WAILEA, HAWAII – In a video interview, Pedram Gerami, MD, professor of dermatology, pathology, and pediatrics, Northwestern University, Chicago, discusses the use of molecular testing for melanoma and suspicious lesions.

Molecular tests are available for various components of diagnosis and prognosis of melanoma, and one of the most popular scenarios for their use is to confirm a diagnosis if a lesion is biopsied and the histopathologist “feels that the diagnosis is ambiguous by standard pathology methods,” Dr. Gerami said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

On average, between 1% and 5% of cases of suspicious lesions may need molecular testing to confirm the diagnosis, he noted. Of the available options for molecular testing, FISH (fluorescence in situ hybridization) testing is the most validated in the setting of ambiguous histology, he said.

Dr. Gerami disclosed serving as a consultant and researcher for Castle Biosciences, Myriad Genetics, and DermTech.

SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – In a video interview, Pedram Gerami, MD, professor of dermatology, pathology, and pediatrics, Northwestern University, Chicago, discusses the use of molecular testing for melanoma and suspicious lesions.

Molecular tests are available for various components of diagnosis and prognosis of melanoma, and one of the most popular scenarios for their use is to confirm a diagnosis if a lesion is biopsied and the histopathologist “feels that the diagnosis is ambiguous by standard pathology methods,” Dr. Gerami said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

On average, between 1% and 5% of cases of suspicious lesions may need molecular testing to confirm the diagnosis, he noted. Of the available options for molecular testing, FISH (fluorescence in situ hybridization) testing is the most validated in the setting of ambiguous histology, he said.

Dr. Gerami disclosed serving as a consultant and researcher for Castle Biosciences, Myriad Genetics, and DermTech.

SDEF and this news organization are owned by the same parent company.

WAILEA, HAWAII – In a video interview, Pedram Gerami, MD, professor of dermatology, pathology, and pediatrics, Northwestern University, Chicago, discusses the use of molecular testing for melanoma and suspicious lesions.

Molecular tests are available for various components of diagnosis and prognosis of melanoma, and one of the most popular scenarios for their use is to confirm a diagnosis if a lesion is biopsied and the histopathologist “feels that the diagnosis is ambiguous by standard pathology methods,” Dr. Gerami said in a video interview at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

On average, between 1% and 5% of cases of suspicious lesions may need molecular testing to confirm the diagnosis, he noted. Of the available options for molecular testing, FISH (fluorescence in situ hybridization) testing is the most validated in the setting of ambiguous histology, he said.

Dr. Gerami disclosed serving as a consultant and researcher for Castle Biosciences, Myriad Genetics, and DermTech.

SDEF and this news organization are owned by the same parent company.

HOUSTON – Hydrogel coils significantly outperformed bare platinum coils in treating patients with medium-sized intracranial aneurysms, reducing the incidence of adverse outcomes by about 9% in an open-label, randomized trial.

Compared against the platinum coils, the self-expandable, hydrophilic coils scored significantly better on a composite endpoint of aneurysm recurrence at 18 months, re-treatment by 18 months, serious morbidity that prevented angiographic follow-up, and death, Christian Taschner, MD, said at the International Stroke Conference sponsored by the America Heart Association.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

HOUSTON – Hydrogel coils significantly outperformed bare platinum coils in treating patients with medium-sized intracranial aneurysms, reducing the incidence of adverse outcomes by about 9% in an open-label, randomized trial.

Compared against the platinum coils, the self-expandable, hydrophilic coils scored significantly better on a composite endpoint of aneurysm recurrence at 18 months, re-treatment by 18 months, serious morbidity that prevented angiographic follow-up, and death, Christian Taschner, MD, said at the International Stroke Conference sponsored by the America Heart Association.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

HOUSTON – Hydrogel coils significantly outperformed bare platinum coils in treating patients with medium-sized intracranial aneurysms, reducing the incidence of adverse outcomes by about 9% in an open-label, randomized trial.

