The availability of lungs for transplant has been severely limited by usable donors, but organs from so-called extended criteria donors – those aged 65 years or older, had a 20 pack-years or more smoking history or history of diabetes mellitus, or were black – were found to be associated with shorter survival than lungs from standard donor lungs, and recipients with more severe lung disease had the lowest survival rates from extended-criteria organs, an analysis of the national donor database found.

“Matching donor quality to recipient severity is critical to achieve optimal outcomes in lung transplantation,” Matthew J. Mulligan, MD, and his colleagues from the University of Maryland, Baltimore, said in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:891-8). Dr. Mulligan previously presented the study results in April 2015 at the annual meeting of the American Association for Thoracic Surgery in Seattle.

The researchers analyzed 10,995 patients who received donor lungs between May 2005 and December 2012, 3,792 of whom received extended-criteria donor (ECD) organs. The study population was taken from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Dr. Mulligan and his coauthors said this is the largest study examining ECD in lung transplants to date.

The goal of the study was to identify donor factors associated with reduced 1-year survival after transplantation, Dr. Mulligan and his colleagues said. “In the current literature, there is a paucity of data to guide the decision of matching donor quality to recipient severity,” the study authors said.

Recipients of extended-criteria lungs had a 41% increased risk of death, compared with recipients standard donor lungs, but individuals with more severe lung disease were at even greater risk with extended-criterial lungs, Dr. Mulligan and his colleagues said. Those who had a lung allocation score (LAS) less than 70 had a 1-year survival of 87% with standard donor lungs vs. 82% with extended-criteria lungs, while those who had a LAS of 70 or greater had survival rates of 80% and 72%, respectively.

Other donor factors that were inconsequential in recipient survival, Dr. Mulligan and his coauthors reported, included an abnormal chest x-ray, purulent secretions on bronchoscopy, blood type, mechanism of death (stroke, blunt trauma, gunshot, asphyxiation, and so on), or diagnosis of coronary artery disease and hypertension.

The researchers also did a Cox regression analysis, and found that recipients of extended-criteria lungs with a LAS greater than 70 had an 81% greater risk of death, compared with 37% for those with a LAS of 70 or greater who received standard-donor lungs, and 42% with a LAS of 70 or less and an extended-criteria donor lung.

These findings support the idea of not using ECD lungs in high-risk individuals with LAS greater than 70. “More important, ECD lungs were associated with the worst survival when transplanted into high-risk recipients,” Dr. Mulligan and his colleagues said.

The authors did acknowledge the inherent limitations of a retrospective analysis, but the large patient population is a redeeming factor of the study, Dr. Mulligan and his colleagues said. “Notwithstanding these limitations, the current study provides a rigorous analysis of a large number of lung transplants in the modern era, and the results reported will be useful to the lung transplant community,” the study authors said.

Dr. Mulligan and his coauthors had no relationships to disclose.

The availability of lungs for transplant has been severely limited by usable donors, but organs from so-called extended criteria donors – those aged 65 years or older, had a 20 pack-years or more smoking history or history of diabetes mellitus, or were black – were found to be associated with shorter survival than lungs from standard donor lungs, and recipients with more severe lung disease had the lowest survival rates from extended-criteria organs, an analysis of the national donor database found.

“Matching donor quality to recipient severity is critical to achieve optimal outcomes in lung transplantation,” Matthew J. Mulligan, MD, and his colleagues from the University of Maryland, Baltimore, said in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:891-8). Dr. Mulligan previously presented the study results in April 2015 at the annual meeting of the American Association for Thoracic Surgery in Seattle.

The researchers analyzed 10,995 patients who received donor lungs between May 2005 and December 2012, 3,792 of whom received extended-criteria donor (ECD) organs. The study population was taken from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Dr. Mulligan and his coauthors said this is the largest study examining ECD in lung transplants to date.

The goal of the study was to identify donor factors associated with reduced 1-year survival after transplantation, Dr. Mulligan and his colleagues said. “In the current literature, there is a paucity of data to guide the decision of matching donor quality to recipient severity,” the study authors said.

Recipients of extended-criteria lungs had a 41% increased risk of death, compared with recipients standard donor lungs, but individuals with more severe lung disease were at even greater risk with extended-criterial lungs, Dr. Mulligan and his colleagues said. Those who had a lung allocation score (LAS) less than 70 had a 1-year survival of 87% with standard donor lungs vs. 82% with extended-criteria lungs, while those who had a LAS of 70 or greater had survival rates of 80% and 72%, respectively.

Other donor factors that were inconsequential in recipient survival, Dr. Mulligan and his coauthors reported, included an abnormal chest x-ray, purulent secretions on bronchoscopy, blood type, mechanism of death (stroke, blunt trauma, gunshot, asphyxiation, and so on), or diagnosis of coronary artery disease and hypertension.

The researchers also did a Cox regression analysis, and found that recipients of extended-criteria lungs with a LAS greater than 70 had an 81% greater risk of death, compared with 37% for those with a LAS of 70 or greater who received standard-donor lungs, and 42% with a LAS of 70 or less and an extended-criteria donor lung.

These findings support the idea of not using ECD lungs in high-risk individuals with LAS greater than 70. “More important, ECD lungs were associated with the worst survival when transplanted into high-risk recipients,” Dr. Mulligan and his colleagues said.

The authors did acknowledge the inherent limitations of a retrospective analysis, but the large patient population is a redeeming factor of the study, Dr. Mulligan and his colleagues said. “Notwithstanding these limitations, the current study provides a rigorous analysis of a large number of lung transplants in the modern era, and the results reported will be useful to the lung transplant community,” the study authors said.

Dr. Mulligan and his coauthors had no relationships to disclose.

The availability of lungs for transplant has been severely limited by usable donors, but organs from so-called extended criteria donors – those aged 65 years or older, had a 20 pack-years or more smoking history or history of diabetes mellitus, or were black – were found to be associated with shorter survival than lungs from standard donor lungs, and recipients with more severe lung disease had the lowest survival rates from extended-criteria organs, an analysis of the national donor database found.

“Matching donor quality to recipient severity is critical to achieve optimal outcomes in lung transplantation,” Matthew J. Mulligan, MD, and his colleagues from the University of Maryland, Baltimore, said in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:891-8). Dr. Mulligan previously presented the study results in April 2015 at the annual meeting of the American Association for Thoracic Surgery in Seattle.

The researchers analyzed 10,995 patients who received donor lungs between May 2005 and December 2012, 3,792 of whom received extended-criteria donor (ECD) organs. The study population was taken from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Dr. Mulligan and his coauthors said this is the largest study examining ECD in lung transplants to date.

The goal of the study was to identify donor factors associated with reduced 1-year survival after transplantation, Dr. Mulligan and his colleagues said. “In the current literature, there is a paucity of data to guide the decision of matching donor quality to recipient severity,” the study authors said.

Recipients of extended-criteria lungs had a 41% increased risk of death, compared with recipients standard donor lungs, but individuals with more severe lung disease were at even greater risk with extended-criterial lungs, Dr. Mulligan and his colleagues said. Those who had a lung allocation score (LAS) less than 70 had a 1-year survival of 87% with standard donor lungs vs. 82% with extended-criteria lungs, while those who had a LAS of 70 or greater had survival rates of 80% and 72%, respectively.

Other donor factors that were inconsequential in recipient survival, Dr. Mulligan and his coauthors reported, included an abnormal chest x-ray, purulent secretions on bronchoscopy, blood type, mechanism of death (stroke, blunt trauma, gunshot, asphyxiation, and so on), or diagnosis of coronary artery disease and hypertension.

The researchers also did a Cox regression analysis, and found that recipients of extended-criteria lungs with a LAS greater than 70 had an 81% greater risk of death, compared with 37% for those with a LAS of 70 or greater who received standard-donor lungs, and 42% with a LAS of 70 or less and an extended-criteria donor lung.

These findings support the idea of not using ECD lungs in high-risk individuals with LAS greater than 70. “More important, ECD lungs were associated with the worst survival when transplanted into high-risk recipients,” Dr. Mulligan and his colleagues said.

