A 16-year-old African-American girl is brought in by her mother for evaluation of skin changes affecting both arms: small, round, slightly scaly, 2- to 3-cm patches on the triceps, antecubitals, and deltoids. The changes manifested in early spring and worsened with the arrival of summer.

The condition has been previously diagnosed as vitiligo by her primary care provider and as fungal infection by an urgent care provider. Nystatin cream and clotrimazole cream have had no effect.

The patient’s history includes eczema, extensive atopy manifesting with seasonal allergies, and childhood asthma. Her siblings also had these problems.

EXAMINATION

Extensive, mottled hypopigmentation is noted on the skin of both arms, in stark contrast to the patient’s type V skin. Very little scale is seen. There are focal areas of slight erythema around the antecubital folds.

What is the diagnosis?

DISCUSSION

This phenomenon is so common in dermatology clinics that it’s a rare day when we don’t see it. This form of hypopigmentation is pityriasis alba (PA), in which areas of eczema don’t tan at all while the surrounding skin darkens with sun exposure. The lateral aspects of the arms are often affected (sparing the sun-protected medial aspects), as are the sides of the face and the posterior neck. The contrast is striking, especially on those with darker skin.

PA occurs mostly in children and young adults, becoming less frequent with age. It differs from vitiligo in that PA involves seasonal, partial pigment loss; vitiligo by contrast manifests with complete pigment loss (leaving utterly white skin) that is almost always permanent.

Treatment consists of sun protection, moisturization to prevent eczema, and use of class IV steroid creams or ointments when lesions appear. Even without treatment, PA usually clears during the winter months—when the surrounding skin loses its tan—only to recur the following spring.

TAKE-HOME LEARNING POINTS

• Pityriasis alba (PA) occurs when patches of eczema fail to tan, producing marked contrast between them and the normal surrounding skin; it is often mistaken for fungal infection.
• PA favors the antecubital, deltoid, and lateral tricep areas, as well as the lateral face.
• PA is more common in atopic individuals who are prone to eczema and appears more dramatic in those with darker skin.
• Vitiligo is a major item in the differential, but color loss with PA is only partial (rather than permanent) and almost always resolves in the winter.
• Once color is lost with PA, treatment is largely ineffective. It is then best to use preventive measures (eg, sunscreen and moisturizer), plus/minus topical steroid creams, for the eczema.

A 16-year-old African-American girl is brought in by her mother for evaluation of skin changes affecting both arms: small, round, slightly scaly, 2- to 3-cm patches on the triceps, antecubitals, and deltoids. The changes manifested in early spring and worsened with the arrival of summer.

The condition has been previously diagnosed as vitiligo by her primary care provider and as fungal infection by an urgent care provider. Nystatin cream and clotrimazole cream have had no effect.

The patient’s history includes eczema, extensive atopy manifesting with seasonal allergies, and childhood asthma. Her siblings also had these problems.

EXAMINATION

Extensive, mottled hypopigmentation is noted on the skin of both arms, in stark contrast to the patient’s type V skin. Very little scale is seen. There are focal areas of slight erythema around the antecubital folds.

What is the diagnosis?

DISCUSSION

This phenomenon is so common in dermatology clinics that it’s a rare day when we don’t see it. This form of hypopigmentation is pityriasis alba (PA), in which areas of eczema don’t tan at all while the surrounding skin darkens with sun exposure. The lateral aspects of the arms are often affected (sparing the sun-protected medial aspects), as are the sides of the face and the posterior neck. The contrast is striking, especially on those with darker skin.

PA occurs mostly in children and young adults, becoming less frequent with age. It differs from vitiligo in that PA involves seasonal, partial pigment loss; vitiligo by contrast manifests with complete pigment loss (leaving utterly white skin) that is almost always permanent.

Treatment consists of sun protection, moisturization to prevent eczema, and use of class IV steroid creams or ointments when lesions appear. Even without treatment, PA usually clears during the winter months—when the surrounding skin loses its tan—only to recur the following spring.

TAKE-HOME LEARNING POINTS

• Pityriasis alba (PA) occurs when patches of eczema fail to tan, producing marked contrast between them and the normal surrounding skin; it is often mistaken for fungal infection.
• PA favors the antecubital, deltoid, and lateral tricep areas, as well as the lateral face.
• PA is more common in atopic individuals who are prone to eczema and appears more dramatic in those with darker skin.
• Vitiligo is a major item in the differential, but color loss with PA is only partial (rather than permanent) and almost always resolves in the winter.
• Once color is lost with PA, treatment is largely ineffective. It is then best to use preventive measures (eg, sunscreen and moisturizer), plus/minus topical steroid creams, for the eczema.

A 16-year-old African-American girl is brought in by her mother for evaluation of skin changes affecting both arms: small, round, slightly scaly, 2- to 3-cm patches on the triceps, antecubitals, and deltoids. The changes manifested in early spring and worsened with the arrival of summer.

The condition has been previously diagnosed as vitiligo by her primary care provider and as fungal infection by an urgent care provider. Nystatin cream and clotrimazole cream have had no effect.

The patient’s history includes eczema, extensive atopy manifesting with seasonal allergies, and childhood asthma. Her siblings also had these problems.

EXAMINATION

Extensive, mottled hypopigmentation is noted on the skin of both arms, in stark contrast to the patient’s type V skin. Very little scale is seen. There are focal areas of slight erythema around the antecubital folds.

What is the diagnosis?

DISCUSSION

This phenomenon is so common in dermatology clinics that it’s a rare day when we don’t see it. This form of hypopigmentation is pityriasis alba (PA), in which areas of eczema don’t tan at all while the surrounding skin darkens with sun exposure. The lateral aspects of the arms are often affected (sparing the sun-protected medial aspects), as are the sides of the face and the posterior neck. The contrast is striking, especially on those with darker skin.

PA occurs mostly in children and young adults, becoming less frequent with age. It differs from vitiligo in that PA involves seasonal, partial pigment loss; vitiligo by contrast manifests with complete pigment loss (leaving utterly white skin) that is almost always permanent.

Treatment consists of sun protection, moisturization to prevent eczema, and use of class IV steroid creams or ointments when lesions appear. Even without treatment, PA usually clears during the winter months—when the surrounding skin loses its tan—only to recur the following spring.

TAKE-HOME LEARNING POINTS

• Pityriasis alba (PA) occurs when patches of eczema fail to tan, producing marked contrast between them and the normal surrounding skin; it is often mistaken for fungal infection.
• PA favors the antecubital, deltoid, and lateral tricep areas, as well as the lateral face.
• PA is more common in atopic individuals who are prone to eczema and appears more dramatic in those with darker skin.
• Vitiligo is a major item in the differential, but color loss with PA is only partial (rather than permanent) and almost always resolves in the winter.
• Once color is lost with PA, treatment is largely ineffective. It is then best to use preventive measures (eg, sunscreen and moisturizer), plus/minus topical steroid creams, for the eczema.

ORLANDO – A novel orally administered antifungal showed a favorable safety and efficacy profile in the treatment of distal lateral subungual onychomycosis, in a phase IIB study presented at the annual meeting of the American Academy of Dermatology.

In the RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study, a randomized, double-blind, placebo-controlled, dose-ranging trial, 259 adults with moderate to severe distal lateral subungual onychomycosis of the large toenail were assigned to either one of four treatment arms. They were given the antifungal, currently named VT-1161, a selective CYP51 inhibitor, at doses of 300 mg or 600 mg once weekly for 10 or 22 weeks, after receiving daily loading doses for the initial 2 weeks. The trial evaluated two dose levels of VT-1161 (300 mg and 600 mg) administered once weekly for either 10 or 22 weeks following an initial 2-week, once-daily loading dose period.

At baseline, the average involvement of the large toenail was 46%, with an average of 4.6 toenails affected. In the intent-to-treat analysis, at 48 weeks, complete cure rates in the four study drug arms ranged from 32% to 42%, compared with 0% in the placebo arm.

Amir Tavakkol, PhD, chief development officer at Viamet Pharmaceuticals, which is developing VT01161, presented the study findings during a late breaking clinical session at the meeting.

