Photo from David Levy

Physicians have reported what they believe is the first case of an allogeneic hematopoietic stem cell transplant (allo-HSCT) curing an adult with congenital dyserythropoietic anemia (CDA).

The patient, David Levy, was previously transfusion-dependent and suffered from iron overload, severe pain, and other adverse effects of his illness.

Levy was denied a transplant for years, but, in 2014, he received a non-myeloablative allo-HSCT from a matched, unrelated donor.

Now, Levy no longer requires transfusions, iron chelation, or immunosuppression, and says he is able to live a normal life.

Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues described Levy’s case in a letter to Bone Marrow Transplantation.

Levy was diagnosed with CDA at 4 months of age and was treated with regular blood transfusions for most of his life. He was 24 when the pain from his illness became so severe that he had to withdraw from graduate school.

“I spent the following years doing nothing—no work, no school, no social contact—because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every 2 to 3 weeks, had undergone a splenectomy, had an enlarged liver, and was suffering from fatigue, heart palpitations, and iron overload.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr Rondelli.”

Dr Rondelli said that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a transplant.

However, Dr Rondelli and his colleagues had reported success with chemotherapy-free allo-HSCT in patients with sickle cell disease. So Dr Rondelli performed Levy’s transplant in 2014.

Levy received a peripheral blood stem cell transplant from an unrelated donor who was a 10/10 HLA match but ABO incompatible. He received conditioning with rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.

Levy also received graft-vs-host disease (GVHD) prophylaxis consisting of high-dose cyclophosphamide, mycophenolate mofetil, and sirolimus. And he received standard antibacterial, antifungal, antiviral, and anti-Pneumocystis jiroveci prophylaxis.

Levy experienced platelet engraftment on day 20 and neutrophil engraftment on day 21. Whole-blood donor-cell chimerism was 98.7% on day 30 and 100% on day 60 and beyond.

Levy did develop transient hemolytic anemia due to the ABO incompatibility. He was given a total of 10 units of packed red blood cells until day 78.

Levy was tapered off all immunosuppression at 12 months and has shown no signs of acute or chronic GVHD.

At 24 months after HSCT, Levy’s hemoglobin was 13.7 g/dL, and his ferritin was 376 ng/mL. He has had no iron chelation since the transplant.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, who is now 35.

“I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Dr Rondelli said the potential of this treatment approach is promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias—perhaps the only possible cure,” he said.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant. This procedure gives some adults the option of a stem cell transplant, which was not previously available.”

Photo from David Levy

Physicians have reported what they believe is the first case of an allogeneic hematopoietic stem cell transplant (allo-HSCT) curing an adult with congenital dyserythropoietic anemia (CDA).

The patient, David Levy, was previously transfusion-dependent and suffered from iron overload, severe pain, and other adverse effects of his illness.

Levy was denied a transplant for years, but, in 2014, he received a non-myeloablative allo-HSCT from a matched, unrelated donor.

Now, Levy no longer requires transfusions, iron chelation, or immunosuppression, and says he is able to live a normal life.

Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues described Levy’s case in a letter to Bone Marrow Transplantation.

Levy was diagnosed with CDA at 4 months of age and was treated with regular blood transfusions for most of his life. He was 24 when the pain from his illness became so severe that he had to withdraw from graduate school.

“I spent the following years doing nothing—no work, no school, no social contact—because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every 2 to 3 weeks, had undergone a splenectomy, had an enlarged liver, and was suffering from fatigue, heart palpitations, and iron overload.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr Rondelli.”

Dr Rondelli said that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a transplant.

However, Dr Rondelli and his colleagues had reported success with chemotherapy-free allo-HSCT in patients with sickle cell disease. So Dr Rondelli performed Levy’s transplant in 2014.

Levy received a peripheral blood stem cell transplant from an unrelated donor who was a 10/10 HLA match but ABO incompatible. He received conditioning with rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.

Levy also received graft-vs-host disease (GVHD) prophylaxis consisting of high-dose cyclophosphamide, mycophenolate mofetil, and sirolimus. And he received standard antibacterial, antifungal, antiviral, and anti-Pneumocystis jiroveci prophylaxis.

Levy experienced platelet engraftment on day 20 and neutrophil engraftment on day 21. Whole-blood donor-cell chimerism was 98.7% on day 30 and 100% on day 60 and beyond.

Levy did develop transient hemolytic anemia due to the ABO incompatibility. He was given a total of 10 units of packed red blood cells until day 78.

Levy was tapered off all immunosuppression at 12 months and has shown no signs of acute or chronic GVHD.

At 24 months after HSCT, Levy’s hemoglobin was 13.7 g/dL, and his ferritin was 376 ng/mL. He has had no iron chelation since the transplant.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, who is now 35.

“I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Dr Rondelli said the potential of this treatment approach is promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias—perhaps the only possible cure,” he said.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant. This procedure gives some adults the option of a stem cell transplant, which was not previously available.”

Photo from David Levy

Physicians have reported what they believe is the first case of an allogeneic hematopoietic stem cell transplant (allo-HSCT) curing an adult with congenital dyserythropoietic anemia (CDA).

The patient, David Levy, was previously transfusion-dependent and suffered from iron overload, severe pain, and other adverse effects of his illness.

Levy was denied a transplant for years, but, in 2014, he received a non-myeloablative allo-HSCT from a matched, unrelated donor.

Now, Levy no longer requires transfusions, iron chelation, or immunosuppression, and says he is able to live a normal life.

