2:00

Death by month 12 occurred

2:02

in 8.6% of patients in

2:05

the ferric carboxymaltose group

2:07

and in 10.3% of those in the placebo group. A

2:11

total of 297 and 332 hospitalizations for heart

2:13

failure, respectively, occurred by month And

2:20

the mean change from baseline to

2:22

six months in the six-minute walk distance

2:24

was 8 and four meters, respectively.

2:27

P equals 0.02. Unmatched

2:30

win ratio, 1.1099% confidence interval, 0.99

2:33

to 1.23. Repeated

2:39

dosing of ferric carboxymaltose

2:41

appeared to be safe, with an acceptable

2:43

adverse event profile in the majority of patients.

2:47

The number of patients with serious

2:49

adverse events occurring during the treatment

2:51

period was similar in the two groups, 27%

2:54

of patients in the ferric carboxymaltose

2:57

group and 26.2% of

2:59

those in the placebo group. Among

3:02

ambulatory patients who had heart failure

3:05

with a reduced ejection fraction and

3:07

iron deficiency, there was no

3:09

apparent difference between ferric carboxymaltose

3:12

and placebo with respect to

3:14

a hierarchical composite of death,

3:16

hospitalizations for heart failure, or

3:19

six-minute walk distance. Peter

3:22

Martens from the Szekenheis-Oost-Limburg-Hank-Belgium

3:26

writes in an editorial that iron deficiency

3:29

is common among patients with heart failure,

3:31

occurring in 40 to 50% of patients

3:34

with chronic heart failure and in up to 80%

3:37

of patients with acute heart failure. Iron

3:40

deficiency worsens the heart

3:42

failure syndrome by affecting energy

3:44

metabolism in myocardial and skeletal

3:46

muscle, the oxidation reduction

3:49

balance, and contractile function.

3:51

Previous randomized controlled trials

3:54

showed that supplementation with intravenous

3:56

ferric carboxymaltose improved

3:59

functional skin. status and exercise capacity

4:02

and induced cardiac reverse remodeling

4:05

in patients with heart failure and reduced

4:07

ejection fraction. In the trial

4:09

now reported by mence and colleagues,

4:12

intravenous iron appeared to be safe,

4:15

but the unmatched win ratio,

4:17

ferric carboxymaltose versus placebo,

4:20

with respect to the hierarchical primary

4:23

endpoint was 1.10, and

4:25

the difference was not significant,

4:28

p equals 0.02. The

4:30

p-value does suggest some

4:32

treatment effect if it would be considered

4:34

in the context of a usual 95% confidence interval.

4:38

The trial by mence and colleagues used

4:40

a more stringent 99% confidence interval. The

4:44

treatment effect of ferric carboxymaltose

4:47

on the 6-minute walk distance was surprisingly

4:50

small in the trial by mence and colleagues,

4:52

and the lack of a long-term reduction

4:55

in hospitalizations for heart failure

4:57

was unexpected given the results

4:59

of the previously reported trials.

5:02

However,

5:03

the number of patients with true iron

5:05

deficiency in the trial by mence and colleagues

5:08

is unclear, and whether the

5:10

absence of true iron deficiency could

5:13

have influenced the observed lower relative

5:15

treatment effect is unknown. Other

5:18

analyses, preferably a meta-analysis

5:21

of individual patient data from all

5:23

intravenous iron trials, should assess

5:25

the importance of the transferrin saturation

5:28

value at baseline. Doing

5:31

so could help redefine the definition

5:33

of iron deficiency in patients with

5:35

heart failure, and, these editorialists

5:38

hope, help clinicians determine which

5:41

patients might benefit from intravenous

5:43

iron supplementation. Like

5:48

prophylaxis in infants with grade 3,

5:51

4, or 5 vesicouretral

5:53

reflux.

5:59

Italy.

