Viral illnesses in pregnancy are not unheard of. When a patient presents with symptoms, we often think of an influenza type of infection that will be cleared within a short period of time and with few negative consequences for the developing fetus. Other infections that can occur include TORCH – Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes – infections, but these are also relatively common.

Rarely do we in the United States consider a gravida’s vulnerability to tropical infectious diseases such as dengue, chikungunya, and now Zika virus. With the popularity and ease of international travel, and the potential for women’s exposure to more exotic diseases, the practice of ob.gyn. must undergo a significant transition in perspective. It is vital for us to understand these illnesses because of their potency and reported injury to both the mother and baby, for several reasons.

First, there is the public health concern. As of June 16, 2016, the Pan American Health Organization of the World Health Organization, reported 39 countries and territories in the Americas with confirmed cases of Zika virus, with 21 of those countries having confirmed cases in pregnant women.

As of June 9, 2016, the Centers for Disease Control and Prevention reported that 234 pregnant women in the United States have laboratory evidence of possible Zika infection, along with 189 pregnant women living in U.S. territories. Since the current outbreak, which began in July 2015 in Brazil, seven countries – accounting for more than 1,600 cases – have reported babies with congenital syndrome associated with Zika virus, the majority of which have been in Brazil. With the Summer Olympics in Rio starting in August 2016, the potential spread of Zika virus is dizzying.

Second, there is the counseling and management concern. Without a treatment or vaccine available, ob.gyns. must stay current on the latest research and findings to inform their patients of the risks associated with travel to an area with confirmed, or areas at risk for developing, Zika virus transmission.

Third, there is a diagnostic concern. Women who have visited areas with Zika virus, or who have had intimate contact with someone who has traveled to these areas, must be diagnosed and then counseled immediately.

We have devoted this Master Class to a discussion of Zika virus and the work being conducted in the United States to understand this disease. We have invited Dr. Yoel Sadovsky, an expert on placental development and trophoblast function, and his colleague, Carolyn Coyne, Ph.D., a leading researcher on host-virus interactions, to address this important topic.

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

Viral illnesses in pregnancy are not unheard of. When a patient presents with symptoms, we often think of an influenza type of infection that will be cleared within a short period of time and with few negative consequences for the developing fetus. Other infections that can occur include TORCH – Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes – infections, but these are also relatively common.

Rarely do we in the United States consider a gravida’s vulnerability to tropical infectious diseases such as dengue, chikungunya, and now Zika virus. With the popularity and ease of international travel, and the potential for women’s exposure to more exotic diseases, the practice of ob.gyn. must undergo a significant transition in perspective. It is vital for us to understand these illnesses because of their potency and reported injury to both the mother and baby, for several reasons.

First, there is the public health concern. As of June 16, 2016, the Pan American Health Organization of the World Health Organization, reported 39 countries and territories in the Americas with confirmed cases of Zika virus, with 21 of those countries having confirmed cases in pregnant women.

As of June 9, 2016, the Centers for Disease Control and Prevention reported that 234 pregnant women in the United States have laboratory evidence of possible Zika infection, along with 189 pregnant women living in U.S. territories. Since the current outbreak, which began in July 2015 in Brazil, seven countries – accounting for more than 1,600 cases – have reported babies with congenital syndrome associated with Zika virus, the majority of which have been in Brazil. With the Summer Olympics in Rio starting in August 2016, the potential spread of Zika virus is dizzying.

Second, there is the counseling and management concern. Without a treatment or vaccine available, ob.gyns. must stay current on the latest research and findings to inform their patients of the risks associated with travel to an area with confirmed, or areas at risk for developing, Zika virus transmission.

Third, there is a diagnostic concern. Women who have visited areas with Zika virus, or who have had intimate contact with someone who has traveled to these areas, must be diagnosed and then counseled immediately.

We have devoted this Master Class to a discussion of Zika virus and the work being conducted in the United States to understand this disease. We have invited Dr. Yoel Sadovsky, an expert on placental development and trophoblast function, and his colleague, Carolyn Coyne, Ph.D., a leading researcher on host-virus interactions, to address this important topic.

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

Viral illnesses in pregnancy are not unheard of. When a patient presents with symptoms, we often think of an influenza type of infection that will be cleared within a short period of time and with few negative consequences for the developing fetus. Other infections that can occur include TORCH – Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes – infections, but these are also relatively common.

Rarely do we in the United States consider a gravida’s vulnerability to tropical infectious diseases such as dengue, chikungunya, and now Zika virus. With the popularity and ease of international travel, and the potential for women’s exposure to more exotic diseases, the practice of ob.gyn. must undergo a significant transition in perspective. It is vital for us to understand these illnesses because of their potency and reported injury to both the mother and baby, for several reasons.

First, there is the public health concern. As of June 16, 2016, the Pan American Health Organization of the World Health Organization, reported 39 countries and territories in the Americas with confirmed cases of Zika virus, with 21 of those countries having confirmed cases in pregnant women.

As of June 9, 2016, the Centers for Disease Control and Prevention reported that 234 pregnant women in the United States have laboratory evidence of possible Zika infection, along with 189 pregnant women living in U.S. territories. Since the current outbreak, which began in July 2015 in Brazil, seven countries – accounting for more than 1,600 cases – have reported babies with congenital syndrome associated with Zika virus, the majority of which have been in Brazil. With the Summer Olympics in Rio starting in August 2016, the potential spread of Zika virus is dizzying.

Second, there is the counseling and management concern. Without a treatment or vaccine available, ob.gyns. must stay current on the latest research and findings to inform their patients of the risks associated with travel to an area with confirmed, or areas at risk for developing, Zika virus transmission.

Third, there is a diagnostic concern. Women who have visited areas with Zika virus, or who have had intimate contact with someone who has traveled to these areas, must be diagnosed and then counseled immediately.

We have devoted this Master Class to a discussion of Zika virus and the work being conducted in the United States to understand this disease. We have invited Dr. Yoel Sadovsky, an expert on placental development and trophoblast function, and his colleague, Carolyn Coyne, Ph.D., a leading researcher on host-virus interactions, to address this important topic.

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

Trainees in congenital cardiac surgery fellowship programs are doing more operations since the programs became accredited in 2007, but no clear parameters have emerged to determine if certification has improved the quality of training, according to an evaluation of fellowship training programs published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016 Jun;151:1488-95).

Overall, the training has become standardized, the fellows’ operative experience is “robust,” and fellows are mostly satisfied since the Accreditation Council of Graduate Medical Education (ACGME) recognized congenital cardiac surgery as a fellowship in 2007, lead study author Dr. Brian Kogon of Emory University, Atlanta, said.

However, Dr. Kogon and his colleagues also found some shortcomings in fellowship training. They received survey responses from 36 of 44 fellows in 12 accredited programs nationwide. To determine if fellows were meeting minimum case requirements, they also reviewed operative logs of 38 of the 44 fellows. They compared their findings to a study of congenital cardiac surgery fellowship programs they did pre-ACGME accreditation (J Thorac Cardiovasc Surg. 2006 Dec;132:1280). “The number of operations performed by the fellows during their training was underwhelming, and most of the fellows were dissatisfied with their operative experience,” Dr. Kogon and his colleagues wrote in the earlier study.

The study found that all fellows achieved the minimum number of 75 total cases the standards require for graduation, with a median of 136; and the minimum standard of 36 specific qualifying cases with a median of 63. However, seven did not meet the minimum of five complex neonate cases. Among other types of operations for which fellows failed to meet the minimum cases were atrioventricular septal defect repair, arch reconstruction including coarctation procedures and systemic-to-pulmonary artery shunt procedures.

The comparative lack of adult cardiac surgery operations was also considered a potential problem, the authors noted, pointing out that “the number of adults who have congenital heart disease now exceeds the number of children who have the disease, and many of these patients will require an operation.”

Another shortcoming the study found was a drop-off in international fellowships since 2007. “This change places us at risk of becoming intellectually isolated and losing international relationships that are critical to the future of our specialty,” Dr. Kogon and his colleagues wrote. Graduated fellows also acknowledged dissatisfaction with their lack of exposure to neonate surgery.

The study also determined the following demographics of the fellows: 83% are men and the median age at graduation was 40 years, with a range of 35-48 years. Only 25% of graduates participated in nonsurgical rotations such as cardiac catheterization and echocardiography.

“Although the operative experience seems to be much more robust, and this finding has been corroborated in other surgical disciplines after the advent of ACGME accreditation, comparing training before and after the accreditation process came into existence is difficult,” Dr. Kogon and his colleagues said.

The study also noted that the Thoracic Surgery Directors Association developed a congenital curriculum for congenital cardiothoracic surgery fellows, but only 28% used that curriculum and only 61% used any formal curriculum. “Unfortunately, regardless of the curriculum, only 50% of the graduates found it helpful,” Dr. Kogon and his colleagues said.

And regardless of the curriculum, only half of the graduates have passed the written qualifying and oral certifying examinations after completing their fellowship. “Although the curriculum is quite robust, the latter statistic suggests that we need either more emphasis on education by the program directors or a better and/or different curriculum,” Dr. Kogon and his colleagues said. However, they added that “after training, former fellows have adequate case volumes and mixes and seem to be thriving in the field.”

Dr. Kogon and his study coauthors had no financial disclosures.

Trainees in congenital cardiac surgery fellowship programs are doing more operations since the programs became accredited in 2007, but no clear parameters have emerged to determine if certification has improved the quality of training, according to an evaluation of fellowship training programs published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016 Jun;151:1488-95).