Compared against the platinum coils, the self-expandable, hydrophilic coils scored significantly better on a composite endpoint of aneurysm recurrence at 18 months, re-treatment by 18 months, serious morbidity that prevented angiographic follow-up, and death, Christian Taschner, MD, said at the International Stroke Conference sponsored by the America Heart Association.

msullivan@frontlinemedcom.com

On Twitter @alz_gal

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Bone marrow aspirate Photo by Chad McNeeley

Two physician groups have published an evidence-based guideline that addresses the initial workup of acute leukemia.

The guideline includes 27 recommendations intended to aid treating physicians and pathologists involved in the diagnostic and prognostic evaluation of acute leukemia samples, including those from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and acute leukemias of ambiguous lineage.

The guideline, which was developed through a collaboration between the College of American Pathologists (CAP) and the American Society of Hematology (ASH), has been published in the Archives of Pathology and Laboratory Medicine.

The recommendations in the guideline will also be available in a pocket guide and via the ASH Pocket Guides app in March.

“With its multidisciplinary perspective, this guideline reflects contemporary, integrated cancer care, and, therefore, it will also help providers realize efficiencies in test management,” said ASH guideline co-chair James W. Vardiman, MD, of the University of Chicago in Illinois.

To create this guideline, Dr Vardiman and his colleagues sought and reviewed relevant published evidence.

The group set out to answer 6 questions for the initial diagnosis of acute leukemias:

1) What clinical and laboratory information should be available?

2) What samples and specimen types should be evaluated?

3) What tests are required for all patients during the initial evaluation?

4) What tests are required for only a subset of patients?

5) Where should laboratory testing be performed?

6) How should the results be reported?

The authors say the guideline’s 27 recommendations answer these questions, providing a framework for the steps involved in the evaluation of acute leukemia samples.

In particular, the guideline includes steps to coordinate and communicate across clinical teams, specifying information that must be shared—particularly among treating physicians and pathologists—for optimal patient outcomes and to avoid duplicative testing.

“The laboratory testing to diagnose acute leukemia and inform treatment is increasingly complex, making this guideline essential,” said CAP guideline co-chair Daniel A. Arber, MD, of the University of Chicago.

“New gene mutations and protein expressions have been described over the last decade in all types of acute leukemia, and many of them impact diagnosis or inform prognosis.”

Children’s Research Hospital

Researchers have identified the first known case of artemisinin-resistant malaria originating in Africa, according to a letter published in NEJM.

Resistant Plasmodium falciparum parasites were detected in a Chinese man who had travelled from Equatorial Guinea to China.

The finding means Africa has joined Southeast Asia in hosting parasites that are partially resistant to the first-line antimalaria drug, artemisinin.

Researchers were able to confirm that the parasites in the current case carried a new mutation in the Kelch13 (K13) gene, the main driver for artemisinin resistance in Asia.

Then, the team set out to determine whether the parasite originated from Africa or Southeast Asia.

“We used whole-genome sequencing and bioinformatics tools we had previously developed—like detectives trying to link the culprit parasite to the crime scene,” explained Arnab Pain, PhD, of King Abdullah University of Science and Technology in Thuwal, Saudi Arabia.

Sequencing and analysis of P falciparum DNA unveiled its origin by disclosing the single nucleotide polymorphisms that vary according to the geographical source of the strain.

The researchers used the nuclear DNA, as well as the one present in 2 organelles of the parasite—the mitochondrium and the apicoplast.

Both methods independently validated the origin of the parasite as West African, confirming the first case of artemisinin resistance mediated by a K13 gene mutation on the African continent.

“The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT [artemisinin-based combination therapy] is the only effective and widely used antimalarial treatment at the moment,” Dr Pain said. “Therefore, it is very important to regularly monitor artemisinin resistance worldwide.”

Children’s Research Hospital

Researchers have identified the first known case of artemisinin-resistant malaria originating in Africa, according to a letter published in NEJM.

Resistant Plasmodium falciparum parasites were detected in a Chinese man who had travelled from Equatorial Guinea to China.

The finding means Africa has joined Southeast Asia in hosting parasites that are partially resistant to the first-line antimalaria drug, artemisinin.

Researchers were able to confirm that the parasites in the current case carried a new mutation in the Kelch13 (K13) gene, the main driver for artemisinin resistance in Asia.