6:01

The efficacy of continuous antibiotic

6:04

prophylaxis in preventing urinary

6:06

tract infection UTI in

6:08

infants with grade 3, 4, or 5

6:11

vesicoeurideral reflux is

6:13

controversial. In this trial

6:15

in 39 European centers, 292 infants 1 to 5 months of age with grade 3,

6:18

4, or 5 vesicoeurideral reflux

6:25

and no previous UTIs were

6:27

randomly assigned to receive continuous

6:29

antibiotic prophylaxis or no

6:32

treatment for 24 months. In

6:34

the intention to treat analysis,

6:37

a first UTI occurred in 21.2% of

6:39

the participants in the prophylaxis group and in 35.6% of the participants

6:42

in the

6:47

untreated group. The number needed

6:49

to treat for two years to prevent

6:52

one UTI was seven children.

6:55

Among untreated participants, 64.4% had

6:58

no UTI during the trial. The incidence of

7:03

new kidney scars and the estimated

7:06

GFR at 24 months did

7:08

not differ substantially between the two

7:10

groups. Pseudomonas species,

7:13

other non-ecolide organisms,

7:16

and antibiotic resistance were

7:18

more common in UTI isolates

7:20

obtained from participants in the

7:22

prophylaxis group than in isolates

7:24

obtained from those in the untreated group.

7:27

Serious adverse events were similar

7:29

in the two groups. In infants

7:32

with grade 3, 4, or 5 vesicoeurideral

7:35

reflux and no previous UTIs,

7:38

continuous antibiotic prophylaxis

7:40

provided a small but significant

7:42

benefit in preventing a first

7:44

UTI despite an increased

7:47

occurrence of non-ecolide organisms

7:50

and antibiotic resistance.

7:53

Tej Matu from Wayne State

7:56

University School of Medicine, Detroit

7:58

writes in an editorial that the use

8:00

of continuous antibiotic prophylaxis

8:03

and the prevention of UTI, particularly

8:05

in children with vesicouretural reflux,

8:08

has been studied extensively during

8:10

the past 15 years. Studies

8:12

have yielded mixed results. The

8:15

results of the trial by Morello and colleagues

8:17

once again showed that continuous

8:20

antibiotic prophylaxis significantly

8:22

reduced the risk of UTI, although

8:24

not among all children considered

8:27

all mass and at the expense of increased

8:29

antimicrobial resistance. Interpretation

8:32

of trial results in terms of numbers needed

8:35

to treat is not helpful. Even

8:37

though it is a valuable metric for treatment

8:39

effectiveness for the population

8:42

as a whole, the number needed to treat does

8:44

not help calculate the individual

8:46

risk-benefit ratio and cannot be

8:49

the sole basis for clinical decision-making.

8:52

Routine use of continuous antibiotic

8:54

prophylaxis for vesicouretural

8:56

reflux is already passe,

8:59

as reflected in the published guidelines

9:01

from professional societies such

9:03

as the American Urological

9:06

Association, the European Association

9:09

of Urology, European Society

9:11

for Pediatric Urology, and the Swedish

9:13

and the Italian Societies for Pediatric

9:16

Nephrology. These bodies all

9:19

recommend a more selective approach

9:21

for using continuous antibiotic prophylaxis

9:24

based on a combination of factors

9:26

that include patient age and sex,

9:28

severity of vesicouretural reflux,

9:31

and the presence of bladder or bowel

9:33

dysfunction or renal scarring.

9:36

Other factors that warrant consideration before

9:38

initiation of long term continuous

9:41

antibiotic prophylaxis include parental

9:43

choice, anticipated adherence

9:45

to medication, status of toilet

9:47

training, and medication expense.

9:50

Thus, the key takeaway message

9:53

from this and other trials is

9:55

that continuous antibiotic prophylaxis

9:58

should be used Judiciously.

10:03

Randomized Control Trial of the FGF21

10:06

Analog Pegozafferman in

10:08

NASH by Rohit Lumba

10:11

from the University of California, San Diego,

10:13

La Jolla. Non-alcoholic

10:17

steatohepatitis NASH

10:19

is characterized by excess fat accumulation,

10:22

hepatic inflammation and cellular

10:25

injury with or without fibrosis.

10:28

The development of clinically significant

10:30

fibrosis in NASH is associated

10:32

with worse liver-related outcomes,

10:34

cardiovascular events and

10:37

death. Pegozafferman

10:39

is a long-acting, glycopegulated,

10:42

pegalated with the use of site-specific

10:44

glycosyl transferases, fibroblast

10:47

growth factor 21 analog

10:49

in development for the treatment of NASH

10:52

and severe hypertriglyceridemia.