Damiano Rondelli, MD, of the University of Illinois at Chicago, and his colleagues described Levy’s case in a letter to Bone Marrow Transplantation.

Levy was diagnosed with CDA at 4 months of age and was treated with regular blood transfusions for most of his life. He was 24 when the pain from his illness became so severe that he had to withdraw from graduate school.

“I spent the following years doing nothing—no work, no school, no social contact—because all I could focus on was managing my pain and getting my health back on track,” Levy said.

By age 32, Levy required transfusions every 2 to 3 weeks, had undergone a splenectomy, had an enlarged liver, and was suffering from fatigue, heart palpitations, and iron overload.

“It was bad,” Levy said. “I had been through enough pain. I was angry and depressed, and I wanted a cure. That’s why I started emailing Dr Rondelli.”

Dr Rondelli said that because of Levy’s range of illnesses and inability to tolerate chemotherapy and radiation, several institutions had denied him the possibility of a transplant.

However, Dr Rondelli and his colleagues had reported success with chemotherapy-free allo-HSCT in patients with sickle cell disease. So Dr Rondelli performed Levy’s transplant in 2014.

Levy received a peripheral blood stem cell transplant from an unrelated donor who was a 10/10 HLA match but ABO incompatible. He received conditioning with rabbit anti-thymocyte globulin, fludarabine, cyclophosphamide, and total body irradiation.

Levy also received graft-vs-host disease (GVHD) prophylaxis consisting of high-dose cyclophosphamide, mycophenolate mofetil, and sirolimus. And he received standard antibacterial, antifungal, antiviral, and anti-Pneumocystis jiroveci prophylaxis.

Levy experienced platelet engraftment on day 20 and neutrophil engraftment on day 21. Whole-blood donor-cell chimerism was 98.7% on day 30 and 100% on day 60 and beyond.

Levy did develop transient hemolytic anemia due to the ABO incompatibility. He was given a total of 10 units of packed red blood cells until day 78.

Levy was tapered off all immunosuppression at 12 months and has shown no signs of acute or chronic GVHD.

At 24 months after HSCT, Levy’s hemoglobin was 13.7 g/dL, and his ferritin was 376 ng/mL. He has had no iron chelation since the transplant.

“The transplant was hard, and I had some complications, but I am back to normal now,” said Levy, who is now 35.

“I still have some pain and some lingering issues from the years my condition was not properly managed, but I can be independent now. That is the most important thing to me.”

Levy is finishing his doctorate in psychology and running group therapy sessions at a behavioral health hospital.

Dr Rondelli said the potential of this treatment approach is promising.

“The use of this transplant protocol may represent a safe therapeutic strategy to treat adult patients with many types of congenital anemias—perhaps the only possible cure,” he said.

“For many adult patients with a blood disorder, treatment options have been limited because they are often not sick enough to qualify for a risky procedure, or they are too sick to tolerate the toxic drugs used alongside a standard transplant. This procedure gives some adults the option of a stem cell transplant, which was not previously available.”

Image by Spencer Phillips

New research appears to explain how 10q21.2 influences the risk of high-hyperdiploid acute lymphoblastic leukemia (HD-ALL).

Previous research indicated that variation in the gene ARID5B at 10q21.2 is associated with HD-ALL.

Now, researchers have reported that the 10q21.2 risk locus for HD-ALL is mediated through the single nucleotide polymorphism (SNP) rs7090445, which disrupts RUNX3 transcription factor binding.

Specifically, the rs7090445-C allele confers an increased risk of HD-ALL through reduced RUNX3-mediated expression of ARID5B.

The researchers described these findings in Nature Communications.

“This study expands our understanding of how genetic risk factors can influence the development of acute lymphoblastic leukemia . . .,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

Dr Houlston and his colleagues focused this research on 10q21.2 because it had previously been implicated in HD-ALL, but it wasn’t clear how the region affects the risk of HD-ALL.

The team said they found that a SNP in the region, rs7090445, is “highly associated” with HD-ALL.

Further investigation revealed that variation at rs7090445 disrupts RUNX3 binding and reduces the expression of ARID5B, as RUNX3 regulates ARID5B expression.

The researchers also discovered that the rs7090445-C risk allele, which is associated with reduced ARID5B expression, is amplified in HD-ALL. The risk allele is “preferentially retained” on additional copies of chromosome 10 in HD-ALL blasts.

“We implicate reduced expression of a gene called ARID5B in the production and release of the immature ‘blast’ cells that characterize [HD-ALL],” Dr Houlston said. “Our study gives a new insight into the causes of the disease and may open up new strategies for prevention.”

Image by Spencer Phillips

New research appears to explain how 10q21.2 influences the risk of high-hyperdiploid acute lymphoblastic leukemia (HD-ALL).

Previous research indicated that variation in the gene ARID5B at 10q21.2 is associated with HD-ALL.

Now, researchers have reported that the 10q21.2 risk locus for HD-ALL is mediated through the single nucleotide polymorphism (SNP) rs7090445, which disrupts RUNX3 transcription factor binding.

Specifically, the rs7090445-C allele confers an increased risk of HD-ALL through reduced RUNX3-mediated expression of ARID5B.

The researchers described these findings in Nature Communications.

“This study expands our understanding of how genetic risk factors can influence the development of acute lymphoblastic leukemia . . .,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

Dr Houlston and his colleagues focused this research on 10q21.2 because it had previously been implicated in HD-ALL, but it wasn’t clear how the region affects the risk of HD-ALL.

