SAN DIEGO – The goal of gene therapy for hemophilia and other genetic diseases is to achieve long-term expression and levels adequate to improve the phenotype of disease, according to Katherine A. High, MD.

“Sometimes people ask me, ‘Why is it taking so long to develop these therapeutics?’ ” Dr. High said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The answer is that gene therapy vectors are arguably one of the most complex therapeutics yet developed.”

Courtesy of Dr. Katherine High

Hemostasis and thrombosis targets in gene therapy trials include hemophilia, as well as peripheral artery disease/claudication and congestive heart failure. In the latter, a prior phase 2b trial of adeno-associated virus (AAV) expressing SERCA2a did not support efficacy (Lancet 2016;387:1178-86), while a current trial of adenovirus 5–vector expressing adenylyl cyclase–type 6 is entering phase 3 study (NCT03360448).

To get a sense of how long it may take for a new class of therapeutics to become established, Dr. High noted that the first monoclonal antibody to be licensed was OKT3 (muromonab-CD3) in 1986, followed by abciximab in 1994, rituximab and daclizumab in 1997, and four additional products in 1998. By 2007, 8 of the top 20 biotech drugs were monoclonal antibodies.

Hemophilia has long been a favored gene therapy target because biology is in its favor. “It has a wide therapeutic window, it does not require tissue-specific expression of transgene, small and large animal models exist, and endpoints are well validated and easy to measure,” she said. “Thus, early gene-therapy clinical investigation since 1998 explored many strategies.”

There are several current investigational efforts in AAV-mediated gene transfer in hemophilia, including:

• A single-arm study to evaluate the efficacy and safety of valoctocogene roxaparvovec in hemophilia A patients at a dose of 4×10¹³ vector genome per kilogram (NCT03392974).
• A dose-ranging study of recombinant AAV2/6 human factor 8 gene therapy SB-525 in subjects with severe hemophilia A (NCT03061201).
• A safety and dose-escalation study of an adeno-associated viral vector for gene transfer in hemophilia A subjects (NCT03370172).

Other approaches in preclinical investigation include lentiviral transduction of hematopoietic stem cells with megakaryocyte-restricted expression, lentiviral transduction of liver cells and endothelial cells, and genome editing using zinc finger nucleases.

“AAV vectors are one of the smallest of all naturally occurring viruses,” said Dr. High, who is also emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia. “The recombinant AAV consists of a highly ordered set of proteins [vector capsid] containing DNA [the active agent].”

Overall goals for a hemophilia gene therapy include long-term expression and levels adequate to prevent bleeds in someone with a normal active lifestyle. “We’d like to see consistency of results from one person to the next, and we’d like to use the lowest possible dose,” she said. “In the setting of gene transfer, the lower the dose, the lower the likelihood of immune responses that need to be managed. Theoretically, the lower the dose, the lower the risk of insertional mutagenesis, and the shorter-term duration of vector shedding in body fluids, including in semen.”

Going forward, a key question for researchers relates to the long-term effect of gene therapy. “How long is long enough?” Dr. High asked. “The longest reported durability is 8 years, with observation ongoing, from studies initially reported in men with severe hemophilia B. The durability in large animal models exceeds 10 years.”

Another unanswered question is what level of factor VIII to aim for in treatment. “Some data suggest that FVIII levels greater than 100 IU/dL are associated with a greater level of thrombosis,” Dr. High said. “So I think somewhere between 12% and 100% is probably the ideal level.”

dbrunk@mdedge.com

SAN DIEGO – The goal of gene therapy for hemophilia and other genetic diseases is to achieve long-term expression and levels adequate to improve the phenotype of disease, according to Katherine A. High, MD.

“Sometimes people ask me, ‘Why is it taking so long to develop these therapeutics?’ ” Dr. High said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The answer is that gene therapy vectors are arguably one of the most complex therapeutics yet developed.”

Courtesy of Dr. Katherine High

Hemostasis and thrombosis targets in gene therapy trials include hemophilia, as well as peripheral artery disease/claudication and congestive heart failure. In the latter, a prior phase 2b trial of adeno-associated virus (AAV) expressing SERCA2a did not support efficacy (Lancet 2016;387:1178-86), while a current trial of adenovirus 5–vector expressing adenylyl cyclase–type 6 is entering phase 3 study (NCT03360448).

To get a sense of how long it may take for a new class of therapeutics to become established, Dr. High noted that the first monoclonal antibody to be licensed was OKT3 (muromonab-CD3) in 1986, followed by abciximab in 1994, rituximab and daclizumab in 1997, and four additional products in 1998. By 2007, 8 of the top 20 biotech drugs were monoclonal antibodies.

Hemophilia has long been a favored gene therapy target because biology is in its favor. “It has a wide therapeutic window, it does not require tissue-specific expression of transgene, small and large animal models exist, and endpoints are well validated and easy to measure,” she said. “Thus, early gene-therapy clinical investigation since 1998 explored many strategies.”

There are several current investigational efforts in AAV-mediated gene transfer in hemophilia, including:

• A single-arm study to evaluate the efficacy and safety of valoctocogene roxaparvovec in hemophilia A patients at a dose of 4×10¹³ vector genome per kilogram (NCT03392974).
• A dose-ranging study of recombinant AAV2/6 human factor 8 gene therapy SB-525 in subjects with severe hemophilia A (NCT03061201).
• A safety and dose-escalation study of an adeno-associated viral vector for gene transfer in hemophilia A subjects (NCT03370172).

Other approaches in preclinical investigation include lentiviral transduction of hematopoietic stem cells with megakaryocyte-restricted expression, lentiviral transduction of liver cells and endothelial cells, and genome editing using zinc finger nucleases.

“AAV vectors are one of the smallest of all naturally occurring viruses,” said Dr. High, who is also emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia. “The recombinant AAV consists of a highly ordered set of proteins [vector capsid] containing DNA [the active agent].”

Overall goals for a hemophilia gene therapy include long-term expression and levels adequate to prevent bleeds in someone with a normal active lifestyle. “We’d like to see consistency of results from one person to the next, and we’d like to use the lowest possible dose,” she said. “In the setting of gene transfer, the lower the dose, the lower the likelihood of immune responses that need to be managed. Theoretically, the lower the dose, the lower the risk of insertional mutagenesis, and the shorter-term duration of vector shedding in body fluids, including in semen.”

Going forward, a key question for researchers relates to the long-term effect of gene therapy. “How long is long enough?” Dr. High asked. “The longest reported durability is 8 years, with observation ongoing, from studies initially reported in men with severe hemophilia B. The durability in large animal models exceeds 10 years.”

Another unanswered question is what level of factor VIII to aim for in treatment. “Some data suggest that FVIII levels greater than 100 IU/dL are associated with a greater level of thrombosis,” Dr. High said. “So I think somewhere between 12% and 100% is probably the ideal level.”

dbrunk@mdedge.com

SAN DIEGO – The goal of gene therapy for hemophilia and other genetic diseases is to achieve long-term expression and levels adequate to improve the phenotype of disease, according to Katherine A. High, MD.

“Sometimes people ask me, ‘Why is it taking so long to develop these therapeutics?’ ” Dr. High said at the biennial summit of the Thrombosis & Hemostasis Societies of North America. “The answer is that gene therapy vectors are arguably one of the most complex therapeutics yet developed.”