10:55

The efficacy and safety of Pegozafferman

10:58

in patients with biopsy-proven,

11:00

non-cerotic NASH are not well

11:02

established. In this Phase IIb

11:05

trial, 222 patients

11:07

with biopsy-confirmed NASH and

11:09

Stage F2 or F3, moderate

11:12

or severe, fibrosis were randomly

11:15

assigned to receive subcutaneous Pegozafferman

11:18

at a dose of 15 mg or 30 mg weekly or 44 mg once

11:20

every 2 weeks or placebo weekly or every 2

11:27

weeks. The percentage of patients

11:29

who met the criteria for improvement

11:32

of fibrosis was 7% in the pooled

11:35

placebo group, 22% in the 15 mg Pegozafferman

11:37

group, 26% in the 30 mg Pegozafferman

11:39

group and 27%

11:44

in the 44 mg Pegozafferman group. The

11:49

percentage of patients who met the criteria

11:51

for NASH resolution was 2%

11:54

in the placebo group, 37% in

11:56

the 15 mg Pegozafferman group. 23% in

12:00

the 30 milligram Pegozaphramin group and 26% in the 44 milligram

12:02

Pegozaphramin group. The

12:08

most common adverse events associated

12:11

with Pegozaphramin therapy were nausea

12:13

and diarrhea. In this

12:16

phase 2b trial, treatment

12:18

with Pegozaphramin led to improvements

12:21

in fibrosis. These results

12:23

support the advancement of Pegozaphramin

12:26

into phase 3 development. In

12:30

an editorial, Mary Ranella

12:32

from the University of Chicago Pritzker

12:35

School of Medicine writes that pharmacotherapy

12:37

in patients with non-alcoholic steatohepatitis,

12:40

NASH, has been a frustrating endeavor

12:43

with failures outnumbering successes

12:45

by some margin, even in late-phase

12:48

clinical trials. The

12:50

complex pathobiologic features

12:53

of NASH, the slow and variable

12:55

natural history of the disease, and the

12:57

nefarious nature of assessing histologic

13:00

endpoints have contributed to the

13:02

difficulty of attaining efficacy

13:04

with pharmacotherapy that is meaningfully

13:07

distinct from that seen with placebo.

13:10

In the trial by Lumba and colleagues,

13:12

a reduction in the level of fibrosis,

13:15

one of two primary endpoints, was

13:17

observed among patients who received Pegozaphramin.

13:20

The results also favored Pegozaphramin

13:23

for the second primary endpoint of

13:25

NASH resolution. As

13:27

promising as they are, the results of

13:30

the trial reported by Lumba and colleagues

13:32

should be interpreted with caution. Durability

13:36

of treatment response has been a critical

13:38

limitation of other FGF21 analogues.

13:42

NASH is a chronic disease

13:44

with pathobiologic features that

13:46

are anchored in energy metabolism, making

13:49

the temporal horizon of NASH therapeutics

13:52

likely to be more akin to that of type 2

13:55

diabetes measured in years

13:57

than hepatitis C, measured in weeks.

14:00

Thus, although the planned 24-week

14:03

open label extension in this trial

14:05

will provide insight into the durability

14:07

of response to PEGO Zaphramin, even

14:10

a 48-week period may be too

14:12

short to assess the durability of response

14:15

for this or any other FGF21-based

14:17

therapy. The

14:19

results of the trial by Lumba and colleagues

14:22

are an encouraging development in NASH

14:24

Therapeutics. These editorialists

14:27

eagerly await determination of

14:29

whether the blistering pace of response

14:31

can be sustained to the end

14:34

of the marathon. Mesigdemide

14:38

plus dexamethasone in relapsed

14:40

and refractory multiple myeloma by

14:43

Paul Richardson from the Dana-Farber

14:45

Cancer Institute, Boston. Despite

14:48

recent progress, multiple myeloma

14:51

remains incurable. Mesigdemide

14:54

is a novel cereblin E3

14:57

ubiquitin ligase modulator

14:59

with potent anti-proliferative and

15:02

cumoricidal activity in preclinical

15:04

models of multiple myeloma, including

15:07

those resistant to lenalidomide

15:09

and pomalidomide. Mesigdemide

15:12

possesses a unique potency owing

15:14

to its cereblin binding interactions.