The team said they found that a SNP in the region, rs7090445, is “highly associated” with HD-ALL.

Further investigation revealed that variation at rs7090445 disrupts RUNX3 binding and reduces the expression of ARID5B, as RUNX3 regulates ARID5B expression.

The researchers also discovered that the rs7090445-C risk allele, which is associated with reduced ARID5B expression, is amplified in HD-ALL. The risk allele is “preferentially retained” on additional copies of chromosome 10 in HD-ALL blasts.

“We implicate reduced expression of a gene called ARID5B in the production and release of the immature ‘blast’ cells that characterize [HD-ALL],” Dr Houlston said. “Our study gives a new insight into the causes of the disease and may open up new strategies for prevention.”

Image by Spencer Phillips

New research appears to explain how 10q21.2 influences the risk of high-hyperdiploid acute lymphoblastic leukemia (HD-ALL).

Previous research indicated that variation in the gene ARID5B at 10q21.2 is associated with HD-ALL.

Now, researchers have reported that the 10q21.2 risk locus for HD-ALL is mediated through the single nucleotide polymorphism (SNP) rs7090445, which disrupts RUNX3 transcription factor binding.

Specifically, the rs7090445-C allele confers an increased risk of HD-ALL through reduced RUNX3-mediated expression of ARID5B.

The researchers described these findings in Nature Communications.

“This study expands our understanding of how genetic risk factors can influence the development of acute lymphoblastic leukemia . . .,” said study author Richard Houlston, MD, PhD, of The Institute of Cancer Research in London, UK.

Dr Houlston and his colleagues focused this research on 10q21.2 because it had previously been implicated in HD-ALL, but it wasn’t clear how the region affects the risk of HD-ALL.

The team said they found that a SNP in the region, rs7090445, is “highly associated” with HD-ALL.

Further investigation revealed that variation at rs7090445 disrupts RUNX3 binding and reduces the expression of ARID5B, as RUNX3 regulates ARID5B expression.

The researchers also discovered that the rs7090445-C risk allele, which is associated with reduced ARID5B expression, is amplified in HD-ALL. The risk allele is “preferentially retained” on additional copies of chromosome 10 in HD-ALL blasts.

“We implicate reduced expression of a gene called ARID5B in the production and release of the immature ‘blast’ cells that characterize [HD-ALL],” Dr Houlston said. “Our study gives a new insight into the causes of the disease and may open up new strategies for prevention.”

For patients undergoing elective permanent colostomy, prophylactic augmentation of the abdominal wall using mesh at the ostomy site prevents the development of parastomal hernia, according to a report published in the April issue of Annals of Surgery.

The incidence of parastomal hernia is expected to rise because of the increasing number of cancer patients surviving with a colostomy, and the rising number of obese patients who have increased tension on the abdominal wall because of their elevated intra-abdominal pressure and larger abdominal radius. Researchers in the Netherlands performed a prospective randomized study, the PREVENT trial, to assess whether augmenting the abdominal wall at the ostomy site, using a lightweight mesh, would be safe, feasible, and effective at preventing parastomal hernia. They reported their findings after 1 year of follow-up; the study will continue until longer-term results are available at 5 years.

castillodominici/Thinkstock

This study was supported by Canisius Wilhelmina Hospital’s surgery research fund, the Netherlands Organization for Health Research and Development, and Covidien/Medtronic. Dr. Brandsma and his associates reported having no relevant financial disclosures.

For patients undergoing elective permanent colostomy, prophylactic augmentation of the abdominal wall using mesh at the ostomy site prevents the development of parastomal hernia, according to a report published in the April issue of Annals of Surgery.

The incidence of parastomal hernia is expected to rise because of the increasing number of cancer patients surviving with a colostomy, and the rising number of obese patients who have increased tension on the abdominal wall because of their elevated intra-abdominal pressure and larger abdominal radius. Researchers in the Netherlands performed a prospective randomized study, the PREVENT trial, to assess whether augmenting the abdominal wall at the ostomy site, using a lightweight mesh, would be safe, feasible, and effective at preventing parastomal hernia. They reported their findings after 1 year of follow-up; the study will continue until longer-term results are available at 5 years.

castillodominici/Thinkstock

This study was supported by Canisius Wilhelmina Hospital’s surgery research fund, the Netherlands Organization for Health Research and Development, and Covidien/Medtronic. Dr. Brandsma and his associates reported having no relevant financial disclosures.

For patients undergoing elective permanent colostomy, prophylactic augmentation of the abdominal wall using mesh at the ostomy site prevents the development of parastomal hernia, according to a report published in the April issue of Annals of Surgery.

The incidence of parastomal hernia is expected to rise because of the increasing number of cancer patients surviving with a colostomy, and the rising number of obese patients who have increased tension on the abdominal wall because of their elevated intra-abdominal pressure and larger abdominal radius. Researchers in the Netherlands performed a prospective randomized study, the PREVENT trial, to assess whether augmenting the abdominal wall at the ostomy site, using a lightweight mesh, would be safe, feasible, and effective at preventing parastomal hernia. They reported their findings after 1 year of follow-up; the study will continue until longer-term results are available at 5 years.

castillodominici/Thinkstock

This study was supported by Canisius Wilhelmina Hospital’s surgery research fund, the Netherlands Organization for Health Research and Development, and Covidien/Medtronic. Dr. Brandsma and his associates reported having no relevant financial disclosures.