Overall, the training has become standardized, the fellows’ operative experience is “robust,” and fellows are mostly satisfied since the Accreditation Council of Graduate Medical Education (ACGME) recognized congenital cardiac surgery as a fellowship in 2007, lead study author Dr. Brian Kogon of Emory University, Atlanta, said.

However, Dr. Kogon and his colleagues also found some shortcomings in fellowship training. They received survey responses from 36 of 44 fellows in 12 accredited programs nationwide. To determine if fellows were meeting minimum case requirements, they also reviewed operative logs of 38 of the 44 fellows. They compared their findings to a study of congenital cardiac surgery fellowship programs they did pre-ACGME accreditation (J Thorac Cardiovasc Surg. 2006 Dec;132:1280). “The number of operations performed by the fellows during their training was underwhelming, and most of the fellows were dissatisfied with their operative experience,” Dr. Kogon and his colleagues wrote in the earlier study.

The study found that all fellows achieved the minimum number of 75 total cases the standards require for graduation, with a median of 136; and the minimum standard of 36 specific qualifying cases with a median of 63. However, seven did not meet the minimum of five complex neonate cases. Among other types of operations for which fellows failed to meet the minimum cases were atrioventricular septal defect repair, arch reconstruction including coarctation procedures and systemic-to-pulmonary artery shunt procedures.

The comparative lack of adult cardiac surgery operations was also considered a potential problem, the authors noted, pointing out that “the number of adults who have congenital heart disease now exceeds the number of children who have the disease, and many of these patients will require an operation.”

Another shortcoming the study found was a drop-off in international fellowships since 2007. “This change places us at risk of becoming intellectually isolated and losing international relationships that are critical to the future of our specialty,” Dr. Kogon and his colleagues wrote. Graduated fellows also acknowledged dissatisfaction with their lack of exposure to neonate surgery.

The study also determined the following demographics of the fellows: 83% are men and the median age at graduation was 40 years, with a range of 35-48 years. Only 25% of graduates participated in nonsurgical rotations such as cardiac catheterization and echocardiography.

“Although the operative experience seems to be much more robust, and this finding has been corroborated in other surgical disciplines after the advent of ACGME accreditation, comparing training before and after the accreditation process came into existence is difficult,” Dr. Kogon and his colleagues said.

The study also noted that the Thoracic Surgery Directors Association developed a congenital curriculum for congenital cardiothoracic surgery fellows, but only 28% used that curriculum and only 61% used any formal curriculum. “Unfortunately, regardless of the curriculum, only 50% of the graduates found it helpful,” Dr. Kogon and his colleagues said.

And regardless of the curriculum, only half of the graduates have passed the written qualifying and oral certifying examinations after completing their fellowship. “Although the curriculum is quite robust, the latter statistic suggests that we need either more emphasis on education by the program directors or a better and/or different curriculum,” Dr. Kogon and his colleagues said. However, they added that “after training, former fellows have adequate case volumes and mixes and seem to be thriving in the field.”

Dr. Kogon and his study coauthors had no financial disclosures.

Trainees in congenital cardiac surgery fellowship programs are doing more operations since the programs became accredited in 2007, but no clear parameters have emerged to determine if certification has improved the quality of training, according to an evaluation of fellowship training programs published in the June issue of the Journal of Thoracic and Cardiovascular Surgery (2016 Jun;151:1488-95).

Overall, the training has become standardized, the fellows’ operative experience is “robust,” and fellows are mostly satisfied since the Accreditation Council of Graduate Medical Education (ACGME) recognized congenital cardiac surgery as a fellowship in 2007, lead study author Dr. Brian Kogon of Emory University, Atlanta, said.

However, Dr. Kogon and his colleagues also found some shortcomings in fellowship training. They received survey responses from 36 of 44 fellows in 12 accredited programs nationwide. To determine if fellows were meeting minimum case requirements, they also reviewed operative logs of 38 of the 44 fellows. They compared their findings to a study of congenital cardiac surgery fellowship programs they did pre-ACGME accreditation (J Thorac Cardiovasc Surg. 2006 Dec;132:1280). “The number of operations performed by the fellows during their training was underwhelming, and most of the fellows were dissatisfied with their operative experience,” Dr. Kogon and his colleagues wrote in the earlier study.

The study found that all fellows achieved the minimum number of 75 total cases the standards require for graduation, with a median of 136; and the minimum standard of 36 specific qualifying cases with a median of 63. However, seven did not meet the minimum of five complex neonate cases. Among other types of operations for which fellows failed to meet the minimum cases were atrioventricular septal defect repair, arch reconstruction including coarctation procedures and systemic-to-pulmonary artery shunt procedures.

The comparative lack of adult cardiac surgery operations was also considered a potential problem, the authors noted, pointing out that “the number of adults who have congenital heart disease now exceeds the number of children who have the disease, and many of these patients will require an operation.”

Another shortcoming the study found was a drop-off in international fellowships since 2007. “This change places us at risk of becoming intellectually isolated and losing international relationships that are critical to the future of our specialty,” Dr. Kogon and his colleagues wrote. Graduated fellows also acknowledged dissatisfaction with their lack of exposure to neonate surgery.

The study also determined the following demographics of the fellows: 83% are men and the median age at graduation was 40 years, with a range of 35-48 years. Only 25% of graduates participated in nonsurgical rotations such as cardiac catheterization and echocardiography.

“Although the operative experience seems to be much more robust, and this finding has been corroborated in other surgical disciplines after the advent of ACGME accreditation, comparing training before and after the accreditation process came into existence is difficult,” Dr. Kogon and his colleagues said.

The study also noted that the Thoracic Surgery Directors Association developed a congenital curriculum for congenital cardiothoracic surgery fellows, but only 28% used that curriculum and only 61% used any formal curriculum. “Unfortunately, regardless of the curriculum, only 50% of the graduates found it helpful,” Dr. Kogon and his colleagues said.

And regardless of the curriculum, only half of the graduates have passed the written qualifying and oral certifying examinations after completing their fellowship. “Although the curriculum is quite robust, the latter statistic suggests that we need either more emphasis on education by the program directors or a better and/or different curriculum,” Dr. Kogon and his colleagues said. However, they added that “after training, former fellows have adequate case volumes and mixes and seem to be thriving in the field.”

Dr. Kogon and his study coauthors had no financial disclosures.

Treating acute respiratory distress syndrome patients with helmets instead of face masks significantly reduced intubation rates and 90-day mortality rates, based on data from a randomized trial of 83 adults published in JAMA.

Acute respiratory distress syndrome (ARDS) can be treated using a face mask, but the mask is often inadequate, forcing patients to undergo intubation that can lead to additional problems including discomfort, delirium, and muscle deterioration, wrote Tianna Hicklin, Ph.D., in a column on the NIH website.

“The proposed mechanism for improved efficacy of these helmets is the preservation of applied pressures and avoidance of air leak. If the helmets indeed do allow clinicians both to be able to increase airway pressures above levels they typically would with mask-NIV and maintain those pressures without unpredictable system leak, that would be of great physiologic importance for patients with acute respiratory failure,” said Dr. Eric J. Gartman.

To explore the potential of noninvasive ventilation (NIV) using a helmet instead of a mask, both of which allow patients to remain awake in the ICU, the researchers randomized 83 adults with ARDS to treatment with either a helmet (44 patients) or a face mask (39 patients).

Intubation incidence was 18% in patients treated with helmets, compared with 62% for those treated with face masks. In addition, patients in the helmet group had significantly more ventilator-free days than the mask group (28 vs. 13; P less than .001), and both hospital mortality and 90-day mortality rates were significantly lower in the helmet group compared to the mask group (27% vs. 49%; P = .04 and 34% vs. 56%; P = .02, respectively)

Adverse event rates were rare, and similar between the helmet and mask groups. Three interface-related skin ulcers occurred in each group; nose ulcers in 7% of the mask group and neck ulcers in 7% of the helmet group.

The study population included adults aged 18 years and older who were admitted to the ICU at the University of Chicago between September 2012 and September 2015 and required face mask NIV. The average age of the patients was 58 years in the helmet group and 61 years in the mask group; there were no significant demographic differences between the groups. The most common causes of acute respiratory failure in both groups were pneumonia and pneumonia caused by immunosuppression.

The study results were limited by several factors including a lack of blinding, the need for a learning curve for clinicians using the helmet, and the potential for patient-ventilator dyssynchrony in the helmet group, noted Dr. Bhakti K. Patel of the University of Chicago and her colleagues (JAMA 2016;315:2435-41). Multicenter studies are needed to support the findings, they added. However, the findings “affirm the far-reaching benefits of spontaneous yet highly supported ventilation in an awake, animated patient over invasive medical ventilation via endotracheal tube,” they wrote. “These findings warrant further investigation of helmet NIV for patients with ARDS and other types of AHRF [acute hypoxemic respiratory failure], particularly with attention to long-term outcomes.”

The researchers had no financial conflicts to disclose.

“While the results of this study are very impressive, it is a single-center study, and obviously a larger multicenter trial (with all types of institutions included – not just large academic centers) would be helpful to elucidate the benefit of this technique and support a change in standard of care in the use of NIV. A change to this system would be a very large culture shift in NIV and would mean a significant amount of training (physician, nursing, respiratory care), purchasing the helmets, and ensuring that it is implemented properly and safely. As stated by the authors, this fact is similar to the change the occurred originally with NIV – but if their results reflect a true benefit over FM-NIV [face mask-noninvasive ventilation], such a large change would certainly be worth the effort,” Dr. Gartman said.