Adverse event rates and discontinuation rates were comparable to placebo through week 60, with no patients discontinuing due to any laboratory abnormalities. Nausea and muscle spasms were the most commonly reported adverse events, which Dr. Tavakkol said seemed to occur in patients given the higher doses. VT-1161 is also being studied for treatment of vulvovaginal candidiasis. In October 2016, the FDA granted the drug Qualified Infectious Disease Product and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis, according to the company.

Viamet sponsored the study and Dr. Tavakkol is an employee of the company.

[email protected]

On Twitter @whitneymcknight

ORLANDO – A novel orally administered antifungal showed a favorable safety and efficacy profile in the treatment of distal lateral subungual onychomycosis, in a phase IIB study presented at the annual meeting of the American Academy of Dermatology.

In the RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study, a randomized, double-blind, placebo-controlled, dose-ranging trial, 259 adults with moderate to severe distal lateral subungual onychomycosis of the large toenail were assigned to either one of four treatment arms. They were given the antifungal, currently named VT-1161, a selective CYP51 inhibitor, at doses of 300 mg or 600 mg once weekly for 10 or 22 weeks, after receiving daily loading doses for the initial 2 weeks. The trial evaluated two dose levels of VT-1161 (300 mg and 600 mg) administered once weekly for either 10 or 22 weeks following an initial 2-week, once-daily loading dose period.

At baseline, the average involvement of the large toenail was 46%, with an average of 4.6 toenails affected. In the intent-to-treat analysis, at 48 weeks, complete cure rates in the four study drug arms ranged from 32% to 42%, compared with 0% in the placebo arm.

Amir Tavakkol, PhD, chief development officer at Viamet Pharmaceuticals, which is developing VT01161, presented the study findings during a late breaking clinical session at the meeting.

Adverse event rates and discontinuation rates were comparable to placebo through week 60, with no patients discontinuing due to any laboratory abnormalities. Nausea and muscle spasms were the most commonly reported adverse events, which Dr. Tavakkol said seemed to occur in patients given the higher doses. VT-1161 is also being studied for treatment of vulvovaginal candidiasis. In October 2016, the FDA granted the drug Qualified Infectious Disease Product and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis, according to the company.

Viamet sponsored the study and Dr. Tavakkol is an employee of the company.

[email protected]

On Twitter @whitneymcknight

ORLANDO – A novel orally administered antifungal showed a favorable safety and efficacy profile in the treatment of distal lateral subungual onychomycosis, in a phase IIB study presented at the annual meeting of the American Academy of Dermatology.

In the RENOVATE (Restoring Nail: An Oral VT-1161 Tablet Evaluation) study, a randomized, double-blind, placebo-controlled, dose-ranging trial, 259 adults with moderate to severe distal lateral subungual onychomycosis of the large toenail were assigned to either one of four treatment arms. They were given the antifungal, currently named VT-1161, a selective CYP51 inhibitor, at doses of 300 mg or 600 mg once weekly for 10 or 22 weeks, after receiving daily loading doses for the initial 2 weeks. The trial evaluated two dose levels of VT-1161 (300 mg and 600 mg) administered once weekly for either 10 or 22 weeks following an initial 2-week, once-daily loading dose period.

At baseline, the average involvement of the large toenail was 46%, with an average of 4.6 toenails affected. In the intent-to-treat analysis, at 48 weeks, complete cure rates in the four study drug arms ranged from 32% to 42%, compared with 0% in the placebo arm.

Amir Tavakkol, PhD, chief development officer at Viamet Pharmaceuticals, which is developing VT01161, presented the study findings during a late breaking clinical session at the meeting.

Adverse event rates and discontinuation rates were comparable to placebo through week 60, with no patients discontinuing due to any laboratory abnormalities. Nausea and muscle spasms were the most commonly reported adverse events, which Dr. Tavakkol said seemed to occur in patients given the higher doses. VT-1161 is also being studied for treatment of vulvovaginal candidiasis. In October 2016, the FDA granted the drug Qualified Infectious Disease Product and Fast Track designations for the treatment of recurrent vulvovaginal candidiasis, according to the company.

Viamet sponsored the study and Dr. Tavakkol is an employee of the company.

[email protected]

On Twitter @whitneymcknight

Despite a record number of applicants and slots filled for first-year residents on the 2017 Match Day, growth in all surgery positions continued to be outpaced by growth in other specialties.

“While it is encouraging to see that the number of categorical surgery positions offered has increased by 101 since 2013, representing an increase of 8.6%, over the same period, the number of positions offered in emergency medicine and family medicine positions have each increased by over 300, representing increases of 17.4% and 11.5%, respectively, and the number of internal medicine positions has increased by over 900, representing an increase of 15.2%,” Patrick Bailey, MD, FACS, medical director of advocacy for the Division of Advocacy and Health Policy at the American College of Surgeons. “The fact that over 35,969 applicants submitted program choices and only 27,688 matched into a PGY-1 position is yet another indication of the need to expand the number of graduate medical education positions available,” he added.

[email protected]

Despite a record number of applicants and slots filled for first-year residents on the 2017 Match Day, growth in all surgery positions continued to be outpaced by growth in other specialties.

“While it is encouraging to see that the number of categorical surgery positions offered has increased by 101 since 2013, representing an increase of 8.6%, over the same period, the number of positions offered in emergency medicine and family medicine positions have each increased by over 300, representing increases of 17.4% and 11.5%, respectively, and the number of internal medicine positions has increased by over 900, representing an increase of 15.2%,” Patrick Bailey, MD, FACS, medical director of advocacy for the Division of Advocacy and Health Policy at the American College of Surgeons. “The fact that over 35,969 applicants submitted program choices and only 27,688 matched into a PGY-1 position is yet another indication of the need to expand the number of graduate medical education positions available,” he added.

[email protected]

Despite a record number of applicants and slots filled for first-year residents on the 2017 Match Day, growth in all surgery positions continued to be outpaced by growth in other specialties.

“While it is encouraging to see that the number of categorical surgery positions offered has increased by 101 since 2013, representing an increase of 8.6%, over the same period, the number of positions offered in emergency medicine and family medicine positions have each increased by over 300, representing increases of 17.4% and 11.5%, respectively, and the number of internal medicine positions has increased by over 900, representing an increase of 15.2%,” Patrick Bailey, MD, FACS, medical director of advocacy for the Division of Advocacy and Health Policy at the American College of Surgeons. “The fact that over 35,969 applicants submitted program choices and only 27,688 matched into a PGY-1 position is yet another indication of the need to expand the number of graduate medical education positions available,” he added.

[email protected]

NATIONAL HARBOR, MD. – Unlike mutation, methylation of homologous recombination DNA repair pathway genes was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer, according to molecular and clinical analyses of 332 patients.

“Methylation may be more readily reversed than mutation, allowing more rapid development of platinum resistance and negating any impact on overall survival,” said Sarah Bernards, a second-year medical student at the University of Washington, Seattle, who presented the findings at the annual meeting of the Society of Gynecologic Oncology.

Amy Karon/Frontline Medical News

NATIONAL HARBOR, MD. – Unlike mutation, methylation of homologous recombination DNA repair pathway genes was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer, according to molecular and clinical analyses of 332 patients.

“Methylation may be more readily reversed than mutation, allowing more rapid development of platinum resistance and negating any impact on overall survival,” said Sarah Bernards, a second-year medical student at the University of Washington, Seattle, who presented the findings at the annual meeting of the Society of Gynecologic Oncology.

Amy Karon/Frontline Medical News

NATIONAL HARBOR, MD. – Unlike mutation, methylation of homologous recombination DNA repair pathway genes was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer, according to molecular and clinical analyses of 332 patients.

“Methylation may be more readily reversed than mutation, allowing more rapid development of platinum resistance and negating any impact on overall survival,” said Sarah Bernards, a second-year medical student at the University of Washington, Seattle, who presented the findings at the annual meeting of the Society of Gynecologic Oncology.

Amy Karon/Frontline Medical News

While much of the drama surrounding the Trump administration’s immigration policy has centered on the so-called travel ban, changes to a specialized visa program may have a bigger impact on foreign doctors in the United States and the employers who hope to hire them.

Starting April 3, U.S. Citizenship and Immigration Services (USCIS) is temporarily suspending its expedited processing of H-1B visas, a primary route used by highly skilled foreign physicians and students to practice and train in the United States.