FROM SEMINARS IN ARTHRITIS & RHEUMATISM

Around two-thirds of patients with severe or refractory sarcoidosis show a significant clinical response to tumor necrosis factor (TNF) antagonists, according to findings from a retrospective, multicenter cohort study.

Biologic agents targeting TNF, such as etanercept, infliximab, and adalimumab, have been introduced as a third-line option for patients with disease that is refractory to other treatments. However, Yvan Jamilloux, MD, of the Hospices Civils de Lyon (France) and his coauthors reported that there are still insufficient data available on efficacy and safety of these drugs in the context of sarcoidosis.

Dr. Jamilloux and his colleagues analyzed data from 132 sarcoidosis patients who received TNF antagonists, 122 (92%) of whom had severe sarcoidosis (Semin Arthritis Rheum. 2017 Mar 8. doi: 10.1016/j.semarthrit.2017.03.005).

Overall, 64% of patients showed clinical improvements in response to TNF antagonists; 18% had a complete response, and 46% had a partial response. However, 33 (25%) patients showed no change, and 14 (11%) had continued disease progression despite treatment with TNF antagonists. In another 16 patients who received a second TNF antagonist, 10 (63%) had a complete or partial clinical response. The investigators could find no differences in response between anti-TNF agents or between monotherapy and a combination with an immunosuppressant.

Pulmonary involvement was associated with a significantly lower clinical response, but none of the other factors examined in a multivariate analysis (sex, age, ethnicity, organ involvement, disease duration, steroid dosage, or prior immunosuppressant use) distinguished responders and nonresponders.

The authors noted that these response rates were lower than those seen in the literature and suggested this may be attributable to the multicenter design, more patients with longer-lasting and more refractory disease, and longer times under biologic therapy (median 12 months).

The researchers reported significant improvements in central nervous system, peripheral nervous system, heart, skin, and upper respiratory tract involvements based on declines in Extrapulmonary Physician Organ Severity Tool (ePOST) scores. There were also improvements in the eye, muscle, and lung, but these were not statistically significant.

TNF-antagonist therapy was associated with a high rate of adverse events. Around half of all patients (52%) experienced adverse events, such as pneumonia, urinary tract infections, bacterial sepsis, and herpes zoster. In 31 patients (23%), these led to treatment cessation.

Nine patients also had severe allergic reactions, four had paradoxical granulomatous reactions, three developed neutralizing antibodies against anti-TNF agents, two patients had demyelinating lesions, and one had a serum sickness-like reaction. All of these events led to discontinuation.

Overall, 128 (97%) of the patients in the study had received corticosteroids as first-line therapy, and 125 (95%) had received at least one second-line immunosuppressive drug over a median duration of 16 months. Most were treated with infliximab (91%) as the first-line TNF antagonist, followed by adalimumab (6%), etanercept (2%), and certolizumab pegol (1%).

Treatment with TNF antagonists was associated with significant reductions in corticosteroid use; the mean daily prednisone dose decreased from 23 mg/day to 11 mg/day over the median 20.5-month follow-up. This was seen even in the 33 patients who showed no change in their disease course after TNF-antagonist therapy.

No conflicts of interest were declared.

[email protected]

FROM SEMINARS IN ARTHRITIS & RHEUMATISM

Around two-thirds of patients with severe or refractory sarcoidosis show a significant clinical response to tumor necrosis factor (TNF) antagonists, according to findings from a retrospective, multicenter cohort study.

Biologic agents targeting TNF, such as etanercept, infliximab, and adalimumab, have been introduced as a third-line option for patients with disease that is refractory to other treatments. However, Yvan Jamilloux, MD, of the Hospices Civils de Lyon (France) and his coauthors reported that there are still insufficient data available on efficacy and safety of these drugs in the context of sarcoidosis.

Dr. Jamilloux and his colleagues analyzed data from 132 sarcoidosis patients who received TNF antagonists, 122 (92%) of whom had severe sarcoidosis (Semin Arthritis Rheum. 2017 Mar 8. doi: 10.1016/j.semarthrit.2017.03.005).

Overall, 64% of patients showed clinical improvements in response to TNF antagonists; 18% had a complete response, and 46% had a partial response. However, 33 (25%) patients showed no change, and 14 (11%) had continued disease progression despite treatment with TNF antagonists. In another 16 patients who received a second TNF antagonist, 10 (63%) had a complete or partial clinical response. The investigators could find no differences in response between anti-TNF agents or between monotherapy and a combination with an immunosuppressant.

Pulmonary involvement was associated with a significantly lower clinical response, but none of the other factors examined in a multivariate analysis (sex, age, ethnicity, organ involvement, disease duration, steroid dosage, or prior immunosuppressant use) distinguished responders and nonresponders.

The authors noted that these response rates were lower than those seen in the literature and suggested this may be attributable to the multicenter design, more patients with longer-lasting and more refractory disease, and longer times under biologic therapy (median 12 months).

The researchers reported significant improvements in central nervous system, peripheral nervous system, heart, skin, and upper respiratory tract involvements based on declines in Extrapulmonary Physician Organ Severity Tool (ePOST) scores. There were also improvements in the eye, muscle, and lung, but these were not statistically significant.

TNF-antagonist therapy was associated with a high rate of adverse events. Around half of all patients (52%) experienced adverse events, such as pneumonia, urinary tract infections, bacterial sepsis, and herpes zoster. In 31 patients (23%), these led to treatment cessation.