Courtesy of Dr. Katherine High

Hemostasis and thrombosis targets in gene therapy trials include hemophilia, as well as peripheral artery disease/claudication and congestive heart failure. In the latter, a prior phase 2b trial of adeno-associated virus (AAV) expressing SERCA2a did not support efficacy (Lancet 2016;387:1178-86), while a current trial of adenovirus 5–vector expressing adenylyl cyclase–type 6 is entering phase 3 study (NCT03360448).

To get a sense of how long it may take for a new class of therapeutics to become established, Dr. High noted that the first monoclonal antibody to be licensed was OKT3 (muromonab-CD3) in 1986, followed by abciximab in 1994, rituximab and daclizumab in 1997, and four additional products in 1998. By 2007, 8 of the top 20 biotech drugs were monoclonal antibodies.

Hemophilia has long been a favored gene therapy target because biology is in its favor. “It has a wide therapeutic window, it does not require tissue-specific expression of transgene, small and large animal models exist, and endpoints are well validated and easy to measure,” she said. “Thus, early gene-therapy clinical investigation since 1998 explored many strategies.”

There are several current investigational efforts in AAV-mediated gene transfer in hemophilia, including:

• A single-arm study to evaluate the efficacy and safety of valoctocogene roxaparvovec in hemophilia A patients at a dose of 4×10¹³ vector genome per kilogram (NCT03392974).
• A dose-ranging study of recombinant AAV2/6 human factor 8 gene therapy SB-525 in subjects with severe hemophilia A (NCT03061201).
• A safety and dose-escalation study of an adeno-associated viral vector for gene transfer in hemophilia A subjects (NCT03370172).

Other approaches in preclinical investigation include lentiviral transduction of hematopoietic stem cells with megakaryocyte-restricted expression, lentiviral transduction of liver cells and endothelial cells, and genome editing using zinc finger nucleases.

“AAV vectors are one of the smallest of all naturally occurring viruses,” said Dr. High, who is also emeritus professor of pediatrics at the University of Pennsylvania, Philadelphia. “The recombinant AAV consists of a highly ordered set of proteins [vector capsid] containing DNA [the active agent].”

Overall goals for a hemophilia gene therapy include long-term expression and levels adequate to prevent bleeds in someone with a normal active lifestyle. “We’d like to see consistency of results from one person to the next, and we’d like to use the lowest possible dose,” she said. “In the setting of gene transfer, the lower the dose, the lower the likelihood of immune responses that need to be managed. Theoretically, the lower the dose, the lower the risk of insertional mutagenesis, and the shorter-term duration of vector shedding in body fluids, including in semen.”

Going forward, a key question for researchers relates to the long-term effect of gene therapy. “How long is long enough?” Dr. High asked. “The longest reported durability is 8 years, with observation ongoing, from studies initially reported in men with severe hemophilia B. The durability in large animal models exceeds 10 years.”

Another unanswered question is what level of factor VIII to aim for in treatment. “Some data suggest that FVIII levels greater than 100 IU/dL are associated with a greater level of thrombosis,” Dr. High said. “So I think somewhere between 12% and 100% is probably the ideal level.”

dbrunk@mdedge.com

Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.

Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.

The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.

“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.

Racial and socioeconomic barriers should also be addressed, they added.

The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.

Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).

Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.

“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.

The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.

Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.

Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.

SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.

Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.

Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.

The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.

“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.

Racial and socioeconomic barriers should also be addressed, they added.

The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.

Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).

Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.

“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.

The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.

Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.

Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.

SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.

Older patients, African Americans, and individuals of low socioeconomic status may be less likely to receive systemic treatment for newly diagnosed multiple myeloma, results of a recent study suggest.

Comorbidities and poor performance indicators also reduced the likelihood of receiving first-line treatment, according to results of the retrospective cohort study published in Clinical Lymphoma, Myeloma & Leukemia.

The findings highlight the need for a “multifaceted approach” to address outcome disparities in multiple myeloma, according to researcher Bita Fakhri, MD, MPH, of the division of oncology at Washington University, St. Louis, and her coinvestigators.

“Particular attention to aging-related issues is essential to ensure older patients will benefit from the advances achieved in the field, similar to young patients,” the investigators wrote.

Racial and socioeconomic barriers should also be addressed, they added.

The retrospective cohort analysis included data on 3,814 patients with active multiple myeloma in the Surveillance, Epidemiology, and End Results–Medicare database from 2007 to 2011. Investigators found that overall, 1,445 patients (38%) had no insurance claims confirming that they had received systemic treatment.

Older age increased the odds of not receiving treatment, with the likelihood increasing by 7% for each year of advancing age (adjusted odds ratio, 1.07; 95% confidence interval, 1.06-1.08). Likewise, African American patients were 26% more likely to have had no treatment (aOR, 1.26; 95% CI, 1.03-1.54), and patients who were enrolled in both Medicaid and Medicare – a proxy for lower income – had a 21% increased odds of no treatment (aOR, 1.21; 95% CI, 1.02-1.42).

Similarly increased odds of no treatment were reported for patients with comorbidities and poor performance status indicators.

“In a subset of older and frail patients, the risks of treatments approved for [multiple myeloma] might outweigh the benefits or might not be in line with the individual’s goals of care,” the investigators wrote.

The study did not track supportive-care treatments that patients may have received instead of active disease treatment, such as bisphosphonates for skeletal lesions or plasmapheresis for hyperviscosity syndrome.

Lack of treatment was associated with poorer survival in the study. Median overall survival was just 9.6 months for individuals with no record of treatment, compared with 32.3 months for patients who had received treatment.

Dr. Fakhri and coauthors reported having no financial disclosures related to the study, which was supported by the National Cancer Institute.

SOURCE: Fakhri B et al. Clin Lymphoma Myeloma Leuk. 2018 Mar;18(3):219-24.

SAN DIEGO – The American Academy of Dermatology’s policies that regulate conflicts of interest among members of its guidelines panels are “pretty good, but could be improved,” Lionel G. Bercovitch, MD, said at the annual meeting of the American Academy Dermatology.

One positive step might be to tighten the current American Academy of Dermatology requirement that more than half of the members in clinical guideline work groups be free of any financial conflicts and the minimum be raised to a higher percentage, such as more than 70%, suggested Dr. Bercovitch, a professor of dermatology at Brown University, Providence, R.I.

Mitchel L. Zoler/Frontline Medical News

• Conflicts of interest are ubiquitous and thus impossible to eliminate.
• Excluding working group members with conflicts can deprive the guidelines of valuable expertise.
• Checks and balances that are already in place in guideline development prevent inappropriate influence from conflicts of interest.
• No evidence has shown that conflicts of interest have inappropriately influenced development of treatment guidelines.

Mitchel L. Zoler/Frontline Medical News

Conflicts of interest may not be as well managed as AAD policies suggest, Dr. Bercovitch noted. He cited a report published in late 2017 that tallied the actual conflicts of 49 people who served as the authors of three AAD guidelines published during 2013-2016. To objectively double check each author’s conflicts the researchers used the Open Payments database run by the Centers for Medicare & Medicaid Services (JAMA Dermatol. 2017 Dec;153[12]:1229-35).

The analysis showed that 40 of the 49 authors (82%) had received some amount of industry payment, 63% had received more than $1,000, and 51% had received more than $10,000. The median amount received from industry was just over $33,000. The analysis also showed that 22 of the 40 authors who received an industry payment had disclosure statements for the guideline they participated in that did not agree with the information in the Open Payments database.

Mitchel L. Zoler/Frontline Medical News

They reported an adjusted analysis of the percentage of authors with relevant conflicts for each of the guidelines examined in the initial study. The percentages shrank to zero, 40%, and 43% of the authors with relevant conflicts, percentages that fell within the AAD’s ceiling for an acceptable percentage of work group members with conflicts.