In a related study published in the Journal of Cardiothoracic and Vascular Anesthesia, patients treated with noninvasive positive pressure ventilation (NPPV) through helmets had significantly lower heart rates, lower average arterial pressure, and improved left ventricular ejection fraction at the end of treatment, compared with patients treated with ventilation masks and controls. Dr. Yi Yang of Capital Medical University in Beijing, China, and colleagues conducted the prospective study of 75 adults experiencing hypoxemia within 24 hours of extubation after Stanford type A aortic dissection. The participants were divided into three 25-patient groups. The control group was treated with high-flux inhalation of oxygen via a Venturi mask, another group was treated with NPPV via a mask, and the third group was treated with NPPV via a helmet. (J Card Vasc Anesth. 2016. http://dx.doi.org/10.1053/j.jvca.2016.03.129).

The study was funded by China’s public welfare industry of health.

Treating acute respiratory distress syndrome patients with helmets instead of face masks significantly reduced intubation rates and 90-day mortality rates, based on data from a randomized trial of 83 adults published in JAMA.

Acute respiratory distress syndrome (ARDS) can be treated using a face mask, but the mask is often inadequate, forcing patients to undergo intubation that can lead to additional problems including discomfort, delirium, and muscle deterioration, wrote Tianna Hicklin, Ph.D., in a column on the NIH website.

“The proposed mechanism for improved efficacy of these helmets is the preservation of applied pressures and avoidance of air leak. If the helmets indeed do allow clinicians both to be able to increase airway pressures above levels they typically would with mask-NIV and maintain those pressures without unpredictable system leak, that would be of great physiologic importance for patients with acute respiratory failure,” said Dr. Eric J. Gartman.

To explore the potential of noninvasive ventilation (NIV) using a helmet instead of a mask, both of which allow patients to remain awake in the ICU, the researchers randomized 83 adults with ARDS to treatment with either a helmet (44 patients) or a face mask (39 patients).

Intubation incidence was 18% in patients treated with helmets, compared with 62% for those treated with face masks. In addition, patients in the helmet group had significantly more ventilator-free days than the mask group (28 vs. 13; P less than .001), and both hospital mortality and 90-day mortality rates were significantly lower in the helmet group compared to the mask group (27% vs. 49%; P = .04 and 34% vs. 56%; P = .02, respectively)

Adverse event rates were rare, and similar between the helmet and mask groups. Three interface-related skin ulcers occurred in each group; nose ulcers in 7% of the mask group and neck ulcers in 7% of the helmet group.

The study population included adults aged 18 years and older who were admitted to the ICU at the University of Chicago between September 2012 and September 2015 and required face mask NIV. The average age of the patients was 58 years in the helmet group and 61 years in the mask group; there were no significant demographic differences between the groups. The most common causes of acute respiratory failure in both groups were pneumonia and pneumonia caused by immunosuppression.

The study results were limited by several factors including a lack of blinding, the need for a learning curve for clinicians using the helmet, and the potential for patient-ventilator dyssynchrony in the helmet group, noted Dr. Bhakti K. Patel of the University of Chicago and her colleagues (JAMA 2016;315:2435-41). Multicenter studies are needed to support the findings, they added. However, the findings “affirm the far-reaching benefits of spontaneous yet highly supported ventilation in an awake, animated patient over invasive medical ventilation via endotracheal tube,” they wrote. “These findings warrant further investigation of helmet NIV for patients with ARDS and other types of AHRF [acute hypoxemic respiratory failure], particularly with attention to long-term outcomes.”

The researchers had no financial conflicts to disclose.

“While the results of this study are very impressive, it is a single-center study, and obviously a larger multicenter trial (with all types of institutions included – not just large academic centers) would be helpful to elucidate the benefit of this technique and support a change in standard of care in the use of NIV. A change to this system would be a very large culture shift in NIV and would mean a significant amount of training (physician, nursing, respiratory care), purchasing the helmets, and ensuring that it is implemented properly and safely. As stated by the authors, this fact is similar to the change the occurred originally with NIV – but if their results reflect a true benefit over FM-NIV [face mask-noninvasive ventilation], such a large change would certainly be worth the effort,” Dr. Gartman said.

In a related study published in the Journal of Cardiothoracic and Vascular Anesthesia, patients treated with noninvasive positive pressure ventilation (NPPV) through helmets had significantly lower heart rates, lower average arterial pressure, and improved left ventricular ejection fraction at the end of treatment, compared with patients treated with ventilation masks and controls. Dr. Yi Yang of Capital Medical University in Beijing, China, and colleagues conducted the prospective study of 75 adults experiencing hypoxemia within 24 hours of extubation after Stanford type A aortic dissection. The participants were divided into three 25-patient groups. The control group was treated with high-flux inhalation of oxygen via a Venturi mask, another group was treated with NPPV via a mask, and the third group was treated with NPPV via a helmet. (J Card Vasc Anesth. 2016. http://dx.doi.org/10.1053/j.jvca.2016.03.129).

The study was funded by China’s public welfare industry of health.

Treating acute respiratory distress syndrome patients with helmets instead of face masks significantly reduced intubation rates and 90-day mortality rates, based on data from a randomized trial of 83 adults published in JAMA.

Acute respiratory distress syndrome (ARDS) can be treated using a face mask, but the mask is often inadequate, forcing patients to undergo intubation that can lead to additional problems including discomfort, delirium, and muscle deterioration, wrote Tianna Hicklin, Ph.D., in a column on the NIH website.

“The proposed mechanism for improved efficacy of these helmets is the preservation of applied pressures and avoidance of air leak. If the helmets indeed do allow clinicians both to be able to increase airway pressures above levels they typically would with mask-NIV and maintain those pressures without unpredictable system leak, that would be of great physiologic importance for patients with acute respiratory failure,” said Dr. Eric J. Gartman.

To explore the potential of noninvasive ventilation (NIV) using a helmet instead of a mask, both of which allow patients to remain awake in the ICU, the researchers randomized 83 adults with ARDS to treatment with either a helmet (44 patients) or a face mask (39 patients).

Intubation incidence was 18% in patients treated with helmets, compared with 62% for those treated with face masks. In addition, patients in the helmet group had significantly more ventilator-free days than the mask group (28 vs. 13; P less than .001), and both hospital mortality and 90-day mortality rates were significantly lower in the helmet group compared to the mask group (27% vs. 49%; P = .04 and 34% vs. 56%; P = .02, respectively)

Adverse event rates were rare, and similar between the helmet and mask groups. Three interface-related skin ulcers occurred in each group; nose ulcers in 7% of the mask group and neck ulcers in 7% of the helmet group.

The study population included adults aged 18 years and older who were admitted to the ICU at the University of Chicago between September 2012 and September 2015 and required face mask NIV. The average age of the patients was 58 years in the helmet group and 61 years in the mask group; there were no significant demographic differences between the groups. The most common causes of acute respiratory failure in both groups were pneumonia and pneumonia caused by immunosuppression.

The study results were limited by several factors including a lack of blinding, the need for a learning curve for clinicians using the helmet, and the potential for patient-ventilator dyssynchrony in the helmet group, noted Dr. Bhakti K. Patel of the University of Chicago and her colleagues (JAMA 2016;315:2435-41). Multicenter studies are needed to support the findings, they added. However, the findings “affirm the far-reaching benefits of spontaneous yet highly supported ventilation in an awake, animated patient over invasive medical ventilation via endotracheal tube,” they wrote. “These findings warrant further investigation of helmet NIV for patients with ARDS and other types of AHRF [acute hypoxemic respiratory failure], particularly with attention to long-term outcomes.”

The researchers had no financial conflicts to disclose.

“While the results of this study are very impressive, it is a single-center study, and obviously a larger multicenter trial (with all types of institutions included – not just large academic centers) would be helpful to elucidate the benefit of this technique and support a change in standard of care in the use of NIV. A change to this system would be a very large culture shift in NIV and would mean a significant amount of training (physician, nursing, respiratory care), purchasing the helmets, and ensuring that it is implemented properly and safely. As stated by the authors, this fact is similar to the change the occurred originally with NIV – but if their results reflect a true benefit over FM-NIV [face mask-noninvasive ventilation], such a large change would certainly be worth the effort,” Dr. Gartman said.

In a related study published in the Journal of Cardiothoracic and Vascular Anesthesia, patients treated with noninvasive positive pressure ventilation (NPPV) through helmets had significantly lower heart rates, lower average arterial pressure, and improved left ventricular ejection fraction at the end of treatment, compared with patients treated with ventilation masks and controls. Dr. Yi Yang of Capital Medical University in Beijing, China, and colleagues conducted the prospective study of 75 adults experiencing hypoxemia within 24 hours of extubation after Stanford type A aortic dissection. The participants were divided into three 25-patient groups. The control group was treated with high-flux inhalation of oxygen via a Venturi mask, another group was treated with NPPV via a mask, and the third group was treated with NPPV via a helmet. (J Card Vasc Anesth. 2016. http://dx.doi.org/10.1053/j.jvca.2016.03.129).

The study was funded by China’s public welfare industry of health.

Urine cultures should be performed in all children clinically suspected of having a urinary tract infection (UTI), results of a study in Pediatrics suggest.

That’s because pyuria may be absent in some children with certain uropathogens.

“Clinicians rely heavily on the degree of pyuria when making a presumptive diagnosis of UTI [but] lack of pyuria on an initial urinalysis may result in delayed diagnosis and delayed antimicrobial therapy,” explained Dr. Nader Shaikh of the University of Pittsburgh and his associates. “We hypothesized, based on some preliminary data in adults, that gram-positive organisms would cause less inflammation of the urinary tract and consequently cause less pyuria on urinalysis than infections caused by gram-negative organisms, in which pyuria is observed in the vast majority of cases.”