Then, the team set out to determine whether the parasite originated from Africa or Southeast Asia.

“We used whole-genome sequencing and bioinformatics tools we had previously developed—like detectives trying to link the culprit parasite to the crime scene,” explained Arnab Pain, PhD, of King Abdullah University of Science and Technology in Thuwal, Saudi Arabia.

Sequencing and analysis of P falciparum DNA unveiled its origin by disclosing the single nucleotide polymorphisms that vary according to the geographical source of the strain.

The researchers used the nuclear DNA, as well as the one present in 2 organelles of the parasite—the mitochondrium and the apicoplast.

Both methods independently validated the origin of the parasite as West African, confirming the first case of artemisinin resistance mediated by a K13 gene mutation on the African continent.

“The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT [artemisinin-based combination therapy] is the only effective and widely used antimalarial treatment at the moment,” Dr Pain said. “Therefore, it is very important to regularly monitor artemisinin resistance worldwide.”

Children’s Research Hospital

Researchers have identified the first known case of artemisinin-resistant malaria originating in Africa, according to a letter published in NEJM.

Resistant Plasmodium falciparum parasites were detected in a Chinese man who had travelled from Equatorial Guinea to China.

The finding means Africa has joined Southeast Asia in hosting parasites that are partially resistant to the first-line antimalaria drug, artemisinin.

Researchers were able to confirm that the parasites in the current case carried a new mutation in the Kelch13 (K13) gene, the main driver for artemisinin resistance in Asia.

Then, the team set out to determine whether the parasite originated from Africa or Southeast Asia.

“We used whole-genome sequencing and bioinformatics tools we had previously developed—like detectives trying to link the culprit parasite to the crime scene,” explained Arnab Pain, PhD, of King Abdullah University of Science and Technology in Thuwal, Saudi Arabia.

Sequencing and analysis of P falciparum DNA unveiled its origin by disclosing the single nucleotide polymorphisms that vary according to the geographical source of the strain.

The researchers used the nuclear DNA, as well as the one present in 2 organelles of the parasite—the mitochondrium and the apicoplast.

Both methods independently validated the origin of the parasite as West African, confirming the first case of artemisinin resistance mediated by a K13 gene mutation on the African continent.

“The spread of artemisinin resistance in Africa would be a major setback in the fight against malaria, as ACT [artemisinin-based combination therapy] is the only effective and widely used antimalarial treatment at the moment,” Dr Pain said. “Therefore, it is very important to regularly monitor artemisinin resistance worldwide.”

University of South Carolina

Myxoma virus (MYXV), a nonhuman oncolytic agent, has demonstrated efficacy in mouse models of multiple myeloma (MM), according to research published in Molecular Therapy—Oncolytics.

MYXV significantly improved overall survival in mice with MM, providing a modest delay in disease progression for about two-thirds of the mice and completely eradicating the disease in a quarter of them.

“[W]e could actually get rid of disease, and it didn’t appear to ever come back,” said study author Eric C. Bartee, PhD, of the Medical University of South Carolina in Charleston.

For the past several years, Dr Bartee has been using MYXV to treat MM in cell culture. He and his colleagues previously showed that MYXV was able to kill human MM cells.

The team found that treatment with MYXV could eradicate MM cells in patient stem cell samples prior to transplant, thereby preventing relapse of MM.

In the current study, Dr Bartee and his colleagues took this one step further by assessing whether treatment with MYXV also has a benefit on disease outside the context of transplantation.

Using a mouse model of MM, the researchers showed that systemic treatment with MYXV reduced tumor burden and led to a modest decrease in disease progression (about 6 days) in 66% of mice.

In 25% of mice, there was complete eradication of disease with no evidence of relapse.

Since MYXV does not replicate in MM cells, the researchers postulated that eradication was caused by the host’s immune system. Investigation of the bone marrow showed that it was unaffected by treatment with MYXV.

This suggested that the immune system remained functional and could combat MM. Indeed, treatment with MYXV led to an increase in CD8+ T cells in the bone marrow, indicating a strong antitumor response.