The discussion on this topic was presented during a forum on dermatoethics at the meeting, structured as a debate in which presenters are assigned an ethical argument or point-of-view to discuss and defend. The position taken by the speaker need not (and often does not) correspond to the speaker’s personal views.

mzoler@mdedge.com
 

SAN DIEGO – The American Academy of Dermatology’s policies that regulate conflicts of interest among members of its guidelines panels are “pretty good, but could be improved,” Lionel G. Bercovitch, MD, said at the annual meeting of the American Academy Dermatology.

One positive step might be to tighten the current American Academy of Dermatology requirement that more than half of the members in clinical guideline work groups be free of any financial conflicts and the minimum be raised to a higher percentage, such as more than 70%, suggested Dr. Bercovitch, a professor of dermatology at Brown University, Providence, R.I.

Mitchel L. Zoler/Frontline Medical News

• Conflicts of interest are ubiquitous and thus impossible to eliminate.
• Excluding working group members with conflicts can deprive the guidelines of valuable expertise.
• Checks and balances that are already in place in guideline development prevent inappropriate influence from conflicts of interest.
• No evidence has shown that conflicts of interest have inappropriately influenced development of treatment guidelines.

Mitchel L. Zoler/Frontline Medical News

Conflicts of interest may not be as well managed as AAD policies suggest, Dr. Bercovitch noted. He cited a report published in late 2017 that tallied the actual conflicts of 49 people who served as the authors of three AAD guidelines published during 2013-2016. To objectively double check each author’s conflicts the researchers used the Open Payments database run by the Centers for Medicare & Medicaid Services (JAMA Dermatol. 2017 Dec;153[12]:1229-35).

The analysis showed that 40 of the 49 authors (82%) had received some amount of industry payment, 63% had received more than $1,000, and 51% had received more than $10,000. The median amount received from industry was just over $33,000. The analysis also showed that 22 of the 40 authors who received an industry payment had disclosure statements for the guideline they participated in that did not agree with the information in the Open Payments database.

Mitchel L. Zoler/Frontline Medical News

They reported an adjusted analysis of the percentage of authors with relevant conflicts for each of the guidelines examined in the initial study. The percentages shrank to zero, 40%, and 43% of the authors with relevant conflicts, percentages that fell within the AAD’s ceiling for an acceptable percentage of work group members with conflicts.

The discussion on this topic was presented during a forum on dermatoethics at the meeting, structured as a debate in which presenters are assigned an ethical argument or point-of-view to discuss and defend. The position taken by the speaker need not (and often does not) correspond to the speaker’s personal views.

mzoler@mdedge.com
 

SAN DIEGO – The American Academy of Dermatology’s policies that regulate conflicts of interest among members of its guidelines panels are “pretty good, but could be improved,” Lionel G. Bercovitch, MD, said at the annual meeting of the American Academy Dermatology.

One positive step might be to tighten the current American Academy of Dermatology requirement that more than half of the members in clinical guideline work groups be free of any financial conflicts and the minimum be raised to a higher percentage, such as more than 70%, suggested Dr. Bercovitch, a professor of dermatology at Brown University, Providence, R.I.

Mitchel L. Zoler/Frontline Medical News

• Conflicts of interest are ubiquitous and thus impossible to eliminate.
• Excluding working group members with conflicts can deprive the guidelines of valuable expertise.
• Checks and balances that are already in place in guideline development prevent inappropriate influence from conflicts of interest.
• No evidence has shown that conflicts of interest have inappropriately influenced development of treatment guidelines.

Mitchel L. Zoler/Frontline Medical News

Conflicts of interest may not be as well managed as AAD policies suggest, Dr. Bercovitch noted. He cited a report published in late 2017 that tallied the actual conflicts of 49 people who served as the authors of three AAD guidelines published during 2013-2016. To objectively double check each author’s conflicts the researchers used the Open Payments database run by the Centers for Medicare & Medicaid Services (JAMA Dermatol. 2017 Dec;153[12]:1229-35).

The analysis showed that 40 of the 49 authors (82%) had received some amount of industry payment, 63% had received more than $1,000, and 51% had received more than $10,000. The median amount received from industry was just over $33,000. The analysis also showed that 22 of the 40 authors who received an industry payment had disclosure statements for the guideline they participated in that did not agree with the information in the Open Payments database.

Mitchel L. Zoler/Frontline Medical News

They reported an adjusted analysis of the percentage of authors with relevant conflicts for each of the guidelines examined in the initial study. The percentages shrank to zero, 40%, and 43% of the authors with relevant conflicts, percentages that fell within the AAD’s ceiling for an acceptable percentage of work group members with conflicts.

The discussion on this topic was presented during a forum on dermatoethics at the meeting, structured as a debate in which presenters are assigned an ethical argument or point-of-view to discuss and defend. The position taken by the speaker need not (and often does not) correspond to the speaker’s personal views.

mzoler@mdedge.com
 

Updated clinical guidelines for diagnosis and treatment of chronic lymphocytic leukemia (CLL) include new and revised recommendations based on major advances in genomics, targeted therapies, and biomarkers that have occurred since the last iteration in 2008.

The guidelines are an update from a consensus document issued a decade ago by the International Workshop on CLL, focusing on the conduct of clinical trials in patients with CLL. The new guidelines are published in Blood.

Major changes or additions include:

Molecular genetics: The updated guidelines recognize the clinical importance of specific genomic alterations/mutations on response to standard chemotherapy or chemoimmunotherapy, including the 17p deletion and mutations in TP53.

“Therefore, the assessment of both del(17p) and TP53 mutation has prognostic and predictive value and should guide therapeutic decisions in routine practice. For clinical trials, it is recommended that molecular genetics be performed prior to treating a patient on protocol,” the guidelines state.

IGHV mutational status: The mutational status of immunoglobulin variable heavy chain (IGHV) genes has been demonstrated to offer important prognostic information, according to the guidelines authors led by Michael Hallek, MD of the University of Cologne, Germany.

Specifically, leukemia with IGHV genes without somatic mutations are associated with worse clinical outcomes, compared with leukemia with IGHV mutations. Patients with mutated IGHV and other prognostic factors such as favorable cytogenetics or minimal residual disease (MRD) negativity generally have excellent outcomes with a chemoimmunotherapy regimen consisting of fludarabine, cyclophosphamide, and rituximab, the authors noted.

Updated clinical guidelines for diagnosis and treatment of chronic lymphocytic leukemia (CLL) include new and revised recommendations based on major advances in genomics, targeted therapies, and biomarkers that have occurred since the last iteration in 2008.

The guidelines are an update from a consensus document issued a decade ago by the International Workshop on CLL, focusing on the conduct of clinical trials in patients with CLL. The new guidelines are published in Blood.

Major changes or additions include:

Molecular genetics: The updated guidelines recognize the clinical importance of specific genomic alterations/mutations on response to standard chemotherapy or chemoimmunotherapy, including the 17p deletion and mutations in TP53.

“Therefore, the assessment of both del(17p) and TP53 mutation has prognostic and predictive value and should guide therapeutic decisions in routine practice. For clinical trials, it is recommended that molecular genetics be performed prior to treating a patient on protocol,” the guidelines state.

IGHV mutational status: The mutational status of immunoglobulin variable heavy chain (IGHV) genes has been demonstrated to offer important prognostic information, according to the guidelines authors led by Michael Hallek, MD of the University of Cologne, Germany.