Nine patients also had severe allergic reactions, four had paradoxical granulomatous reactions, three developed neutralizing antibodies against anti-TNF agents, two patients had demyelinating lesions, and one had a serum sickness-like reaction. All of these events led to discontinuation.

Overall, 128 (97%) of the patients in the study had received corticosteroids as first-line therapy, and 125 (95%) had received at least one second-line immunosuppressive drug over a median duration of 16 months. Most were treated with infliximab (91%) as the first-line TNF antagonist, followed by adalimumab (6%), etanercept (2%), and certolizumab pegol (1%).

Treatment with TNF antagonists was associated with significant reductions in corticosteroid use; the mean daily prednisone dose decreased from 23 mg/day to 11 mg/day over the median 20.5-month follow-up. This was seen even in the 33 patients who showed no change in their disease course after TNF-antagonist therapy.

No conflicts of interest were declared.

[email protected]

FROM SEMINARS IN ARTHRITIS & RHEUMATISM

Around two-thirds of patients with severe or refractory sarcoidosis show a significant clinical response to tumor necrosis factor (TNF) antagonists, according to findings from a retrospective, multicenter cohort study.

Biologic agents targeting TNF, such as etanercept, infliximab, and adalimumab, have been introduced as a third-line option for patients with disease that is refractory to other treatments. However, Yvan Jamilloux, MD, of the Hospices Civils de Lyon (France) and his coauthors reported that there are still insufficient data available on efficacy and safety of these drugs in the context of sarcoidosis.

Dr. Jamilloux and his colleagues analyzed data from 132 sarcoidosis patients who received TNF antagonists, 122 (92%) of whom had severe sarcoidosis (Semin Arthritis Rheum. 2017 Mar 8. doi: 10.1016/j.semarthrit.2017.03.005).

Overall, 64% of patients showed clinical improvements in response to TNF antagonists; 18% had a complete response, and 46% had a partial response. However, 33 (25%) patients showed no change, and 14 (11%) had continued disease progression despite treatment with TNF antagonists. In another 16 patients who received a second TNF antagonist, 10 (63%) had a complete or partial clinical response. The investigators could find no differences in response between anti-TNF agents or between monotherapy and a combination with an immunosuppressant.

Pulmonary involvement was associated with a significantly lower clinical response, but none of the other factors examined in a multivariate analysis (sex, age, ethnicity, organ involvement, disease duration, steroid dosage, or prior immunosuppressant use) distinguished responders and nonresponders.

The authors noted that these response rates were lower than those seen in the literature and suggested this may be attributable to the multicenter design, more patients with longer-lasting and more refractory disease, and longer times under biologic therapy (median 12 months).

The researchers reported significant improvements in central nervous system, peripheral nervous system, heart, skin, and upper respiratory tract involvements based on declines in Extrapulmonary Physician Organ Severity Tool (ePOST) scores. There were also improvements in the eye, muscle, and lung, but these were not statistically significant.

TNF-antagonist therapy was associated with a high rate of adverse events. Around half of all patients (52%) experienced adverse events, such as pneumonia, urinary tract infections, bacterial sepsis, and herpes zoster. In 31 patients (23%), these led to treatment cessation.

Nine patients also had severe allergic reactions, four had paradoxical granulomatous reactions, three developed neutralizing antibodies against anti-TNF agents, two patients had demyelinating lesions, and one had a serum sickness-like reaction. All of these events led to discontinuation.

Overall, 128 (97%) of the patients in the study had received corticosteroids as first-line therapy, and 125 (95%) had received at least one second-line immunosuppressive drug over a median duration of 16 months. Most were treated with infliximab (91%) as the first-line TNF antagonist, followed by adalimumab (6%), etanercept (2%), and certolizumab pegol (1%).

Treatment with TNF antagonists was associated with significant reductions in corticosteroid use; the mean daily prednisone dose decreased from 23 mg/day to 11 mg/day over the median 20.5-month follow-up. This was seen even in the 33 patients who showed no change in their disease course after TNF-antagonist therapy.

No conflicts of interest were declared.

[email protected]

Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.

A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.

grandeduc/Thinkstock

[email protected]

On Twitter @IDPractitioner

Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.

A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.

grandeduc/Thinkstock

[email protected]

On Twitter @IDPractitioner

Global cases of HIV from 2015 to 2035 would be reduced by over 50% if the Joint United Nations Program on HIV/AIDS 95/95/95 target is met and a moderately effective HIV vaccine is introduced by 2020, according to new research published in Proceedings of the National Academy of Sciences.

A custom model based on current rates of diagnosis and treatment in 127 countries predicts that a total of 49 million new cases of HIV would occur globally from 2015 to 2035, investigators said. Achieving the UNAIDS goal of 95% disease diagnosis, 95% antiretroviral coverage, and 95% viral suppression by 2030 would avert 25 million cases by 2035. Achieving the more modest 90/90/90 target would avert 22 million cases within the same time period.

grandeduc/Thinkstock

[email protected]

On Twitter @IDPractitioner

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

To the Editor:
Vismodegib, a first-in-class inhibitor of the hedgehog signaling pathway, is useful in the treatment of advanced basal cell carcinomas (BCCs).¹ Common side effects of vismodegib include alopecia (58%), muscle spasms (71%), and dysgeusia (71%).² Some of these side effects have been hypothesized to be mechanism related.^3,4 Keratoacanthomas have been reported to occur after vismodegib treatment of BCC.⁵ We report 3 cases illustrating reversible cutaneous side effects of vismodegib: alopecia, follicular dermatitis, and drug hypersensitivity reaction.