Under the existing “premium processing” system, foreign medical graduates – usually sponsored by a U.S. institution – pay an extra $1,200 when submitting an H-1B petition to ensure a response from USCIS within 15 days. Standard processing of H-1B applications takes 6-10 months. USCIS is terminating the expedited reviews for up to 6 months to address long-standing H-1B petitions and to reduce backlogs, according to a March announcement by the agency.

In the meantime, many foreign medical students and physicians will lose top training spots and jobs as their H-1B applications linger in the system, said Jennifer A. Minear, a Richmond, Va.–based attorney and national treasurer for the American Immigration Lawyers Association.

Changing rules, uncertain futures

The H-1B processing change has left Amr Marawan, MD, unsure if a job offer may fall through and if he will be able to work in the United States at all over the next year.

Dr. Marawan, a native of Cairo, Egypt, will finish his internal medicine residency at the University of Tennessee, Chattanooga, in June and had planned to pursue a cardiology fellowship under a continuation of his J-1 alien physician visa. After the 2016 election, he decided instead to take a position as assistant professor of internal medicine at Virginia Commonwealth University in Richmond.

Courtesy Amr Marawan

Foreign medical students face rough road

Medical students applying for residencies and fellowships may also be detoured by the premium processing ban. Students who planned to train under an H-1B visa had to wait until Match Day on March 17 to file their H-1B petitions, Ms. Minear said. There is little chance they can complete all paperwork and state approvals needed in order to submit an H-1B application before April 3.

“What this really means is that physicians effectively cannot do their residencies or fellowships in H-1B status this year because they cannot file the petitions in time for a July 1 start date,” Ms. Minear said. “Effectively, what it does is force all foreign doctors who want to do residency or fellowship in the U.S. to do their training in J-1 status.”

A large number of foreign medical students already complete their training in J-1 status; however, many residency and fellowship programs agree to sponsor students in H-1B status as an attractive recruiting incentive for top talent, Ms. Minear said. Foreign doctors often prefer the latter status because they are exempt from the 2-year requirement to return home.

Foreign medical students matching to residency programs generally have the option to apply for a J-1 visa and can still train in the United States, said Matthew Shick, JD, government relations director for the Association of American Medical Colleges. He noted that the premium processing suspension will have a greater impact on faculty, scientists, and hospital staff.

However, medical students applying for J-1 visas also may experience processing delays because of President Trump’s March 6 Executive Order on immigration. A provision in that order increases uniform screening procedures for all visa classes and nationalities, while another provision suspends the Visa Interview Waiver Program. The suspension means that certain visa applicants seeking to renew a visa must be interviewed in person by a consular officer. The Hawaii federal court that blocked much of the that Executive Order did not halt the additional screening requirements or stay the Visa Interview Waiver Program rollback. Both provisions remain in effect.

Taskforce requests carve-out

The IMG Taskforce is urging USCIS to exempt physicians from the premium processing ban. In a March 8 letter to the agency, the task force outlined examples of how IMGs benefit the country and described how application delays could harm patient care and impair U.S. medical institutions.

“The hope is that this would encourage a review and a rethink of that shift and that upon that review, H-1B cap exempt petitions would across the board be considered for continued premium processing,” Ms. Harris said in an interview. “And/or, perhaps a greater lead time than merely 4 weeks’ notice [would be granted] so that people may be able complete their obligations.”

A group of U.S. senators also has requested that USCIS reconsider the premium processing suspension as it relates to physicians. Sen. Amy Klobuchar (D-Minn.) said that the suspension will exacerbate physician shortages, particularly in rural areas.

“The [waiver] program has helped address chronic physician shortages in rural America and other underserved areas for over two decades,” Sen. Klobuchar wrote in a March 10 letter. “We understand USCIS is facing a backlog, but USCIS has addressed this problem in the past without suspending premium processing for Conrad 30 doctors. We have every faith that USCIS can address its administrative needs without sacrificing support to this successful, time-tested program.”

Ms. Gwathmey would not comment on whether USCIS would consider an exception to the suspension for physicians. As with all affected workloads, USCIS is cognizant of processing time sensitivities for IMGs who are applying to change their status to H-1B, Ms. Gwathmey said in an interview.

“USCIS will be monitoring this workload during the coming months and will evaluate any time sensitive impacts prior to the resumption of premium processing services,” she said.

Dr. Marawan meanwhile is exhausting all efforts to keep his job offer. He is considering the option of filing an H-1B application now, before his state approval comes through, in the hopes of securing premium processing, he said. However, the option comes with a catch. Foreign doctors can file an H-1B petition without a J-1 waiver, but they can’t request a change of status from J-1 to H-1B without leaving the United States unless they have the waiver. This means if Dr. Marawan’s petition is approved by USCIS, he must go back to Egypt to apply for an H-1B visa at the U.S. Embassy in Cairo.

But with increased security delays for visa applicants and reports of foreign travelers being denied entry at U.S. airports, Dr. Marawan said he is fearful.

“Once you step out [of the United States], you never know what’s going to happen,” he said. “Sometimes visas get struck. Sometimes there’s a lot of security checks. Egypt is not included in the travel ban, but it’s always hard. There’s a lot of stories of people who are rejected getting their visas for different reasons. It’s worrisome.”

[email protected]
 

On Twitter @legal_med

While much of the drama surrounding the Trump administration’s immigration policy has centered on the so-called travel ban, changes to a specialized visa program may have a bigger impact on foreign doctors in the United States and the employers who hope to hire them.

Starting April 3, U.S. Citizenship and Immigration Services (USCIS) is temporarily suspending its expedited processing of H-1B visas, a primary route used by highly skilled foreign physicians and students to practice and train in the United States.

Under the existing “premium processing” system, foreign medical graduates – usually sponsored by a U.S. institution – pay an extra $1,200 when submitting an H-1B petition to ensure a response from USCIS within 15 days. Standard processing of H-1B applications takes 6-10 months. USCIS is terminating the expedited reviews for up to 6 months to address long-standing H-1B petitions and to reduce backlogs, according to a March announcement by the agency.

In the meantime, many foreign medical students and physicians will lose top training spots and jobs as their H-1B applications linger in the system, said Jennifer A. Minear, a Richmond, Va.–based attorney and national treasurer for the American Immigration Lawyers Association.

Changing rules, uncertain futures

The H-1B processing change has left Amr Marawan, MD, unsure if a job offer may fall through and if he will be able to work in the United States at all over the next year.

Dr. Marawan, a native of Cairo, Egypt, will finish his internal medicine residency at the University of Tennessee, Chattanooga, in June and had planned to pursue a cardiology fellowship under a continuation of his J-1 alien physician visa. After the 2016 election, he decided instead to take a position as assistant professor of internal medicine at Virginia Commonwealth University in Richmond.

Courtesy Amr Marawan

Foreign medical students face rough road

Medical students applying for residencies and fellowships may also be detoured by the premium processing ban. Students who planned to train under an H-1B visa had to wait until Match Day on March 17 to file their H-1B petitions, Ms. Minear said. There is little chance they can complete all paperwork and state approvals needed in order to submit an H-1B application before April 3.

“What this really means is that physicians effectively cannot do their residencies or fellowships in H-1B status this year because they cannot file the petitions in time for a July 1 start date,” Ms. Minear said. “Effectively, what it does is force all foreign doctors who want to do residency or fellowship in the U.S. to do their training in J-1 status.”

A large number of foreign medical students already complete their training in J-1 status; however, many residency and fellowship programs agree to sponsor students in H-1B status as an attractive recruiting incentive for top talent, Ms. Minear said. Foreign doctors often prefer the latter status because they are exempt from the 2-year requirement to return home.

Foreign medical students matching to residency programs generally have the option to apply for a J-1 visa and can still train in the United States, said Matthew Shick, JD, government relations director for the Association of American Medical Colleges. He noted that the premium processing suspension will have a greater impact on faculty, scientists, and hospital staff.

However, medical students applying for J-1 visas also may experience processing delays because of President Trump’s March 6 Executive Order on immigration. A provision in that order increases uniform screening procedures for all visa classes and nationalities, while another provision suspends the Visa Interview Waiver Program. The suspension means that certain visa applicants seeking to renew a visa must be interviewed in person by a consular officer. The Hawaii federal court that blocked much of the that Executive Order did not halt the additional screening requirements or stay the Visa Interview Waiver Program rollback. Both provisions remain in effect.