Specifically, leukemia with IGHV genes without somatic mutations are associated with worse clinical outcomes, compared with leukemia with IGHV mutations. Patients with mutated IGHV and other prognostic factors such as favorable cytogenetics or minimal residual disease (MRD) negativity generally have excellent outcomes with a chemoimmunotherapy regimen consisting of fludarabine, cyclophosphamide, and rituximab, the authors noted.

Updated clinical guidelines for diagnosis and treatment of chronic lymphocytic leukemia (CLL) include new and revised recommendations based on major advances in genomics, targeted therapies, and biomarkers that have occurred since the last iteration in 2008.

The guidelines are an update from a consensus document issued a decade ago by the International Workshop on CLL, focusing on the conduct of clinical trials in patients with CLL. The new guidelines are published in Blood.

Major changes or additions include:

Molecular genetics: The updated guidelines recognize the clinical importance of specific genomic alterations/mutations on response to standard chemotherapy or chemoimmunotherapy, including the 17p deletion and mutations in TP53.

“Therefore, the assessment of both del(17p) and TP53 mutation has prognostic and predictive value and should guide therapeutic decisions in routine practice. For clinical trials, it is recommended that molecular genetics be performed prior to treating a patient on protocol,” the guidelines state.

IGHV mutational status: The mutational status of immunoglobulin variable heavy chain (IGHV) genes has been demonstrated to offer important prognostic information, according to the guidelines authors led by Michael Hallek, MD of the University of Cologne, Germany.

Specifically, leukemia with IGHV genes without somatic mutations are associated with worse clinical outcomes, compared with leukemia with IGHV mutations. Patients with mutated IGHV and other prognostic factors such as favorable cytogenetics or minimal residual disease (MRD) negativity generally have excellent outcomes with a chemoimmunotherapy regimen consisting of fludarabine, cyclophosphamide, and rituximab, the authors noted.

Antibiotic resistance leads to “nightmare” bacteria. PPIs aren’t responsible for cognitive decline. Levothyroxine comes with risks for older patients. And Medicare formulary changes could be on the way.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Antibiotic resistance leads to “nightmare” bacteria. PPIs aren’t responsible for cognitive decline. Levothyroxine comes with risks for older patients. And Medicare formulary changes could be on the way.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Antibiotic resistance leads to “nightmare” bacteria. PPIs aren’t responsible for cognitive decline. Levothyroxine comes with risks for older patients. And Medicare formulary changes could be on the way.

Listen to the MDedge Daily News podcast for all the details on today’s top news.


 

Patients with HIV often also have herpes simplex virus type 2 (HSV-2) infection in part because lesions act as entry portals to susceptible HIV target cells. Some research also has suggested that HSV-2 accelerates HIV progression by upregulating HIV replication and increasing HIV viral load, but data are inconclusive, say researchers from the Iranian Research Center for HIV/AIDS, Pasteur Institute of Iran, Iranian Society for Support of Patients With Infectious Disease, Kermanshah University of Medical Sciences, Tehran University of Medical Sciences, and Zanjan University of Medical Sciences in Iran. They conducted a study to investigate HSV-2 seroprevalence in patients with and without HIV and to find out whether HSV-2 serostatus changed as CD4 counts and HIV viral load changed after 1 year.

The researchers compared 116 HIV patients who were not on HAART with 85 healthy controls. The prevalence and incidence of HSV-2 infection were low in the HIV cases and “negligible” in the control group: 18% of naïve HIV patients had HSV-2 IgG, and none of the control patients did.

Few data exist about HSV-2 seroconversion in HIV patients, the researchers say. In this study, HSV-2 seroconversion was found in 2.43% of HIV patients after 1 year.

Co-infection with HSV-2 had no association with CD4 count and HIV RNA viral load changes in the study participants at baseline or over time, the researchers say. CD4 counts after 1 year were 550 cells/mm³ in the HSV-2 seropositive patients and 563 cells/mm³ in the control group. The viral load in the seropositive group was 3.97 log copies/mL, and 3.49 log copies/mL in the seronegative group.

The researchers conclude that HIV-HSV-2 co-infection does not seem to play a role in HIV infection progression.

Patients with HIV often also have herpes simplex virus type 2 (HSV-2) infection in part because lesions act as entry portals to susceptible HIV target cells. Some research also has suggested that HSV-2 accelerates HIV progression by upregulating HIV replication and increasing HIV viral load, but data are inconclusive, say researchers from the Iranian Research Center for HIV/AIDS, Pasteur Institute of Iran, Iranian Society for Support of Patients With Infectious Disease, Kermanshah University of Medical Sciences, Tehran University of Medical Sciences, and Zanjan University of Medical Sciences in Iran. They conducted a study to investigate HSV-2 seroprevalence in patients with and without HIV and to find out whether HSV-2 serostatus changed as CD4 counts and HIV viral load changed after 1 year.

The researchers compared 116 HIV patients who were not on HAART with 85 healthy controls. The prevalence and incidence of HSV-2 infection were low in the HIV cases and “negligible” in the control group: 18% of naïve HIV patients had HSV-2 IgG, and none of the control patients did.

Few data exist about HSV-2 seroconversion in HIV patients, the researchers say. In this study, HSV-2 seroconversion was found in 2.43% of HIV patients after 1 year.

Co-infection with HSV-2 had no association with CD4 count and HIV RNA viral load changes in the study participants at baseline or over time, the researchers say. CD4 counts after 1 year were 550 cells/mm³ in the HSV-2 seropositive patients and 563 cells/mm³ in the control group. The viral load in the seropositive group was 3.97 log copies/mL, and 3.49 log copies/mL in the seronegative group.

The researchers conclude that HIV-HSV-2 co-infection does not seem to play a role in HIV infection progression.

Patients with HIV often also have herpes simplex virus type 2 (HSV-2) infection in part because lesions act as entry portals to susceptible HIV target cells. Some research also has suggested that HSV-2 accelerates HIV progression by upregulating HIV replication and increasing HIV viral load, but data are inconclusive, say researchers from the Iranian Research Center for HIV/AIDS, Pasteur Institute of Iran, Iranian Society for Support of Patients With Infectious Disease, Kermanshah University of Medical Sciences, Tehran University of Medical Sciences, and Zanjan University of Medical Sciences in Iran. They conducted a study to investigate HSV-2 seroprevalence in patients with and without HIV and to find out whether HSV-2 serostatus changed as CD4 counts and HIV viral load changed after 1 year.

The researchers compared 116 HIV patients who were not on HAART with 85 healthy controls. The prevalence and incidence of HSV-2 infection were low in the HIV cases and “negligible” in the control group: 18% of naïve HIV patients had HSV-2 IgG, and none of the control patients did.

Few data exist about HSV-2 seroconversion in HIV patients, the researchers say. In this study, HSV-2 seroconversion was found in 2.43% of HIV patients after 1 year.

Co-infection with HSV-2 had no association with CD4 count and HIV RNA viral load changes in the study participants at baseline or over time, the researchers say. CD4 counts after 1 year were 550 cells/mm³ in the HSV-2 seropositive patients and 563 cells/mm³ in the control group. The viral load in the seropositive group was 3.97 log copies/mL, and 3.49 log copies/mL in the seronegative group.

The researchers conclude that HIV-HSV-2 co-infection does not seem to play a role in HIV infection progression.

American Indians/Alaska Natives (AI/AN) have a disproportionately high rate of suicide—more than 3.5 times those of racial/ethnic groups with the lowest rates, according to a CDC study. And the rate has been steadily rising since 2003.