15:17

In this phase 1-2 study, the

15:19

investigators administered oral mesigdemide

15:22

in combination with dexamethasone

15:24

to patients with relapsed and refractory

15:27

myeloma. In phase 1, in

15:29

which 77 patients were enrolled, the

15:31

most common dose-limiting toxic

15:33

effects were neutropenia and

15:36

febrile neutropenia. On the basis

15:38

of the phase 1 findings, investigators

15:40

determined the recommended phase 2 dose

15:43

of mesigdemide to be 1 milligram

15:45

given once daily in combination

15:47

with dexamethasone for 21 days, followed

15:51

by 7 days off in each 28-day cycle. In

15:55

phase 2, in which 101 patients

15:58

with heavily pretreated multiple myeloma

16:01

received the dose identified in phase one.

16:03

The most common adverse events, almost

16:06

all of which proved to be reversible, included

16:08

neutropenia in 77%

16:11

of the patients and infection in 65%, grade

16:14

three 29%, grade four 6%. No

16:18

unexpected toxic effects were encountered.

16:21

An overall response occurred in 41% of

16:24

the patients. The median

16:26

duration of response was 7.6 months, and

16:30

the median progression free survival

16:32

was 4.4 months, with a median

16:34

follow up of 7.5 months. The

16:38

all oral combination of mesigdemide

16:40

plus dexamethasone showed promising

16:43

efficacy in patients with heavily

16:45

pretreated multiple myeloma, with

16:47

treatment related adverse events consisting

16:50

mainly of myelotoxic effects.

16:54

In a science behind the study editorial,

16:57

Jake Short from Monash University,

16:59

Clayton, Victoria, Australia writes

17:02

that despite a plethora of recent therapeutic

17:05

advances, multiple myeloma remains

17:08

incurable. The median survival is

17:10

just above five years. A

17:12

cancer of antibody producing

17:14

cells, multiple myeloma is peculiar

17:17

in that it is sensitive to drugs that

17:19

disturb protein homeostasis,

17:22

including proteasome inhibitors and

17:24

thalidomide analogs. In

17:26

most patients though, malignant plasma

17:29

cells eventually develop resistance

17:31

to such agents. Of interest

17:33

therefore, is this phase one two clinical

17:36

trial reported by Richardson and colleagues

17:38

that reflects a growing scientific

17:40

understanding of drug target

17:42

engagement. Richardson and

17:44

colleagues found that an overall

17:47

response to mesigdemide occurred

17:49

in 41% of the patients in

17:52

a heavily pretreated and imid

17:54

immunomodulatory imide drug

17:57

refractory population, which is

17:59

an encouraging encouraging outcome for what

18:01

is called an all-oral dexamethasone

18:04

doublet. However, the effect

18:06

on median progression-free survival, 4.4 months,

18:08

was modest. In

18:12

theory, mesigdemide is an

18:14

immune-modulatory imide drug,

18:16

but it's called a cell-mod, short

18:19

for cereblin E3 ligase-modulatory

18:23

drug. Cell-mods are rationally

18:25

developed with the use of deep insight

18:27

into the structural biology of the

18:30

cereblin imide-neo-substrate

18:32

axis. Although mesigdemide

18:34

is active in cells with low levels

18:37

of cereblin, it cannot work in

18:39

the complete absence of cereblin

18:41

or overcome cereblin-independent

18:43

resistance mechanisms. Further

18:46

studies will determine the safety and efficacy

18:48

of mesigdemide concomitant with

18:51

other anti-myeloma therapies. Concurrently,

18:54

the myeloma field is being revolutionized

18:57

by immunotherapies such as bispecific

18:59

antibodies and chimeric antigen

19:02

receptor T-cells. Because

19:04

mesigdemide bears the same

19:06

immunostimulatory hallmarks of

19:08

its imide forebears, it may also

19:11

partner well with these immune-effector

19:13

cell-based approaches. Asthma

19:17

in Adults, a clinical practice

19:20

article by Giselle Mosnaim from

19:22

the North Shore University Health System,

19:24

Evanston, Illinois. The

19:27

National Asthma Education and Prevention

19:29

Program Expert Panel 3

19:31

report defines asthma as

19:33

a complex disorder characterized

19:36

by variable and recurring symptoms,

19:38

airflow obstruction, bronchial

19:40

hyper-responsiveness, and an underlying

19:43

inflammation, and notes that

19:45

the interaction of these features of asthma

19:47

determines the clinical manifestations

19:50

and severity of asthma and the response

19:52

to treatment. Asthma guidelines

19:55

state that a definitive diagnosis of asthma

19:57

should be based on the presence of character.