The authors did acknowledge the inherent limitations of a retrospective analysis, but the large patient population is a redeeming factor of the study, Dr. Mulligan and his colleagues said. “Notwithstanding these limitations, the current study provides a rigorous analysis of a large number of lung transplants in the modern era, and the results reported will be useful to the lung transplant community,” the study authors said.

Dr. Mulligan and his coauthors had no relationships to disclose.

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderately to severely active Crohn’s disease in certain adults.

Specifically, the new approval for the human monoclonal antibody, which was previously approved for the treatment of psoriasis and psoriatic arthritis, is for Crohn’s disease patients aged 18 years or older who fail or cannot tolerate treatment with immunomodulators or corticosteroids but who never failed treatment with a tumor necrosis factor (TNF) blocker, or who fail or cannot tolerate treatment with one or more TNF blockers, according to a statement from the drug’s maker, Janssen Biotech.

The drug is the first biologic agent to target interleukin (IL)-12 and IL-23 in Crohn’s disease, and its approval was based on findings in more than 1,300 patients across three Janssen Biotech–sponsored phase III studies (UNITI-1, UNITI-2, IM-UNITI) demonstrating its efficacy with respect to clinical response and remission rates.

“Crohn’s disease is a complex condition to treat, and not all therapies work for every patient. The FDA approval of Stelara represents an important advancement in treating patients with Crohn’s disease, as this therapy offers an alternate mechanism of action to induce and maintain clinical remission over time,” study investigator William J. Sandborn, MD, of the University of California, San Diego, said in the statement.

[email protected]

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderately to severely active Crohn’s disease in certain adults.

Specifically, the new approval for the human monoclonal antibody, which was previously approved for the treatment of psoriasis and psoriatic arthritis, is for Crohn’s disease patients aged 18 years or older who fail or cannot tolerate treatment with immunomodulators or corticosteroids but who never failed treatment with a tumor necrosis factor (TNF) blocker, or who fail or cannot tolerate treatment with one or more TNF blockers, according to a statement from the drug’s maker, Janssen Biotech.

The drug is the first biologic agent to target interleukin (IL)-12 and IL-23 in Crohn’s disease, and its approval was based on findings in more than 1,300 patients across three Janssen Biotech–sponsored phase III studies (UNITI-1, UNITI-2, IM-UNITI) demonstrating its efficacy with respect to clinical response and remission rates.

“Crohn’s disease is a complex condition to treat, and not all therapies work for every patient. The FDA approval of Stelara represents an important advancement in treating patients with Crohn’s disease, as this therapy offers an alternate mechanism of action to induce and maintain clinical remission over time,” study investigator William J. Sandborn, MD, of the University of California, San Diego, said in the statement.

[email protected]

The Food and Drug Administration has approved ustekinumab (Stelara) for the treatment of moderately to severely active Crohn’s disease in certain adults.

Specifically, the new approval for the human monoclonal antibody, which was previously approved for the treatment of psoriasis and psoriatic arthritis, is for Crohn’s disease patients aged 18 years or older who fail or cannot tolerate treatment with immunomodulators or corticosteroids but who never failed treatment with a tumor necrosis factor (TNF) blocker, or who fail or cannot tolerate treatment with one or more TNF blockers, according to a statement from the drug’s maker, Janssen Biotech.

The drug is the first biologic agent to target interleukin (IL)-12 and IL-23 in Crohn’s disease, and its approval was based on findings in more than 1,300 patients across three Janssen Biotech–sponsored phase III studies (UNITI-1, UNITI-2, IM-UNITI) demonstrating its efficacy with respect to clinical response and remission rates.

“Crohn’s disease is a complex condition to treat, and not all therapies work for every patient. The FDA approval of Stelara represents an important advancement in treating patients with Crohn’s disease, as this therapy offers an alternate mechanism of action to induce and maintain clinical remission over time,” study investigator William J. Sandborn, MD, of the University of California, San Diego, said in the statement.

[email protected]

New federal regulations aim to strengthen the current requirements on reporting of clinical trial information.

The new rule offers a checklist to help determine which clinical trials are subject to regulations and who is responsible for information that appears on ClinicalTrials.gov. In addition, the rule does the following:

ClinicalTrials.gov

• Expands the scope of trials for which results must be submitted to include Food and Drug Administration–regulated products that have not yet been approved, licensed, or cleared.

• Requires additional information be submitted to ClinicalTrials.gov, including demographic information about trial participants.

• Expands adverse-event reporting.

• Adds potential penalties for noncompliance.

Simultaneously, the National Institutes of Health issued a complimentary policy for all trials it funds, regardless of whether the trials would be subject to the final rule.

Current federal requirements for reporting of clinical trial information were originally enacted as part of the FDA Amendments Act of 2007. However, a 2015 analysis of trials listed on ClinicalTrials.gov from 2007 to 2012 found a woeful lack of compliance: Study results were posted for 13% of trials covered by reporting requirements (N Engl J Med. 2015;372:1031-9).

“Organizations will need to ensure that their systems, procedures, and organizational values all promote complete and timely clinical trial reporting,” wrote Deborah Zarin, MD, of the National Library of Medicine, Bethesda, Md., and her colleagues in a special report on the final rule (N Engl J Med. 2016 Sep 16. doi: 10.1056/NEJMsr1611785). “In the end, the parties responsible for clinical trials will be held accountable by the public.”

The final rule applies to most interventional studies of drugs, biologics, and devices regulated by FDA, but it will not apply to phase I trials of pharmaceuticals or small feasibility studies of devices. It specifies how and when information collected in a clinical trial should be collected and submitted to ClinicalTrials.gov but does not dictate how clinical trials should be designed or conducted.

“Expanding the registration information in ClinicalTrials.gov improves people’s ability to find clinical trials in which they may be able to participate and access investigational therapies,” NIH officials said in a statement. “More information about the scientific results of trials, whether positive or negative, may help inform healthcare providers and patients regarding medical decisions. Additional information will help researchers avoid unnecessary duplication of studies, focus on areas in need of study and improve study design, ultimately advancing the development of clinical interventions.”

“Many U.S. academic medical centers, including those that conduct the most clinical trials, will find that the majority of their clinical trials fall under the [FDA Amendments Act], the NIH policy, or both,” Dr. Zarin and her colleagues wrote. “We hope that sponsors and other relevant entities will go considerably above and beyond the minimum requirements and expectations, making an effort to honor the contributions of all study participants and ensure that others in the scientific community have access to complete and high-quality information about every clinical trial under their stewardship.”

The final rule was published in the Federal Register on Sept. 21 and becomes effective on Jan. 18, 2017.

[email protected]

New federal regulations aim to strengthen the current requirements on reporting of clinical trial information.

The new rule offers a checklist to help determine which clinical trials are subject to regulations and who is responsible for information that appears on ClinicalTrials.gov. In addition, the rule does the following:

ClinicalTrials.gov

• Expands the scope of trials for which results must be submitted to include Food and Drug Administration–regulated products that have not yet been approved, licensed, or cleared.

• Requires additional information be submitted to ClinicalTrials.gov, including demographic information about trial participants.

• Expands adverse-event reporting.

• Adds potential penalties for noncompliance.

Simultaneously, the National Institutes of Health issued a complimentary policy for all trials it funds, regardless of whether the trials would be subject to the final rule.

Current federal requirements for reporting of clinical trial information were originally enacted as part of the FDA Amendments Act of 2007. However, a 2015 analysis of trials listed on ClinicalTrials.gov from 2007 to 2012 found a woeful lack of compliance: Study results were posted for 13% of trials covered by reporting requirements (N Engl J Med. 2015;372:1031-9).

“Organizations will need to ensure that their systems, procedures, and organizational values all promote complete and timely clinical trial reporting,” wrote Deborah Zarin, MD, of the National Library of Medicine, Bethesda, Md., and her colleagues in a special report on the final rule (N Engl J Med. 2016 Sep 16. doi: 10.1056/NEJMsr1611785). “In the end, the parties responsible for clinical trials will be held accountable by the public.”