Those at highest risk are young people aged 10 to 24 years: More than one-third of suicides have occurred in that group compared with 11% of whites in the same age group.

In the CDC study, about 70% of AI/AN decedents lived in nonmetropolitan areas, including rural areas, which underscores the importance of implementing suicide prevention strategies in rural AI/AN communities, the researchers say. Rural areas often have fewer mental health services due to provider shortages and social barriers, among other factors. The researchers point out that in their study AI/AN had lower odds than did white decedents of having received a mental health diagnosis or mental health treatment.

The researchers also found suggestions of “suicide contagion”; AI/AN decedents were more than twice as likely to have a friend’s or family member’s suicide contribute to their death. Community-level programs that focus on “postvention,” such as survivor support groups, should be considered, the researchers say. They also advise that media should focus on “safe reporting of suicides,” for example, by not using sensationalized headlines.

Nearly 28% of the people who died had reported alcohol abuse problems, and 49% had used alcohol in the hours before their death. The researchers caution that differences in the prevalence of alcohol use among AI/AN might be a symptom of “disproportionate exposure to poverty, historical trauma, and other contexts of inequity and should not be viewed as inherent to AI/AN culture.”

American Indians/Alaska Natives (AI/AN) have a disproportionately high rate of suicide—more than 3.5 times those of racial/ethnic groups with the lowest rates, according to a CDC study. And the rate has been steadily rising since 2003.

Those at highest risk are young people aged 10 to 24 years: More than one-third of suicides have occurred in that group compared with 11% of whites in the same age group.

In the CDC study, about 70% of AI/AN decedents lived in nonmetropolitan areas, including rural areas, which underscores the importance of implementing suicide prevention strategies in rural AI/AN communities, the researchers say. Rural areas often have fewer mental health services due to provider shortages and social barriers, among other factors. The researchers point out that in their study AI/AN had lower odds than did white decedents of having received a mental health diagnosis or mental health treatment.

The researchers also found suggestions of “suicide contagion”; AI/AN decedents were more than twice as likely to have a friend’s or family member’s suicide contribute to their death. Community-level programs that focus on “postvention,” such as survivor support groups, should be considered, the researchers say. They also advise that media should focus on “safe reporting of suicides,” for example, by not using sensationalized headlines.

Nearly 28% of the people who died had reported alcohol abuse problems, and 49% had used alcohol in the hours before their death. The researchers caution that differences in the prevalence of alcohol use among AI/AN might be a symptom of “disproportionate exposure to poverty, historical trauma, and other contexts of inequity and should not be viewed as inherent to AI/AN culture.”

American Indians/Alaska Natives (AI/AN) have a disproportionately high rate of suicide—more than 3.5 times those of racial/ethnic groups with the lowest rates, according to a CDC study. And the rate has been steadily rising since 2003.

Those at highest risk are young people aged 10 to 24 years: More than one-third of suicides have occurred in that group compared with 11% of whites in the same age group.

In the CDC study, about 70% of AI/AN decedents lived in nonmetropolitan areas, including rural areas, which underscores the importance of implementing suicide prevention strategies in rural AI/AN communities, the researchers say. Rural areas often have fewer mental health services due to provider shortages and social barriers, among other factors. The researchers point out that in their study AI/AN had lower odds than did white decedents of having received a mental health diagnosis or mental health treatment.

The researchers also found suggestions of “suicide contagion”; AI/AN decedents were more than twice as likely to have a friend’s or family member’s suicide contribute to their death. Community-level programs that focus on “postvention,” such as survivor support groups, should be considered, the researchers say. They also advise that media should focus on “safe reporting of suicides,” for example, by not using sensationalized headlines.

Nearly 28% of the people who died had reported alcohol abuse problems, and 49% had used alcohol in the hours before their death. The researchers caution that differences in the prevalence of alcohol use among AI/AN might be a symptom of “disproportionate exposure to poverty, historical trauma, and other contexts of inequity and should not be viewed as inherent to AI/AN culture.”

Image from Darryl Leja, NHGRI

Through extensive analyses of data from The Cancer Genome Atlas (TCGA), researchers have produced a new resource known as the Pan-Cancer Atlas.

Multiple research groups analyzed data on more than 10,000 tumors spanning 33 types of cancer, including acute myeloid leukemia and diffuse large B-cell lymphoma.

The work revealed new insights regarding cells of origin, oncogenic processes, and signaling pathways.

These insights make up the Pan-Cancer Atlas and are described in 27 papers published in Cell Press journals. The entire collection of papers is available through a portal on cell.com.

The Pan-Cancer Atlas is the final output of TCGA, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to “collect, select, and analyze human tissues for genomic alterations on a very large scale.”

“This project is the culmination of more than a decade of ground-breaking work,” said Francis S. Collins, MD, PhD, director of the National Institutes of Health.

“This analysis provides cancer researchers with unprecedented understanding of how, where, and why tumors arise in humans, enabling better informed clinical trials and future treatments.”

The project focused on genome sequencing as well as other analyses, such as investigating gene and protein expression profiles and associating them with clinical and imaging data.

“The Pan-Cancer Atlas effort complements the over 30 tumor-specific papers that have been published by TCGA in the last decade and expands upon earlier pan-cancer work that was published in 2013,” said Jean Claude Zenklusen, PhD, director of the TCGA Program Office at NCI.

The Pan-Cancer Atlas is divided into 3 main categories—cell of origin, oncogenic processes, and signaling pathways—each anchored by a summary paper that recaps the core findings for the topic. Companion papers report in-depth explorations of individual topics within these categories.

Cell of origin

In the first Pan-Cancer Atlas summary paper, the authors review the findings from analyses using a technique called molecular clustering, which groups tumors by parameters such as genes being expressed, abnormality of chromosome numbers in tumor cells, and DNA modifications.

The analyses suggest that tumor types cluster by their possible cells of origin, a finding that has implications for the classification and treatment of various cancers.

“Rather than the organ of origin, we can now use molecular features to identify the cancer’s cell of origin,” said Li Ding, PhD, of Washington University School of Medicine in St. Louis, Missouri.

“We are looking at what genes are turned on in the tumor, and that brings us to a particular cell type. For example, squamous cell cancers can arise in the lung, bladder, cervix, and some tumors of the head and neck. We traditionally have treated cancers in these areas as completely different diseases, but, [by] studying their molecular features, we now know such cancers are closely related.”

“This new molecular-based classification system should greatly help in the clinic, where it is already explaining some of the similar clinical behavior of what we thought were different tumor types,” said Charles Perou, PhD, of UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

“These findings also provide many new therapeutic opportunities, which can and will be tested in the next phase of human clinical trials.”

Oncogenic processes

The second Pan-Cancer Atlas summary paper presents a broad view of the TCGA findings on the processes that lead to cancer development and progression.

The research revealed insights into 3 critical oncogenic processes—germline and somatic mutations, the influence of the tumor’s underlying genome and epigenome on gene and protein expression, and the interplay of tumor and immune cells.

“For the 10,000 tumors we analyzed, we now know—in detail—the inherited mutations driving cancer and the genetic errors that accumulate as people age, increasing the risk of cancer,” Dr Ding said. “This is the first definitive summary of the genetics behind 33 major types of cancer.”

“TCGA has created a catalogue of alterations that occur in a variety of cancer types,” said Katherine Hoadley, PhD, of University of North Carolina at Chapel Hill.

“Having this catalogue of alterations is really important for us to look, in future studies, at why these alterations are there and to predict outcomes for patients.”