Dr. Shaikh and his coinvestigators looked at patients under the age of 18 years admitted to the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center between 2007 and 2013 with a UTI. Of 46,158 relevant hospital visits over the course of the study period, 1,181 children were ultimately selected for inclusion. Urine samples were tested for the presence of uropathogens, followed by analysis for the presence of pyuria, defined as having 5 or more white blood cells per high-powered field or at least 10 white blood cells per mm³ of urine (Pediatrics. 2016. doi: 10.1542/peds.2016-0087).

Only 150 subjects (13%) did not have pyuria; the remaining 1,031 (87%) of subjects did. Escherichia coli was found in 999 of the 1,181 (85%) subjects included, of which 892 (89%) had pyuria. Additionally, of the 27 children found to have Staphylococcus saprophyticus, all had pyuria. High rates of pyuria also were found in children whose urine had Proteus species and Enterobacter species uropathogens: 25 of 31 (81%) and 13 of 15 (87%), respectively.

However, the presence of three other pathogens suggested a lower association between pyuria and UTI. Pseudomonas aeruginosa was found in 13 children, of which 8 (62%) had pyuria; similarly, those with Enterococcus species uropathogens had a 54% chance of having pyuria (19 of 35) and those with Klebsiella species had a 74% chance (34 of 46). The takeaway, therefore, is that pyuria may not always be present in cases of UTI, especially if these pathogens are the cause of it; in fact, “the odds of pyuria were three to five times lower” with these pathogens, compared with E. coli.

“The most recent American Academy of Pediatrics guideline suggests that pyuria should be present when diagnosing a UTI [but] only 90% of children with UTI exhibit pyuria even when the urine specimen is collected by bladder catheterization or suprapubic aspiration,” Dr. Shaikh and his associates found, adding that the “findings of our study offer an additional explanation for the absence of pyuria – some uropathogens may not elicit a strong host inflammatory response – [and] suggest that bedside biomarkers that are more sensitive and specific than pyuria are needed to improve the accuracy of early diagnosis.”

There was no outside funding involved with this study. Dr. Shaikh and his coauthors did not report any relevant financial disclosures.

[email protected]

Urine cultures should be performed in all children clinically suspected of having a urinary tract infection (UTI), results of a study in Pediatrics suggest.

That’s because pyuria may be absent in some children with certain uropathogens.

“Clinicians rely heavily on the degree of pyuria when making a presumptive diagnosis of UTI [but] lack of pyuria on an initial urinalysis may result in delayed diagnosis and delayed antimicrobial therapy,” explained Dr. Nader Shaikh of the University of Pittsburgh and his associates. “We hypothesized, based on some preliminary data in adults, that gram-positive organisms would cause less inflammation of the urinary tract and consequently cause less pyuria on urinalysis than infections caused by gram-negative organisms, in which pyuria is observed in the vast majority of cases.”

Dr. Shaikh and his coinvestigators looked at patients under the age of 18 years admitted to the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center between 2007 and 2013 with a UTI. Of 46,158 relevant hospital visits over the course of the study period, 1,181 children were ultimately selected for inclusion. Urine samples were tested for the presence of uropathogens, followed by analysis for the presence of pyuria, defined as having 5 or more white blood cells per high-powered field or at least 10 white blood cells per mm³ of urine (Pediatrics. 2016. doi: 10.1542/peds.2016-0087).

Only 150 subjects (13%) did not have pyuria; the remaining 1,031 (87%) of subjects did. Escherichia coli was found in 999 of the 1,181 (85%) subjects included, of which 892 (89%) had pyuria. Additionally, of the 27 children found to have Staphylococcus saprophyticus, all had pyuria. High rates of pyuria also were found in children whose urine had Proteus species and Enterobacter species uropathogens: 25 of 31 (81%) and 13 of 15 (87%), respectively.

However, the presence of three other pathogens suggested a lower association between pyuria and UTI. Pseudomonas aeruginosa was found in 13 children, of which 8 (62%) had pyuria; similarly, those with Enterococcus species uropathogens had a 54% chance of having pyuria (19 of 35) and those with Klebsiella species had a 74% chance (34 of 46). The takeaway, therefore, is that pyuria may not always be present in cases of UTI, especially if these pathogens are the cause of it; in fact, “the odds of pyuria were three to five times lower” with these pathogens, compared with E. coli.

“The most recent American Academy of Pediatrics guideline suggests that pyuria should be present when diagnosing a UTI [but] only 90% of children with UTI exhibit pyuria even when the urine specimen is collected by bladder catheterization or suprapubic aspiration,” Dr. Shaikh and his associates found, adding that the “findings of our study offer an additional explanation for the absence of pyuria – some uropathogens may not elicit a strong host inflammatory response – [and] suggest that bedside biomarkers that are more sensitive and specific than pyuria are needed to improve the accuracy of early diagnosis.”

There was no outside funding involved with this study. Dr. Shaikh and his coauthors did not report any relevant financial disclosures.

[email protected]

Urine cultures should be performed in all children clinically suspected of having a urinary tract infection (UTI), results of a study in Pediatrics suggest.

That’s because pyuria may be absent in some children with certain uropathogens.

“Clinicians rely heavily on the degree of pyuria when making a presumptive diagnosis of UTI [but] lack of pyuria on an initial urinalysis may result in delayed diagnosis and delayed antimicrobial therapy,” explained Dr. Nader Shaikh of the University of Pittsburgh and his associates. “We hypothesized, based on some preliminary data in adults, that gram-positive organisms would cause less inflammation of the urinary tract and consequently cause less pyuria on urinalysis than infections caused by gram-negative organisms, in which pyuria is observed in the vast majority of cases.”

Dr. Shaikh and his coinvestigators looked at patients under the age of 18 years admitted to the Children’s Hospital of Pittsburgh at the University of Pittsburgh Medical Center between 2007 and 2013 with a UTI. Of 46,158 relevant hospital visits over the course of the study period, 1,181 children were ultimately selected for inclusion. Urine samples were tested for the presence of uropathogens, followed by analysis for the presence of pyuria, defined as having 5 or more white blood cells per high-powered field or at least 10 white blood cells per mm³ of urine (Pediatrics. 2016. doi: 10.1542/peds.2016-0087).

Only 150 subjects (13%) did not have pyuria; the remaining 1,031 (87%) of subjects did. Escherichia coli was found in 999 of the 1,181 (85%) subjects included, of which 892 (89%) had pyuria. Additionally, of the 27 children found to have Staphylococcus saprophyticus, all had pyuria. High rates of pyuria also were found in children whose urine had Proteus species and Enterobacter species uropathogens: 25 of 31 (81%) and 13 of 15 (87%), respectively.

However, the presence of three other pathogens suggested a lower association between pyuria and UTI. Pseudomonas aeruginosa was found in 13 children, of which 8 (62%) had pyuria; similarly, those with Enterococcus species uropathogens had a 54% chance of having pyuria (19 of 35) and those with Klebsiella species had a 74% chance (34 of 46). The takeaway, therefore, is that pyuria may not always be present in cases of UTI, especially if these pathogens are the cause of it; in fact, “the odds of pyuria were three to five times lower” with these pathogens, compared with E. coli.

“The most recent American Academy of Pediatrics guideline suggests that pyuria should be present when diagnosing a UTI [but] only 90% of children with UTI exhibit pyuria even when the urine specimen is collected by bladder catheterization or suprapubic aspiration,” Dr. Shaikh and his associates found, adding that the “findings of our study offer an additional explanation for the absence of pyuria – some uropathogens may not elicit a strong host inflammatory response – [and] suggest that bedside biomarkers that are more sensitive and specific than pyuria are needed to improve the accuracy of early diagnosis.”

There was no outside funding involved with this study. Dr. Shaikh and his coauthors did not report any relevant financial disclosures.

[email protected]

Due to many reasons, the healthcare paradigm has shifted, dictating alternative staffing models to manage the burgeoning inpatient census of hospital-based physicians. Herein, we will briefly describe the Emory University Division of Hospital Medicine (EDHM) approach to utilizing advanced practice providers (APPs) in the care of inpatients and summarize key components of the program that improve sustainability for providers.

The EDHM in Atlanta matriculated APPs into its service in 2004. Currently, there are 22 APPs across all Emory HM sites. The largest group is at Emory University Hospital Midtown (EUHM).

At EUHM, the addition of a renal service created concern for increased workload for the physicians. APPs were recruited to bridge the gap in 2011. Initially, the role was ill-defined, but over time, with physician and administrative leadership buy-in and support, the role has evolved. Currently at EUHM, APPs are practicing in other HM services, allowing them to practice near or at the top of their scope of practice. The 12 hospitalist APPs at EUHM practice in four roles: nocturnist, frontline provider in the observation unit, dedicated renal service, and generalist on an overflow team.

Along with the rapid growth of APPs on the service came the need for structured leadership, improved onboarding procedures, competency maintenance, advocacy, and professional development activities. Essentially, we needed to create a career track parallel to that of the physicians without compromising the portion of our scopes of our practice that overlap (i.e., patient care) while supporting our regulatory differences.