A 53-year-old man with a locally advanced BCC of the right medial canthus began experiencing progressive and diffuse hair loss on the beard area, parietal scalp, eyelashes, and eyebrows after 2 months of vismodegib treatment. At 12 months of treatment, he had complete loss of eyelashes and eyebrows (Figure, A). After vismodegib was discontinued due to disease progression, all of his hair began regrowing within several months, with complete hair regrowth observed at 20 months after the last dose (Figure, B).

A 55-year-old man with several locally advanced BCCs developed new-onset mildly pruritic, acneform lesions on the chest and back after 4 months of vismodegib treatment. Biopsy of the lesions showed a folliculocentric mixed dermal infiltrate. The patient did not have a history of follicular dermatitis. The dermatitis resolved several months after onset without treatment, despite continued vismodegib.

A 55-year-old man with locally advanced BCCs developed erythematous dermal plaques on the arms and chest after 2 months of vismodegib treatment. Lesions were asymptomatic. He was not using any other medications and did not have any contact allergen exposures. Punch biopsy showed superficial and deep perivascular dermatitis with occasional eosinophils, consistent with drug hypersensitivity. Although lesions spontaneously resolved without treatment after 1 month, he experienced a couple more bouts of these lesions over the next year. He continued vismodegib for 2 years without return of this eruption.

The average time frame for hair regrowth after vismodegib cessation has not been characterized and awaits future larger studies. The frequency of follicular dermatitis and drug eruption also has not been determined and may require careful observation by dermatologists in larger numbers of treated patients. 

Because the hedgehog pathway is critical for normal hair follicle function, follicle-based toxicities of vismodegib including alopecia and folliculitis could be hypothesized to reflect effective blockade of the pathway.⁶ Currently, there are no data that these changes correlate with tumor response. 

Although alopecia is a recognized side effect of vismodegib, regrowth has not been previously reported.^1,2 Knowledge of the reversibility of alopecia as well as other toxicities has the potential to influence patient decision-making on drug initiation and adherence.

ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.

Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.

Study details

For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.

Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.

A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.

Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.

When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.

“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.

Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.

In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.

“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”

Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.

[email protected]

ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.

Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.

Study details

For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.

Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.

A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.

Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.

When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.

“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.

Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.

In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.

“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”

Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.

[email protected]

ORLANDO – A large proportion of patients with advanced non–small cell lung cancer (NSCLC) are not being tested for tumor associated–epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations according to national guidelines. This situation may be leading to suboptimal treatment, a large retrospective cohort study suggests.

Guidelines from the American Society of Clinical Oncology and the National Comprehensive Cancer Network recommend testing before first-line therapy for all treatment-eligible patients with nonsquamous histology and for those patients with squamous histology who are nonsmokers or who have mixed cell types or small tumor samples. Additionally, the guidelines recommend that results be made available within 2 weeks of the lab’s receipt of the sample so that they can be used to inform treatment decisions.

Study details

For the study, the investigators identified 16,316 patients with advanced NSCLC from 206 community clinics across the United States participating in the Flatiron Network. All patients were treated between 2014 and 2016.

Cross-checking of the total Flatiron population against the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results databases suggested that it is a good national representation, according to Mr. Rughani.

A record review showed that the rate of EGFR and ALK testing among study patients ranged widely across clinics, from 0% to 100% for both the nonsquamous cases and the squamous cases, according to results reported in a poster session. The median was 79% for the former and 16% for the latter.

Overall, 22% of the nonsquamous cohort and 79% of the squamous cohort did not have any evidence of testing in their records. For the latter, a sampling of records was unable to verify whether testing was appropriately matched to eligibility criteria.

When testing was performed, 35% of EGFR test results and 37% of ALK test results were not available to the treating clinician until more than 4 weeks after the date of the advanced cancer diagnosis.

“The delays were mostly attributed to nonlab factors. When we isolated the time that the lab took to turn it around, it was under 2 weeks for the vast majority of patients,” Mr. Rughani reported. Possible nonlab culprit factors include clinic work flows, insurance-related issues, and families’ and patients’ hesitancy to be tested, he said.

Delays in receipt of positive test results appeared to influence choice of first-line therapy. Among patients in whom these results were available before first-line therapy, 80% of those found to have an EGFR-mutated tumor received an EGFR–tyrosine kinase inhibitor, and 77% of those found to have ALK-rearranged tumors received an ALK inhibitor.

In sharp contrast, among patients in whom positive test results did not become available until after the start of first-line therapy, respective values were just 43% and 42%.

“Anecdotally, we saw that some patients would go on to Avastin [bevacizumab] in the front line when the results were delayed, and then, ultimately, they would have the opportunity to receive an EGFR[–tyrosine kinase inhibitor] or something like that in later lines,” commented Mr. Rughani. “So, that impacted treatment decisions there.”

Mr. Rughani disclosed stock and other ownership interests in Flatiron Health.

[email protected]

The decline in U.S. influenza activity that started in February paused during the week ending March 11, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatient visits for influenza-like illness (ILI) stayed at 3.7% for a second consecutive week after declining for 3 weeks in a row. The peak for the season, 5.2%, came during the week ending Feb. 11, CDC data show. The national baseline is 2.2%.