The final rule applies to most interventional studies of drugs, biologics, and devices regulated by FDA, but it will not apply to phase I trials of pharmaceuticals or small feasibility studies of devices. It specifies how and when information collected in a clinical trial should be collected and submitted to ClinicalTrials.gov but does not dictate how clinical trials should be designed or conducted.

“Expanding the registration information in ClinicalTrials.gov improves people’s ability to find clinical trials in which they may be able to participate and access investigational therapies,” NIH officials said in a statement. “More information about the scientific results of trials, whether positive or negative, may help inform healthcare providers and patients regarding medical decisions. Additional information will help researchers avoid unnecessary duplication of studies, focus on areas in need of study and improve study design, ultimately advancing the development of clinical interventions.”

“Many U.S. academic medical centers, including those that conduct the most clinical trials, will find that the majority of their clinical trials fall under the [FDA Amendments Act], the NIH policy, or both,” Dr. Zarin and her colleagues wrote. “We hope that sponsors and other relevant entities will go considerably above and beyond the minimum requirements and expectations, making an effort to honor the contributions of all study participants and ensure that others in the scientific community have access to complete and high-quality information about every clinical trial under their stewardship.”

The final rule was published in the Federal Register on Sept. 21 and becomes effective on Jan. 18, 2017.

[email protected]

New federal regulations aim to strengthen the current requirements on reporting of clinical trial information.

The new rule offers a checklist to help determine which clinical trials are subject to regulations and who is responsible for information that appears on ClinicalTrials.gov. In addition, the rule does the following:

ClinicalTrials.gov

• Expands the scope of trials for which results must be submitted to include Food and Drug Administration–regulated products that have not yet been approved, licensed, or cleared.

• Requires additional information be submitted to ClinicalTrials.gov, including demographic information about trial participants.

• Expands adverse-event reporting.

• Adds potential penalties for noncompliance.

Simultaneously, the National Institutes of Health issued a complimentary policy for all trials it funds, regardless of whether the trials would be subject to the final rule.

Current federal requirements for reporting of clinical trial information were originally enacted as part of the FDA Amendments Act of 2007. However, a 2015 analysis of trials listed on ClinicalTrials.gov from 2007 to 2012 found a woeful lack of compliance: Study results were posted for 13% of trials covered by reporting requirements (N Engl J Med. 2015;372:1031-9).

“Organizations will need to ensure that their systems, procedures, and organizational values all promote complete and timely clinical trial reporting,” wrote Deborah Zarin, MD, of the National Library of Medicine, Bethesda, Md., and her colleagues in a special report on the final rule (N Engl J Med. 2016 Sep 16. doi: 10.1056/NEJMsr1611785). “In the end, the parties responsible for clinical trials will be held accountable by the public.”

The final rule applies to most interventional studies of drugs, biologics, and devices regulated by FDA, but it will not apply to phase I trials of pharmaceuticals or small feasibility studies of devices. It specifies how and when information collected in a clinical trial should be collected and submitted to ClinicalTrials.gov but does not dictate how clinical trials should be designed or conducted.

“Expanding the registration information in ClinicalTrials.gov improves people’s ability to find clinical trials in which they may be able to participate and access investigational therapies,” NIH officials said in a statement. “More information about the scientific results of trials, whether positive or negative, may help inform healthcare providers and patients regarding medical decisions. Additional information will help researchers avoid unnecessary duplication of studies, focus on areas in need of study and improve study design, ultimately advancing the development of clinical interventions.”

“Many U.S. academic medical centers, including those that conduct the most clinical trials, will find that the majority of their clinical trials fall under the [FDA Amendments Act], the NIH policy, or both,” Dr. Zarin and her colleagues wrote. “We hope that sponsors and other relevant entities will go considerably above and beyond the minimum requirements and expectations, making an effort to honor the contributions of all study participants and ensure that others in the scientific community have access to complete and high-quality information about every clinical trial under their stewardship.”

The final rule was published in the Federal Register on Sept. 21 and becomes effective on Jan. 18, 2017.

[email protected]

Micrograph showing GVHD

Image from PLOS ONE

The US Food and Drug Administration (FDA) has granted orphan drug designation to a programmed cellular immunotherapy known as ProTmune™.

The designation is for ProTmune to be used as graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT).

This indication covers a range of diseases, including hematologic malignancies and genetic disorders.

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

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

About ProTmune

ProTmune is produced by modulating a donor-sourced, mobilized peripheral blood graft ex vivo with 2 small molecules—FT1050 and FT4145—to enhance the biological properties and therapeutic function of the graft’s immune cells.

The programmed mobilized peripheral blood graft is administered to a patient as a one-time intravenous infusion.

ProTmune is being developed by Fate Therapeutics, Inc.

The company is conducting a phase 1/2 trial testing ProTmune for the prevention of acute GVHD and cytomegalovirus infection in adults with hematologic malignancies who are undergoing allogeneic HSCT.

ProTmune was previously granted fast track designation from the FDA.

“The granting of both orphan drug and fast track designations for ProTmune validates the product candidate’s unique therapeutic potential to address life-threatening complications and improve the curative potential of allogeneic [HSCT],” said Scott Wolchko, president and chief executive officer of Fate Therapeutics.

“Graft-versus-host disease is a significant cause of morbidity and mortality in patients undergoing allogeneic [HSCT], and there are no FDA-approved therapies to prevent its occurrence. Through our development of ProTmune, we seek to transform the allogeneic [HSCT] paradigm by providing immunocompromised patients a therapeutically optimized donor graft containing immune cells with reduced alloreactivity and enhanced infection-fighting and anti-tumor properties.”

Micrograph showing GVHD

Image from PLOS ONE

The US Food and Drug Administration (FDA) has granted orphan drug designation to a programmed cellular immunotherapy known as ProTmune™.

The designation is for ProTmune to be used as graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT).

This indication covers a range of diseases, including hematologic malignancies and genetic disorders.

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

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

About ProTmune

ProTmune is produced by modulating a donor-sourced, mobilized peripheral blood graft ex vivo with 2 small molecules—FT1050 and FT4145—to enhance the biological properties and therapeutic function of the graft’s immune cells.

The programmed mobilized peripheral blood graft is administered to a patient as a one-time intravenous infusion.

ProTmune is being developed by Fate Therapeutics, Inc.

The company is conducting a phase 1/2 trial testing ProTmune for the prevention of acute GVHD and cytomegalovirus infection in adults with hematologic malignancies who are undergoing allogeneic HSCT.

ProTmune was previously granted fast track designation from the FDA.

“The granting of both orphan drug and fast track designations for ProTmune validates the product candidate’s unique therapeutic potential to address life-threatening complications and improve the curative potential of allogeneic [HSCT],” said Scott Wolchko, president and chief executive officer of Fate Therapeutics.

“Graft-versus-host disease is a significant cause of morbidity and mortality in patients undergoing allogeneic [HSCT], and there are no FDA-approved therapies to prevent its occurrence. Through our development of ProTmune, we seek to transform the allogeneic [HSCT] paradigm by providing immunocompromised patients a therapeutically optimized donor graft containing immune cells with reduced alloreactivity and enhanced infection-fighting and anti-tumor properties.”

Micrograph showing GVHD

Image from PLOS ONE

The US Food and Drug Administration (FDA) has granted orphan drug designation to a programmed cellular immunotherapy known as ProTmune™.

The designation is for ProTmune to be used as graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplant (HSCT).

This indication covers a range of diseases, including hematologic malignancies and genetic disorders.

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

The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.

About ProTmune

ProTmune is produced by modulating a donor-sourced, mobilized peripheral blood graft ex vivo with 2 small molecules—FT1050 and FT4145—to enhance the biological properties and therapeutic function of the graft’s immune cells.

The programmed mobilized peripheral blood graft is administered to a patient as a one-time intravenous infusion.

ProTmune is being developed by Fate Therapeutics, Inc.

