPR-Cas9 editing

15:00

of the HBG-1 and HBG-2

15:03

promoters to treat sickle cell

15:06

disease, by

15:07

Akshay Sharma

15:09

from St. Jude Children's Research

15:11

Hospital, Memphis, Tennessee.

15:15

Sickle cell disease is caused

15:17

by a defect in the beta globin

15:20

subunit of adult hemoglobin.

15:23

Sickle hemoglobin polymerizes

15:25

under hypoxic conditions, producing

15:28

deformed red cells that hemolyse

15:30

and cause vasoocclusion that results

15:33

in progressive organ damage and

15:36

early death.

15:37

Elevated fetal hemoglobin levels

15:39

in red cells protect against

15:42

complications of sickle cell

15:44

disease.

15:59

Gamoglobin Gene Promoters

16:02

that increases fetal hemoglobin

16:05

expression in red cell progeny.

16:08

In preclinical experiments,

16:10

these investigators found that CRISPR-Cas9

16:13

disruption of the HPG-1 and

16:16

HPG-2 gene promoters

16:18

was an effective strategy for induction

16:21

of fetal hemoglobin.

16:23

Then, a Phase 1-2 clinical

16:25

study assessed the safety and

16:28

adverse effect profile of OTQ-923

16:32

in three participants with severe

16:34

sickle cell disease. The

16:37

participants received autologous

16:39

OTQ-923 after

16:42

myeloblative conditioning and

16:44

were followed for 6 to 18 months.

16:48

At the end of the follow-up period, all

16:50

the participants had engraftment

16:53

and stable induction of fetal

16:55

hemoglobin. Fetal hemoglobin

16:57

as a percentage of total hemoglobin, 19

16:59

to 26.8%, with

17:03

fetal hemoglobin broadly distributed

17:06

in red cells. F-cells as

17:08

a percentage of red cells, 69.7 to 87.8%.

17:14

Manifestations of sickle cell

17:16

disease decreased during

17:19

the follow-up period.

17:21

Infusion of autologous OTQ-923

17:24

into three participants

17:27

with severe sickle cell disease

17:29

resulted in sustained induction

17:32

of red cell fetal hemoglobin

17:34

and clinical improvement in

17:36

disease severity.

17:40

Considering biased data

17:42

as informative artifacts in

17:45

AI-assisted healthcare,

17:47

a review article by Khadijah Ferryman

17:50

from Johns Hopkins Bloomberg School

17:52

of Public Health, Baltimore.

17:55

Artificial intelligence, AI

17:58

tools used in medicine like

18:00

AI used in other fields, work

18:02

by detecting patterns in large

18:05

volumes of data.

18:06

AI tools are able to detect

18:09

these patterns because they can learn

18:12

or be trained to recognize certain

18:14

features in the data.

18:16

However, medical AI tools

18:19

trained with data that are skewed

18:21

in some way can exhibit bias.

18:24

And when that bias matches patterns

18:27

of injustice, the use of the tools

18:29

can lead to inequity and discrimination.

18:33

Technical solutions such as attempting

18:35

to fixed biased clinical data

18:38

used for AI training are well-intentioned.

18:41

But what undergirds all these

18:43

initiatives is the notion that skewed

18:46

clinical data are garbage,

18:48

as in the computer science adage, garbage

18:51

in, garbage out.

18:52

Instead, these authors propose

18:55

thinking of clinical data as artifacts

18:58

that, when examined, can be

19:00

informative about the societies

19:03

and institutions in which they

19:05

are found.

19:06

Viewing biased clinical data

19:08

as artifacts can identify values,

19:11

practices, and patterns of inequity

19:14

in medicine and healthcare.

19:16

Examining clinical data as

19:18

artifacts can also provide alternatives

19:21

to current methods of medical AI

19:24

development.

19:25

Moreover, this framing of data

19:28

as artifacts expands the approach

19:30

to fixing biased AI from

19:33

a narrowly technical view to

19:35

a socio-technical perspective

19:37

that considers historical and

19:40

current social contexts as key

19:42

factors in addressing bias.

19:45

This broader approach contributes

19:47

to the public health goal of understanding

19:50

population inequities and also

19:53

provides novel ways to use

19:55

AI as a means of detecting

19:57

patterns of racial and ethnic careers.