The professional development plans incorporated findings from APP exit interviews at the University of Maryland Medical Center highlighting the following retention issues:1

1. Length of time for credentialing
2. Role clarity
3. Inadequate clinical orientation
4. Feelings of clinical incompetence
5. Feelings of isolation

With the instillation of APP leadership, the team created a comprehensive APP program. The Hospital Medicine APP program at EUHM includes the following components:

• APP representation at monthly clinical operation meetings and quarterly education council meetings to ensure that APP competency and regulatory issues are always represented.
• Orientation personally tailored to the APP’s level of clinical expertise, with a post-orientation meeting with leadership and remediation, if needed.
• APP incentives to teach NP or PA students, conduct in-services, join committees, or participate in other leadership opportunities.
• APPs invited to attend and/or present at all divisional small and large group learning opportunities (e.g., Grand Rounds, Lunch and Learn, Journal Club).
• APPs allocated time and space to meet and discuss practice issues.
• Newly developed Mini-Hospitalist Academy, which offers monthly workshops to all hospitalist physicians and APPs, from novice to expert.
• Dedicated APP Ongoing Professional Performance Evaluation (OPPE) program.
• In addition to the annual monetary support offered for educational opportunities, the division offers an annual Faculty Development Award. This award is by application for eligible educational opportunities; APPs are welcome to apply and have consistently been awarded support to pursue myriad opportunities.

This successful APP-physician collaboration is driven by a committed group of professionals who are sensitive to the shifting healthcare paradigm. Our APPs and physicians are constantly adapting their practice so that our collaboration is safe, evidence-based, and professionally fulfilling. TH

Yvonne Brown, DNP, MSN, ACNP-C, FNP-C, nurse practitioner, lead advanced practice provider, Division of Hospital Medicine, Emory Healthcare, Emory University Hospital Midtown, Atlanta

Reference

1. Bahouth MN, Esposito-Herr MB. Orientation program for hospital-based nurse practitioners. AACN Adv Crit Care. 2009;20(1):82-90.

Due to many reasons, the healthcare paradigm has shifted, dictating alternative staffing models to manage the burgeoning inpatient census of hospital-based physicians. Herein, we will briefly describe the Emory University Division of Hospital Medicine (EDHM) approach to utilizing advanced practice providers (APPs) in the care of inpatients and summarize key components of the program that improve sustainability for providers.

The EDHM in Atlanta matriculated APPs into its service in 2004. Currently, there are 22 APPs across all Emory HM sites. The largest group is at Emory University Hospital Midtown (EUHM).

At EUHM, the addition of a renal service created concern for increased workload for the physicians. APPs were recruited to bridge the gap in 2011. Initially, the role was ill-defined, but over time, with physician and administrative leadership buy-in and support, the role has evolved. Currently at EUHM, APPs are practicing in other HM services, allowing them to practice near or at the top of their scope of practice. The 12 hospitalist APPs at EUHM practice in four roles: nocturnist, frontline provider in the observation unit, dedicated renal service, and generalist on an overflow team.

Along with the rapid growth of APPs on the service came the need for structured leadership, improved onboarding procedures, competency maintenance, advocacy, and professional development activities. Essentially, we needed to create a career track parallel to that of the physicians without compromising the portion of our scopes of our practice that overlap (i.e., patient care) while supporting our regulatory differences.

The professional development plans incorporated findings from APP exit interviews at the University of Maryland Medical Center highlighting the following retention issues:1

1. Length of time for credentialing
2. Role clarity
3. Inadequate clinical orientation
4. Feelings of clinical incompetence
5. Feelings of isolation

With the instillation of APP leadership, the team created a comprehensive APP program. The Hospital Medicine APP program at EUHM includes the following components:

• APP representation at monthly clinical operation meetings and quarterly education council meetings to ensure that APP competency and regulatory issues are always represented.
• Orientation personally tailored to the APP’s level of clinical expertise, with a post-orientation meeting with leadership and remediation, if needed.
• APP incentives to teach NP or PA students, conduct in-services, join committees, or participate in other leadership opportunities.
• APPs invited to attend and/or present at all divisional small and large group learning opportunities (e.g., Grand Rounds, Lunch and Learn, Journal Club).
• APPs allocated time and space to meet and discuss practice issues.
• Newly developed Mini-Hospitalist Academy, which offers monthly workshops to all hospitalist physicians and APPs, from novice to expert.
• Dedicated APP Ongoing Professional Performance Evaluation (OPPE) program.
• In addition to the annual monetary support offered for educational opportunities, the division offers an annual Faculty Development Award. This award is by application for eligible educational opportunities; APPs are welcome to apply and have consistently been awarded support to pursue myriad opportunities.

This successful APP-physician collaboration is driven by a committed group of professionals who are sensitive to the shifting healthcare paradigm. Our APPs and physicians are constantly adapting their practice so that our collaboration is safe, evidence-based, and professionally fulfilling. TH

Yvonne Brown, DNP, MSN, ACNP-C, FNP-C, nurse practitioner, lead advanced practice provider, Division of Hospital Medicine, Emory Healthcare, Emory University Hospital Midtown, Atlanta

Reference

1. Bahouth MN, Esposito-Herr MB. Orientation program for hospital-based nurse practitioners. AACN Adv Crit Care. 2009;20(1):82-90.

Due to many reasons, the healthcare paradigm has shifted, dictating alternative staffing models to manage the burgeoning inpatient census of hospital-based physicians. Herein, we will briefly describe the Emory University Division of Hospital Medicine (EDHM) approach to utilizing advanced practice providers (APPs) in the care of inpatients and summarize key components of the program that improve sustainability for providers.

The EDHM in Atlanta matriculated APPs into its service in 2004. Currently, there are 22 APPs across all Emory HM sites. The largest group is at Emory University Hospital Midtown (EUHM).

At EUHM, the addition of a renal service created concern for increased workload for the physicians. APPs were recruited to bridge the gap in 2011. Initially, the role was ill-defined, but over time, with physician and administrative leadership buy-in and support, the role has evolved. Currently at EUHM, APPs are practicing in other HM services, allowing them to practice near or at the top of their scope of practice. The 12 hospitalist APPs at EUHM practice in four roles: nocturnist, frontline provider in the observation unit, dedicated renal service, and generalist on an overflow team.

Along with the rapid growth of APPs on the service came the need for structured leadership, improved onboarding procedures, competency maintenance, advocacy, and professional development activities. Essentially, we needed to create a career track parallel to that of the physicians without compromising the portion of our scopes of our practice that overlap (i.e., patient care) while supporting our regulatory differences.

The professional development plans incorporated findings from APP exit interviews at the University of Maryland Medical Center highlighting the following retention issues:1

1. Length of time for credentialing
2. Role clarity
3. Inadequate clinical orientation
4. Feelings of clinical incompetence
5. Feelings of isolation

With the instillation of APP leadership, the team created a comprehensive APP program. The Hospital Medicine APP program at EUHM includes the following components:

• APP representation at monthly clinical operation meetings and quarterly education council meetings to ensure that APP competency and regulatory issues are always represented.
• Orientation personally tailored to the APP’s level of clinical expertise, with a post-orientation meeting with leadership and remediation, if needed.
• APP incentives to teach NP or PA students, conduct in-services, join committees, or participate in other leadership opportunities.
• APPs invited to attend and/or present at all divisional small and large group learning opportunities (e.g., Grand Rounds, Lunch and Learn, Journal Club).
• APPs allocated time and space to meet and discuss practice issues.
• Newly developed Mini-Hospitalist Academy, which offers monthly workshops to all hospitalist physicians and APPs, from novice to expert.
• Dedicated APP Ongoing Professional Performance Evaluation (OPPE) program.
• In addition to the annual monetary support offered for educational opportunities, the division offers an annual Faculty Development Award. This award is by application for eligible educational opportunities; APPs are welcome to apply and have consistently been awarded support to pursue myriad opportunities.

This successful APP-physician collaboration is driven by a committed group of professionals who are sensitive to the shifting healthcare paradigm. Our APPs and physicians are constantly adapting their practice so that our collaboration is safe, evidence-based, and professionally fulfilling. TH

Yvonne Brown, DNP, MSN, ACNP-C, FNP-C, nurse practitioner, lead advanced practice provider, Division of Hospital Medicine, Emory Healthcare, Emory University Hospital Midtown, Atlanta

Reference

1. Bahouth MN, Esposito-Herr MB. Orientation program for hospital-based nurse practitioners. AACN Adv Crit Care. 2009;20(1):82-90.

Laura Franco, MD

COPENHAGEN—Results of a new study suggest that vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) can both confer an increased risk of major bleeding, but the type of bleeding tends to differ with the type of anticoagulant.

The research showed that patients taking VKAs were more likely to be hospitalized for intracranial hemorrhage (ICH), while patients taking NOACs were more likely to be hospitalized for gastrointestinal (GI) bleeding.

In addition, the 30-day mortality rate was significantly lower in patients who were taking NOACs than in those who were taking VKAs. However, there was no significant difference between the 2 treatment groups when the researchers assessed mortality according to the type of major bleeding.

Laura Franco, MD, of the University of Perugia in Italy, presented these findings at the 21st Congress of the European Hematology Association (abstract S139*).

For this study, Dr Franco and her colleagues wanted to evaluate the real-life clinical presentation, management, and outcome of major bleeding in patients on anticoagulants.

So the team analyzed a cohort of patients treated at 9 Italian hospitals and a group of patients enrolled in Germany’s Dresden NOAC registry.

Between September 2013 and May 2016, there were 874 patients who were hospitalized for major bleeding—220 of whom who were taking NOACs and 654 of whom were taking VKAs.

Overall, 44% (n=386) of patients were hospitalized for an ICH, and 30% (n=261) were hospitalized for GI bleeding.

The incidence of ICH was 22% (n=48) among patients who received NOACs and 52% (n=338) among patients who received VKAs. The odds ratio was 0.26 (95% CI, 0.18-0.37; P<0.001).

The incidence of GI major bleeding was 46% (n=102) in the NOAC group and 24% (n=159) in the VKA group. The odds ratio was 2.69 (95% CI, 1.95-3.70; P<0.001).

