Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.

Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.

Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.

The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).

These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.

The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.

Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.

If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.

One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.

This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.

Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.

Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.

Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.

The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).

These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.

The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.

Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.

If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.

One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.

This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.

Adding the thrombopoietin-receptor agonist eltrombopag to standard immunosuppressive therapy markedly improved the frequency, speed, and robustness of hematologic recovery in a phase I-II trial of patients with severe aplastic anemia, according to a report published online April 20 in the New England Journal of Medicine.

Previously, researchers found that eltrombopag was effective against aplastic anemia that was refractory to immunosuppression, inducing higher platelet counts, hemoglobin levels, and neutrophil numbers when used as a single agent. They then examined whether adding the drug to immunosuppression in treatment-naive patients would improve the response in this nonrandomized prospective trial, said Danielle M. Townsley, MD, of the hematology branch, National Heart, Lung, and Blood Institute, and her associates.

Ninety-two consecutive patients aged 3-82 years were divided into three cohorts with different timing and duration of treatment. Cohort 1 (30 patients) received eltrombopag from day 14 to 6 months; cohort 2 (31 patients) received it from day 14 to 3 months; and cohort 3 (31 patients) received it from day 1 to 6 months.

The primary efficacy endpoint – the rate of complete hematologic response at 6 months – was highest, at 58%, in cohort 3, which had the earliest initiation and the longest duration of eltrombopag treatment. It was lowest, at 26%, in cohort 2, which had the shortest duration of eltrombopag treatment. The rate of complete hematologic response was intermediate in cohort 1, at 33% (N Engl J Med. 2017 Apr 20. doi:10.1056/NEJMoa1613878).

These complete response rates all exceeded those reported historically, which range from 10% to 20%. Moreover, the rate of partial or complete hematologic response was 87% across all three cohorts, compared with the 66% partial or complete response rate that would be expected with standard immunosuppression alone. Absolute neutrophil counts and platelet counts in all three cohorts also were higher at both 3 and 6 months than were those that have been reported historically.

The average time to independence from transfusions in the entire study population was 1 month, and clinically meaningful improvements in neutrophil levels were seen within a few weeks of initiating eltrombopag.

Two cases of severe cutaneous eruptions led to discontinuation of the study drug. Liver abnormalities were frequent but transient and did not limit the use of eltrombopag.

If these results are validated in future studies, and if no unexpected late complications are identified, adding eltrombopag to standard immunosuppressive therapy “may help patients optimize the timing of allogeneic stem-cell transplantation or avoid it. Of particular interest would be use of eltrombopag in combination with less toxic immunosuppressive regimens that omit antithymocyte globulin, particularly in older patients, in patients with coexisting conditions, and in developing countries where aplastic anemia is prevalent and conventional therapies [are] extremely costly,” Dr. Townsley and her associates noted.

One such confirmatory study, a large randomized placebo-controlled trial (NCT02099747), is now underway in Europe, they wrote.

This trial was supported by the National Heart, Lung, and Blood Institute. Dr. Townsley and her associates reported ties to GlaxoSmithKline and Novartis, makers of eltrombopag.

A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.

Related: Colorectal Screening: Available but Underused

Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.

Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was  reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.

Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.

The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.

Related: Cancer Prevention and Gastrointestinal Risk

Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.

Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.

A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.

Related: Colorectal Screening: Available but Underused

Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.

Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was  reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.

Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.

The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.

Related: Cancer Prevention and Gastrointestinal Risk

Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.

Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.

A 46-year-old woman went to her family doctor after 3 months of abdominal bloating, fatigue, nausea, vomiting, anorexia, and weight loss. Ultrasound imaging revealed hepatic lesions and a mass in the colon; she was diagnosed with colon cancer. The cancer had metastasized to an extent that complete resection wasn’t possible, so she received palliative-intent therapy for the next 18 months.

Related: Colorectal Screening: Available but Underused

Initially, the patient responded to the treatment but then presented to the emergency department (ED) with a severe headache. A CT scan revealed that the cancer had spread to her brain. However, this time resection was possible, and she recovered well.

Three weeks later the patient was back in the ED with an infection. A new CT scan showed no evidence of abscess (one of the differential diagnoses). A transthoracic echocardiogram showed a right atrial lesion, and further imaging confirmed a lesion in the right atrium. “Unexpectedly,” her clinicians reported, the lesion originated from the distal inferior vena cava (IVC): She had shown no signs of symptoms of pulmonary embolus or occlusion of the IVC.