Taskforce requests carve-out

The IMG Taskforce is urging USCIS to exempt physicians from the premium processing ban. In a March 8 letter to the agency, the task force outlined examples of how IMGs benefit the country and described how application delays could harm patient care and impair U.S. medical institutions.

“The hope is that this would encourage a review and a rethink of that shift and that upon that review, H-1B cap exempt petitions would across the board be considered for continued premium processing,” Ms. Harris said in an interview. “And/or, perhaps a greater lead time than merely 4 weeks’ notice [would be granted] so that people may be able complete their obligations.”

A group of U.S. senators also has requested that USCIS reconsider the premium processing suspension as it relates to physicians. Sen. Amy Klobuchar (D-Minn.) said that the suspension will exacerbate physician shortages, particularly in rural areas.

“The [waiver] program has helped address chronic physician shortages in rural America and other underserved areas for over two decades,” Sen. Klobuchar wrote in a March 10 letter. “We understand USCIS is facing a backlog, but USCIS has addressed this problem in the past without suspending premium processing for Conrad 30 doctors. We have every faith that USCIS can address its administrative needs without sacrificing support to this successful, time-tested program.”

Ms. Gwathmey would not comment on whether USCIS would consider an exception to the suspension for physicians. As with all affected workloads, USCIS is cognizant of processing time sensitivities for IMGs who are applying to change their status to H-1B, Ms. Gwathmey said in an interview.

“USCIS will be monitoring this workload during the coming months and will evaluate any time sensitive impacts prior to the resumption of premium processing services,” she said.

Dr. Marawan meanwhile is exhausting all efforts to keep his job offer. He is considering the option of filing an H-1B application now, before his state approval comes through, in the hopes of securing premium processing, he said. However, the option comes with a catch. Foreign doctors can file an H-1B petition without a J-1 waiver, but they can’t request a change of status from J-1 to H-1B without leaving the United States unless they have the waiver. This means if Dr. Marawan’s petition is approved by USCIS, he must go back to Egypt to apply for an H-1B visa at the U.S. Embassy in Cairo.

But with increased security delays for visa applicants and reports of foreign travelers being denied entry at U.S. airports, Dr. Marawan said he is fearful.

“Once you step out [of the United States], you never know what’s going to happen,” he said. “Sometimes visas get struck. Sometimes there’s a lot of security checks. Egypt is not included in the travel ban, but it’s always hard. There’s a lot of stories of people who are rejected getting their visas for different reasons. It’s worrisome.”

[email protected]
 

On Twitter @legal_med

While much of the drama surrounding the Trump administration’s immigration policy has centered on the so-called travel ban, changes to a specialized visa program may have a bigger impact on foreign doctors in the United States and the employers who hope to hire them.

Starting April 3, U.S. Citizenship and Immigration Services (USCIS) is temporarily suspending its expedited processing of H-1B visas, a primary route used by highly skilled foreign physicians and students to practice and train in the United States.

Under the existing “premium processing” system, foreign medical graduates – usually sponsored by a U.S. institution – pay an extra $1,200 when submitting an H-1B petition to ensure a response from USCIS within 15 days. Standard processing of H-1B applications takes 6-10 months. USCIS is terminating the expedited reviews for up to 6 months to address long-standing H-1B petitions and to reduce backlogs, according to a March announcement by the agency.

In the meantime, many foreign medical students and physicians will lose top training spots and jobs as their H-1B applications linger in the system, said Jennifer A. Minear, a Richmond, Va.–based attorney and national treasurer for the American Immigration Lawyers Association.

Changing rules, uncertain futures

The H-1B processing change has left Amr Marawan, MD, unsure if a job offer may fall through and if he will be able to work in the United States at all over the next year.

Dr. Marawan, a native of Cairo, Egypt, will finish his internal medicine residency at the University of Tennessee, Chattanooga, in June and had planned to pursue a cardiology fellowship under a continuation of his J-1 alien physician visa. After the 2016 election, he decided instead to take a position as assistant professor of internal medicine at Virginia Commonwealth University in Richmond.

Courtesy Amr Marawan

Foreign medical students face rough road

Medical students applying for residencies and fellowships may also be detoured by the premium processing ban. Students who planned to train under an H-1B visa had to wait until Match Day on March 17 to file their H-1B petitions, Ms. Minear said. There is little chance they can complete all paperwork and state approvals needed in order to submit an H-1B application before April 3.

“What this really means is that physicians effectively cannot do their residencies or fellowships in H-1B status this year because they cannot file the petitions in time for a July 1 start date,” Ms. Minear said. “Effectively, what it does is force all foreign doctors who want to do residency or fellowship in the U.S. to do their training in J-1 status.”

A large number of foreign medical students already complete their training in J-1 status; however, many residency and fellowship programs agree to sponsor students in H-1B status as an attractive recruiting incentive for top talent, Ms. Minear said. Foreign doctors often prefer the latter status because they are exempt from the 2-year requirement to return home.

Foreign medical students matching to residency programs generally have the option to apply for a J-1 visa and can still train in the United States, said Matthew Shick, JD, government relations director for the Association of American Medical Colleges. He noted that the premium processing suspension will have a greater impact on faculty, scientists, and hospital staff.

However, medical students applying for J-1 visas also may experience processing delays because of President Trump’s March 6 Executive Order on immigration. A provision in that order increases uniform screening procedures for all visa classes and nationalities, while another provision suspends the Visa Interview Waiver Program. The suspension means that certain visa applicants seeking to renew a visa must be interviewed in person by a consular officer. The Hawaii federal court that blocked much of the that Executive Order did not halt the additional screening requirements or stay the Visa Interview Waiver Program rollback. Both provisions remain in effect.

Taskforce requests carve-out

The IMG Taskforce is urging USCIS to exempt physicians from the premium processing ban. In a March 8 letter to the agency, the task force outlined examples of how IMGs benefit the country and described how application delays could harm patient care and impair U.S. medical institutions.

“The hope is that this would encourage a review and a rethink of that shift and that upon that review, H-1B cap exempt petitions would across the board be considered for continued premium processing,” Ms. Harris said in an interview. “And/or, perhaps a greater lead time than merely 4 weeks’ notice [would be granted] so that people may be able complete their obligations.”

A group of U.S. senators also has requested that USCIS reconsider the premium processing suspension as it relates to physicians. Sen. Amy Klobuchar (D-Minn.) said that the suspension will exacerbate physician shortages, particularly in rural areas.

“The [waiver] program has helped address chronic physician shortages in rural America and other underserved areas for over two decades,” Sen. Klobuchar wrote in a March 10 letter. “We understand USCIS is facing a backlog, but USCIS has addressed this problem in the past without suspending premium processing for Conrad 30 doctors. We have every faith that USCIS can address its administrative needs without sacrificing support to this successful, time-tested program.”

Ms. Gwathmey would not comment on whether USCIS would consider an exception to the suspension for physicians. As with all affected workloads, USCIS is cognizant of processing time sensitivities for IMGs who are applying to change their status to H-1B, Ms. Gwathmey said in an interview.

“USCIS will be monitoring this workload during the coming months and will evaluate any time sensitive impacts prior to the resumption of premium processing services,” she said.

Dr. Marawan meanwhile is exhausting all efforts to keep his job offer. He is considering the option of filing an H-1B application now, before his state approval comes through, in the hopes of securing premium processing, he said. However, the option comes with a catch. Foreign doctors can file an H-1B petition without a J-1 waiver, but they can’t request a change of status from J-1 to H-1B without leaving the United States unless they have the waiver. This means if Dr. Marawan’s petition is approved by USCIS, he must go back to Egypt to apply for an H-1B visa at the U.S. Embassy in Cairo.

But with increased security delays for visa applicants and reports of foreign travelers being denied entry at U.S. airports, Dr. Marawan said he is fearful.

“Once you step out [of the United States], you never know what’s going to happen,” he said. “Sometimes visas get struck. Sometimes there’s a lot of security checks. Egypt is not included in the travel ban, but it’s always hard. There’s a lot of stories of people who are rejected getting their visas for different reasons. It’s worrisome.”