The company is conducting a phase 1/2 trial testing ProTmune for the prevention of acute GVHD and cytomegalovirus infection in adults with hematologic malignancies who are undergoing allogeneic HSCT.

ProTmune was previously granted fast track designation from the FDA.

“The granting of both orphan drug and fast track designations for ProTmune validates the product candidate’s unique therapeutic potential to address life-threatening complications and improve the curative potential of allogeneic [HSCT],” said Scott Wolchko, president and chief executive officer of Fate Therapeutics.

“Graft-versus-host disease is a significant cause of morbidity and mortality in patients undergoing allogeneic [HSCT], and there are no FDA-approved therapies to prevent its occurrence. Through our development of ProTmune, we seek to transform the allogeneic [HSCT] paradigm by providing immunocompromised patients a therapeutically optimized donor graft containing immune cells with reduced alloreactivity and enhanced infection-fighting and anti-tumor properties.”

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers say they have discovered a type of macrophage that may protect against lung infections during chemotherapy.

These macrophages, found in the lungs of mice, were able to survive chemotherapy.

The macrophages could remove bacteria when activated by a vaccine, which improved survival in mice with lethal bacterial pneumonia that had received chemotherapy and were therefore depleted of neutrophils.

The researchers said these results suggest the cells—known as vaccine-induced macrophages (ViMs)— might be able to protect cancer patients from life-threatening infections.

“We have identified a new form of housekeeping macrophage in mice that may, in future, be harnessed to protect against lung infections—like bacterial pneumonia—that remain one of the greatest threats to survival of cancer patients during chemotherapy,” said Peter Murray, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Murray and his colleagues detailed this discovery in PNAS.

Working in a mouse model that mimics infection in chemotherapy-treated patients, the researchers found that vaccination protected mice from Pseudomonas aeruginosa pneumonia.

The quest to understand how such protection was possible in the absence of neutrophils led the team to discover ViMs.

The researchers found that ViMs were produced in the lungs following vaccination, proliferated locally, and could persist for at least a month.

Analyses suggested ViMs are closely related to alveolar macrophages, which originate in the embryo, reside in the air-exposed surfaces of alveoli, and are self-maintained in adults.

“All lines of cellular and molecular evidence in this study point to alveolar macrophages as the source of ViMs,” Dr Murray said.

However, unlike alveolar macrophages, the population of ViMs remained stable during chemotherapy and exhibited enhanced phagocytic activity.

When ViMs were transferred to unvaccinated mice depleted of neutrophils via chemotherapy, the animals were protected from lethal Pseudomonas infections.

“We now know that increasing the number of ViMs in the tissue can compensate for the immune deficit caused by chemotherapy,” said study author Akinobu Kamei, MD, of St. Jude Children’s Research Hospital.

“In this study, we relied on vaccination prior to chemotherapy. Going forward, we will explore other, more practical methods for use at the bedside to effectively induce tissue-resident macrophages like ViMs.”

The possible approaches include using drugs or cytokines to induce protection in the immune-compromised host.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers say they have discovered a type of macrophage that may protect against lung infections during chemotherapy.

These macrophages, found in the lungs of mice, were able to survive chemotherapy.

The macrophages could remove bacteria when activated by a vaccine, which improved survival in mice with lethal bacterial pneumonia that had received chemotherapy and were therefore depleted of neutrophils.

The researchers said these results suggest the cells—known as vaccine-induced macrophages (ViMs)— might be able to protect cancer patients from life-threatening infections.

“We have identified a new form of housekeeping macrophage in mice that may, in future, be harnessed to protect against lung infections—like bacterial pneumonia—that remain one of the greatest threats to survival of cancer patients during chemotherapy,” said Peter Murray, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Murray and his colleagues detailed this discovery in PNAS.

Working in a mouse model that mimics infection in chemotherapy-treated patients, the researchers found that vaccination protected mice from Pseudomonas aeruginosa pneumonia.

The quest to understand how such protection was possible in the absence of neutrophils led the team to discover ViMs.

The researchers found that ViMs were produced in the lungs following vaccination, proliferated locally, and could persist for at least a month.

Analyses suggested ViMs are closely related to alveolar macrophages, which originate in the embryo, reside in the air-exposed surfaces of alveoli, and are self-maintained in adults.

“All lines of cellular and molecular evidence in this study point to alveolar macrophages as the source of ViMs,” Dr Murray said.

However, unlike alveolar macrophages, the population of ViMs remained stable during chemotherapy and exhibited enhanced phagocytic activity.

When ViMs were transferred to unvaccinated mice depleted of neutrophils via chemotherapy, the animals were protected from lethal Pseudomonas infections.

“We now know that increasing the number of ViMs in the tissue can compensate for the immune deficit caused by chemotherapy,” said study author Akinobu Kamei, MD, of St. Jude Children’s Research Hospital.

“In this study, we relied on vaccination prior to chemotherapy. Going forward, we will explore other, more practical methods for use at the bedside to effectively induce tissue-resident macrophages like ViMs.”

The possible approaches include using drugs or cytokines to induce protection in the immune-compromised host.

Cancer patient

receiving chemotherapy

Photo by Rhoda Baer

Researchers say they have discovered a type of macrophage that may protect against lung infections during chemotherapy.

These macrophages, found in the lungs of mice, were able to survive chemotherapy.

The macrophages could remove bacteria when activated by a vaccine, which improved survival in mice with lethal bacterial pneumonia that had received chemotherapy and were therefore depleted of neutrophils.

The researchers said these results suggest the cells—known as vaccine-induced macrophages (ViMs)— might be able to protect cancer patients from life-threatening infections.

“We have identified a new form of housekeeping macrophage in mice that may, in future, be harnessed to protect against lung infections—like bacterial pneumonia—that remain one of the greatest threats to survival of cancer patients during chemotherapy,” said Peter Murray, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

Dr Murray and his colleagues detailed this discovery in PNAS.

Working in a mouse model that mimics infection in chemotherapy-treated patients, the researchers found that vaccination protected mice from Pseudomonas aeruginosa pneumonia.

The quest to understand how such protection was possible in the absence of neutrophils led the team to discover ViMs.

The researchers found that ViMs were produced in the lungs following vaccination, proliferated locally, and could persist for at least a month.

Analyses suggested ViMs are closely related to alveolar macrophages, which originate in the embryo, reside in the air-exposed surfaces of alveoli, and are self-maintained in adults.

“All lines of cellular and molecular evidence in this study point to alveolar macrophages as the source of ViMs,” Dr Murray said.

However, unlike alveolar macrophages, the population of ViMs remained stable during chemotherapy and exhibited enhanced phagocytic activity.

When ViMs were transferred to unvaccinated mice depleted of neutrophils via chemotherapy, the animals were protected from lethal Pseudomonas infections.

“We now know that increasing the number of ViMs in the tissue can compensate for the immune deficit caused by chemotherapy,” said study author Akinobu Kamei, MD, of St. Jude Children’s Research Hospital.

“In this study, we relied on vaccination prior to chemotherapy. Going forward, we will explore other, more practical methods for use at the bedside to effectively induce tissue-resident macrophages like ViMs.”

The possible approaches include using drugs or cytokines to induce protection in the immune-compromised host.

70-year-old slides
Photo from the Institute
of Evolutionary Biology

A new study published in PNAS has provided insights regarding the origin and spread of European malaria.

The malaria-causing parasites Plasmodium vivax and Plasmodium falciparum were eradicated in Europe in the mid-twentieth century.

Now, researchers have recovered genetic data from European samples of malaria preserved on microscope slides in the 1940s.

The team performed second-generation sequencing on DNA extracted from 3 of the slides, which generated millions of sequences of malaria-causing parasites.

The researchers were then able to reconstruct the parasites’ mitochondrial genomes and compare them with those of present-day samples worldwide.

“The European sequence of P vivax is closely related to the most common strain currently found in Central and South America,” said study author Carles Lalueza-Fox, PhD, of the Institute of Evolutionary Biology (Consejo Superior de Investigaciones Científicas-Universitat Pompeu Fabra) in Barcelona, Spain.