Related: Strollin’ the Colon: A Collaborated Effort to Provide Education and Screening Outreach for the Improvement of Awareness, Access, and Early Detection of Colorectal Cancer

Tumor thrombus is rarely reported with colorectal cancer cases, so the patient’s clinicians at first thought the mass in the IVC was bland thrombus, managed with anticoagulation alone. The clinicians felt that the assumption was  reasonable, given the link between malignancy and venous thromboembolism; also because the patient had an indwelling central venous catheter. Contrast-enhanced CT scan and contrast-enhanced ultrasound, however, supported the diagnosis of tumor thrombus.

Due to the rarity of tumor thrombus in colorectal cancer, there are no guidelines for diagnosis and management, the clinicians say. In the patient’s case, consultation with cardiologists, radiologists, and gastrointestinal specialists at the cancer center resulted in an offer to extract the thrombus, but the risks and the fact that she was asymptomatic led the patient to decline. She was instead restarted on palliative chemotherapy with heparin in case part of the thrombus was indeed bland thrombus.

The patient’s condition deteriorated over the next 3 months. She and her team agreed that supportive care at home was best. The patient still had no symptoms from the tumor thrombus when she died.

Related: Cancer Prevention and Gastrointestinal Risk

Autopsy supported the suspicion that the original lesion was partly tumor thrombus and partly bland thrombus, reduced by anticoagulation. But autopsy results revealed no embolization of tumor thrombus or bland thrombus into the pulmonary arteries, although there were extensive metastases in the brain, lung, liver, adrenals, and ovaries. Ultimately, the patient’s death was attributed not to the tumor thrombus that extended into the right atrium but to multiorgan failure due to cancer--validating the decisions to not choose surgery for the thrombus.

Source:
Meyers D, Nixon NA, Franko A, Ng D, Tam VC. BMJ Case Rep. 2017;2017:pii:bcr2016218107.
doi: 10.1136/bcr-2016-218107.

Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.

The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.

The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.

PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.

Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.

The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.

The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.

PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.

Pre-exposure prophylaxis ( PrEP)—just 1 pill every day—can reduce the risk HIV infection by > 90%. A recent study shows that > 40% of chlamydia infections and 42% of gonorrhea infections also could be prevented over the next decade if 40% of homosexual and bisexual men took PrEP for HIV and were tested and treated every 6 months.

The CDC estimates that nearly 500,000 men are at “substantial risk” for HIV infection and could benefit from PrEP. But recent evidence suggests that some men may use condoms less when they are taking PrEP. According to researchers from the CDC and The Rollins School of Public Health at Emory University, PrEP prevented some STIs even with a 40% reduction in condom use.

The CDC recommends testing patients who use PrEP for bacterial STIs at least once every 6 months even if they don’t have symptoms. The study found that increasing STI testing from twice a year to 4 times a year would not dramatically affect the prevention of chlamydia or gonorrhea.

PrEP’s effectiveness in preventing HIV is well documented, the CDC says. The new study shows the “potential impact” that following the CDC’s clinical guidelines for PrEP can have on preventing bacterial STIs as well. But about one third of primary health care providers had not heard of PrEP as recently as 2015, the CDC says. To address that need, the CDC has been leading education efforts targeting providers, offering the guidelines, step-by-step PrEP checklists, and interview guides, along with a hotline to answer providers’ questions about when and how to offer PrEP.

Photo courtesy of GSK

Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.

In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.

Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.

The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.

“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).

She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.

Patients and treatment

This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.

At baseline, the patients’ median neutrophil count was 310/mm³ (range, 0-1810), their median reticulocyte count was 19,950/mm³ (range, 1600-60,400), and their median platelet count was 9000/mm³ (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).

All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.

They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.

Patients were also split into 3 cohorts according to treatment duration:

• Cohort 1 received eltrombopag from day 14 to the 6-month mark.
• Cohort 2 received eltrombopag from day 14 to the 3-month mark.
• Cohort 3 received eltrombopag from day 1 to 6 months.

Response

The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm³, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm³.

Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.

For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.

In cohort 1, the ORR was 80%, and the CR rate was 33%.

In cohort 2, the ORR was 87%, and the CR rate was 26%.

In cohort 3, the ORR was 94%, and the CR rate was 58%.

The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.

Relapse

Thirty-two percent of responding patients (25/78) relapsed after 6 months.

After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.

Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.

Photo courtesy of GSK

Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.

In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.

Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.

The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.

“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).

She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.

Patients and treatment

This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.

At baseline, the patients’ median neutrophil count was 310/mm³ (range, 0-1810), their median reticulocyte count was 19,950/mm³ (range, 1600-60,400), and their median platelet count was 9000/mm³ (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).

All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.

They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.