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A) Endometrial polyp INCORRECT
Endometrial polyps on ultrasonography appear as focal echogenic (hyperechoic) masses or as nonspecific endometrial thickening.¹ Color Doppler often demonstrates a vascular stalk, which is a nonspecific finding that also can be seen in submucosal fibroids and endometrial cancer.² On sonohysterography (SHG), endometrial polyps typically appear as well-defined echogenic/hyperechoic polypoid lesions (tissue appearance similar to that of normal endometrium) protruding into the endometrial canal but still preserving the endometrial−myometrial interface.^2,3

B) Submucosal fibroid CORRECT
Submucosal fibroids on ultrasonography appear as heterogeneous hypoechoic lesions distorting the endometrial cavity.¹ In contrast to endometrial polyps, which involve the endometrium only, submucosal (intracavitary) fibroids originate in the myometrium, as clarified in Figures 3A & B. SHG demonstrates a broad-based mixed hypoechoic/isoechoic lesion protruding into the endometrial canal but preserving the echogenic endometrium, distinguishing myometrial from endometrial lesions. Submucosal fibroids often distort the endometrial myometrial interface and demonstrate acoustic shadowing.^2,3

C) Endometrial carcinoma INCORRECT
Endometrial carcinoma on SHG appears as an irregular inhomogeneous lobulated vascular mass distorting the endometrial−myometrial interface.³ Additionally, irregular frond-like projections can be seen extending from the mass into the endometrial cavity, which are distended with echogenic fluid.²

D) Endometrial hyperplasia INCORRECT
On ultrasonography, endometrial hyperplasia has a nonspecific appearance, often presenting as diffuse smooth endometrial thickening.¹ SHG typically demonstrates diffuse thickening of the echogenic endometrial stripe without a focal lesion and, when a focal lesion is present, can mimic a broad-based endometrial polyp.^2,3

A) Endometrial polyp INCORRECT
Endometrial polyps on ultrasonography appear as focal echogenic (hyperechoic) masses or as nonspecific endometrial thickening.¹ Color Doppler often demonstrates a vascular stalk, which is a nonspecific finding that also can be seen in submucosal fibroids and endometrial cancer.² On sonohysterography (SHG), endometrial polyps typically appear as well-defined echogenic/hyperechoic polypoid lesions (tissue appearance similar to that of normal endometrium) protruding into the endometrial canal but still preserving the endometrial−myometrial interface.^2,3

B) Submucosal fibroid CORRECT
Submucosal fibroids on ultrasonography appear as heterogeneous hypoechoic lesions distorting the endometrial cavity.¹ In contrast to endometrial polyps, which involve the endometrium only, submucosal (intracavitary) fibroids originate in the myometrium, as clarified in Figures 3A & B. SHG demonstrates a broad-based mixed hypoechoic/isoechoic lesion protruding into the endometrial canal but preserving the echogenic endometrium, distinguishing myometrial from endometrial lesions. Submucosal fibroids often distort the endometrial myometrial interface and demonstrate acoustic shadowing.^2,3

C) Endometrial carcinoma INCORRECT
Endometrial carcinoma on SHG appears as an irregular inhomogeneous lobulated vascular mass distorting the endometrial−myometrial interface.³ Additionally, irregular frond-like projections can be seen extending from the mass into the endometrial cavity, which are distended with echogenic fluid.²

D) Endometrial hyperplasia INCORRECT
On ultrasonography, endometrial hyperplasia has a nonspecific appearance, often presenting as diffuse smooth endometrial thickening.¹ SHG typically demonstrates diffuse thickening of the echogenic endometrial stripe without a focal lesion and, when a focal lesion is present, can mimic a broad-based endometrial polyp.^2,3

A) Endometrial polyp INCORRECT
Endometrial polyps on ultrasonography appear as focal echogenic (hyperechoic) masses or as nonspecific endometrial thickening.¹ Color Doppler often demonstrates a vascular stalk, which is a nonspecific finding that also can be seen in submucosal fibroids and endometrial cancer.² On sonohysterography (SHG), endometrial polyps typically appear as well-defined echogenic/hyperechoic polypoid lesions (tissue appearance similar to that of normal endometrium) protruding into the endometrial canal but still preserving the endometrial−myometrial interface.^2,3

B) Submucosal fibroid CORRECT
Submucosal fibroids on ultrasonography appear as heterogeneous hypoechoic lesions distorting the endometrial cavity.¹ In contrast to endometrial polyps, which involve the endometrium only, submucosal (intracavitary) fibroids originate in the myometrium, as clarified in Figures 3A & B. SHG demonstrates a broad-based mixed hypoechoic/isoechoic lesion protruding into the endometrial canal but preserving the echogenic endometrium, distinguishing myometrial from endometrial lesions. Submucosal fibroids often distort the endometrial myometrial interface and demonstrate acoustic shadowing.^2,3

C) Endometrial carcinoma INCORRECT
Endometrial carcinoma on SHG appears as an irregular inhomogeneous lobulated vascular mass distorting the endometrial−myometrial interface.³ Additionally, irregular frond-like projections can be seen extending from the mass into the endometrial cavity, which are distended with echogenic fluid.²

D) Endometrial hyperplasia INCORRECT
On ultrasonography, endometrial hyperplasia has a nonspecific appearance, often presenting as diffuse smooth endometrial thickening.¹ SHG typically demonstrates diffuse thickening of the echogenic endometrial stripe without a focal lesion and, when a focal lesion is present, can mimic a broad-based endometrial polyp.^2,3

Surgeries for cervical intraepithelial neoplasia (CIN) have been linked to preterm birth, low birth weight, and pregnancy loss, among other adverse effects. But the mechanisms have not been entirely explained. Are the outcomes due to the surgery, the immunologic factors, or the risk factors associated with CIN?

Related: PAP Test/HPV Co-test: Quality Improvement Initiative to Identify Approaches for Integrative Clinical Care Management

The greater risk of pregnancy problems derives primarily from the treatment not from characteristics of human papillomavirus or CIN, say researchers from Kaiser Permanente Northwest, Duke University, and GlaxoSmithKline. They compared 322 women who had undergone excisional and ablative cervical surgery with 4,307 women who had not and with 847 women who had undergone only diagnostic procedures.

Of the treated women, 163 had a live birth within 1 year of treatment. Women who had undergone thick excisional cervical surgical procedures ( ≥ 1.0 cm) had approximately double the risk of preterm birth and low-birth-weight infants compared with that of the other 2 groups. The risk was higher if the baby was born within 1 year of surgery.  The risk of cesarean delivery rose 20% with excisional surgery. The treated women did not have a substantially higher risk of dysfunctional labor.

Related: More Evidence of HPV’s Role in Cancer

Among the women who had cervical surgery, 21% lost the pregnancy (25% of those with ablative and 19% of those with excisional surgery). By contrast, 18% of the unexposed women and 20% of the diagnostic-only group experienced pregnancy loss. The researchers say the positive association between pregnancy loss and ablative surgical treatment has not been previously reported. “These findings suggest that efforts to minimize excision thickness in cervical surgeries are prudent,” the researchers advise.

Source:
Weinmann S, Naleway A, Swamy G, et al. PLoS One. 2017;12(1):e0165276.
doi:  10.1371/journal.pone.0165276.

Surgeries for cervical intraepithelial neoplasia (CIN) have been linked to preterm birth, low birth weight, and pregnancy loss, among other adverse effects. But the mechanisms have not been entirely explained. Are the outcomes due to the surgery, the immunologic factors, or the risk factors associated with CIN?

Related: PAP Test/HPV Co-test: Quality Improvement Initiative to Identify Approaches for Integrative Clinical Care Management

The greater risk of pregnancy problems derives primarily from the treatment not from characteristics of human papillomavirus or CIN, say researchers from Kaiser Permanente Northwest, Duke University, and GlaxoSmithKline. They compared 322 women who had undergone excisional and ablative cervical surgery with 4,307 women who had not and with 847 women who had undergone only diagnostic procedures.

Of the treated women, 163 had a live birth within 1 year of treatment. Women who had undergone thick excisional cervical surgical procedures ( ≥ 1.0 cm) had approximately double the risk of preterm birth and low-birth-weight infants compared with that of the other 2 groups. The risk was higher if the baby was born within 1 year of surgery.  The risk of cesarean delivery rose 20% with excisional surgery. The treated women did not have a substantially higher risk of dysfunctional labor.