The researchers noted that, although these results are promising, there are hurdles that must be overcome before this treatment can be brought to the clinic. One hurdle is large-scale production of clinical-grade virus. Another is demonstrating a high response rate.

“I think the major next question is ‘How do you get that response rate from 25% to 50% to 80% to 100%?’” Dr Bartee said. “How do you define the patients in which it works?”

University of South Carolina

Myxoma virus (MYXV), a nonhuman oncolytic agent, has demonstrated efficacy in mouse models of multiple myeloma (MM), according to research published in Molecular Therapy—Oncolytics.

MYXV significantly improved overall survival in mice with MM, providing a modest delay in disease progression for about two-thirds of the mice and completely eradicating the disease in a quarter of them.

“[W]e could actually get rid of disease, and it didn’t appear to ever come back,” said study author Eric C. Bartee, PhD, of the Medical University of South Carolina in Charleston.

For the past several years, Dr Bartee has been using MYXV to treat MM in cell culture. He and his colleagues previously showed that MYXV was able to kill human MM cells.

The team found that treatment with MYXV could eradicate MM cells in patient stem cell samples prior to transplant, thereby preventing relapse of MM.

In the current study, Dr Bartee and his colleagues took this one step further by assessing whether treatment with MYXV also has a benefit on disease outside the context of transplantation.

Using a mouse model of MM, the researchers showed that systemic treatment with MYXV reduced tumor burden and led to a modest decrease in disease progression (about 6 days) in 66% of mice.

In 25% of mice, there was complete eradication of disease with no evidence of relapse.

Since MYXV does not replicate in MM cells, the researchers postulated that eradication was caused by the host’s immune system. Investigation of the bone marrow showed that it was unaffected by treatment with MYXV.

This suggested that the immune system remained functional and could combat MM. Indeed, treatment with MYXV led to an increase in CD8+ T cells in the bone marrow, indicating a strong antitumor response.

The researchers noted that, although these results are promising, there are hurdles that must be overcome before this treatment can be brought to the clinic. One hurdle is large-scale production of clinical-grade virus. Another is demonstrating a high response rate.

“I think the major next question is ‘How do you get that response rate from 25% to 50% to 80% to 100%?’” Dr Bartee said. “How do you define the patients in which it works?”

University of South Carolina

Myxoma virus (MYXV), a nonhuman oncolytic agent, has demonstrated efficacy in mouse models of multiple myeloma (MM), according to research published in Molecular Therapy—Oncolytics.

MYXV significantly improved overall survival in mice with MM, providing a modest delay in disease progression for about two-thirds of the mice and completely eradicating the disease in a quarter of them.

“[W]e could actually get rid of disease, and it didn’t appear to ever come back,” said study author Eric C. Bartee, PhD, of the Medical University of South Carolina in Charleston.

For the past several years, Dr Bartee has been using MYXV to treat MM in cell culture. He and his colleagues previously showed that MYXV was able to kill human MM cells.

The team found that treatment with MYXV could eradicate MM cells in patient stem cell samples prior to transplant, thereby preventing relapse of MM.

In the current study, Dr Bartee and his colleagues took this one step further by assessing whether treatment with MYXV also has a benefit on disease outside the context of transplantation.

Using a mouse model of MM, the researchers showed that systemic treatment with MYXV reduced tumor burden and led to a modest decrease in disease progression (about 6 days) in 66% of mice.

In 25% of mice, there was complete eradication of disease with no evidence of relapse.

Since MYXV does not replicate in MM cells, the researchers postulated that eradication was caused by the host’s immune system. Investigation of the bone marrow showed that it was unaffected by treatment with MYXV.

This suggested that the immune system remained functional and could combat MM. Indeed, treatment with MYXV led to an increase in CD8+ T cells in the bone marrow, indicating a strong antitumor response.

The researchers noted that, although these results are promising, there are hurdles that must be overcome before this treatment can be brought to the clinic. One hurdle is large-scale production of clinical-grade virus. Another is demonstrating a high response rate.

“I think the major next question is ‘How do you get that response rate from 25% to 50% to 80% to 100%?’” Dr Bartee said. “How do you define the patients in which it works?”