“This suggests that the pathogen was introduced to the Americas by European colonists after Columbus. In contrast, the European sequence of P falciparum belongs to a strain which has only been found in India. This indicates that the pathogen of the most severe form of malaria was introduced to Europe from the Indian subcontinent, probably some 2500 years ago.”

The European samples the researchers analyzed were dated between 1942 and 1944. They originate from an old antimalarial center inaugurated in 1925 in Sant Jaume d’Enveja, on the Ebro Delta, located in Spain’s north-eastern region of Tarragona.

The center’s head, Ildefonso Canicio, spent decades treating malaria sufferers who worked in the area’s rice fields and ultimately contracted the disease himself.

Following Dr Canicio’s death in 1961, some of his slides, which were used for diagnostic purposes, were saved from destruction when they were recognized by his descendants, who allowed them to be used in the current study.

“It is still possible to see malaria-carrying parasites on the slides when they are studied under the microscope,” Dr Lalueza-Fox said. “However, the quantity of the pathogen’s DNA available in a single drop of blood is very limited, and when you add to that the issue of poor preservation after 70 years, it is clear why this type of study has never been carried out.”

Still, the researchers said this study has shown that historic specimens can be an important source of insight into the genetics of extinct or eradicated pathogens.

“Analyzing the nuclear genome in these pathogens will allow us to know more about the mutations which have made current-day strains resistant to different drugs, given that the European Plasmodium which has been retrieved is older than all of these treatments,” said study author Pere Gelabert, also of the Institute of Evolutionary Biology.

70-year-old slides
Photo from the Institute
of Evolutionary Biology

A new study published in PNAS has provided insights regarding the origin and spread of European malaria.

The malaria-causing parasites Plasmodium vivax and Plasmodium falciparum were eradicated in Europe in the mid-twentieth century.

Now, researchers have recovered genetic data from European samples of malaria preserved on microscope slides in the 1940s.

The team performed second-generation sequencing on DNA extracted from 3 of the slides, which generated millions of sequences of malaria-causing parasites.

The researchers were then able to reconstruct the parasites’ mitochondrial genomes and compare them with those of present-day samples worldwide.

“The European sequence of P vivax is closely related to the most common strain currently found in Central and South America,” said study author Carles Lalueza-Fox, PhD, of the Institute of Evolutionary Biology (Consejo Superior de Investigaciones Científicas-Universitat Pompeu Fabra) in Barcelona, Spain.

“This suggests that the pathogen was introduced to the Americas by European colonists after Columbus. In contrast, the European sequence of P falciparum belongs to a strain which has only been found in India. This indicates that the pathogen of the most severe form of malaria was introduced to Europe from the Indian subcontinent, probably some 2500 years ago.”

The European samples the researchers analyzed were dated between 1942 and 1944. They originate from an old antimalarial center inaugurated in 1925 in Sant Jaume d’Enveja, on the Ebro Delta, located in Spain’s north-eastern region of Tarragona.

The center’s head, Ildefonso Canicio, spent decades treating malaria sufferers who worked in the area’s rice fields and ultimately contracted the disease himself.

Following Dr Canicio’s death in 1961, some of his slides, which were used for diagnostic purposes, were saved from destruction when they were recognized by his descendants, who allowed them to be used in the current study.

“It is still possible to see malaria-carrying parasites on the slides when they are studied under the microscope,” Dr Lalueza-Fox said. “However, the quantity of the pathogen’s DNA available in a single drop of blood is very limited, and when you add to that the issue of poor preservation after 70 years, it is clear why this type of study has never been carried out.”

Still, the researchers said this study has shown that historic specimens can be an important source of insight into the genetics of extinct or eradicated pathogens.

“Analyzing the nuclear genome in these pathogens will allow us to know more about the mutations which have made current-day strains resistant to different drugs, given that the European Plasmodium which has been retrieved is older than all of these treatments,” said study author Pere Gelabert, also of the Institute of Evolutionary Biology.

70-year-old slides
Photo from the Institute
of Evolutionary Biology

A new study published in PNAS has provided insights regarding the origin and spread of European malaria.

The malaria-causing parasites Plasmodium vivax and Plasmodium falciparum were eradicated in Europe in the mid-twentieth century.

Now, researchers have recovered genetic data from European samples of malaria preserved on microscope slides in the 1940s.

The team performed second-generation sequencing on DNA extracted from 3 of the slides, which generated millions of sequences of malaria-causing parasites.

The researchers were then able to reconstruct the parasites’ mitochondrial genomes and compare them with those of present-day samples worldwide.

“The European sequence of P vivax is closely related to the most common strain currently found in Central and South America,” said study author Carles Lalueza-Fox, PhD, of the Institute of Evolutionary Biology (Consejo Superior de Investigaciones Científicas-Universitat Pompeu Fabra) in Barcelona, Spain.

“This suggests that the pathogen was introduced to the Americas by European colonists after Columbus. In contrast, the European sequence of P falciparum belongs to a strain which has only been found in India. This indicates that the pathogen of the most severe form of malaria was introduced to Europe from the Indian subcontinent, probably some 2500 years ago.”

The European samples the researchers analyzed were dated between 1942 and 1944. They originate from an old antimalarial center inaugurated in 1925 in Sant Jaume d’Enveja, on the Ebro Delta, located in Spain’s north-eastern region of Tarragona.

The center’s head, Ildefonso Canicio, spent decades treating malaria sufferers who worked in the area’s rice fields and ultimately contracted the disease himself.

Following Dr Canicio’s death in 1961, some of his slides, which were used for diagnostic purposes, were saved from destruction when they were recognized by his descendants, who allowed them to be used in the current study.

“It is still possible to see malaria-carrying parasites on the slides when they are studied under the microscope,” Dr Lalueza-Fox said. “However, the quantity of the pathogen’s DNA available in a single drop of blood is very limited, and when you add to that the issue of poor preservation after 70 years, it is clear why this type of study has never been carried out.”

Still, the researchers said this study has shown that historic specimens can be an important source of insight into the genetics of extinct or eradicated pathogens.

“Analyzing the nuclear genome in these pathogens will allow us to know more about the mutations which have made current-day strains resistant to different drugs, given that the European Plasmodium which has been retrieved is older than all of these treatments,” said study author Pere Gelabert, also of the Institute of Evolutionary Biology.

Drug production

Photo courtesy of the FDA

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have set up a new working group, or “cluster,” on rare diseases.

This means the EMA and FDA will hold regular meetings via teleconference to share information on the regulation of medicines for rare diseases.

The cluster will provide a forum for the confidential exchange of draft documents, proposed policies, and detailed information supporting the scientific basis for decision-making on medicine development.

The agencies will exchange information on topics such as:

• The design of clinical trials in small populations and the use of statistical analysis methods
• The selection and validation of trial endpoints
• Preclinical evidence to support development programs
• The design of post-marketing studies—in particular, in the context of early access mechanisms such as the EMA’s conditional marketing authorization and the FDA’s accelerated approval
• Risk management strategies for long-term safety issues with medicines for rare diseases.

The first meeting of the rare diseases cluster took place on September 23, 2016. The cluster will initially meet once a month via teleconference and will be chaired jointly by the FDA and EMA.

The creation of this cluster is the latest step in the EMA’s and FDA’s wider objective to expand and reinforce international collaboration.

The clusters established by the agencies focus on areas where the parties involved could benefit from an intensified exchange of information and strengthened collaboration.

The existing EMA/FDA clusters address issues related to patient engagement, biosimilars, orphan medicines, cancer drugs, medicines for children, and pharmacovigilance, among other topics.

Drug production

Photo courtesy of the FDA

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have set up a new working group, or “cluster,” on rare diseases.

This means the EMA and FDA will hold regular meetings via teleconference to share information on the regulation of medicines for rare diseases.

The cluster will provide a forum for the confidential exchange of draft documents, proposed policies, and detailed information supporting the scientific basis for decision-making on medicine development.