Related: More Evidence of HPV’s Role in Cancer

Among the women who had cervical surgery, 21% lost the pregnancy (25% of those with ablative and 19% of those with excisional surgery). By contrast, 18% of the unexposed women and 20% of the diagnostic-only group experienced pregnancy loss. The researchers say the positive association between pregnancy loss and ablative surgical treatment has not been previously reported. “These findings suggest that efforts to minimize excision thickness in cervical surgeries are prudent,” the researchers advise.

Source:
Weinmann S, Naleway A, Swamy G, et al. PLoS One. 2017;12(1):e0165276.
doi:  10.1371/journal.pone.0165276.

Surgeries for cervical intraepithelial neoplasia (CIN) have been linked to preterm birth, low birth weight, and pregnancy loss, among other adverse effects. But the mechanisms have not been entirely explained. Are the outcomes due to the surgery, the immunologic factors, or the risk factors associated with CIN?

Related: PAP Test/HPV Co-test: Quality Improvement Initiative to Identify Approaches for Integrative Clinical Care Management

The greater risk of pregnancy problems derives primarily from the treatment not from characteristics of human papillomavirus or CIN, say researchers from Kaiser Permanente Northwest, Duke University, and GlaxoSmithKline. They compared 322 women who had undergone excisional and ablative cervical surgery with 4,307 women who had not and with 847 women who had undergone only diagnostic procedures.

Of the treated women, 163 had a live birth within 1 year of treatment. Women who had undergone thick excisional cervical surgical procedures ( ≥ 1.0 cm) had approximately double the risk of preterm birth and low-birth-weight infants compared with that of the other 2 groups. The risk was higher if the baby was born within 1 year of surgery.  The risk of cesarean delivery rose 20% with excisional surgery. The treated women did not have a substantially higher risk of dysfunctional labor.

Related: More Evidence of HPV’s Role in Cancer

Among the women who had cervical surgery, 21% lost the pregnancy (25% of those with ablative and 19% of those with excisional surgery). By contrast, 18% of the unexposed women and 20% of the diagnostic-only group experienced pregnancy loss. The researchers say the positive association between pregnancy loss and ablative surgical treatment has not been previously reported. “These findings suggest that efforts to minimize excision thickness in cervical surgeries are prudent,” the researchers advise.

Source:
Weinmann S, Naleway A, Swamy G, et al. PLoS One. 2017;12(1):e0165276.
doi:  10.1371/journal.pone.0165276.

High-dose immunosuppressive therapy and autologous hematopoietic cell transplant (HDIT/HCT) has had “highly promising” results for patients with relapsing-remitting multiple sclerosis (MS), according to researchers from the HALT-MS trial. In the 5-year study, 69% of 24 participants survived without progression of disability, relapse, or new brain lesions, despite not taking MS medications.

Findings published at the 3-year mark were encouraging. The event-free survival rate was 78%. The extended findings suggest that “onetime treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications” for these patients, said NIAID Director Anthony Fauci, MD.

The treatment “resets” the immune system, the researchers say. First, doctors collect the patient’s blood-forming stem cells, then give the patient chemotherapy to deplete the immune system. Finally, the doctors return the patient’s stem cells to rebuild the immune system.

Adverse events were consistent with those routinely observed after HDIT/HCT. Adverse effects recorded at 4 and 5 years were not related to the transplant and were not considered severe. Three patients died, but their deaths were not related to the study treatments.

Five years later, most trial participants remained in remission and stabilized, and some showed improvements, such as recovering mobility.

High-dose immunosuppressive therapy and autologous hematopoietic cell transplant (HDIT/HCT) has had “highly promising” results for patients with relapsing-remitting multiple sclerosis (MS), according to researchers from the HALT-MS trial. In the 5-year study, 69% of 24 participants survived without progression of disability, relapse, or new brain lesions, despite not taking MS medications.

Findings published at the 3-year mark were encouraging. The event-free survival rate was 78%. The extended findings suggest that “onetime treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications” for these patients, said NIAID Director Anthony Fauci, MD.

The treatment “resets” the immune system, the researchers say. First, doctors collect the patient’s blood-forming stem cells, then give the patient chemotherapy to deplete the immune system. Finally, the doctors return the patient’s stem cells to rebuild the immune system.

Adverse events were consistent with those routinely observed after HDIT/HCT. Adverse effects recorded at 4 and 5 years were not related to the transplant and were not considered severe. Three patients died, but their deaths were not related to the study treatments.

Five years later, most trial participants remained in remission and stabilized, and some showed improvements, such as recovering mobility.

High-dose immunosuppressive therapy and autologous hematopoietic cell transplant (HDIT/HCT) has had “highly promising” results for patients with relapsing-remitting multiple sclerosis (MS), according to researchers from the HALT-MS trial. In the 5-year study, 69% of 24 participants survived without progression of disability, relapse, or new brain lesions, despite not taking MS medications.

Findings published at the 3-year mark were encouraging. The event-free survival rate was 78%. The extended findings suggest that “onetime treatment with HDIT/HCT may be substantially more effective than long-term treatment with the best available medications” for these patients, said NIAID Director Anthony Fauci, MD.

The treatment “resets” the immune system, the researchers say. First, doctors collect the patient’s blood-forming stem cells, then give the patient chemotherapy to deplete the immune system. Finally, the doctors return the patient’s stem cells to rebuild the immune system.

Adverse events were consistent with those routinely observed after HDIT/HCT. Adverse effects recorded at 4 and 5 years were not related to the transplant and were not considered severe. Three patients died, but their deaths were not related to the study treatments.

Five years later, most trial participants remained in remission and stabilized, and some showed improvements, such as recovering mobility.

Lab mouse

The lungs may play a previously unrecognized role in blood production, according to preclinical research published in Nature.

Researchers discovered large numbers of megakaryocytes in the lungs of mice and found these cells produced roughly half of the animals’ platelets.

The team also identified a pool of hematopoietic progenitors in the extravascular spaces of mouse lungs that were capable of multi-lineage bone marrow reconstitution.

“This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said study author Mark R. Looney, MD, of the University of California - San Francisco.

“What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The researchers believe these findings could have major implications for understanding diseases in which patients suffer from thrombocytopenia.

Imaging reveals surprise

This research was made possible by a refinement of a technique known as 2-photon intravital imaging. This approach allowed the researchers to visualize the behavior of individual cells within the blood vessels of a living mouse lung.

Dr Looney and his colleagues used the technique to examine interactions between the immune system and circulating platelets in the lungs in a mouse strain engineered so that platelets emit bright green fluorescence (GFP+).

In this way, the team noticed a large population of megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said study author Emma Lefrançais, PhD, a postdoctoral researcher in Dr Looney’s lab.

More detailed imaging sessions revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature. This suggests that roughly half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.

Subsequent experiments also revealed a variety of previously overlooked hematopoietic progenitors outside the lung vasculature.

Transplants provide more insight

The discovery of megakaryocytes and hematopoietic progenitors in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a set of lung transplant studies.

The team transplanted lungs from wild-type mice into mice with GFP+ megakaryocytes and vice-versa. The researchers said they observed proplatelet formation from GFP+ megakaryocytes in the lung vasculature of the GFP+ mice but not in the wild-type mice.

This suggests the megakaryocytes releasing platelets in the lung circulation originate from outside the lungs, the researchers said. And subsequent experiments suggested the megakaryocytes originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, a postdoctoral researcher in Dr Looney’s lab.

“It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with GFP+ megakaryocyte progenitors into mutant mice with low platelet counts.

The transplants successfully restored platelet levels to normal, an effect that persisted over a few months of observation—much longer than the lifespan of individual megakaryocytes or platelets.

To the researchers, this indicated that resident megakaryocyte progenitors in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy megakaryocytes to restore proper platelet production.

Finally, the researchers tested whether lung hematopoietic progenitors were capable of multi-lineage bone marrow reconstitution.

They found that cells originating from transplanted lungs traveled to damaged bone marrow and contributed to the production of platelets and other blood cells, including neutrophils, B cells, and T cells.