Patients were also split into 3 cohorts according to treatment duration:

• Cohort 1 received eltrombopag from day 14 to the 6-month mark.
• Cohort 2 received eltrombopag from day 14 to the 3-month mark.
• Cohort 3 received eltrombopag from day 1 to 6 months.

Response

The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm³, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm³.

Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.

For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.

In cohort 1, the ORR was 80%, and the CR rate was 33%.

In cohort 2, the ORR was 87%, and the CR rate was 26%.

In cohort 3, the ORR was 94%, and the CR rate was 58%.

The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.

Relapse

Thirty-two percent of responding patients (25/78) relapsed after 6 months.

After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.

Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.

Photo courtesy of GSK

Adding eltrombopag to immunosuppressive therapy (IST) can produce high rates of response in treatment-naïve severe aplastic anemia (SAA), according to research published in NEJM.

In patients who received eltrombopag for 6 months, the overall response rate (ORR) was 94%, and the complete response (CR) rate was 58%.

Researchers noted that these rates are “markedly higher” than response rates observed in historical controls who received IST alone.

The team also said the safety profile of eltrombopag in this study was consistent with the known safety profile of the drug.

“[E]ltrombopag plus standard immunosuppressive therapy appeared to increase the overall response rate and substantially increase the frequency, speed, and robustness of hematologic recovery in patients with SAA compared to historical controls,” said study author Danielle Townsley, MD, of the National Heart, Lung and Blood Institute (NHLBI).

She and her colleagues at NHLBI conducted this research through a Cooperative Research and Development Agreement with Novartis, the company that markets eltrombopag as Promacta/Revolade.

Patients and treatment

This phase 1/2 trial included 92 patients with treatment-naïve SAA. The patients’ median age was 32 (range, 3-82), and 54% of them were male.

At baseline, the patients’ median neutrophil count was 310/mm³ (range, 0-1810), their median reticulocyte count was 19,950/mm³ (range, 1600-60,400), and their median platelet count was 9000/mm³ (range, 0-37,000). Their median thrombopoietin level was 3163 pg/ml (range, 1806-4955).

All patients received horse antithymocyte globulin on days 1 to 4 and cyclosporine from day 1 to 6 months. The patients also received eltrombopag at an age-dependent dose.

They received eltrombopag at 150 mg daily if they were 12 years or older, 75 mg daily if they were 6 to 11, and 2.5 mg/kg/day if they were 2 to 5 years of age.

Patients were also split into 3 cohorts according to treatment duration:

• Cohort 1 received eltrombopag from day 14 to the 6-month mark.
• Cohort 2 received eltrombopag from day 14 to the 3-month mark.
• Cohort 3 received eltrombopag from day 1 to 6 months.

Response

The study’s primary efficacy endpoint was hematologic CR at 6 months. CR was defined as an absolute neutrophil count of at least 1000/mm³, a hemoglobin level of at least 10 g/dL, and a platelet count of at least 100,000/mm³.

Secondary endpoints included partial response (PR) and ORR, among other endpoints. ORR was the rate of CR plus PR. Patients had a PR if they had blood counts that no longer met the criteria for SAA but they did not meet criteria for CR.

For all cohorts, at 6 months, the ORR was 87%, and the CR rate was 39%.

In cohort 1, the ORR was 80%, and the CR rate was 33%.

In cohort 2, the ORR was 87%, and the CR rate was 26%.

In cohort 3, the ORR was 94%, and the CR rate was 58%.

The researchers noted that ORRs were higher across all cohorts than the ORR observed in a historical cohort (66%). The cohort consisted of 102 patients who had received standard IST while serving as controls in 1 of 2 recent NHLBI clinical trials.

Relapse

Thirty-two percent of responding patients (25/78) relapsed after 6 months.

After the study protocol was amended to allow the continuation of low-dose cyclosporine from 6 months to 2 years, the frequency of relapse decreased.

Fourteen percent of responders receiving low-dose cyclosporine beyond 6 months relapsed (6/43), compared to 54% of patients who stopped cyclosporine at 6 months (19/35).

Restarting full-dose cyclosporine reversed relapse and increased blood counts in 13 of 25 patients. Adding eltrombopag reversed relapse in an additional 10 patients.

Survival

The 2-year overall survival rate was 97% for the entire study population and 99% when data were censored for transplant.

Twelve patients under went transplant after eltrombopag. Six of them had not responded or were still transfusion-dependent, 3 relapsed, and 3 had clonal evolution.

Three patients died—1 while on study and 2 after transplant.

Clonal evolution and PNH

The researchers said the frequency of clonal evolution in this study was similar to that observed in the historical cohort of patients who received standard IST. The rate of clonal evolution at 2 years was 8% in both groups.