Signaling pathways

The final Pan-Cancer Atlas summary paper details TCGA research on the genomic alterations in the signaling pathways that control cell-cycle progression, cell death, and cell growth. The work highlights the similarities and differences in these processes across a range of cancers.

The researchers believe these studies have revealed new patterns of potential vulnerabilities that might aid the development of targeted and combination therapies.

Image from Darryl Leja, NHGRI

Through extensive analyses of data from The Cancer Genome Atlas (TCGA), researchers have produced a new resource known as the Pan-Cancer Atlas.

Multiple research groups analyzed data on more than 10,000 tumors spanning 33 types of cancer, including acute myeloid leukemia and diffuse large B-cell lymphoma.

The work revealed new insights regarding cells of origin, oncogenic processes, and signaling pathways.

These insights make up the Pan-Cancer Atlas and are described in 27 papers published in Cell Press journals. The entire collection of papers is available through a portal on cell.com.

The Pan-Cancer Atlas is the final output of TCGA, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to “collect, select, and analyze human tissues for genomic alterations on a very large scale.”

“This project is the culmination of more than a decade of ground-breaking work,” said Francis S. Collins, MD, PhD, director of the National Institutes of Health.

“This analysis provides cancer researchers with unprecedented understanding of how, where, and why tumors arise in humans, enabling better informed clinical trials and future treatments.”

The project focused on genome sequencing as well as other analyses, such as investigating gene and protein expression profiles and associating them with clinical and imaging data.

“The Pan-Cancer Atlas effort complements the over 30 tumor-specific papers that have been published by TCGA in the last decade and expands upon earlier pan-cancer work that was published in 2013,” said Jean Claude Zenklusen, PhD, director of the TCGA Program Office at NCI.

The Pan-Cancer Atlas is divided into 3 main categories—cell of origin, oncogenic processes, and signaling pathways—each anchored by a summary paper that recaps the core findings for the topic. Companion papers report in-depth explorations of individual topics within these categories.

Cell of origin

In the first Pan-Cancer Atlas summary paper, the authors review the findings from analyses using a technique called molecular clustering, which groups tumors by parameters such as genes being expressed, abnormality of chromosome numbers in tumor cells, and DNA modifications.

The analyses suggest that tumor types cluster by their possible cells of origin, a finding that has implications for the classification and treatment of various cancers.

“Rather than the organ of origin, we can now use molecular features to identify the cancer’s cell of origin,” said Li Ding, PhD, of Washington University School of Medicine in St. Louis, Missouri.

“We are looking at what genes are turned on in the tumor, and that brings us to a particular cell type. For example, squamous cell cancers can arise in the lung, bladder, cervix, and some tumors of the head and neck. We traditionally have treated cancers in these areas as completely different diseases, but, [by] studying their molecular features, we now know such cancers are closely related.”

“This new molecular-based classification system should greatly help in the clinic, where it is already explaining some of the similar clinical behavior of what we thought were different tumor types,” said Charles Perou, PhD, of UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

“These findings also provide many new therapeutic opportunities, which can and will be tested in the next phase of human clinical trials.”

Oncogenic processes

The second Pan-Cancer Atlas summary paper presents a broad view of the TCGA findings on the processes that lead to cancer development and progression.

The research revealed insights into 3 critical oncogenic processes—germline and somatic mutations, the influence of the tumor’s underlying genome and epigenome on gene and protein expression, and the interplay of tumor and immune cells.

“For the 10,000 tumors we analyzed, we now know—in detail—the inherited mutations driving cancer and the genetic errors that accumulate as people age, increasing the risk of cancer,” Dr Ding said. “This is the first definitive summary of the genetics behind 33 major types of cancer.”

“TCGA has created a catalogue of alterations that occur in a variety of cancer types,” said Katherine Hoadley, PhD, of University of North Carolina at Chapel Hill.

“Having this catalogue of alterations is really important for us to look, in future studies, at why these alterations are there and to predict outcomes for patients.”

Signaling pathways

The final Pan-Cancer Atlas summary paper details TCGA research on the genomic alterations in the signaling pathways that control cell-cycle progression, cell death, and cell growth. The work highlights the similarities and differences in these processes across a range of cancers.

The researchers believe these studies have revealed new patterns of potential vulnerabilities that might aid the development of targeted and combination therapies.

Image from Darryl Leja, NHGRI

Through extensive analyses of data from The Cancer Genome Atlas (TCGA), researchers have produced a new resource known as the Pan-Cancer Atlas.

Multiple research groups analyzed data on more than 10,000 tumors spanning 33 types of cancer, including acute myeloid leukemia and diffuse large B-cell lymphoma.

The work revealed new insights regarding cells of origin, oncogenic processes, and signaling pathways.

These insights make up the Pan-Cancer Atlas and are described in 27 papers published in Cell Press journals. The entire collection of papers is available through a portal on cell.com.

The Pan-Cancer Atlas is the final output of TCGA, a joint effort of the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI) to “collect, select, and analyze human tissues for genomic alterations on a very large scale.”

“This project is the culmination of more than a decade of ground-breaking work,” said Francis S. Collins, MD, PhD, director of the National Institutes of Health.

“This analysis provides cancer researchers with unprecedented understanding of how, where, and why tumors arise in humans, enabling better informed clinical trials and future treatments.”

The project focused on genome sequencing as well as other analyses, such as investigating gene and protein expression profiles and associating them with clinical and imaging data.

“The Pan-Cancer Atlas effort complements the over 30 tumor-specific papers that have been published by TCGA in the last decade and expands upon earlier pan-cancer work that was published in 2013,” said Jean Claude Zenklusen, PhD, director of the TCGA Program Office at NCI.

The Pan-Cancer Atlas is divided into 3 main categories—cell of origin, oncogenic processes, and signaling pathways—each anchored by a summary paper that recaps the core findings for the topic. Companion papers report in-depth explorations of individual topics within these categories.

Cell of origin

In the first Pan-Cancer Atlas summary paper, the authors review the findings from analyses using a technique called molecular clustering, which groups tumors by parameters such as genes being expressed, abnormality of chromosome numbers in tumor cells, and DNA modifications.

The analyses suggest that tumor types cluster by their possible cells of origin, a finding that has implications for the classification and treatment of various cancers.

“Rather than the organ of origin, we can now use molecular features to identify the cancer’s cell of origin,” said Li Ding, PhD, of Washington University School of Medicine in St. Louis, Missouri.

“We are looking at what genes are turned on in the tumor, and that brings us to a particular cell type. For example, squamous cell cancers can arise in the lung, bladder, cervix, and some tumors of the head and neck. We traditionally have treated cancers in these areas as completely different diseases, but, [by] studying their molecular features, we now know such cancers are closely related.”

“This new molecular-based classification system should greatly help in the clinic, where it is already explaining some of the similar clinical behavior of what we thought were different tumor types,” said Charles Perou, PhD, of UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina.

“These findings also provide many new therapeutic opportunities, which can and will be tested in the next phase of human clinical trials.”

Oncogenic processes

The second Pan-Cancer Atlas summary paper presents a broad view of the TCGA findings on the processes that lead to cancer development and progression.

The research revealed insights into 3 critical oncogenic processes—germline and somatic mutations, the influence of the tumor’s underlying genome and epigenome on gene and protein expression, and the interplay of tumor and immune cells.

“For the 10,000 tumors we analyzed, we now know—in detail—the inherited mutations driving cancer and the genetic errors that accumulate as people age, increasing the risk of cancer,” Dr Ding said. “This is the first definitive summary of the genetics behind 33 major types of cancer.”