The researchers said these experiments suggest the lungs play host to a variety of hematopoietic progenitors capable of reconstituting damaged bone marrow and restoring the production of many components of the blood.

“To our knowledge, this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Dr Looney said.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Dr Looney noted.

The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of this study for Nature.

“The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

Lab mouse

The lungs may play a previously unrecognized role in blood production, according to preclinical research published in Nature.

Researchers discovered large numbers of megakaryocytes in the lungs of mice and found these cells produced roughly half of the animals’ platelets.

The team also identified a pool of hematopoietic progenitors in the extravascular spaces of mouse lungs that were capable of multi-lineage bone marrow reconstitution.

“This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said study author Mark R. Looney, MD, of the University of California - San Francisco.

“What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The researchers believe these findings could have major implications for understanding diseases in which patients suffer from thrombocytopenia.

Imaging reveals surprise

This research was made possible by a refinement of a technique known as 2-photon intravital imaging. This approach allowed the researchers to visualize the behavior of individual cells within the blood vessels of a living mouse lung.

Dr Looney and his colleagues used the technique to examine interactions between the immune system and circulating platelets in the lungs in a mouse strain engineered so that platelets emit bright green fluorescence (GFP+).

In this way, the team noticed a large population of megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said study author Emma Lefrançais, PhD, a postdoctoral researcher in Dr Looney’s lab.

More detailed imaging sessions revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature. This suggests that roughly half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.

Subsequent experiments also revealed a variety of previously overlooked hematopoietic progenitors outside the lung vasculature.

Transplants provide more insight

The discovery of megakaryocytes and hematopoietic progenitors in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a set of lung transplant studies.

The team transplanted lungs from wild-type mice into mice with GFP+ megakaryocytes and vice-versa. The researchers said they observed proplatelet formation from GFP+ megakaryocytes in the lung vasculature of the GFP+ mice but not in the wild-type mice.

This suggests the megakaryocytes releasing platelets in the lung circulation originate from outside the lungs, the researchers said. And subsequent experiments suggested the megakaryocytes originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, a postdoctoral researcher in Dr Looney’s lab.

“It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with GFP+ megakaryocyte progenitors into mutant mice with low platelet counts.

The transplants successfully restored platelet levels to normal, an effect that persisted over a few months of observation—much longer than the lifespan of individual megakaryocytes or platelets.

To the researchers, this indicated that resident megakaryocyte progenitors in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy megakaryocytes to restore proper platelet production.

Finally, the researchers tested whether lung hematopoietic progenitors were capable of multi-lineage bone marrow reconstitution.

They found that cells originating from transplanted lungs traveled to damaged bone marrow and contributed to the production of platelets and other blood cells, including neutrophils, B cells, and T cells.

The researchers said these experiments suggest the lungs play host to a variety of hematopoietic progenitors capable of reconstituting damaged bone marrow and restoring the production of many components of the blood.

“To our knowledge, this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Dr Looney said.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Dr Looney noted.

The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of this study for Nature.

“The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

Lab mouse

The lungs may play a previously unrecognized role in blood production, according to preclinical research published in Nature.

Researchers discovered large numbers of megakaryocytes in the lungs of mice and found these cells produced roughly half of the animals’ platelets.

The team also identified a pool of hematopoietic progenitors in the extravascular spaces of mouse lungs that were capable of multi-lineage bone marrow reconstitution.

“This finding definitely suggests a more sophisticated view of the lungs—that they’re not just for respiration but also a key partner in formation of crucial aspects of the blood,” said study author Mark R. Looney, MD, of the University of California - San Francisco.

“What we’ve observed here in mice strongly suggests the lung may play a key role in blood formation in humans as well.”

The researchers believe these findings could have major implications for understanding diseases in which patients suffer from thrombocytopenia.

Imaging reveals surprise

This research was made possible by a refinement of a technique known as 2-photon intravital imaging. This approach allowed the researchers to visualize the behavior of individual cells within the blood vessels of a living mouse lung.

Dr Looney and his colleagues used the technique to examine interactions between the immune system and circulating platelets in the lungs in a mouse strain engineered so that platelets emit bright green fluorescence (GFP+).

In this way, the team noticed a large population of megakaryocytes in the lung vasculature. Though megakaryocytes had been observed in the lung before, they were generally thought to live and produce platelets primarily in the bone marrow.

“When we discovered this massive population of megakaryocytes that appeared to be living in the lung, we realized we had to follow this up,” said study author Emma Lefrançais, PhD, a postdoctoral researcher in Dr Looney’s lab.

More detailed imaging sessions revealed megakaryocytes in the act of producing more than 10 million platelets per hour within the lung vasculature. This suggests that roughly half of a mouse’s total platelet production occurs in the lung, not the bone marrow, as researchers had long presumed.

Subsequent experiments also revealed a variety of previously overlooked hematopoietic progenitors outside the lung vasculature.

Transplants provide more insight

The discovery of megakaryocytes and hematopoietic progenitors in the lung raised questions about how these cells move back and forth between the lung and bone marrow. To address these questions, the researchers conducted a set of lung transplant studies.

The team transplanted lungs from wild-type mice into mice with GFP+ megakaryocytes and vice-versa. The researchers said they observed proplatelet formation from GFP+ megakaryocytes in the lung vasculature of the GFP+ mice but not in the wild-type mice.

This suggests the megakaryocytes releasing platelets in the lung circulation originate from outside the lungs, the researchers said. And subsequent experiments suggested the megakaryocytes originate in the bone marrow.

“It’s fascinating that megakaryocytes travel all the way from the bone marrow to the lungs to produce platelets,” said Guadalupe Ortiz-Muñoz, PhD, a postdoctoral researcher in Dr Looney’s lab.

“It’s possible that the lung is an ideal bioreactor for platelet production because of the mechanical force of the blood, or perhaps because of some molecular signaling we don’t yet know about.”

In another experiment, the researchers transplanted lungs with GFP+ megakaryocyte progenitors into mutant mice with low platelet counts.

The transplants successfully restored platelet levels to normal, an effect that persisted over a few months of observation—much longer than the lifespan of individual megakaryocytes or platelets.

To the researchers, this indicated that resident megakaryocyte progenitors in the transplanted lungs had become activated by the recipient mouse’s low platelet counts and had produced healthy megakaryocytes to restore proper platelet production.

Finally, the researchers tested whether lung hematopoietic progenitors were capable of multi-lineage bone marrow reconstitution.

They found that cells originating from transplanted lungs traveled to damaged bone marrow and contributed to the production of platelets and other blood cells, including neutrophils, B cells, and T cells.

The researchers said these experiments suggest the lungs play host to a variety of hematopoietic progenitors capable of reconstituting damaged bone marrow and restoring the production of many components of the blood.

“To our knowledge, this is the first description of blood progenitors resident in the lung, and it raises a lot of questions with clinical relevance for the millions of people who suffer from thrombocytopenia,” Dr Looney said.

In particular, the study suggests that researchers who have proposed treating platelet diseases with platelets produced from engineered megakaryocytes should look to the lungs as a resource for platelet production, Dr Looney noted.

The study also presents new avenues of research for stem cell biologists to explore how the bone marrow and lung collaborate to produce a healthy blood system through the mutual exchange of stem cells.

“These observations alter existing paradigms regarding blood cell formation, lung biology and disease, and transplantation,” said pulmonologist Guy A. Zimmerman, MD, who is associate chair of the Department of Internal Medicine at the University of Utah School of Medicine and was an independent reviewer of this study for Nature.

“The findings have direct clinical relevance and provide a rich group of questions for future studies of platelet genesis and megakaryocyte function in lung inflammation and other inflammatory conditions, bleeding and thrombotic disorders, and transplantation.”

Image by Andre E.X. Brown

New research has revealed sex-based differences in utilization and outcomes of catheter-directed thrombolysis (CDT) in patients with deep vein thrombosis (DVT).

The study showed that CDT use was more common in men than women, although use of the procedure increased over time for both sexes.

There were significant between-sex differences in the rates of some bleeding complications and certain in-hospital outcomes, but in-hospital mortality rates were similar between the sexes.

Riyaz Bashir, MD, of Temple University in Philadelphia, Pennsylvania, and his colleagues reported these findings in Vascular Medicine.