20:01

symptoms such as wheeze, cough,

20:03

chest tightness and shortness of breath, and

20:06

variable expiratory airflow obstruction.

20:09

The three main goals of asthma management

20:11

are control of symptoms, reduction in

20:14

risk of exacerbations, and minimization

20:16

of adverse effects of medications.

20:19

Every visit should include a review

20:21

of inhaler technique, medication adherence,

20:24

coexisting conditions, ongoing

20:27

exposures to environmental triggers,

20:29

and confirmation of a correct diagnosis

20:32

of asthma. In patients with mild

20:34

asthma, the preferred treatment option is

20:37

an inhaled glucocorticoid for motorol

20:39

combination as needed, and

20:41

alternative options include the use of combination

20:44

inhaled glucocorticoid albuterol

20:47

as needed, or low-dose maintenance

20:49

inhaled glucocorticoid plus

20:51

a short-acting beta-2 agonist

20:54

reliever as needed. Combination

20:57

inhaled glucocorticoid for motorol maintenance

20:59

and reliever therapy is the preferred

21:02

treatment for moderate to severe asthma

21:04

as compared with an inhaled glucocorticoid

21:07

with long-acting beta-2 agonist

21:09

maintenance plus as needed short-acting

21:11

beta-2 agonist reliever therapy.

21:16

A 37-year-old man with a rash,

21:19

a case record of the Massachusetts General

21:21

Hospital by Frank Vollpicelli and colleagues.

21:24

A 37-year-old man was admitted to the

21:26

hospital because of a rash. Nine

21:29

days earlier, a diffuse rash

21:31

had developed on the hands and feet. During

21:34

the next three days, the rash spread

21:36

proximately to the arms and the legs,

21:39

then extended to the groin, trunk, and

21:41

face. Six days before

21:43

this admission, the patient noticed new

21:46

throat tightness and lip swelling. Three

21:48

days before this admission, when difficulty

21:50

with swallowing and shortness of breath developed,

21:53

the patient sought evaluation at

21:55

an emergency department. Vital signs

21:57

and results of routine laboratory tests

21:59

were were reportedly normal and the patient

22:02

was discharged home. During

22:04

the next three days, the symptoms did not

22:06

abate and the patient sought evaluation

22:09

in the emergency department of this hospital.

22:12

The patient described having difficulty

22:14

with opening his mouth because of pain

22:16

in his lips as well as mild

22:18

difficulty with swallowing and breathing.

22:21

The rash had become more confluent

22:23

over the arms, legs, chest, back, face,

22:26

and groin, and there was increased

22:28

redness and swelling. Laboratory

22:31

evaluation revealed lymphopenia

22:34

and an elevated globulin gap,

22:36

which is the difference between levels of

22:38

total protein and albumin. Acute

22:42

HIV infection frequently manifests

22:45

with systemic symptoms, including

22:47

fatigue, fever, myalgias, lymphadenopathy,

22:51

and pharyngitis or mucositis,

22:53

which may cause oral ulcerations.

22:56

Patients may also have headache, nausea,

22:58

diarrhea, or a maculopapular

23:01

rash that may involve the palms

23:04

and soles. Many of the features

23:06

of this patient's presentation fit neatly

23:09

into the symptoms of acute or early HIV

23:11

infection. When acute HIV

23:14

infection is suspected, it is important

23:16

to also consider co-infection

23:18

with other sexually transmitted diseases.

23:21

The most common manifestations of secondary

23:24

syphilis is a diffuse maculopapular

23:27

rash that classically includes

23:29

the palms and soles, as

23:31

was seen in this patient. A

23:35

doctrine in name only,

23:37

strengthening prohibitions against

23:40

the corporate practice of medicine, a

23:42

perspective by Jane Zhu from

23:44

Oregon Health and Science University, Portland.