The incidence of 30-day mortality was significantly higher in the VKA group than the NOAC group—17% and 10%, respectively. The adjusted hazard ratio (aHR) was 0.59 (95% CI, 0.36-0.94, P=0.012).

However, when the researchers looked at 30-day mortality according to the site of major bleeding, they observed no significant differences between the NOAC and VKA groups.

The incidence of 30-day mortality among patients with ICH was 25% in both the NOAC and VKA groups (aHR=1.07; 95% CI, 0.57-1.97). And the incidence of 30-day mortality among patients with GI bleeding was 7% in the NOAC group and 10% in the VKA group (aHR=0.66; 95% CI, 0.26-1.68).

*Data in the abstract differ from data presented at the meeting.

Laura Franco, MD

COPENHAGEN—Results of a new study suggest that vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) can both confer an increased risk of major bleeding, but the type of bleeding tends to differ with the type of anticoagulant.

The research showed that patients taking VKAs were more likely to be hospitalized for intracranial hemorrhage (ICH), while patients taking NOACs were more likely to be hospitalized for gastrointestinal (GI) bleeding.

In addition, the 30-day mortality rate was significantly lower in patients who were taking NOACs than in those who were taking VKAs. However, there was no significant difference between the 2 treatment groups when the researchers assessed mortality according to the type of major bleeding.

Laura Franco, MD, of the University of Perugia in Italy, presented these findings at the 21st Congress of the European Hematology Association (abstract S139*).

For this study, Dr Franco and her colleagues wanted to evaluate the real-life clinical presentation, management, and outcome of major bleeding in patients on anticoagulants.

So the team analyzed a cohort of patients treated at 9 Italian hospitals and a group of patients enrolled in Germany’s Dresden NOAC registry.

Between September 2013 and May 2016, there were 874 patients who were hospitalized for major bleeding—220 of whom who were taking NOACs and 654 of whom were taking VKAs.

Overall, 44% (n=386) of patients were hospitalized for an ICH, and 30% (n=261) were hospitalized for GI bleeding.

The incidence of ICH was 22% (n=48) among patients who received NOACs and 52% (n=338) among patients who received VKAs. The odds ratio was 0.26 (95% CI, 0.18-0.37; P<0.001).

The incidence of GI major bleeding was 46% (n=102) in the NOAC group and 24% (n=159) in the VKA group. The odds ratio was 2.69 (95% CI, 1.95-3.70; P<0.001).

The incidence of 30-day mortality was significantly higher in the VKA group than the NOAC group—17% and 10%, respectively. The adjusted hazard ratio (aHR) was 0.59 (95% CI, 0.36-0.94, P=0.012).

However, when the researchers looked at 30-day mortality according to the site of major bleeding, they observed no significant differences between the NOAC and VKA groups.

The incidence of 30-day mortality among patients with ICH was 25% in both the NOAC and VKA groups (aHR=1.07; 95% CI, 0.57-1.97). And the incidence of 30-day mortality among patients with GI bleeding was 7% in the NOAC group and 10% in the VKA group (aHR=0.66; 95% CI, 0.26-1.68).

*Data in the abstract differ from data presented at the meeting.

Laura Franco, MD

COPENHAGEN—Results of a new study suggest that vitamin K antagonists (VKAs) and non-VKA oral anticoagulants (NOACs) can both confer an increased risk of major bleeding, but the type of bleeding tends to differ with the type of anticoagulant.

The research showed that patients taking VKAs were more likely to be hospitalized for intracranial hemorrhage (ICH), while patients taking NOACs were more likely to be hospitalized for gastrointestinal (GI) bleeding.

In addition, the 30-day mortality rate was significantly lower in patients who were taking NOACs than in those who were taking VKAs. However, there was no significant difference between the 2 treatment groups when the researchers assessed mortality according to the type of major bleeding.

Laura Franco, MD, of the University of Perugia in Italy, presented these findings at the 21st Congress of the European Hematology Association (abstract S139*).

For this study, Dr Franco and her colleagues wanted to evaluate the real-life clinical presentation, management, and outcome of major bleeding in patients on anticoagulants.

So the team analyzed a cohort of patients treated at 9 Italian hospitals and a group of patients enrolled in Germany’s Dresden NOAC registry.

Between September 2013 and May 2016, there were 874 patients who were hospitalized for major bleeding—220 of whom who were taking NOACs and 654 of whom were taking VKAs.

Overall, 44% (n=386) of patients were hospitalized for an ICH, and 30% (n=261) were hospitalized for GI bleeding.

The incidence of ICH was 22% (n=48) among patients who received NOACs and 52% (n=338) among patients who received VKAs. The odds ratio was 0.26 (95% CI, 0.18-0.37; P<0.001).

The incidence of GI major bleeding was 46% (n=102) in the NOAC group and 24% (n=159) in the VKA group. The odds ratio was 2.69 (95% CI, 1.95-3.70; P<0.001).

The incidence of 30-day mortality was significantly higher in the VKA group than the NOAC group—17% and 10%, respectively. The adjusted hazard ratio (aHR) was 0.59 (95% CI, 0.36-0.94, P=0.012).

However, when the researchers looked at 30-day mortality according to the site of major bleeding, they observed no significant differences between the NOAC and VKA groups.

The incidence of 30-day mortality among patients with ICH was 25% in both the NOAC and VKA groups (aHR=1.07; 95% CI, 0.57-1.97). And the incidence of 30-day mortality among patients with GI bleeding was 7% in the NOAC group and 10% in the VKA group (aHR=0.66; 95% CI, 0.26-1.68).

*Data in the abstract differ from data presented at the meeting.

CML cells

Image by Difu Wu

Researchers have used a tiny force probe to compare how healthy hematopoietic cells and cancerous ones respond to stress.

They found that cells harvested from the bone marrow of 5 patients with chronic myeloid leukemia (CML) appeared much stiffer than comparable samples taken from 5 healthy volunteers.

In addition, the researchers were able to identify areas of localized brittle failure events in the CML cells.

“What makes this work so exciting to us is not simply seeing a difference between the stiffness of healthy and cancerous cells but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” said study author Françoise Argoul, PhD, of the French National Centre for Research (CNRS) in Lyon, France.

Dr Argoul and her colleagues described this work in Physical Biology.

The researchers believe the mechanical signatures obtained by squeezing or deforming cells could potentially assist physicians in determining the presence of CML and other hematologic malignancies.

The mechanical data might also provide clues as to how long the cells have been affected by the cancer.

“We would like to construct a hematopoietic cancer cell chart where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” Dr Argoul said.

Thinking about how the technique might be applied in a hospital setting, she added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures.

However, before the researchers can even progress to testing cells inside the body and preparing for clinical trials, they must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab.

CML cells

Image by Difu Wu

Researchers have used a tiny force probe to compare how healthy hematopoietic cells and cancerous ones respond to stress.

They found that cells harvested from the bone marrow of 5 patients with chronic myeloid leukemia (CML) appeared much stiffer than comparable samples taken from 5 healthy volunteers.

In addition, the researchers were able to identify areas of localized brittle failure events in the CML cells.

“What makes this work so exciting to us is not simply seeing a difference between the stiffness of healthy and cancerous cells but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” said study author Françoise Argoul, PhD, of the French National Centre for Research (CNRS) in Lyon, France.

Dr Argoul and her colleagues described this work in Physical Biology.

The researchers believe the mechanical signatures obtained by squeezing or deforming cells could potentially assist physicians in determining the presence of CML and other hematologic malignancies.

The mechanical data might also provide clues as to how long the cells have been affected by the cancer.

“We would like to construct a hematopoietic cancer cell chart where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” Dr Argoul said.

Thinking about how the technique might be applied in a hospital setting, she added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures.

However, before the researchers can even progress to testing cells inside the body and preparing for clinical trials, they must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab.

CML cells

Image by Difu Wu

Researchers have used a tiny force probe to compare how healthy hematopoietic cells and cancerous ones respond to stress.

They found that cells harvested from the bone marrow of 5 patients with chronic myeloid leukemia (CML) appeared much stiffer than comparable samples taken from 5 healthy volunteers.

In addition, the researchers were able to identify areas of localized brittle failure events in the CML cells.

“What makes this work so exciting to us is not simply seeing a difference between the stiffness of healthy and cancerous cells but observing that the cancerous cells also lost their dynamic ductility and behaved as more breakable objects,” said study author Françoise Argoul, PhD, of the French National Centre for Research (CNRS) in Lyon, France.

Dr Argoul and her colleagues described this work in Physical Biology.

The researchers believe the mechanical signatures obtained by squeezing or deforming cells could potentially assist physicians in determining the presence of CML and other hematologic malignancies.

The mechanical data might also provide clues as to how long the cells have been affected by the cancer.

“We would like to construct a hematopoietic cancer cell chart where the loss of cell mechanical functions could be graded, depending on the leukemia and its stage of evolution,” Dr Argoul said.

Thinking about how the technique might be applied in a hospital setting, she added that biopsy needles could, in principle, be adapted to allow local sensing of internal soft tissue structures.

However, before the researchers can even progress to testing cells inside the body and preparing for clinical trials, they must first build up sufficient information from their measurements on isolated cells under a range of conditions in the lab.

Skin biopsy showing GVHD

Image courtesy of PLOS ONE

A study published in Blood has revealed a protein that could be used to diagnose chronic graft-versus-host disease (cGVHD).

Investigators found elevated levels of the protein, CXCL10, in the blood of transplant recipients around the time they developed cGVHD.

The team therefore believes that testing a transplant patient for this protein could potentially enable early diagnosis of cGVHD.

“Diagnostic tests are desperately needed to make blood and marrow transplants safer,” said study author Kirk Schultz, of BC Children’s Hospital in Vancouver, British Columbia, Canada.