Abstaining from the consumption of tap water at health care facilities can dramatically reduce the risk of Mycobacterium abscessus infections among patients and staff, according to a new study published in Clinical Infectious Diseases.

“Outbreaks of [M. abscessus] and other rapidly growing mycobacteria are common and have been associated with colonized plumbing systems in commercial buildings and health care facilities,” wrote the authors, led by Arthur W. Baker, MD, MPH, of Duke University, Durham, N.C., adding that “Infections due to M. abscessus are difficult to diagnose and typically require months of therapy using multiple antibiotics” (Clin Infect Dis. 2017 Jan 10. doi: 10.1093/cid/ciw877).

nikkytok/Thinkstock

dchitnis@frontlinemedcom.com

Abstaining from the consumption of tap water at health care facilities can dramatically reduce the risk of Mycobacterium abscessus infections among patients and staff, according to a new study published in Clinical Infectious Diseases.

“Outbreaks of [M. abscessus] and other rapidly growing mycobacteria are common and have been associated with colonized plumbing systems in commercial buildings and health care facilities,” wrote the authors, led by Arthur W. Baker, MD, MPH, of Duke University, Durham, N.C., adding that “Infections due to M. abscessus are difficult to diagnose and typically require months of therapy using multiple antibiotics” (Clin Infect Dis. 2017 Jan 10. doi: 10.1093/cid/ciw877).

nikkytok/Thinkstock

dchitnis@frontlinemedcom.com

Abstaining from the consumption of tap water at health care facilities can dramatically reduce the risk of Mycobacterium abscessus infections among patients and staff, according to a new study published in Clinical Infectious Diseases.

“Outbreaks of [M. abscessus] and other rapidly growing mycobacteria are common and have been associated with colonized plumbing systems in commercial buildings and health care facilities,” wrote the authors, led by Arthur W. Baker, MD, MPH, of Duke University, Durham, N.C., adding that “Infections due to M. abscessus are difficult to diagnose and typically require months of therapy using multiple antibiotics” (Clin Infect Dis. 2017 Jan 10. doi: 10.1093/cid/ciw877).

nikkytok/Thinkstock

dchitnis@frontlinemedcom.com

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

follicular lymphoma

The US Food and Drug Administration (FDA) has granted orphan designation to G100 for the treatment of follicular lymphoma.

G100 is a synthetic small-molecule toll-like receptor-4 agonist, glucopyranosyl lipid A, formulated in a stable emulsion.

The FDA grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases/disorders affecting fewer than 200,000 people in the US.

Orphan designation provides companies with certain incentives to develop products for rare diseases. This includes a 50% tax break on research and development, a fee waiver, access to federal grants, and 7 years of market exclusivity if the product is approved.

G100 is being developed by Immune Design. The company says G100 works by leveraging the activation of innate and adaptive immunity in the tumor microenvironment to create an immune response against the tumor’s pre-existing antigens.

According to Immune Design, clinical and preclinical data have demonstrated G100’s ability to activate tumor-infiltrating lymphocytes, macrophages, and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor.

The ensuing induction of local and systemic immune responses has been shown to result in local and abscopal tumor control in preclinical studies.

In fact, G100, when combined with local radiation, demonstrated efficacy against A20 lymphoma in mice. This research was presented in a poster at the 2016 ASH Annual Meeting (abstract 4166).

In this study, investigators evaluated the immune response and therapeutic effects of intratumoral G100 alone, local radiation alone, and concomitant G100 and local radiation in mice with A20 lymphoma.

The investigators said the combination therapy demonstrated:

• Synergistic antitumor effects in both injected as well as uninjected tumors (abscopal effects)
• Synergistic induction of pro-inflammatory cytokine and chemokine environment, as well as induction of genes governing antigen processing and presentation
• Increased infiltration of T cells, including CD4 and CD8 T cells, in treated tumors.

In contrast, tumors that received only radiation had significantly lower T-cell levels than untreated tumors.

“These findings highlight the potential beneficial effect that immunotherapy with G100 could provide when given with radiation by modulating the tumor microenvironment to generate a systemic, durable, T-cell anti-tumor response,” said study investigator Ramesh Rengan, MD, of the University of Washington in Seattle.