19:59

missing data, and population

20:02

inequities that are relevant to

20:05

health equity.

20:08

A 53-year-old woman with celiac

20:10

disease and upper gastrointestinal

20:13

bleeding. A case record of the

20:15

Massachusetts General Hospital

20:17

by Nikhru Hashimi and colleagues.

20:21

A 53-year-old woman with celiac

20:24

disease was transferred to the ICU

20:27

of this hospital for the management

20:29

of upper gastrointestinal bleeding

20:31

with hemorrhagic shock. Approximately

20:34

three weeks earlier, fatigue,

20:37

malaise, anorexia, generalized

20:39

weakness, and watery diarrhea

20:42

developed.

20:43

Two weeks later, the diarrhea

20:45

increased in frequency and became

20:47

bloody. The patient presented

20:49

to an emergency department. She was

20:52

found to be in hemorrhagic shock

20:54

and received intensive care and resuscitation.

20:58

Severe coagulopathy and hypoalbuminemia

21:01

were detected.

21:03

Imaging reportedly revealed

21:05

fatty liver, a large retroperitoneal

21:08

mass, and horseshoe kidney. During

21:11

the first seven hospital days,

21:13

diarrhea continued with an output

21:16

of up to 2 liters of green

21:18

liquid stool daily.

21:20

On hospital day seven, paracentesis

21:23

was performed for the treatment of abdominal

21:25

distension, and 3.7 liters of acidic fluid was

21:27

removed. The

21:32

next day, there was an output of

21:34

copious black stool. The

21:36

hemoglobin level decreased from 8.1

21:38

grams per deciliter to 5.1 grams per deciliter.

21:44

Esophagogastroduodenoscopy

21:46

reportedly showed a bleeding esophageal

21:49

varix. The patient was transferred

21:52

by helicopter to the ICU of this

21:54

hospital.

21:59

in fat-soluble vitamins as

22:02

well as osteoporosis were

22:04

detected.

22:05

The constellation of fatty

22:08

liver without morphologic features

22:10

of cirrhosis, evidence of portal

22:12

hypertension, and extrahepatic

22:15

and intestinal findings in the history

22:18

and on physical examination and

22:20

imaging suggested a syndromic

22:23

diagnosis.

22:24

Turner syndrome was suspected.

22:27

In patients with Turner syndrome,

22:30

nearly every organ system can

22:32

be involved.

22:35

Sucralose and erythritol,

22:38

not too sweet, a clinical

22:40

implications of basic research article

22:43

by Herbert Tilgh from the Medical

22:45

University of Innsbruck,

22:47

Austria. Relative

22:49

intake of simple carbohydrates,

22:52

sugars, threatens health and

22:54

provokes metabolic disease.

22:56

Historically, a reduced intake

22:59

of sugar, achieved either by adaptation

23:01

of dietary habits or by replacement

23:04

with artificial sweeteners, was thought

23:06

to confer beneficial metabolic

23:09

effects, a belief that led to the

23:11

development of chemically synthesized,

23:14

that is, artificial sweeteners

23:16

by the food industry.

23:18

Several artificial sweeteners have

23:20

been approved by the Food and Drug Administration

23:23

and similarly by the European Food

23:25

Safety Authority as food additives

23:28

and U.S. revenues for sugar

23:30

substitutes are expected to reach $10 billion

23:34

by the end of this decade.

23:37

The initial idea was that artificial

23:39

sweeteners are rarely absorbed,

23:42

low caloric, and therefore could

23:44

provide beneficial metabolic effects

23:47

as compared with excessive intake

23:49

of sugar that could be exploited

23:51

safely in humans.

23:53

Today, artificial sweeteners are

23:56

widely used in processed foods,

23:58

soft drinks, soft drinks, and

24:00

candy.

24:01

Meanwhile, the initial view of artificial

24:04

sweeteners as inert and healthy

24:06

compounds is being challenged

24:09

and the World Health Organization has recently

24:12

issued a provisional recommendation

24:14

against the use of artificial sweeteners

24:17

to control body weight.

24:19

In two recent preclinical

24:21

studies by Zani et al. and

24:24

Wachowski et al.,

24:25

the use of the artificial sweeteners

24:28

sucralose and erythritol

24:30

was found to be associated with

24:32

detrimental effects on immunity

24:35

and cardiovascular health, although

24:38

a mitigating effect on the risk of

24:40

autoimmune disease was noted.