“At this time, there are no good tests to diagnose cGVHD, and the disease can only be identified too late—when it is already established. If we can diagnose it earlier and better, then treatments can be used to stop it before it becomes a chronic, disabling disease.”

For this study, Dr Schultz and his colleagues searched for cGVHD biomarkers in blood samples from 2 groups of adult patients—36 cGVHD patients who were at least 1 month from diagnosis and 31 time-matched control subjects without cGVHD.

This revealed 11 potential biomarkers. The investigators went on to test the validity of these biomarkers in 2 replication cohorts, which included a total of 134 patients with cGVHD and 154 control subjects.

Results showed that the inflammatory protein CXCL10 was consistently elevated in patients with cGVHD. This protein appears to impact a patient’s normal immune cells, preventing the body from fighting cGVHD.

The investigators also found evidence to suggest that another protein, sBAFF, is a biomarker of cGVHD.

Although these results may bring us one step closer to a diagnostic test for cGVHD, the team said further study is needed in larger patient groups.

Skin biopsy showing GVHD

Image courtesy of PLOS ONE

A study published in Blood has revealed a protein that could be used to diagnose chronic graft-versus-host disease (cGVHD).

Investigators found elevated levels of the protein, CXCL10, in the blood of transplant recipients around the time they developed cGVHD.

The team therefore believes that testing a transplant patient for this protein could potentially enable early diagnosis of cGVHD.

“Diagnostic tests are desperately needed to make blood and marrow transplants safer,” said study author Kirk Schultz, of BC Children’s Hospital in Vancouver, British Columbia, Canada.

“At this time, there are no good tests to diagnose cGVHD, and the disease can only be identified too late—when it is already established. If we can diagnose it earlier and better, then treatments can be used to stop it before it becomes a chronic, disabling disease.”

For this study, Dr Schultz and his colleagues searched for cGVHD biomarkers in blood samples from 2 groups of adult patients—36 cGVHD patients who were at least 1 month from diagnosis and 31 time-matched control subjects without cGVHD.

This revealed 11 potential biomarkers. The investigators went on to test the validity of these biomarkers in 2 replication cohorts, which included a total of 134 patients with cGVHD and 154 control subjects.

Results showed that the inflammatory protein CXCL10 was consistently elevated in patients with cGVHD. This protein appears to impact a patient’s normal immune cells, preventing the body from fighting cGVHD.

The investigators also found evidence to suggest that another protein, sBAFF, is a biomarker of cGVHD.

Although these results may bring us one step closer to a diagnostic test for cGVHD, the team said further study is needed in larger patient groups.

Skin biopsy showing GVHD

Image courtesy of PLOS ONE

A study published in Blood has revealed a protein that could be used to diagnose chronic graft-versus-host disease (cGVHD).

Investigators found elevated levels of the protein, CXCL10, in the blood of transplant recipients around the time they developed cGVHD.

The team therefore believes that testing a transplant patient for this protein could potentially enable early diagnosis of cGVHD.

“Diagnostic tests are desperately needed to make blood and marrow transplants safer,” said study author Kirk Schultz, of BC Children’s Hospital in Vancouver, British Columbia, Canada.

“At this time, there are no good tests to diagnose cGVHD, and the disease can only be identified too late—when it is already established. If we can diagnose it earlier and better, then treatments can be used to stop it before it becomes a chronic, disabling disease.”

For this study, Dr Schultz and his colleagues searched for cGVHD biomarkers in blood samples from 2 groups of adult patients—36 cGVHD patients who were at least 1 month from diagnosis and 31 time-matched control subjects without cGVHD.

This revealed 11 potential biomarkers. The investigators went on to test the validity of these biomarkers in 2 replication cohorts, which included a total of 134 patients with cGVHD and 154 control subjects.

Results showed that the inflammatory protein CXCL10 was consistently elevated in patients with cGVHD. This protein appears to impact a patient’s normal immune cells, preventing the body from fighting cGVHD.

The investigators also found evidence to suggest that another protein, sBAFF, is a biomarker of cGVHD.

Although these results may bring us one step closer to a diagnostic test for cGVHD, the team said further study is needed in larger patient groups.

Bottles of thalidomide

Researchers say they have identified the molecular mechanism of thalidomide and other immunomodulatory drugs (IMiDs), a finding that is relevant to the treatment of multiple myeloma and other hematologic malignancies.

Previous research showed that cereblon, a cellular protein, plays an important role in the function of IMiDs.

However, the exact details of how cereblon mediates the effects of IMiDs were not clear.

The new study, published in Nature Medicine, provides an explanation.

Researchers found that, inside cells, cereblon usually binds to the proteins CD147 and MCT1. Among other things, these 2 proteins promote proliferation, metabolism, and the formation of new blood vessels. In cancers such as multiple myeloma, tumor cells contain particularly high levels of CD147 and MCT1.

As a protein complex, CD147 and MCT1 always occur as a pair. However, to find their other half and become activated, the proteins require the help of cereblon.

Binding to cereblon promotes development and stability of the complex, which, in return, stimulates cell growth and facilitates the excretion of metabolic products like lactate.

In diseases such as multiple myeloma, an increased abundance of this protein complex enables tumor cells to multiply and spread rapidly.

If such a cancer is treated with IMiDs, the drug virtually displaces the complex from its binding to cereblon. As a result, CD147 and MCT1 can no longer be activated, and they vanish.

“Ultimately, this causes the tumor cells to die,” said study author Ruth Eichner, MD, of Technische Universität München in Munich, Germany.

But the disruption of the protein complex is also responsible for the severe birth defects that can occur in the children of women who take thalidomide and other IMiDs when pregnant.

“The mechanisms are identical,” said study author Florian Bassermann, MD, PhD, of Technische Universität München.

“A specific inactivation of the protein complex resulted in the same developmental defects observed after thalidomide treatment.”

The researchers said this confirms the prevailing hypothesis that the typical IMiD-induced birth defects are related to the reduced and abnormal formation of new blood vessels. That’s because, without CD147 and MCT1, blood vessels cannot develop properly.

The team also said these findings could be used to assess the efficacy of IMiD treatment before actually giving an IMiD to the patient.

“The disappearance of the protein complex could only be observed in patients that had responded well to this type of treatment,” Dr Bassermann explained.

Therefore, he and his colleagues believe this information could be used to assess a patient’s response before starting an IMiD. A sample of the patient’s tumor cells could be cultured and treated with IMiDs. If the cells showed a disruption of the complex, the patient would most likely benefit from IMiD treatment.

The researchers also think the results of this study could lead to the development of new anticancer therapies.

The team said the CD147-MCT1 protein complex is a particularly attractive target for tumor treatment, as it is mainly found on the surface of cells and virtually links the inside to the outside of the cell.

Therefore, inactivation of the complex might be achieved using specifically produced antibodies and other distinctive drugs—a possibility Dr Bassermann and his team are now exploring.

Bottles of thalidomide

Researchers say they have identified the molecular mechanism of thalidomide and other immunomodulatory drugs (IMiDs), a finding that is relevant to the treatment of multiple myeloma and other hematologic malignancies.

Previous research showed that cereblon, a cellular protein, plays an important role in the function of IMiDs.

However, the exact details of how cereblon mediates the effects of IMiDs were not clear.

The new study, published in Nature Medicine, provides an explanation.

Researchers found that, inside cells, cereblon usually binds to the proteins CD147 and MCT1. Among other things, these 2 proteins promote proliferation, metabolism, and the formation of new blood vessels. In cancers such as multiple myeloma, tumor cells contain particularly high levels of CD147 and MCT1.

As a protein complex, CD147 and MCT1 always occur as a pair. However, to find their other half and become activated, the proteins require the help of cereblon.

Binding to cereblon promotes development and stability of the complex, which, in return, stimulates cell growth and facilitates the excretion of metabolic products like lactate.

In diseases such as multiple myeloma, an increased abundance of this protein complex enables tumor cells to multiply and spread rapidly.

If such a cancer is treated with IMiDs, the drug virtually displaces the complex from its binding to cereblon. As a result, CD147 and MCT1 can no longer be activated, and they vanish.

“Ultimately, this causes the tumor cells to die,” said study author Ruth Eichner, MD, of Technische Universität München in Munich, Germany.

But the disruption of the protein complex is also responsible for the severe birth defects that can occur in the children of women who take thalidomide and other IMiDs when pregnant.

“The mechanisms are identical,” said study author Florian Bassermann, MD, PhD, of Technische Universität München.

“A specific inactivation of the protein complex resulted in the same developmental defects observed after thalidomide treatment.”

The researchers said this confirms the prevailing hypothesis that the typical IMiD-induced birth defects are related to the reduced and abnormal formation of new blood vessels. That’s because, without CD147 and MCT1, blood vessels cannot develop properly.

The team also said these findings could be used to assess the efficacy of IMiD treatment before actually giving an IMiD to the patient.

“The disappearance of the protein complex could only be observed in patients that had responded well to this type of treatment,” Dr Bassermann explained.

Therefore, he and his colleagues believe this information could be used to assess a patient’s response before starting an IMiD. A sample of the patient’s tumor cells could be cultured and treated with IMiDs. If the cells showed a disruption of the complex, the patient would most likely benefit from IMiD treatment.

The researchers also think the results of this study could lead to the development of new anticancer therapies.

The team said the CD147-MCT1 protein complex is a particularly attractive target for tumor treatment, as it is mainly found on the surface of cells and virtually links the inside to the outside of the cell.

Therefore, inactivation of the complex might be achieved using specifically produced antibodies and other distinctive drugs—a possibility Dr Bassermann and his team are now exploring.