“As shown in this model, G100 may hold potential as a treatment for lymphoma patients.”

To test that theory, Immune Design is conducting a phase 1/2 trial of G100 given with local radiation or the anti-PD-1 agent pembrolizumab to patients with follicular lymphoma.

SEATTLE – Zika virus RNA lingered longer in semen than in any other body fluid but was cleared by 95% of men after 3 months, according to investigators from the Centers for Disease Control and Prevention.

The findings support the agency’s recommendation that men abstain from sex or use a condom for 6 months after coming down with symptoms. There had been concern following case reports of two men with semen positive for Zika RNA beyond 180 days, but further study supported the recommendation.

Many wondered if 6 months was too short, creating “a lot of anxiety and some confusion. It was good to find that [6 months is fine],” said senior CDC epidemiologist and lead investigator Gabriela Paz-Bailey, MD. “Based on our findings, late detection seems rare,” and the longest any infectious virus has been found in semen is 69 days.

The investigation team collected body fluids for 6 months from 150 patients in Puerto Rico who had confirmed Zika infection. Samples included semen samples from 55 men and vaginal secretions from 95 women in the study. Most of the participants presented to a hospital with symptoms, but some were household contacts who didn’t remember symptoms until asked.

“We found that two out of every three people who have evidence of infection reported symptoms,” which was higher than what was expected for an infection thought to be asymptomatic in many who remembered symptoms only when drilled by persistent epidemiologists. “You have to ask the questions,” Dr. Paz-Bailey said at the annual Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The samples were tested by reverse transcriptase polymerase chain reaction to see how long viral RNA stayed in various body fluids. Urine often is used to screen patients for Zika RNA, but the team found that virus evidence lasts longer in serum. While half of patients still had Zika RNA in their serum 2 weeks after symptom onset, and 5% were positive after about 2 months, urine was positive for Zika RNA in half of patients for only about a week. After 39 days, only 5% had RNA in their urine.

“It was thought that you could detect the virus more often in urine. We found the opposite. This is new. Serum may be a superior diagnostic specimen compared to urine,” Dr. Paz-Bailey said.

Additionally, RNA was found in semen longer than any other fluid, with about half of men positive after a month and 5% at about 3 months. The maximum for detection of Zika RNA in semen was 125 days. Meanwhile, RNA was largely undetectable in saliva and vaginal fluids after a week.

Until now, the 6-month window for men has been based on case reports and cross-sectional observations, mostly of travelers returning to the United States. The new findings bolster the 6-month abstinence or condom use recommendation but also support advice that women avoid pregnancy for 2 months following symptom onset, although the evidence for a 2-month window in women isn’t as strong.

The serum findings “suggest that the risk of intrauterine transmission ... is small” in women trying to conceive toward the end of the 2-month period, but “we will continue to monitor women of reproductive age to inform evaluations of these recommendations,” Dr. Paz-Bailey and her colleagues said in a report published after the presentation (N Engl J Med. 2017 Feb 14. doi: 10.1056/NEJMoa1613108).

It’s unclear if finding Zika RNA in body fluids means that there’s still active virus that can be transmitted. The team is plating out their specimens to see if they grow live virus.

The results are from an interim analysis. CDC plans to recruit at least 300 people into the study.

Dr. Paz-Bailey had no relevant financial disclosures. CDC funded the work.

aotto@frontlinemedcom.com

SEATTLE – Zika virus RNA lingered longer in semen than in any other body fluid but was cleared by 95% of men after 3 months, according to investigators from the Centers for Disease Control and Prevention.

The findings support the agency’s recommendation that men abstain from sex or use a condom for 6 months after coming down with symptoms. There had been concern following case reports of two men with semen positive for Zika RNA beyond 180 days, but further study supported the recommendation.

Many wondered if 6 months was too short, creating “a lot of anxiety and some confusion. It was good to find that [6 months is fine],” said senior CDC epidemiologist and lead investigator Gabriela Paz-Bailey, MD. “Based on our findings, late detection seems rare,” and the longest any infectious virus has been found in semen is 69 days.