The agencies will exchange information on topics such as:

• The design of clinical trials in small populations and the use of statistical analysis methods
• The selection and validation of trial endpoints
• Preclinical evidence to support development programs
• The design of post-marketing studies—in particular, in the context of early access mechanisms such as the EMA’s conditional marketing authorization and the FDA’s accelerated approval
• Risk management strategies for long-term safety issues with medicines for rare diseases.

The first meeting of the rare diseases cluster took place on September 23, 2016. The cluster will initially meet once a month via teleconference and will be chaired jointly by the FDA and EMA.

The creation of this cluster is the latest step in the EMA’s and FDA’s wider objective to expand and reinforce international collaboration.

The clusters established by the agencies focus on areas where the parties involved could benefit from an intensified exchange of information and strengthened collaboration.

The existing EMA/FDA clusters address issues related to patient engagement, biosimilars, orphan medicines, cancer drugs, medicines for children, and pharmacovigilance, among other topics.

Drug production

Photo courtesy of the FDA

The European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have set up a new working group, or “cluster,” on rare diseases.

This means the EMA and FDA will hold regular meetings via teleconference to share information on the regulation of medicines for rare diseases.

The cluster will provide a forum for the confidential exchange of draft documents, proposed policies, and detailed information supporting the scientific basis for decision-making on medicine development.

The agencies will exchange information on topics such as:

• The design of clinical trials in small populations and the use of statistical analysis methods
• The selection and validation of trial endpoints
• Preclinical evidence to support development programs
• The design of post-marketing studies—in particular, in the context of early access mechanisms such as the EMA’s conditional marketing authorization and the FDA’s accelerated approval
• Risk management strategies for long-term safety issues with medicines for rare diseases.

The first meeting of the rare diseases cluster took place on September 23, 2016. The cluster will initially meet once a month via teleconference and will be chaired jointly by the FDA and EMA.

The creation of this cluster is the latest step in the EMA’s and FDA’s wider objective to expand and reinforce international collaboration.

The clusters established by the agencies focus on areas where the parties involved could benefit from an intensified exchange of information and strengthened collaboration.

The existing EMA/FDA clusters address issues related to patient engagement, biosimilars, orphan medicines, cancer drugs, medicines for children, and pharmacovigilance, among other topics.

Intramural ventricular septal defects (VSD), residual defects that can occur after repair of conotruncal defects in newborns, increase the risk of complications and death if they’re not detected and closed during the index operation. While various methods have been tried to find these defects during surgery, researchers from Children’s Hospital of Philadelphia (CHOP) reported that the use of transesophageal echocardiography (TEE) has a good chance of finding VSDs and giving cardiac surgeons the opportunity to correct these residual defects.

“TEE has modest sensitivity but high specificity for identifying intramural VSDs and can identify most defects requiring reinterventions,” Jyoti Patel, MD, and her coauthors reported in a study published in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:688-95).

Courtesy JTCVS/AATS

Previous studies have shown that intraoperative TEE is safe for evaluating operations in congenital heart disease, but this is the first study to evaluate the modality for detecting intramural VSDs, Dr. Patel and her colleagues said.

Dr. Patel and her coinvestigators analyzed results of TEE and postoperative transthoracic echocardiography (TTE) in patients who had biventricular repair of conotruncal anomalies at CHOP from January 2006 through June 2013. Intramural VSDs occurred in 34 of 337 patients who met the inclusion criteria out of a total population of 903. Actually, 462 patients had biventricular repairs of conotruncal defects involving baffle closure of a VSD, but 125 were excluded for various reasons, including 105 for inadequate intraoperative TEE.

TTE identified a total of 177 residual VSDs, 34 of which were intramural in nature. Among the evaluated procedures, both TEE at the end of the index operation and TTE detected VSD in 19 patients; TTE alone found VSD in 15. “Sensitivity was 56% and specificity was 100% for TEE to identify intramural VSDs,” Dr. Patel and her colleagues said.

What’s more, both TTE and TEE combined identified peripatch VSDs in 90 patients, while TTE only in 53 and TEE only in 15, “yielding a sensitivity of 63% and specificity of 92%,” Dr. Patel and her colleagues said.

Of the VSDs that required catheterization or reintervention during surgery, intraoperative TEE detected six of seven intramural VSDs and all five peripatch VSDs, the study found.

“In this study, TEE identified most intramural VSDs and all peripatch VSDs that required subsequent reintervention,” Dr. Patel and her colleagues said.

“This finding underscores the importance of adequate imaging of the superior aspect of the VSD patch during intraoperative TEE for conotruncal anomalies, given that many intramural defects may be repaired during the initial operation.”

Coauthor Andrew Glatz, MD, disclosed receiving consulting fees from Bristol-Myers Squibb, and coauthor Chitra Ravishankar, MD, disclosed lecture fees from Danone Medical. Dr. Patel and the remaining coauthors had no financial relationships to disclose.

Intramural ventricular septal defects (VSD), residual defects that can occur after repair of conotruncal defects in newborns, increase the risk of complications and death if they’re not detected and closed during the index operation. While various methods have been tried to find these defects during surgery, researchers from Children’s Hospital of Philadelphia (CHOP) reported that the use of transesophageal echocardiography (TEE) has a good chance of finding VSDs and giving cardiac surgeons the opportunity to correct these residual defects.

“TEE has modest sensitivity but high specificity for identifying intramural VSDs and can identify most defects requiring reinterventions,” Jyoti Patel, MD, and her coauthors reported in a study published in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:688-95).

Courtesy JTCVS/AATS

Previous studies have shown that intraoperative TEE is safe for evaluating operations in congenital heart disease, but this is the first study to evaluate the modality for detecting intramural VSDs, Dr. Patel and her colleagues said.

Dr. Patel and her coinvestigators analyzed results of TEE and postoperative transthoracic echocardiography (TTE) in patients who had biventricular repair of conotruncal anomalies at CHOP from January 2006 through June 2013. Intramural VSDs occurred in 34 of 337 patients who met the inclusion criteria out of a total population of 903. Actually, 462 patients had biventricular repairs of conotruncal defects involving baffle closure of a VSD, but 125 were excluded for various reasons, including 105 for inadequate intraoperative TEE.

TTE identified a total of 177 residual VSDs, 34 of which were intramural in nature. Among the evaluated procedures, both TEE at the end of the index operation and TTE detected VSD in 19 patients; TTE alone found VSD in 15. “Sensitivity was 56% and specificity was 100% for TEE to identify intramural VSDs,” Dr. Patel and her colleagues said.

What’s more, both TTE and TEE combined identified peripatch VSDs in 90 patients, while TTE only in 53 and TEE only in 15, “yielding a sensitivity of 63% and specificity of 92%,” Dr. Patel and her colleagues said.

Of the VSDs that required catheterization or reintervention during surgery, intraoperative TEE detected six of seven intramural VSDs and all five peripatch VSDs, the study found.

“In this study, TEE identified most intramural VSDs and all peripatch VSDs that required subsequent reintervention,” Dr. Patel and her colleagues said.

“This finding underscores the importance of adequate imaging of the superior aspect of the VSD patch during intraoperative TEE for conotruncal anomalies, given that many intramural defects may be repaired during the initial operation.”

Coauthor Andrew Glatz, MD, disclosed receiving consulting fees from Bristol-Myers Squibb, and coauthor Chitra Ravishankar, MD, disclosed lecture fees from Danone Medical. Dr. Patel and the remaining coauthors had no financial relationships to disclose.

Intramural ventricular septal defects (VSD), residual defects that can occur after repair of conotruncal defects in newborns, increase the risk of complications and death if they’re not detected and closed during the index operation. While various methods have been tried to find these defects during surgery, researchers from Children’s Hospital of Philadelphia (CHOP) reported that the use of transesophageal echocardiography (TEE) has a good chance of finding VSDs and giving cardiac surgeons the opportunity to correct these residual defects.

“TEE has modest sensitivity but high specificity for identifying intramural VSDs and can identify most defects requiring reinterventions,” Jyoti Patel, MD, and her coauthors reported in a study published in the September issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152:688-95).