“TCGA has created a catalogue of alterations that occur in a variety of cancer types,” said Katherine Hoadley, PhD, of University of North Carolina at Chapel Hill.

“Having this catalogue of alterations is really important for us to look, in future studies, at why these alterations are there and to predict outcomes for patients.”

Signaling pathways

The final Pan-Cancer Atlas summary paper details TCGA research on the genomic alterations in the signaling pathways that control cell-cycle progression, cell death, and cell growth. The work highlights the similarities and differences in these processes across a range of cancers.

The researchers believe these studies have revealed new patterns of potential vulnerabilities that might aid the development of targeted and combination therapies.

University of Delaware

Biomedical engineers have developed hydrogels that can act as an “injectable bandage,” according to preclinical research published in Acta Biomaterialia.

The team engineered injectable hydrogels that were able to promote hemostasis and facilitate wound healing in vitro.

“Injectable hydrogels are promising materials for achieving hemostasis in case of internal injuries and bleeding, as these biomaterials can be introduced into a wound site using minimally invasive approaches,” said study author Akhilesh K. Gaharwar, PhD, of Texas A&M University in College Station, Texas.

“An ideal injectable bandage should solidify after injection in the wound area and promote a natural clotting cascade. In addition, the injectable bandage should initiate wound healing response after achieving hemostasis.”

To create their injectable hydrogels, Dr Gaharwar and his colleagues used a thickening agent known as kappa-carrageenan, which is obtained from seaweed, as well as clay-based nanoparticles known as nanosilicates.

It is the charged characteristics of the nanosilicates that provide the hydrogels with hemostatic ability, according to the researchers.

Specifically, the team said adding nanosilicates to kappa-carrageenan increases protein adsorption on the hydrogels, which enhances cell adhesion and spreading, increases platelet binding, and reduces blood clotting time.

“Interestingly, we also found that these injectable bandages can show a prolonged release of therapeutics that can be used to heal the wound,” said study author Giriraj Lokhande, a graduate student in Dr Gaharwar’s lab.

“The negative surface charge of nanoparticles enabled electrostatic interactions with therapeutics, thus resulting in the slow release of therapeutics.”

The researchers encapsulated vascular endothelial growth factor (VEGF) in the hydrogels and observed sustained release of VEGF in experiments. The hydrogels containing VEGF promoted faster wound healing than control hydrogels.

The researchers said a “range of therapeutic biomacromolecules” could be delivered in the same way as the VEGF.

University of Delaware

Biomedical engineers have developed hydrogels that can act as an “injectable bandage,” according to preclinical research published in Acta Biomaterialia.

The team engineered injectable hydrogels that were able to promote hemostasis and facilitate wound healing in vitro.

“Injectable hydrogels are promising materials for achieving hemostasis in case of internal injuries and bleeding, as these biomaterials can be introduced into a wound site using minimally invasive approaches,” said study author Akhilesh K. Gaharwar, PhD, of Texas A&M University in College Station, Texas.

“An ideal injectable bandage should solidify after injection in the wound area and promote a natural clotting cascade. In addition, the injectable bandage should initiate wound healing response after achieving hemostasis.”

To create their injectable hydrogels, Dr Gaharwar and his colleagues used a thickening agent known as kappa-carrageenan, which is obtained from seaweed, as well as clay-based nanoparticles known as nanosilicates.

It is the charged characteristics of the nanosilicates that provide the hydrogels with hemostatic ability, according to the researchers.

Specifically, the team said adding nanosilicates to kappa-carrageenan increases protein adsorption on the hydrogels, which enhances cell adhesion and spreading, increases platelet binding, and reduces blood clotting time.

“Interestingly, we also found that these injectable bandages can show a prolonged release of therapeutics that can be used to heal the wound,” said study author Giriraj Lokhande, a graduate student in Dr Gaharwar’s lab.

“The negative surface charge of nanoparticles enabled electrostatic interactions with therapeutics, thus resulting in the slow release of therapeutics.”

The researchers encapsulated vascular endothelial growth factor (VEGF) in the hydrogels and observed sustained release of VEGF in experiments. The hydrogels containing VEGF promoted faster wound healing than control hydrogels.

The researchers said a “range of therapeutic biomacromolecules” could be delivered in the same way as the VEGF.

University of Delaware

Biomedical engineers have developed hydrogels that can act as an “injectable bandage,” according to preclinical research published in Acta Biomaterialia.

The team engineered injectable hydrogels that were able to promote hemostasis and facilitate wound healing in vitro.

“Injectable hydrogels are promising materials for achieving hemostasis in case of internal injuries and bleeding, as these biomaterials can be introduced into a wound site using minimally invasive approaches,” said study author Akhilesh K. Gaharwar, PhD, of Texas A&M University in College Station, Texas.

“An ideal injectable bandage should solidify after injection in the wound area and promote a natural clotting cascade. In addition, the injectable bandage should initiate wound healing response after achieving hemostasis.”

To create their injectable hydrogels, Dr Gaharwar and his colleagues used a thickening agent known as kappa-carrageenan, which is obtained from seaweed, as well as clay-based nanoparticles known as nanosilicates.

It is the charged characteristics of the nanosilicates that provide the hydrogels with hemostatic ability, according to the researchers.

Specifically, the team said adding nanosilicates to kappa-carrageenan increases protein adsorption on the hydrogels, which enhances cell adhesion and spreading, increases platelet binding, and reduces blood clotting time.

“Interestingly, we also found that these injectable bandages can show a prolonged release of therapeutics that can be used to heal the wound,” said study author Giriraj Lokhande, a graduate student in Dr Gaharwar’s lab.

“The negative surface charge of nanoparticles enabled electrostatic interactions with therapeutics, thus resulting in the slow release of therapeutics.”

The researchers encapsulated vascular endothelial growth factor (VEGF) in the hydrogels and observed sustained release of VEGF in experiments. The hydrogels containing VEGF promoted faster wound healing than control hydrogels.

The researchers said a “range of therapeutic biomacromolecules” could be delivered in the same way as the VEGF.

Red and white blood cells

A portable device could be used to monitor patients’ white blood cell (WBC) levels at home, without the need for blood samples, according to researchers.

The team created a prototype that records video of blood cells flowing through capillaries just below the skin surface at the base of the fingernail.

The group is developing a computer algorithm that, in early testing, has been able to analyze the videos and determine if WBC levels are too low.

The researchers believe this type of device could be used to prevent infections among chemotherapy recipients.

“Our vision is that patients will have this portable device that they can take home, and they can monitor daily how they are reacting to the treatment,” said Carlos Castro-Gonzalez, PhD, of the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts.

“If they go below the [safe WBC] threshold, then preventive treatment can be deployed.”

Dr Castro-Gonzalez and his colleagues described their prototype, and the testing of it, in Scientific Reports.

The device consists of a wide-field microscope that emits blue light, which penetrates about 50 to 150 microns below the skin and is reflected back to a video camera.

The researchers decided to image the skin at the base of the nail because the capillaries there are very close to the skin surface. These capillaries are so narrow that WBCs must squeeze through one at a time, making them easier to see.

The researchers tested the device in 11 patients at various points during their chemotherapy treatment.

The device does not provide precise WBC counts but allowed the team to differentiate cases of severe neutropenia (<500 neutrophils per μL) from non-neutropenic cases (>1500 neutrophils per μL).

To obtain enough data to make these classifications, the researchers recorded 1 minute of video per patient. Three blinded human assistants then watched the videos and noted whenever a WBC passed by.