The investigation team collected body fluids for 6 months from 150 patients in Puerto Rico who had confirmed Zika infection. Samples included semen samples from 55 men and vaginal secretions from 95 women in the study. Most of the participants presented to a hospital with symptoms, but some were household contacts who didn’t remember symptoms until asked.

“We found that two out of every three people who have evidence of infection reported symptoms,” which was higher than what was expected for an infection thought to be asymptomatic in many who remembered symptoms only when drilled by persistent epidemiologists. “You have to ask the questions,” Dr. Paz-Bailey said at the annual Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The samples were tested by reverse transcriptase polymerase chain reaction to see how long viral RNA stayed in various body fluids. Urine often is used to screen patients for Zika RNA, but the team found that virus evidence lasts longer in serum. While half of patients still had Zika RNA in their serum 2 weeks after symptom onset, and 5% were positive after about 2 months, urine was positive for Zika RNA in half of patients for only about a week. After 39 days, only 5% had RNA in their urine.

“It was thought that you could detect the virus more often in urine. We found the opposite. This is new. Serum may be a superior diagnostic specimen compared to urine,” Dr. Paz-Bailey said.

Additionally, RNA was found in semen longer than any other fluid, with about half of men positive after a month and 5% at about 3 months. The maximum for detection of Zika RNA in semen was 125 days. Meanwhile, RNA was largely undetectable in saliva and vaginal fluids after a week.

Until now, the 6-month window for men has been based on case reports and cross-sectional observations, mostly of travelers returning to the United States. The new findings bolster the 6-month abstinence or condom use recommendation but also support advice that women avoid pregnancy for 2 months following symptom onset, although the evidence for a 2-month window in women isn’t as strong.

The serum findings “suggest that the risk of intrauterine transmission ... is small” in women trying to conceive toward the end of the 2-month period, but “we will continue to monitor women of reproductive age to inform evaluations of these recommendations,” Dr. Paz-Bailey and her colleagues said in a report published after the presentation (N Engl J Med. 2017 Feb 14. doi: 10.1056/NEJMoa1613108).

It’s unclear if finding Zika RNA in body fluids means that there’s still active virus that can be transmitted. The team is plating out their specimens to see if they grow live virus.

The results are from an interim analysis. CDC plans to recruit at least 300 people into the study.

Dr. Paz-Bailey had no relevant financial disclosures. CDC funded the work.

aotto@frontlinemedcom.com

SEATTLE – Zika virus RNA lingered longer in semen than in any other body fluid but was cleared by 95% of men after 3 months, according to investigators from the Centers for Disease Control and Prevention.

The findings support the agency’s recommendation that men abstain from sex or use a condom for 6 months after coming down with symptoms. There had been concern following case reports of two men with semen positive for Zika RNA beyond 180 days, but further study supported the recommendation.

Many wondered if 6 months was too short, creating “a lot of anxiety and some confusion. It was good to find that [6 months is fine],” said senior CDC epidemiologist and lead investigator Gabriela Paz-Bailey, MD. “Based on our findings, late detection seems rare,” and the longest any infectious virus has been found in semen is 69 days.

The investigation team collected body fluids for 6 months from 150 patients in Puerto Rico who had confirmed Zika infection. Samples included semen samples from 55 men and vaginal secretions from 95 women in the study. Most of the participants presented to a hospital with symptoms, but some were household contacts who didn’t remember symptoms until asked.

“We found that two out of every three people who have evidence of infection reported symptoms,” which was higher than what was expected for an infection thought to be asymptomatic in many who remembered symptoms only when drilled by persistent epidemiologists. “You have to ask the questions,” Dr. Paz-Bailey said at the annual Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The samples were tested by reverse transcriptase polymerase chain reaction to see how long viral RNA stayed in various body fluids. Urine often is used to screen patients for Zika RNA, but the team found that virus evidence lasts longer in serum. While half of patients still had Zika RNA in their serum 2 weeks after symptom onset, and 5% were positive after about 2 months, urine was positive for Zika RNA in half of patients for only about a week. After 39 days, only 5% had RNA in their urine.