23:48

In the late 1800s, corporations

23:51

began hiring US physicians and

23:54

profiting directly from their services

23:56

without being bound by professional

23:59

ethics.

24:01

concerned about this commercialization

24:03

of medicine and potentially to avoid competition

24:06

and tighter government regulation, the

24:08

American Medical Association revised

24:10

its principles of medical ethics, condemning

24:13

as unprofessional any contractual

24:16

arrangement that interfered with

24:18

physician practice. States

24:20

soon followed by adopting the Corporate

24:23

Practice of Medicine, CPOM, doctrine,

24:26

which generally bars unlicensed

24:29

lay entities from owning or

24:31

controlling medical practices. Today,

24:34

rapid corporatization of healthcare

24:36

raises new questions about the usefulness

24:38

of the CPOM doctrine. Why,

24:41

despite the existence of CPOM

24:44

laws in many states, has the

24:46

corporate land grab in healthcare

24:49

continued? And how can the CPOM

24:51

doctrine be strengthened to protect

24:54

both the medical profession and the public

24:56

interest? A renewed examination

24:59

of CPOM laws may be warranted.

25:02

States seeking to counter the corporatization

25:05

of medicine could strengthen their CPOM

25:07

laws in several ways. First,

25:10

they could close existing loopholes

25:12

that permit corporate ownership. Second,

25:16

states could regulate the Management

25:18

Services Organization, MSO,

25:20

model. As currently proposed

25:22

in California, states could require

25:25

that professional corporations retain

25:27

ultimate control over both clinical

25:30

and business decisions and require

25:32

maintenance of physician, board seats,

25:35

and equity in the practice when

25:37

there are ownership changes. Third,

25:40

states could loosen the grip that

25:43

corporate investors can have on

25:45

clinical practices by barring

25:47

physician contracts from including

25:49

restrictive provisions and protecting

25:52

whistleblowers from retaliation when

25:54

they raise patient safety or ethical

25:57

concerns.

25:58

Finally, broader information.

25:59

enforcement is needed if CPOM restrictions

26:02

are to have meaningful effects. If

26:05

sharpened, honed, and enforced,

26:07

CPOM laws could be useful

26:09

guardrails to ensure that physicians'

26:12

clinical decisions and professional autonomy

26:15

aren't superseded by corporate

26:18

pressures. The

26:20

Accelerated Approval Program for

26:22

Cancer Drugs, Finding the Right

26:25

Balance. A Perspective by Bisal

26:27

Gawali from Queen's University, Kingston,

26:30

Ontario, Canada. The

26:33

Food and Drug Administration approves about

26:35

two-thirds of new cancer drugs on

26:37

the basis of clinical trials that

26:40

use surrogate endpoints, such

26:42

as laboratory values or radiographic

26:45

findings, rather than clinical

26:47

endpoints that assess survival

26:49

or how patients feel or function.

26:52

The Accelerated Approval Program allows

26:54

drugs designed to treat serious conditions

26:56

for which there is an unmet medical need

26:59

to be approved on the basis of changes

27:01

in surrogate measures that are only

27:03

reasonably expected to predict

27:06

clinical outcomes. Because

27:08

in certain fields of medicine, such

27:10

as cancer, a drug's effects on

27:12

surrogate measures, such as tumor

27:15

size, are often more pronounced

27:17

and occur more rapidly than effects on

27:19

a patient's clinical status, trials

27:22

focused on surrogate measures can

27:24

enroll fewer patients and can

27:26

be completed more quickly than

27:28

trials with clinical endpoints, thereby

27:31

enabling products to reach the market

27:33

earlier. Since clinical endpoints,

27:36

such as survival, are generally

27:38

what matter to patients, however, the

27:41

FDA requires that the clinical

27:43

benefits of drugs granted accelerated

27:45

approval be confirmed in subsequent

27:48

trials. Implementation of

27:50

the Accelerated Approval Program has

27:52

been rocky in recent years. These

27:55

authors and others have called for reform

27:58

of the Accelerated Approval Program. and

28:00

Congress enacted several critical changes

28:03

as part of the Food and Drug Omnibus

28:05

Reform Act of 2022. Recently,

28:09

the FDA proposed guidance that would

28:11

update this pathway for cancer drugs.