However, since submitting their paper, the researchers have been developing a computer algorithm to perform the same task automatically.

“Based on the feature-set that our human raters identified, we are now developing an AI and machine-vision algorithm, with preliminary results that indicate the same accuracy as the raters,” said study author Aurélien Bourquard, PhD, of MIT.

The researchers have applied for patents on the technology and launched a company called Leuko, which is working on commercializing the technology with help from MIT.

To move the technology further toward commercialization, the researchers are building a new automated prototype.

“Automating the measurement process is key to making a viable home-use device,” said study author Ian Butterworth, of MIT. “The imaging needs to take place in the right spot on the patient’s finger, and the operation of the device must be straightforward.”

Using this new prototype, the researchers plan to test the device with additional cancer patients. And the team is investigating whether they can get accurate results with shorter lengths of video.

They also plan to adapt the technology so it can generate more precise WBC counts, which would make it useful for monitoring bone marrow transplant recipients or people with certain infectious diseases, Dr Castro-Gonzalez said.

This could also make it possible to determine whether chemotherapy patients can receive their next dose sooner than usual.

“There is a balancing act that oncologists must do,” said study author Alvaro Sanchez-Ferro, MD, of Centro Integral en Neurociencias A.C. HM CINAC in Madrid, Spain.

“Normally, doctors want to make chemotherapy as intensive as possible but without getting people too immunosuppressed. Current 21-day cycles are based on statistics of what most patients can take, but if you are ready early, then they can potentially bring you back early, and that can translate into better survival.”

Red and white blood cells

A portable device could be used to monitor patients’ white blood cell (WBC) levels at home, without the need for blood samples, according to researchers.

The team created a prototype that records video of blood cells flowing through capillaries just below the skin surface at the base of the fingernail.

The group is developing a computer algorithm that, in early testing, has been able to analyze the videos and determine if WBC levels are too low.

The researchers believe this type of device could be used to prevent infections among chemotherapy recipients.

“Our vision is that patients will have this portable device that they can take home, and they can monitor daily how they are reacting to the treatment,” said Carlos Castro-Gonzalez, PhD, of the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts.

“If they go below the [safe WBC] threshold, then preventive treatment can be deployed.”

Dr Castro-Gonzalez and his colleagues described their prototype, and the testing of it, in Scientific Reports.

The device consists of a wide-field microscope that emits blue light, which penetrates about 50 to 150 microns below the skin and is reflected back to a video camera.

The researchers decided to image the skin at the base of the nail because the capillaries there are very close to the skin surface. These capillaries are so narrow that WBCs must squeeze through one at a time, making them easier to see.

The researchers tested the device in 11 patients at various points during their chemotherapy treatment.

The device does not provide precise WBC counts but allowed the team to differentiate cases of severe neutropenia (<500 neutrophils per μL) from non-neutropenic cases (>1500 neutrophils per μL).

To obtain enough data to make these classifications, the researchers recorded 1 minute of video per patient. Three blinded human assistants then watched the videos and noted whenever a WBC passed by.

However, since submitting their paper, the researchers have been developing a computer algorithm to perform the same task automatically.

“Based on the feature-set that our human raters identified, we are now developing an AI and machine-vision algorithm, with preliminary results that indicate the same accuracy as the raters,” said study author Aurélien Bourquard, PhD, of MIT.

The researchers have applied for patents on the technology and launched a company called Leuko, which is working on commercializing the technology with help from MIT.

To move the technology further toward commercialization, the researchers are building a new automated prototype.

“Automating the measurement process is key to making a viable home-use device,” said study author Ian Butterworth, of MIT. “The imaging needs to take place in the right spot on the patient’s finger, and the operation of the device must be straightforward.”

Using this new prototype, the researchers plan to test the device with additional cancer patients. And the team is investigating whether they can get accurate results with shorter lengths of video.

They also plan to adapt the technology so it can generate more precise WBC counts, which would make it useful for monitoring bone marrow transplant recipients or people with certain infectious diseases, Dr Castro-Gonzalez said.

This could also make it possible to determine whether chemotherapy patients can receive their next dose sooner than usual.

“There is a balancing act that oncologists must do,” said study author Alvaro Sanchez-Ferro, MD, of Centro Integral en Neurociencias A.C. HM CINAC in Madrid, Spain.

“Normally, doctors want to make chemotherapy as intensive as possible but without getting people too immunosuppressed. Current 21-day cycles are based on statistics of what most patients can take, but if you are ready early, then they can potentially bring you back early, and that can translate into better survival.”

Red and white blood cells

A portable device could be used to monitor patients’ white blood cell (WBC) levels at home, without the need for blood samples, according to researchers.

The team created a prototype that records video of blood cells flowing through capillaries just below the skin surface at the base of the fingernail.

The group is developing a computer algorithm that, in early testing, has been able to analyze the videos and determine if WBC levels are too low.

The researchers believe this type of device could be used to prevent infections among chemotherapy recipients.

“Our vision is that patients will have this portable device that they can take home, and they can monitor daily how they are reacting to the treatment,” said Carlos Castro-Gonzalez, PhD, of the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts.

“If they go below the [safe WBC] threshold, then preventive treatment can be deployed.”

Dr Castro-Gonzalez and his colleagues described their prototype, and the testing of it, in Scientific Reports.

The device consists of a wide-field microscope that emits blue light, which penetrates about 50 to 150 microns below the skin and is reflected back to a video camera.

The researchers decided to image the skin at the base of the nail because the capillaries there are very close to the skin surface. These capillaries are so narrow that WBCs must squeeze through one at a time, making them easier to see.

The researchers tested the device in 11 patients at various points during their chemotherapy treatment.

The device does not provide precise WBC counts but allowed the team to differentiate cases of severe neutropenia (<500 neutrophils per μL) from non-neutropenic cases (>1500 neutrophils per μL).

To obtain enough data to make these classifications, the researchers recorded 1 minute of video per patient. Three blinded human assistants then watched the videos and noted whenever a WBC passed by.

However, since submitting their paper, the researchers have been developing a computer algorithm to perform the same task automatically.

“Based on the feature-set that our human raters identified, we are now developing an AI and machine-vision algorithm, with preliminary results that indicate the same accuracy as the raters,” said study author Aurélien Bourquard, PhD, of MIT.

The researchers have applied for patents on the technology and launched a company called Leuko, which is working on commercializing the technology with help from MIT.

To move the technology further toward commercialization, the researchers are building a new automated prototype.

“Automating the measurement process is key to making a viable home-use device,” said study author Ian Butterworth, of MIT. “The imaging needs to take place in the right spot on the patient’s finger, and the operation of the device must be straightforward.”

Using this new prototype, the researchers plan to test the device with additional cancer patients. And the team is investigating whether they can get accurate results with shorter lengths of video.

They also plan to adapt the technology so it can generate more precise WBC counts, which would make it useful for monitoring bone marrow transplant recipients or people with certain infectious diseases, Dr Castro-Gonzalez said.

This could also make it possible to determine whether chemotherapy patients can receive their next dose sooner than usual.

“There is a balancing act that oncologists must do,” said study author Alvaro Sanchez-Ferro, MD, of Centro Integral en Neurociencias A.C. HM CINAC in Madrid, Spain.

“Normally, doctors want to make chemotherapy as intensive as possible but without getting people too immunosuppressed. Current 21-day cycles are based on statistics of what most patients can take, but if you are ready early, then they can potentially bring you back early, and that can translate into better survival.”