Courtesy JTCVS/AATS

Previous studies have shown that intraoperative TEE is safe for evaluating operations in congenital heart disease, but this is the first study to evaluate the modality for detecting intramural VSDs, Dr. Patel and her colleagues said.

Dr. Patel and her coinvestigators analyzed results of TEE and postoperative transthoracic echocardiography (TTE) in patients who had biventricular repair of conotruncal anomalies at CHOP from January 2006 through June 2013. Intramural VSDs occurred in 34 of 337 patients who met the inclusion criteria out of a total population of 903. Actually, 462 patients had biventricular repairs of conotruncal defects involving baffle closure of a VSD, but 125 were excluded for various reasons, including 105 for inadequate intraoperative TEE.

TTE identified a total of 177 residual VSDs, 34 of which were intramural in nature. Among the evaluated procedures, both TEE at the end of the index operation and TTE detected VSD in 19 patients; TTE alone found VSD in 15. “Sensitivity was 56% and specificity was 100% for TEE to identify intramural VSDs,” Dr. Patel and her colleagues said.

What’s more, both TTE and TEE combined identified peripatch VSDs in 90 patients, while TTE only in 53 and TEE only in 15, “yielding a sensitivity of 63% and specificity of 92%,” Dr. Patel and her colleagues said.

Of the VSDs that required catheterization or reintervention during surgery, intraoperative TEE detected six of seven intramural VSDs and all five peripatch VSDs, the study found.

“In this study, TEE identified most intramural VSDs and all peripatch VSDs that required subsequent reintervention,” Dr. Patel and her colleagues said.

“This finding underscores the importance of adequate imaging of the superior aspect of the VSD patch during intraoperative TEE for conotruncal anomalies, given that many intramural defects may be repaired during the initial operation.”

Coauthor Andrew Glatz, MD, disclosed receiving consulting fees from Bristol-Myers Squibb, and coauthor Chitra Ravishankar, MD, disclosed lecture fees from Danone Medical. Dr. Patel and the remaining coauthors had no financial relationships to disclose.

As investigational transcatheter mitral valve therapies continue to explode onto the scene, cardiac surgeons must act now to seize and assert their place in the multidisciplinary team with interventional, imaging, and heart failure colleagues to deliver these treatments to people with complex mitral valve regurgitation, an expert opinion report in the August issue of the Journal of Thoracic and Cardiovascular Surgery states (J Thorac Cardiovasc Surg. 2016;152:330-6).

“There is a growing population of patients with primary and secondary mitral regurgitation underserved by surgical therapy because of comorbid risk,” Vinay Badhwar, MD, of West Virginia University and his colleagues said. “This has led to a tremendous activity of device development.”

With more than 25 different transcatheter mitral valve devices in development (MitraClip, Abbott Vascular, is the only FDA-approved transcatheter for primary mitral regurgitation [MR]), cardiac surgeons will soon have the tools to offer transcatheter mitral valve repair (TMVr) and transcatheter mitral valve replacement (TMVR) to more complex patients who have MR along with other health problems. Today about half of those patients do not get surgery because they are too frail, Dr. Badhwar and his colleagues said.

The authors used the astrophysical phrase “event horizon” to define the current state of transcatheter mitral valve therapies – “a point of no return.” They expect surgery to remain the treatment of choice for MR for the next 10 years. “However, as our patient cohorts become increasingly more complex and transcatheter mitral therapies more facile, the day when this will become a daily clinical reality will soon be upon us,” Dr. Badhwar and his colleagues said.

The multidisciplinary team approach will be integral in achieving the full potential of transcatheter mitral valve replacement or repair, Dr. Badhwar and his coauthors said. While surgery is the most effective treatment for primary MR, cardiac surgeons are challenged to introduce transcatheter treatments in patients who have other health problems. “The best way to adjudicate innovative surgical and interventional mitral therapies is through a robust collaboration within a well-functioning heart team that includes not only a cardiac surgeon and interventional cardiologist but also an imaging specialist,” the authors said.

The time to reach out to those other specialties is now, before those investigational devices start emerging from the development pipeline, Dr. Badhwar and his colleagues said. “This will soon enable the team-based mitral specialist to be facile in safely transitioning patients from open mitral surgery to TMVr or TMVR as most appropriate for durable long-term outcomes.”

Dr. Badhwar disclosed he is an uncompensated member of the Abbott Vascular advisory board. Coauthor Vinod Thourani, MD, disclosed relationships with Edwards Lifesciences, Medtronic Cardiovascular, Abbott Vascular, St. Jude Medical, Mitralign, and AtriCure. Coauthor Michael Mack, MD, serves on the Edwards Lifesciences steering committee Partner Trial and is an uncompensated co-principal investigator of the Abbott Vascular Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy Trial.

As investigational transcatheter mitral valve therapies continue to explode onto the scene, cardiac surgeons must act now to seize and assert their place in the multidisciplinary team with interventional, imaging, and heart failure colleagues to deliver these treatments to people with complex mitral valve regurgitation, an expert opinion report in the August issue of the Journal of Thoracic and Cardiovascular Surgery states (J Thorac Cardiovasc Surg. 2016;152:330-6).

“There is a growing population of patients with primary and secondary mitral regurgitation underserved by surgical therapy because of comorbid risk,” Vinay Badhwar, MD, of West Virginia University and his colleagues said. “This has led to a tremendous activity of device development.”

With more than 25 different transcatheter mitral valve devices in development (MitraClip, Abbott Vascular, is the only FDA-approved transcatheter for primary mitral regurgitation [MR]), cardiac surgeons will soon have the tools to offer transcatheter mitral valve repair (TMVr) and transcatheter mitral valve replacement (TMVR) to more complex patients who have MR along with other health problems. Today about half of those patients do not get surgery because they are too frail, Dr. Badhwar and his colleagues said.

The authors used the astrophysical phrase “event horizon” to define the current state of transcatheter mitral valve therapies – “a point of no return.” They expect surgery to remain the treatment of choice for MR for the next 10 years. “However, as our patient cohorts become increasingly more complex and transcatheter mitral therapies more facile, the day when this will become a daily clinical reality will soon be upon us,” Dr. Badhwar and his colleagues said.

The multidisciplinary team approach will be integral in achieving the full potential of transcatheter mitral valve replacement or repair, Dr. Badhwar and his coauthors said. While surgery is the most effective treatment for primary MR, cardiac surgeons are challenged to introduce transcatheter treatments in patients who have other health problems. “The best way to adjudicate innovative surgical and interventional mitral therapies is through a robust collaboration within a well-functioning heart team that includes not only a cardiac surgeon and interventional cardiologist but also an imaging specialist,” the authors said.

The time to reach out to those other specialties is now, before those investigational devices start emerging from the development pipeline, Dr. Badhwar and his colleagues said. “This will soon enable the team-based mitral specialist to be facile in safely transitioning patients from open mitral surgery to TMVr or TMVR as most appropriate for durable long-term outcomes.”

Dr. Badhwar disclosed he is an uncompensated member of the Abbott Vascular advisory board. Coauthor Vinod Thourani, MD, disclosed relationships with Edwards Lifesciences, Medtronic Cardiovascular, Abbott Vascular, St. Jude Medical, Mitralign, and AtriCure. Coauthor Michael Mack, MD, serves on the Edwards Lifesciences steering committee Partner Trial and is an uncompensated co-principal investigator of the Abbott Vascular Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy Trial.

As investigational transcatheter mitral valve therapies continue to explode onto the scene, cardiac surgeons must act now to seize and assert their place in the multidisciplinary team with interventional, imaging, and heart failure colleagues to deliver these treatments to people with complex mitral valve regurgitation, an expert opinion report in the August issue of the Journal of Thoracic and Cardiovascular Surgery states (J Thorac Cardiovasc Surg. 2016;152:330-6).

“There is a growing population of patients with primary and secondary mitral regurgitation underserved by surgical therapy because of comorbid risk,” Vinay Badhwar, MD, of West Virginia University and his colleagues said. “This has led to a tremendous activity of device development.”