28:14

Although its draft guidance includes important

28:16

provisions, these authors discuss

28:19

ways the agency could go further

28:22

to ensure that the accelerated approval

28:24

program provides the most possible

28:26

benefit for patients with cancer.

28:31

A shared mission, a perspective

28:33

by Howard Holtz from the Kupermann

28:35

Barnabas Medical Center, Livingston,

28:38

New Jersey. One of the joys

28:40

of practicing medicine is collaborating

28:43

with other practitioners. As a

28:45

generalist physician in internal

28:47

medicine, Dr. Holtz has teamed

28:49

up with many specialists from acupuncturists

28:52

to zoonoses experts to

28:55

try to solve problems for patients. The

28:57

process is exciting, marked

29:00

by common purpose and mutual

29:02

learning as they collaborate to find safer

29:04

paths for patients. In healthcare,

29:07

colleagues make Dr. Holtz' climb

29:09

easier, especially when he faces the

29:11

most difficult clinical challenges, and

29:13

for patients, knowing that their care

29:16

team is working together provides solace

29:18

and boosts confidence in the medical profession.

29:21

Unfortunately, this joy is a

29:23

fast-receiving light in healthcare.

29:26

Healthcare in Dr. Holtz' community has

29:28

been transformed in the past ten years,

29:31

mirroring the national trend of

29:33

business consolidation. It is

29:35

now dominated by two large

29:37

entities, one a Leviathan

29:40

hospital system, the other an outpatient

29:42

clinic system that was owned by private

29:45

equity firms and was recently resold

29:48

to a corporation. Dr. Holtz

29:50

remains in the shrinking minority of

29:52

physicians who own their own small

29:55

private practices. Even if

29:57

the consolidations continue and practices

29:59

continue, like his vanish, Dr.

30:01

Holtz believes that the principle of collaborative

30:04

care in the patient's interest must

30:07

be protected as a trust between

30:09

physician and patient. Though

30:11

the culture of corporate care discourages

30:14

communication to professionals outside

30:16

a particular system, physicians have

30:18

the autonomy and ethical responsibility

30:21

to work together for the benefit

30:24

of their patients. Dr. Holtz

30:26

asks his fellow practitioners to

30:28

respect the necessity of sharing

30:31

information with one another, regardless

30:33

of the changing landscape of health

30:36

care delivery. In

30:39

our images in Clinical Medicine, a

30:42

46-year-old woman presented with shortness

30:44

of breath, dry cough, and painful

30:46

rash on the upper arms. Erythematous

30:49

plaques and patches were seen in the lateral

30:52

aspects of the upper arms, and Erythematous

30:55

patches, papules, and pustules

30:57

were seen on the ventral surfaces

30:59

of the hands. These findings,

31:01

known as sleeve sign and

31:04

inverse gatrons papules, respectively,

31:07

are rare cutaneous findings associated

31:10

with dermatomyositis. Laboratory

31:13

testing showed strong positivity

31:15

for anti-melanoma differentiation-associated

31:18

protein 5, anti-MDA5

31:22

antibody. Progressive

31:24

dyspnea developed in the patient. A

31:26

final diagnosis of anti-MDA5

31:30

hypomyopathic dermatomyositis

31:33

with rapidly progressive interstitial

31:36

lung disease was made. Despite

31:38

the use of aggressive immunosuppressive

31:41

therapy, the patient died from

31:43

respiratory failure two months after

31:46

her initial presentation. In

31:49

another image, a 34-year-old

31:51

man had shortness of breath that worsened

31:53

when he lay flat. The abdominal

31:56

wall paradoxically moved

31:58

inward during inspiration. and

32:00

outward during expiration when

32:03

the patient lay supine. Shown

32:05

in a video at NEJM.org.

32:07

A diagnosis of bilateral diaphragmatic

32:10

paralysis was made. This

32:13

concludes our summary. Let

32:16

us know what you think about our audio

32:18

summaries. Any comments or suggestions

32:21

may be sent to audio at

32:23

NEJM.org.

32:26

Thank you for listening.