[email protected]

The decline in U.S. influenza activity that started in February paused during the week ending March 11, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatient visits for influenza-like illness (ILI) stayed at 3.7% for a second consecutive week after declining for 3 weeks in a row. The peak for the season, 5.2%, came during the week ending Feb. 11, CDC data show. The national baseline is 2.2%.

[email protected]

The decline in U.S. influenza activity that started in February paused during the week ending March 11, according to the U.S. Centers for Disease Control and Prevention.

The proportion of outpatient visits for influenza-like illness (ILI) stayed at 3.7% for a second consecutive week after declining for 3 weeks in a row. The peak for the season, 5.2%, came during the week ending Feb. 11, CDC data show. The national baseline is 2.2%.

[email protected]

At one time, respiratory failure was the primary cause of death in young men and boys with muscular dystrophies, but since improvements in ventilator support have addressed this problem, cardiac complications such as cardiomyopathy have become the main cause of death in this group, with the highest risk of death in people with Duchenne muscular dystrophy (DMD). Researchers from Rome have reported that the novel use of ventricular assist devices in this population can prolong life.

Gianluigi Perri, MD, PhD, of University Hospital and Bambino Gesù Children Hospital in Rome, and his coauthors, shared their experience treating seven patients with dystrophinopathies and dilated cardiomyopathy (DCM) with left ventricular assist devices (LVADs) from February 2011 to February 2016 (J Thorac Cardiovasc Surg. 2017 March;153:669-74). “Our experience indicates that the use of an LVAD as destination therapy in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options,” Dr. Perri and his coauthors said.

Heart transplantation is considered the procedure of choice for children with severe advanced heart failure, but transplantation is contraindicated for children with dystrophinopathies because of the risk of respiratory failure and progression of skeletal myopathy leads to limited functional capacity. Hence, Dr. Perri and his coauthors developed their alternative treatment for end-stage heart failure in these children. They used the Jarvik 2000 LVAD (Jarvik Heart Inc., New York) as destination therapy.

Six of the seven patients they operated on had DMD and one had beta-2 sarcoglycan deficit. Their ages ranged from 14.2 to 23.4 years. Two patients had early complications: retropharyngeal bleeding and cholecystectomy; and abdominal bleeding and splenectomy. Two different patients had late complications: gastrostomy; and osteolysis and infection at the pedestal site. Three patients died after the operation: one of stroke at 15 months; one of severe bleeding about 28 months later; and one of lung infection 45 months afterward. Follow-up for the surviving patients ranged from about 2 months to 40 months. Median hospital stay was 77 days.

Dr. Perri and his coauthors noted that the DMD Care Considerations Working Group expanded acceptable therapies for DMD cardiomyopathy to include novel treatments such as mechanical circulatory support and implantable cardioverter-defibrillators.

“Although the best approach remains unclear, it does seem clear that treatment should be more aggressive,” the researchers said. The limited life expectancy of these patients makes transplantation a complicated choice when a shortage of donors is a concern. “Therefore, the alternative therapeutic option is the use of LVAD,” Dr. Perri and his coauthors said.

These patients need care at centers “with a high level of experience of patients with DMD,” the researchers stated. Common comorbidities such as severe kyphoscoliosis and respiratory muscle weakness in this population increase surgical risks.

Dr. Perri and his coauthors used a surgical technique that involved avoiding the left thoracotomy approach common in adults who undergo VAD implantation, because of respiratory insufficiency in these younger patients. They also used cardiopulmonary bypass in all but one patient who had a minimally invasive off-pump procedure through a left anterior minithoracotomy.

The researchers “strongly suggest” noninvasive ventilation after surgery to assist in pulmonary function often compromised by scoliosis and muscle weakness. “Our experience shows that postoperative care can be extremely challenging and is often burdened by unexpected complications,” they noted.

Kyphoscoliosis poses challenges when placing drains, and complications of these patients should be treated only in a specialized center. “Indeed, one of our patients died in a peripheral hospital because they underwent bronchoscopic examination with an endoscope that caused severe and intractable retropharyngeal bleeding,” they said.

The researchers no relevant financial relationships to disclose.

At one time, respiratory failure was the primary cause of death in young men and boys with muscular dystrophies, but since improvements in ventilator support have addressed this problem, cardiac complications such as cardiomyopathy have become the main cause of death in this group, with the highest risk of death in people with Duchenne muscular dystrophy (DMD). Researchers from Rome have reported that the novel use of ventricular assist devices in this population can prolong life.

Gianluigi Perri, MD, PhD, of University Hospital and Bambino Gesù Children Hospital in Rome, and his coauthors, shared their experience treating seven patients with dystrophinopathies and dilated cardiomyopathy (DCM) with left ventricular assist devices (LVADs) from February 2011 to February 2016 (J Thorac Cardiovasc Surg. 2017 March;153:669-74). “Our experience indicates that the use of an LVAD as destination therapy in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options,” Dr. Perri and his coauthors said.

Heart transplantation is considered the procedure of choice for children with severe advanced heart failure, but transplantation is contraindicated for children with dystrophinopathies because of the risk of respiratory failure and progression of skeletal myopathy leads to limited functional capacity. Hence, Dr. Perri and his coauthors developed their alternative treatment for end-stage heart failure in these children. They used the Jarvik 2000 LVAD (Jarvik Heart Inc., New York) as destination therapy.