24:43

These studies and others challenge

24:45

the perception of a beneficial

24:48

effect of some artificial sweeteners.

24:53

Project NextGen

24:55

defeating SARS-CoV-2

24:57

and preparing for the next pandemic.

25:00

A perspective by Xavier Becerra

25:02

from the Office of the Secretary of Health

25:05

and Human Services, Washington,

25:07

DC.

25:09

Although our public health emergency

25:11

has ended, SARS-CoV-2 continues

25:14

to evolve and pose challenges

25:16

to human health.

25:18

The goal for the next generation of vaccines

25:21

and treatments is to be effective irrespective

25:24

of that evolution, to protect

25:26

against infection, transmission,

25:28

and severe illness.

25:30

The Biden administration has therefore

25:33

announced Project NextGen,

25:35

which will coordinate a whole of government

25:38

effort to advance innovations from

25:40

labs through clinical trials and

25:42

safely deliver them to the public.

25:45

It aims to bring new vaccines and

25:47

treatments to market by investing

25:49

in research and development, expanding

25:52

manufacturing capability and innovation,

25:55

and providing updated and streamlined

25:58

regulatory guidance.

25:59

This $5 billion investment

26:02

will focus on three main areas.

26:05

Vaccines that provide broader immunity,

26:08

both against new SARS-CoV-2

26:11

variants and across the family

26:13

of epidemic-prone Sarpaco

26:15

viruses. Vaccines that

26:18

generate effective mucosal immunity

26:20

to block infection and transmission.

26:23

And monoclonal antibodies that

26:25

can weather viral evolution

26:28

and serve as a basis for our arsenal

26:31

against new threats from beta-coronaviruses.

26:35

Why is government investment

26:37

needed at this time and for

26:39

this effort? Although there is consensus

26:42

that these tools are critical for

26:44

our fight moving forward, current

26:46

market forces have made development

26:49

slow.

26:50

The U.S. government has committed to accelerating

26:53

the science by streamlining development

26:55

processes, using such strategies

26:58

as standardizing assays, standardizing

27:01

protocols, and providing timely

27:04

regulatory guidance. Toward

27:08

Jerry Neuropalliative Care for

27:10

Patients with Dementia, a

27:12

perspective by Krista Harrison

27:14

from the University of California, San

27:17

Francisco.

27:19

Today, an estimated 6.7 million

27:22

people over 65 years of

27:25

age in the U.S. are living with

27:27

dementia, and they are cared for,

27:29

in part, by 11 million

27:32

unpaid caregivers. Worldwide,

27:35

more than 55 million people have

27:37

dementia, and 10 million new cases

27:40

are diagnosed each year.

27:42

New anti-amyloid and emerging

27:45

anti-tow therapies are focusing

27:47

attention on early screening and

27:50

diagnosis for dementia syndromes,

27:52

which are progressive serious illnesses.

27:56

In parallel with new treatments, however,

27:58

we need new care.

27:59

models that can mitigate suffering,

28:02

enhance care quality, and expand

28:05

support for persons living with

28:07

dementia and their care partners.

28:10

Goals that are aligned with the U.S. National

28:13

Plan to Address Alzheimer's Disease

28:15

and the World Health Organization's Global

28:18

Action Plan on the Public Health Response

28:21

to Dementia. To achieve

28:23

these goals, these authors propose

28:26

a gerry neuropalliative approach

28:28

to dementia that would infuse principles

28:31

from geriatric, palliative,

28:33

and dementia care into every stage

28:36

and aspect of care, regardless

28:38

of the discipline of the clinician involved.

28:43

Geri neuropalliative dementia care would combine core

28:45

principles from these relevant

28:48

disciplines. Geriatrics-informed

28:50

care, including attention to

28:52

multiple coexisting conditions,

28:55

function, and care transitions,

28:57

palliative care communication skills

28:59

to support prognostic and anticipatory

29:02

guidance, and neurology-informed

29:05

diagnostic skills that incorporate

29:08

use of biomarkers, neuroimaging,

29:11

and neuropathology.