“It was thought that you could detect the virus more often in urine. We found the opposite. This is new. Serum may be a superior diagnostic specimen compared to urine,” Dr. Paz-Bailey said.

Additionally, RNA was found in semen longer than any other fluid, with about half of men positive after a month and 5% at about 3 months. The maximum for detection of Zika RNA in semen was 125 days. Meanwhile, RNA was largely undetectable in saliva and vaginal fluids after a week.

Until now, the 6-month window for men has been based on case reports and cross-sectional observations, mostly of travelers returning to the United States. The new findings bolster the 6-month abstinence or condom use recommendation but also support advice that women avoid pregnancy for 2 months following symptom onset, although the evidence for a 2-month window in women isn’t as strong.

The serum findings “suggest that the risk of intrauterine transmission ... is small” in women trying to conceive toward the end of the 2-month period, but “we will continue to monitor women of reproductive age to inform evaluations of these recommendations,” Dr. Paz-Bailey and her colleagues said in a report published after the presentation (N Engl J Med. 2017 Feb 14. doi: 10.1056/NEJMoa1613108).

It’s unclear if finding Zika RNA in body fluids means that there’s still active virus that can be transmitted. The team is plating out their specimens to see if they grow live virus.

The results are from an interim analysis. CDC plans to recruit at least 300 people into the study.

Dr. Paz-Bailey had no relevant financial disclosures. CDC funded the work.

aotto@frontlinemedcom.com

HOUSTON – Even when patients on an oral anticoagulant have the dreaded complication of an intracerebral hemorrhage, resumption of their oral anticoagulation regimen appears to produce the best midterm outcomes, based on a meta-analysis of data from more than 1,000 patients collected in three observational studies.

Resumption of oral anticoagulation therapy (OAT) is a “major dilemma” when managing patients who developed an intracerebral hemorrhage (ICH) while on OAT, said Alessandro Biffi, MD, explaining why he performed this meta-analysis that he presented at the International Stroke Conference sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

HOUSTON – Even when patients on an oral anticoagulant have the dreaded complication of an intracerebral hemorrhage, resumption of their oral anticoagulation regimen appears to produce the best midterm outcomes, based on a meta-analysis of data from more than 1,000 patients collected in three observational studies.

Resumption of oral anticoagulation therapy (OAT) is a “major dilemma” when managing patients who developed an intracerebral hemorrhage (ICH) while on OAT, said Alessandro Biffi, MD, explaining why he performed this meta-analysis that he presented at the International Stroke Conference sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

HOUSTON – Even when patients on an oral anticoagulant have the dreaded complication of an intracerebral hemorrhage, resumption of their oral anticoagulation regimen appears to produce the best midterm outcomes, based on a meta-analysis of data from more than 1,000 patients collected in three observational studies.

Resumption of oral anticoagulation therapy (OAT) is a “major dilemma” when managing patients who developed an intracerebral hemorrhage (ICH) while on OAT, said Alessandro Biffi, MD, explaining why he performed this meta-analysis that he presented at the International Stroke Conference sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.

Prenatal care is important for every pregnancy. It ensures the health and safety of the mother and baby throughout gestation, and alerts the ob.gyn. to any possible complications that may arise. Today, more than ever before, we have a wide array of powerful tools to augment the care we provide for our patients – from imaging technologies, to genomic screens, to advances in fetal surgery. However, every pregnancy can present its own set of challenges, and successful delivery of a healthy newborn cannot be taken for granted.

The importance of proper prenatal care is most essential to women with higher-risk pregnancies, which includes those involving multiple fetuses. From the babies’ perspective, complications of multiple fetuses can include intrauterine growth restriction, cerebral palsy, and stillbirth; from the mother’s perspective, complications of multiple fetuses can include preterm labor, gestational diabetes mellitus, preeclampsia, and placental abruption.

Dr. Reece, who specializes in maternal-fetal medicine, is vice president for medical affairs at the University of Maryland, Baltimore, as well as the John Z. and Akiko K. Bowers Distinguished Professor and dean of the school of medicine. Dr. Reece said he had no relevant financial disclosures. He is the medical editor of this column. Contact him at obnews@frontlinemedcom.com.