“The data provided some interesting findings,” Dr Bashir said. “In addition to differences in utilization, we were able to find variations in the incidence of a number of complications, including bleeding that requires blood transfusion, intracranial hemorrhage, gastrointestinal bleeding, and acute kidney injury, as well as the incidence of angioplasty, stenting, and adjunctive IVC filter placement.”

For this study, Dr Bashir and his colleagues analyzed data from the Nationwide Inpatient Sample database.

The team identified 108,243 patients age 18 or older with a primary discharge diagnosis of proximal lower extremity or caval DVT between January 2005 and December 2011. Of those patients, 4826 (4.5%) were treated with CDT.

The researchers found that women underwent CDT less often than men—4.1% and 4.9%, respectively (P<0.01).

But the rates of CDT use increased between 2005 and 2011 for both sexes—from 2.1% to 5.9% in women (P<0.01) and from 2.5% to 7.5% (P<0.01) in men.

The rate of in-hospital mortality was similar between women (1.2%) and men (1.3%, P=0.76).

Likewise, there was no significant between-sex difference in length of hospital stay or total hospital charges. The average length of stay was 7.0 ± 5.7 days for men and 7.1 ± 5.5 days for women (P=0.55).

Average total hospital charges were $88,837 ± 68,284 for men and $91,487 ± 77,129 for women (P=0.28).

Women were more likely than men to:

• Require blood transfusions—11.7% and 8.8%, respectively, (P<0.01)
• Undergo angioplasty—64.1% and 54.3%, respectively (P<0.01)
• Undergo stenting—32.2% and 19.9%, respectively (P<0.01)
• Receive an inferior vena cava filter—37.0% and 32.1%, respectively (P<0.01).

Men were more likely than women to:

• Experience acute kidney injury—9.9% and 6.5%, respectively (P<0.01)
• Have an intracranial hemorrhage (ICH)—1.2% and 0.5%, respectively (P=0.03)
• Experience gastrointestinal bleeding—2.2% and 0.9%, respectively (P<0.01).

The researchers noted that the higher rate of ICH among men overall was due to a higher incidence of ICH among men over the age of 75.

There was no significant difference between men and women when it came to procedure-related hemorrhage—1.4% and 1.2%, respectively (P=0.45).

“Future research should focus on uncovering why these sex-based differences exist,” Dr Bashir said. “The answers to those questions could help shape future treatment guidelines for patients who are suitable candidates for CDT.”

Image by Andre E.X. Brown

New research has revealed sex-based differences in utilization and outcomes of catheter-directed thrombolysis (CDT) in patients with deep vein thrombosis (DVT).

The study showed that CDT use was more common in men than women, although use of the procedure increased over time for both sexes.

There were significant between-sex differences in the rates of some bleeding complications and certain in-hospital outcomes, but in-hospital mortality rates were similar between the sexes.

Riyaz Bashir, MD, of Temple University in Philadelphia, Pennsylvania, and his colleagues reported these findings in Vascular Medicine.

“The data provided some interesting findings,” Dr Bashir said. “In addition to differences in utilization, we were able to find variations in the incidence of a number of complications, including bleeding that requires blood transfusion, intracranial hemorrhage, gastrointestinal bleeding, and acute kidney injury, as well as the incidence of angioplasty, stenting, and adjunctive IVC filter placement.”

For this study, Dr Bashir and his colleagues analyzed data from the Nationwide Inpatient Sample database.

The team identified 108,243 patients age 18 or older with a primary discharge diagnosis of proximal lower extremity or caval DVT between January 2005 and December 2011. Of those patients, 4826 (4.5%) were treated with CDT.

The researchers found that women underwent CDT less often than men—4.1% and 4.9%, respectively (P<0.01).

But the rates of CDT use increased between 2005 and 2011 for both sexes—from 2.1% to 5.9% in women (P<0.01) and from 2.5% to 7.5% (P<0.01) in men.

The rate of in-hospital mortality was similar between women (1.2%) and men (1.3%, P=0.76).

Likewise, there was no significant between-sex difference in length of hospital stay or total hospital charges. The average length of stay was 7.0 ± 5.7 days for men and 7.1 ± 5.5 days for women (P=0.55).

Average total hospital charges were $88,837 ± 68,284 for men and $91,487 ± 77,129 for women (P=0.28).

Women were more likely than men to:

• Require blood transfusions—11.7% and 8.8%, respectively, (P<0.01)
• Undergo angioplasty—64.1% and 54.3%, respectively (P<0.01)
• Undergo stenting—32.2% and 19.9%, respectively (P<0.01)
• Receive an inferior vena cava filter—37.0% and 32.1%, respectively (P<0.01).

Men were more likely than women to:

• Experience acute kidney injury—9.9% and 6.5%, respectively (P<0.01)
• Have an intracranial hemorrhage (ICH)—1.2% and 0.5%, respectively (P=0.03)
• Experience gastrointestinal bleeding—2.2% and 0.9%, respectively (P<0.01).

The researchers noted that the higher rate of ICH among men overall was due to a higher incidence of ICH among men over the age of 75.

There was no significant difference between men and women when it came to procedure-related hemorrhage—1.4% and 1.2%, respectively (P=0.45).

“Future research should focus on uncovering why these sex-based differences exist,” Dr Bashir said. “The answers to those questions could help shape future treatment guidelines for patients who are suitable candidates for CDT.”

Image by Andre E.X. Brown

New research has revealed sex-based differences in utilization and outcomes of catheter-directed thrombolysis (CDT) in patients with deep vein thrombosis (DVT).

The study showed that CDT use was more common in men than women, although use of the procedure increased over time for both sexes.

There were significant between-sex differences in the rates of some bleeding complications and certain in-hospital outcomes, but in-hospital mortality rates were similar between the sexes.

Riyaz Bashir, MD, of Temple University in Philadelphia, Pennsylvania, and his colleagues reported these findings in Vascular Medicine.

“The data provided some interesting findings,” Dr Bashir said. “In addition to differences in utilization, we were able to find variations in the incidence of a number of complications, including bleeding that requires blood transfusion, intracranial hemorrhage, gastrointestinal bleeding, and acute kidney injury, as well as the incidence of angioplasty, stenting, and adjunctive IVC filter placement.”

For this study, Dr Bashir and his colleagues analyzed data from the Nationwide Inpatient Sample database.

The team identified 108,243 patients age 18 or older with a primary discharge diagnosis of proximal lower extremity or caval DVT between January 2005 and December 2011. Of those patients, 4826 (4.5%) were treated with CDT.

The researchers found that women underwent CDT less often than men—4.1% and 4.9%, respectively (P<0.01).

But the rates of CDT use increased between 2005 and 2011 for both sexes—from 2.1% to 5.9% in women (P<0.01) and from 2.5% to 7.5% (P<0.01) in men.

The rate of in-hospital mortality was similar between women (1.2%) and men (1.3%, P=0.76).

Likewise, there was no significant between-sex difference in length of hospital stay or total hospital charges. The average length of stay was 7.0 ± 5.7 days for men and 7.1 ± 5.5 days for women (P=0.55).

Average total hospital charges were $88,837 ± 68,284 for men and $91,487 ± 77,129 for women (P=0.28).

Women were more likely than men to:

• Require blood transfusions—11.7% and 8.8%, respectively, (P<0.01)
• Undergo angioplasty—64.1% and 54.3%, respectively (P<0.01)
• Undergo stenting—32.2% and 19.9%, respectively (P<0.01)
• Receive an inferior vena cava filter—37.0% and 32.1%, respectively (P<0.01).

Men were more likely than women to:

• Experience acute kidney injury—9.9% and 6.5%, respectively (P<0.01)
• Have an intracranial hemorrhage (ICH)—1.2% and 0.5%, respectively (P=0.03)
• Experience gastrointestinal bleeding—2.2% and 0.9%, respectively (P<0.01).

The researchers noted that the higher rate of ICH among men overall was due to a higher incidence of ICH among men over the age of 75.

There was no significant difference between men and women when it came to procedure-related hemorrhage—1.4% and 1.2%, respectively (P=0.45).

“Future research should focus on uncovering why these sex-based differences exist,” Dr Bashir said. “The answers to those questions could help shape future treatment guidelines for patients who are suitable candidates for CDT.”