Six of the seven patients they operated on had DMD and one had beta-2 sarcoglycan deficit. Their ages ranged from 14.2 to 23.4 years. Two patients had early complications: retropharyngeal bleeding and cholecystectomy; and abdominal bleeding and splenectomy. Two different patients had late complications: gastrostomy; and osteolysis and infection at the pedestal site. Three patients died after the operation: one of stroke at 15 months; one of severe bleeding about 28 months later; and one of lung infection 45 months afterward. Follow-up for the surviving patients ranged from about 2 months to 40 months. Median hospital stay was 77 days.

Dr. Perri and his coauthors noted that the DMD Care Considerations Working Group expanded acceptable therapies for DMD cardiomyopathy to include novel treatments such as mechanical circulatory support and implantable cardioverter-defibrillators.

“Although the best approach remains unclear, it does seem clear that treatment should be more aggressive,” the researchers said. The limited life expectancy of these patients makes transplantation a complicated choice when a shortage of donors is a concern. “Therefore, the alternative therapeutic option is the use of LVAD,” Dr. Perri and his coauthors said.

These patients need care at centers “with a high level of experience of patients with DMD,” the researchers stated. Common comorbidities such as severe kyphoscoliosis and respiratory muscle weakness in this population increase surgical risks.

Dr. Perri and his coauthors used a surgical technique that involved avoiding the left thoracotomy approach common in adults who undergo VAD implantation, because of respiratory insufficiency in these younger patients. They also used cardiopulmonary bypass in all but one patient who had a minimally invasive off-pump procedure through a left anterior minithoracotomy.

The researchers “strongly suggest” noninvasive ventilation after surgery to assist in pulmonary function often compromised by scoliosis and muscle weakness. “Our experience shows that postoperative care can be extremely challenging and is often burdened by unexpected complications,” they noted.

Kyphoscoliosis poses challenges when placing drains, and complications of these patients should be treated only in a specialized center. “Indeed, one of our patients died in a peripheral hospital because they underwent bronchoscopic examination with an endoscope that caused severe and intractable retropharyngeal bleeding,” they said.

The researchers no relevant financial relationships to disclose.

At one time, respiratory failure was the primary cause of death in young men and boys with muscular dystrophies, but since improvements in ventilator support have addressed this problem, cardiac complications such as cardiomyopathy have become the main cause of death in this group, with the highest risk of death in people with Duchenne muscular dystrophy (DMD). Researchers from Rome have reported that the novel use of ventricular assist devices in this population can prolong life.

Gianluigi Perri, MD, PhD, of University Hospital and Bambino Gesù Children Hospital in Rome, and his coauthors, shared their experience treating seven patients with dystrophinopathies and dilated cardiomyopathy (DCM) with left ventricular assist devices (LVADs) from February 2011 to February 2016 (J Thorac Cardiovasc Surg. 2017 March;153:669-74). “Our experience indicates that the use of an LVAD as destination therapy in patients with dystrophinopathies with end-stage DCM is feasible, suggesting that it may be suitable as a palliative therapy for the treatment of these patients with no other therapeutic options,” Dr. Perri and his coauthors said.

Heart transplantation is considered the procedure of choice for children with severe advanced heart failure, but transplantation is contraindicated for children with dystrophinopathies because of the risk of respiratory failure and progression of skeletal myopathy leads to limited functional capacity. Hence, Dr. Perri and his coauthors developed their alternative treatment for end-stage heart failure in these children. They used the Jarvik 2000 LVAD (Jarvik Heart Inc., New York) as destination therapy.

Six of the seven patients they operated on had DMD and one had beta-2 sarcoglycan deficit. Their ages ranged from 14.2 to 23.4 years. Two patients had early complications: retropharyngeal bleeding and cholecystectomy; and abdominal bleeding and splenectomy. Two different patients had late complications: gastrostomy; and osteolysis and infection at the pedestal site. Three patients died after the operation: one of stroke at 15 months; one of severe bleeding about 28 months later; and one of lung infection 45 months afterward. Follow-up for the surviving patients ranged from about 2 months to 40 months. Median hospital stay was 77 days.

Dr. Perri and his coauthors noted that the DMD Care Considerations Working Group expanded acceptable therapies for DMD cardiomyopathy to include novel treatments such as mechanical circulatory support and implantable cardioverter-defibrillators.

“Although the best approach remains unclear, it does seem clear that treatment should be more aggressive,” the researchers said. The limited life expectancy of these patients makes transplantation a complicated choice when a shortage of donors is a concern. “Therefore, the alternative therapeutic option is the use of LVAD,” Dr. Perri and his coauthors said.

These patients need care at centers “with a high level of experience of patients with DMD,” the researchers stated. Common comorbidities such as severe kyphoscoliosis and respiratory muscle weakness in this population increase surgical risks.

Dr. Perri and his coauthors used a surgical technique that involved avoiding the left thoracotomy approach common in adults who undergo VAD implantation, because of respiratory insufficiency in these younger patients. They also used cardiopulmonary bypass in all but one patient who had a minimally invasive off-pump procedure through a left anterior minithoracotomy.

The researchers “strongly suggest” noninvasive ventilation after surgery to assist in pulmonary function often compromised by scoliosis and muscle weakness. “Our experience shows that postoperative care can be extremely challenging and is often burdened by unexpected complications,” they noted.

Kyphoscoliosis poses challenges when placing drains, and complications of these patients should be treated only in a specialized center. “Indeed, one of our patients died in a peripheral hospital because they underwent bronchoscopic examination with an endoscope that caused severe and intractable retropharyngeal bleeding,” they said.

The researchers no relevant financial relationships to disclose.