With more than 25 different transcatheter mitral valve devices in development (MitraClip, Abbott Vascular, is the only FDA-approved transcatheter for primary mitral regurgitation [MR]), cardiac surgeons will soon have the tools to offer transcatheter mitral valve repair (TMVr) and transcatheter mitral valve replacement (TMVR) to more complex patients who have MR along with other health problems. Today about half of those patients do not get surgery because they are too frail, Dr. Badhwar and his colleagues said.

The authors used the astrophysical phrase “event horizon” to define the current state of transcatheter mitral valve therapies – “a point of no return.” They expect surgery to remain the treatment of choice for MR for the next 10 years. “However, as our patient cohorts become increasingly more complex and transcatheter mitral therapies more facile, the day when this will become a daily clinical reality will soon be upon us,” Dr. Badhwar and his colleagues said.

The multidisciplinary team approach will be integral in achieving the full potential of transcatheter mitral valve replacement or repair, Dr. Badhwar and his coauthors said. While surgery is the most effective treatment for primary MR, cardiac surgeons are challenged to introduce transcatheter treatments in patients who have other health problems. “The best way to adjudicate innovative surgical and interventional mitral therapies is through a robust collaboration within a well-functioning heart team that includes not only a cardiac surgeon and interventional cardiologist but also an imaging specialist,” the authors said.

The time to reach out to those other specialties is now, before those investigational devices start emerging from the development pipeline, Dr. Badhwar and his colleagues said. “This will soon enable the team-based mitral specialist to be facile in safely transitioning patients from open mitral surgery to TMVr or TMVR as most appropriate for durable long-term outcomes.”

Dr. Badhwar disclosed he is an uncompensated member of the Abbott Vascular advisory board. Coauthor Vinod Thourani, MD, disclosed relationships with Edwards Lifesciences, Medtronic Cardiovascular, Abbott Vascular, St. Jude Medical, Mitralign, and AtriCure. Coauthor Michael Mack, MD, serves on the Edwards Lifesciences steering committee Partner Trial and is an uncompensated co-principal investigator of the Abbott Vascular Clinical Outcomes Assessment of the MitraClip Percutaneous Therapy Trial.

Nikesh Ardeshna, MD

Dr. Ardeshna is the Medical Director of Adult Epilepsy Services at Royal Oak Hospital, Beaumont Health System, in Royal Oak, Michigan.

A 55-year-old woman with a past medical history of hypertension was brought to a local emergency department by ambulance after a co-worker noticed her repeating the phrase “I have to close the store, I have to close the store” to herself after the store was already closed. The patient did not recall this time period.

In the emergency room a drug screen was negative and a computed tomography (CT) scan of the head was negative. A routine EEG was normal. A diagnosis of a seizure was made and the patient was started on levetiracetam (Keppra) 1000 mg PO q12hrs.

The patient had a consultation with an epileptologist the following week. The consultation revealed that the patient family noticed that she had periods where she would stare, her speech would not make sense, and it would appear as though she was “chewing something.” The patient denied such symptoms. The patient’s family believed these symptoms had been present for at least 5 years, but thought they were due to tiredness. When questioned, the patient recalled at least 2 instances where she has fallen asleep in bed and woken up on the floor.

When asked about potential head trauma, the patient stated she was involved in a car accident 7 months ago, but the cause was not determined. The patient was driving, there was no inclement weather, and her car veered off the road and into the ditch. The patient was not intoxicated. She was not injured as a result of the accident.

Diagnosis: partial epilepsy with and without secondary generalization.

Questions and Discussion:

• Although the patient only recently received an official diagnosis of seizure, it is likely that she was having seizures for many years (at least 5 years per history).
  • Because of the long patient history with seizures, the more accurate diagnosis for this patient is complex partial epilepsy with secondary generalization.
• Does a normal routine EEG change the diagnosis?
  • No. An EEG can be normal in a patient with epilepsy.
• What further testing should be ordered?
  • The standard of care is to use dedicated magnetic resonance imaging (MRI) testing MRI-protocol for epilepsy.
• What was the likely cause of the car accident?
  • A seizure was the likely cause of the car accident.

Nikesh Ardeshna, MD

Dr. Ardeshna is the Medical Director of Adult Epilepsy Services at Royal Oak Hospital, Beaumont Health System, in Royal Oak, Michigan.

A 55-year-old woman with a past medical history of hypertension was brought to a local emergency department by ambulance after a co-worker noticed her repeating the phrase “I have to close the store, I have to close the store” to herself after the store was already closed. The patient did not recall this time period.

In the emergency room a drug screen was negative and a computed tomography (CT) scan of the head was negative. A routine EEG was normal. A diagnosis of a seizure was made and the patient was started on levetiracetam (Keppra) 1000 mg PO q12hrs.

The patient had a consultation with an epileptologist the following week. The consultation revealed that the patient family noticed that she had periods where she would stare, her speech would not make sense, and it would appear as though she was “chewing something.” The patient denied such symptoms. The patient’s family believed these symptoms had been present for at least 5 years, but thought they were due to tiredness. When questioned, the patient recalled at least 2 instances where she has fallen asleep in bed and woken up on the floor.

When asked about potential head trauma, the patient stated she was involved in a car accident 7 months ago, but the cause was not determined. The patient was driving, there was no inclement weather, and her car veered off the road and into the ditch. The patient was not intoxicated. She was not injured as a result of the accident.

Diagnosis: partial epilepsy with and without secondary generalization.

Questions and Discussion:

• Although the patient only recently received an official diagnosis of seizure, it is likely that she was having seizures for many years (at least 5 years per history).
  • Because of the long patient history with seizures, the more accurate diagnosis for this patient is complex partial epilepsy with secondary generalization.
• Does a normal routine EEG change the diagnosis?
  • No. An EEG can be normal in a patient with epilepsy.
• What further testing should be ordered?
  • The standard of care is to use dedicated magnetic resonance imaging (MRI) testing MRI-protocol for epilepsy.
• What was the likely cause of the car accident?
  • A seizure was the likely cause of the car accident.

Nikesh Ardeshna, MD

Dr. Ardeshna is the Medical Director of Adult Epilepsy Services at Royal Oak Hospital, Beaumont Health System, in Royal Oak, Michigan.

A 55-year-old woman with a past medical history of hypertension was brought to a local emergency department by ambulance after a co-worker noticed her repeating the phrase “I have to close the store, I have to close the store” to herself after the store was already closed. The patient did not recall this time period.

In the emergency room a drug screen was negative and a computed tomography (CT) scan of the head was negative. A routine EEG was normal. A diagnosis of a seizure was made and the patient was started on levetiracetam (Keppra) 1000 mg PO q12hrs.

The patient had a consultation with an epileptologist the following week. The consultation revealed that the patient family noticed that she had periods where she would stare, her speech would not make sense, and it would appear as though she was “chewing something.” The patient denied such symptoms. The patient’s family believed these symptoms had been present for at least 5 years, but thought they were due to tiredness. When questioned, the patient recalled at least 2 instances where she has fallen asleep in bed and woken up on the floor.

When asked about potential head trauma, the patient stated she was involved in a car accident 7 months ago, but the cause was not determined. The patient was driving, there was no inclement weather, and her car veered off the road and into the ditch. The patient was not intoxicated. She was not injured as a result of the accident.

Diagnosis: partial epilepsy with and without secondary generalization.

Questions and Discussion:

• Although the patient only recently received an official diagnosis of seizure, it is likely that she was having seizures for many years (at least 5 years per history).
  • Because of the long patient history with seizures, the more accurate diagnosis for this patient is complex partial epilepsy with secondary generalization.
• Does a normal routine EEG change the diagnosis?
  • No. An EEG can be normal in a patient with epilepsy.
• What further testing should be ordered?
  • The standard of care is to use dedicated magnetic resonance imaging (MRI) testing MRI-protocol for epilepsy.
• What was the likely cause of the car accident?
  • A seizure was the likely cause of the car accident.