Bottles of thalidomide

Researchers say they have identified the molecular mechanism of thalidomide and other immunomodulatory drugs (IMiDs), a finding that is relevant to the treatment of multiple myeloma and other hematologic malignancies.

Previous research showed that cereblon, a cellular protein, plays an important role in the function of IMiDs.

However, the exact details of how cereblon mediates the effects of IMiDs were not clear.

The new study, published in Nature Medicine, provides an explanation.

Researchers found that, inside cells, cereblon usually binds to the proteins CD147 and MCT1. Among other things, these 2 proteins promote proliferation, metabolism, and the formation of new blood vessels. In cancers such as multiple myeloma, tumor cells contain particularly high levels of CD147 and MCT1.

As a protein complex, CD147 and MCT1 always occur as a pair. However, to find their other half and become activated, the proteins require the help of cereblon.

Binding to cereblon promotes development and stability of the complex, which, in return, stimulates cell growth and facilitates the excretion of metabolic products like lactate.

In diseases such as multiple myeloma, an increased abundance of this protein complex enables tumor cells to multiply and spread rapidly.

If such a cancer is treated with IMiDs, the drug virtually displaces the complex from its binding to cereblon. As a result, CD147 and MCT1 can no longer be activated, and they vanish.

“Ultimately, this causes the tumor cells to die,” said study author Ruth Eichner, MD, of Technische Universität München in Munich, Germany.

But the disruption of the protein complex is also responsible for the severe birth defects that can occur in the children of women who take thalidomide and other IMiDs when pregnant.

“The mechanisms are identical,” said study author Florian Bassermann, MD, PhD, of Technische Universität München.

“A specific inactivation of the protein complex resulted in the same developmental defects observed after thalidomide treatment.”

The researchers said this confirms the prevailing hypothesis that the typical IMiD-induced birth defects are related to the reduced and abnormal formation of new blood vessels. That’s because, without CD147 and MCT1, blood vessels cannot develop properly.

The team also said these findings could be used to assess the efficacy of IMiD treatment before actually giving an IMiD to the patient.

“The disappearance of the protein complex could only be observed in patients that had responded well to this type of treatment,” Dr Bassermann explained.

Therefore, he and his colleagues believe this information could be used to assess a patient’s response before starting an IMiD. A sample of the patient’s tumor cells could be cultured and treated with IMiDs. If the cells showed a disruption of the complex, the patient would most likely benefit from IMiD treatment.

The researchers also think the results of this study could lead to the development of new anticancer therapies.

The team said the CD147-MCT1 protein complex is a particularly attractive target for tumor treatment, as it is mainly found on the surface of cells and virtually links the inside to the outside of the cell.

Therefore, inactivation of the complex might be achieved using specifically produced antibodies and other distinctive drugs—a possibility Dr Bassermann and his team are now exploring.

Long-term pioglitazone is not only safe for patients with nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes but is associated with significant improvements in fatty liver disease outcomes, compared with placebo, research suggests.

Investigators randomized 101 individuals with biopsy-proven NASH and either prediabetes or type 2 diabetes to 18 months of 45 mg/day of pioglitazone or placebo, followed by an 18 month open-label phase of pioglitazone, in addition to a hypocaloric diet, according to a paper published online June 20 in the Annals of Internal Medicine.

©pixologicstudio/thinkstockphotos.com

Among patients randomized to pioglitazone, 58% achieved at least a two-point reduction in their NASH activity score, without a worsening of fibrosis, compared with only 17% of the placebo group (P less than .001).

The pioglitazone group also showed a significantly greater likelihood that their NASH would resolve, with 51% of the treatment group achieving resolution, compared with 19% of the placebo group (P less than .001).

Pioglitazone treatment was also associated with significantly greater improvements in steatosis, inflammation, and ballooning necrosis, as well as mean histologic scores and fibrosis scores (Ann Intern Med. 2016 Jun 20. doi: 10.7326/M15-1774).

The study also showed that only 12% of the pioglitazone group showed progression of any fibrosis, compared with 28% of the placebo group (P = .039), while pioglitazone was associated with significant 2.5 kg weight gain over placebo.

“Because thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes hepatic ‘lipotoxicity’ in NASH (which is also a prominent feature of T2DM), they may be more helpful for treating steatohepatitis in this population,” wrote Dr. Kenneth Cusi, from the division of endocrinology at the University of Florida, Gainesville, and his coauthors.

However, the authors noted that there have been relatively few studies of pioglitazone and its effects on steatohepatitis in individuals with prediabetes or type 2 diabetes.

“This study also has implications for patients with prediabetes and NASH (about half of our participants) because hepatic steatosis is a risk factor for T2DM, even in nonobese patients,” the authors wrote. They suggested that future studies could explore whether the reversal of hepatic steatosis or nonalcoholic steatohepatitis in patients with prediabetes may help to halt the development of type 2 diabetes.

The study was supported by the Burroughs Wellcome Fund and the American Diabetes Association. One author reported nonfinancial support from Takeda Pharmaceuticals in the form of study medication and placebo, and grants and consultancies from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

Long-term pioglitazone is not only safe for patients with nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes but is associated with significant improvements in fatty liver disease outcomes, compared with placebo, research suggests.

Investigators randomized 101 individuals with biopsy-proven NASH and either prediabetes or type 2 diabetes to 18 months of 45 mg/day of pioglitazone or placebo, followed by an 18 month open-label phase of pioglitazone, in addition to a hypocaloric diet, according to a paper published online June 20 in the Annals of Internal Medicine.

©pixologicstudio/thinkstockphotos.com

Among patients randomized to pioglitazone, 58% achieved at least a two-point reduction in their NASH activity score, without a worsening of fibrosis, compared with only 17% of the placebo group (P less than .001).

The pioglitazone group also showed a significantly greater likelihood that their NASH would resolve, with 51% of the treatment group achieving resolution, compared with 19% of the placebo group (P less than .001).

Pioglitazone treatment was also associated with significantly greater improvements in steatosis, inflammation, and ballooning necrosis, as well as mean histologic scores and fibrosis scores (Ann Intern Med. 2016 Jun 20. doi: 10.7326/M15-1774).

The study also showed that only 12% of the pioglitazone group showed progression of any fibrosis, compared with 28% of the placebo group (P = .039), while pioglitazone was associated with significant 2.5 kg weight gain over placebo.

“Because thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes hepatic ‘lipotoxicity’ in NASH (which is also a prominent feature of T2DM), they may be more helpful for treating steatohepatitis in this population,” wrote Dr. Kenneth Cusi, from the division of endocrinology at the University of Florida, Gainesville, and his coauthors.

However, the authors noted that there have been relatively few studies of pioglitazone and its effects on steatohepatitis in individuals with prediabetes or type 2 diabetes.

“This study also has implications for patients with prediabetes and NASH (about half of our participants) because hepatic steatosis is a risk factor for T2DM, even in nonobese patients,” the authors wrote. They suggested that future studies could explore whether the reversal of hepatic steatosis or nonalcoholic steatohepatitis in patients with prediabetes may help to halt the development of type 2 diabetes.

The study was supported by the Burroughs Wellcome Fund and the American Diabetes Association. One author reported nonfinancial support from Takeda Pharmaceuticals in the form of study medication and placebo, and grants and consultancies from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.

Long-term pioglitazone is not only safe for patients with nonalcoholic steatohepatitis (NASH) and prediabetes or type 2 diabetes but is associated with significant improvements in fatty liver disease outcomes, compared with placebo, research suggests.

Investigators randomized 101 individuals with biopsy-proven NASH and either prediabetes or type 2 diabetes to 18 months of 45 mg/day of pioglitazone or placebo, followed by an 18 month open-label phase of pioglitazone, in addition to a hypocaloric diet, according to a paper published online June 20 in the Annals of Internal Medicine.

©pixologicstudio/thinkstockphotos.com

Among patients randomized to pioglitazone, 58% achieved at least a two-point reduction in their NASH activity score, without a worsening of fibrosis, compared with only 17% of the placebo group (P less than .001).

The pioglitazone group also showed a significantly greater likelihood that their NASH would resolve, with 51% of the treatment group achieving resolution, compared with 19% of the placebo group (P less than .001).

Pioglitazone treatment was also associated with significantly greater improvements in steatosis, inflammation, and ballooning necrosis, as well as mean histologic scores and fibrosis scores (Ann Intern Med. 2016 Jun 20. doi: 10.7326/M15-1774).

The study also showed that only 12% of the pioglitazone group showed progression of any fibrosis, compared with 28% of the placebo group (P = .039), while pioglitazone was associated with significant 2.5 kg weight gain over placebo.

“Because thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes hepatic ‘lipotoxicity’ in NASH (which is also a prominent feature of T2DM), they may be more helpful for treating steatohepatitis in this population,” wrote Dr. Kenneth Cusi, from the division of endocrinology at the University of Florida, Gainesville, and his coauthors.

However, the authors noted that there have been relatively few studies of pioglitazone and its effects on steatohepatitis in individuals with prediabetes or type 2 diabetes.

“This study also has implications for patients with prediabetes and NASH (about half of our participants) because hepatic steatosis is a risk factor for T2DM, even in nonobese patients,” the authors wrote. They suggested that future studies could explore whether the reversal of hepatic steatosis or nonalcoholic steatohepatitis in patients with prediabetes may help to halt the development of type 2 diabetes.

The study was supported by the Burroughs Wellcome Fund and the American Diabetes Association. One author reported nonfinancial support from Takeda Pharmaceuticals in the form of study medication and placebo, and grants and consultancies from pharmaceutical companies outside the submitted work. No other conflicts of interest were declared.