29:13

The effort required to accomplish this

29:15

ambitious paradigm shift would

29:17

be substantial, yet we

29:19

need to consider the cost to society

29:22

of failing to achieve the goal of

29:24

mitigating suffering for this population,

29:27

given that the United States may be

29:30

home to more than 13 million people

29:33

with dementia by 2060.

29:37

Sexual and gender minority

29:40

refugees, preparing clinicians

29:42

for the international anti-LGBTQI-plus

29:47

crisis. A perspective by

29:49

Carl St. Jr. from the

29:51

Boston University Chobanian

29:54

and Abidijian School of Medicine.

29:59

transgender, queer, intersex,

30:02

and other sexual and gender minority

30:04

people in every region of the world

30:07

face marginalization and

30:09

repression. Amid global

30:11

outcry, Ugandan President

30:13

Joeri Museveni, on May 29, signed

30:16

into law one of the

30:18

most egregious anti-LGBTQI-plus

30:22

pieces of legislation in the

30:25

world, which criminalizes identifying

30:28

as LGBTQI-plus.

30:31

This sweeping law imposes

30:33

a death sentence on persons

30:35

found guilty of aggravated

30:37

homosexuality and punishes

30:40

the promotion of LGBTQI-plus

30:43

identities with a prison sentence

30:45

of up to twenty years.

30:48

At least 67 countries

30:50

ban sexual conduct between

30:53

consenting adults of the same sex.

30:56

According to a report from the United

30:58

Nations High Commissioner for Refugees

31:00

on LGBTQI-plus people

31:03

in forced displacement and statelessness,

31:06

regressive laws that foster

31:08

hostile environments for LGBTQI-plus

31:12

persons will most likely result

31:15

in increasing numbers of such

31:17

people fleeing their home countries

31:20

and seeking sanctuary elsewhere.

31:23

As refugees and asylum seekers,

31:25

including LGBTQI-plus

31:28

persons, interact with healthcare

31:31

systems, which asylum seekers must

31:33

often do as a requirement of their

31:35

petition for asylum,

31:37

clinicians should be prepared to

31:39

assess and address their health

31:42

and legal needs.

31:43

To assist patients seeking asylum

31:46

on the basis of their LGBTQI-plus

31:49

identity, clinicians need to

31:51

know how to probe and document

31:53

experiences of adverse childhood

31:56

events and trauma, abuse, harassment,

31:59

discrimination, and sexual harassment.

31:59

and wrongful imprisonment

32:02

using a trauma-informed and

32:04

culturally informed approach.

32:07

In the context of increasing

32:09

anti-LGBTQI plus

32:12

interpersonal violence and legislation,

32:15

healthcare settings can serve as

32:17

safe and reparative spaces

32:20

for refugees and asylum

32:22

seekers. In

32:25

our images in clinical medicine, a man

32:28

in Colombia presented with a three-week

32:30

history of fever, pale stools,

32:33

and progressive colicky abdominal

32:35

pain. He had tenderness in the

32:37

right upper quadrant and jaundice.

32:40

Endoscopic retrograde cholangiopancreatography

32:44

was performed, during which a

32:46

worm was seen protruding from

32:48

the bile ampulla.

32:50

After extraction, the worm was identified

32:53

as an adult, ascoris lumbricoides

32:56

roundworm. The bile duct was

32:58

subsequently canalized and visualized

33:00

with injection of contrast material,

33:03

revealing two other worms,

33:05

which were removed with the use of a balloon

33:08

catheter.

33:09

A diagnosis of biliary

33:11

ascoriasis was made,

33:13

courses of albendazole to treat

33:15

the infection, and piperacillin tazobactam

33:19

to treat secondary cholangitis

33:21

were prescribed, and the patient's symptoms

33:24

abated within one week after

33:26

the extraction procedure. In

33:29

another image, a 73-year-old

33:32

woman presented with a two-day history

33:34

of left flank pain. The platelet

33:37

count was 652,000 per cubic millimeter, and

33:41

CT of the abdomen showed left

33:43

renal artery thrombosis and

33:45

left renal infarction.

33:48

Owing to a persistently elevated

33:50

platelet count, genetic testing

33:52

was performed for the JAK2V617F

33:55

variant, and the result was positive.

33:59

A

34:01

diagnosis of essential thrombocythemia

34:04

was made.

34:05

Essential thrombocythemia may

34:07

be complicated by arterial.