In the current study, 7 patients had clonal evolution at 2 years. Five patients had loss of chromosome 7, which was associated with dysplastic bone marrow changes in 3 patients.

One patient with a complex karyotype progressed to acute myeloid leukemia.

Two patients developed hemolytic paroxysmal nocturnal hemoglobinuria (PNH).

Safety

Two severe adverse events (AEs) were attributed to eltrombopag. Both were cutaneous eruptions—a grade 2 and a grade 3 event. Both AEs led to discontinuation of the drug.

Seven patients briefly stopped taking eltrombopag during the first 2 weeks of treatment due to transient elevations in liver enzymes.

AEs not attributed to eltrombopag were neutropenic infections and AEs known to be associated with IST.

The single patient who died on study was a non-responder who died 3 months after starting treatment. The death was due to paraneoplastic encephalopathy, which was attributed to thymoma that predated study entry.

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Lab mouse

Cutting certain amino acids from the diet slows tumor growth and prolongs survival in mouse models of malignancy, according to research published in Nature.

Researchers found that removing 2 non-essential amino acids—serine and glycine (SG)—from the diet of mice slowed the development of lymphoma and intestinal cancer.

The SG-free diet also made lymphoma more susceptible to reactive oxygen species (ROS).

As chemotherapy and radiotherapy boost levels of ROS, the researchers believe an SG-free diet could make conventional cancer treatments more effective.

“Our findings suggest that restricting specific amino acids through a controlled diet plan could be an additional part of treatment for some cancer patients in future, helping to make other treatments more effective,” said study author Oliver Maddocks, PhD, of the University of Glasgow in the UK.

He and his colleagues tested the SG-free diet in mouse models of lymphoma (Eμ-Myc) and observed decreased tumor volume and lymphoma cell numbers as well as a significant improvement in survival compared to controls.

The median survival (from the time of diet change at day 60) was 192 days for mice on the SG-free diet and 59 days for mice on the control diet (P=0.0367).

To test whether increasing ROS could enhance the anticancer effects of the SG-free diet, the researchers crossed Eμ-Myc mice with mice that don’t express Tigar, a protein that can support tumor development by limiting ROS.

The researchers found that Tigar ^-/- mice on the SG-free diet had significantly better survival than Tigar ^-/- mice on the control diet (P=0.0451).

The median survival was 50.5 days for Tigar ^+/+ mice on the control diet, 80 days for Tigar ^+/+ mice on the SG-free diet, 107 days for Tigar ^-/- mice on the control diet, and 226 days for Tigar ^-/- mice on the SG-free diet.

The researchers also found the SG-free diet was less effective in cancers with an activated Kras gene (such as prostate cancer) because the faulty gene boosted the cancer cells’ ability to make their own serine and glycine. The team said this could help in selecting which tumors could be best targeted by diet therapy.

“This is a really interesting look at how cutting off the supply of nutrients essential to cancer cell growth and division could help restrain tumors,” said Emma Smith, PhD, of Cancer Research UK, which funded this study.

“The next steps are clinical trials in people to see if giving a specialized diet that lacks these amino acids is safe and helps slow tumor growth as seen in mice. We’d also need to work out which patients are most likely to benefit, depending on the characteristics of their cancer.”

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

Photo by Daniel Gay

A new type of hemoglobin-based oxygen carrier has shown early promise as a potential blood substitute, according to researchers.

The team created nanoparticles consisting of bovine hemoglobin coated with the polymer polydopamine (PDA).

Lab tests showed that hemoglobin-PDA nanoparticles effectively carried oxygen, caused minimal cell damage, and acted as antioxidants, scavenging for potentially damaging free radicals and reactive oxygen species (ROS).

Hong Zhou, PhD, of the Beijing Institute of Transfusion Medicine in China, and colleagues reported these results in Biomacromolecules.

Past attempts to develop chemically modified hemoglobin as a blood substitute have been hindered by the formation of methemoglobin.

Methemoglobin doesn’t bind oxygen and therefore decreases the amount of oxygen blood delivers in the body. In addition, the generation of methemoglobin produces hydrogen peroxide, which leads to cell damage.

Dr Zhou and colleagues wanted to see if packaging hemoglobin in a benign envelope could prevent these problems. So the team developed a one-step method for wrapping hemoglobin—extracted from bovine red cells—in PDA.

The researchers said their simple preparation method meant the nanoparticles maintained the integrity of hemoglobin’s chemical structure without introducing any toxic reagent.

In addition, the PDA coating allowed hemoglobin to maintain its oxygen-carrying ability by preventing the formation of methemoglobin.

The researchers found the hemoglobin-PDA nanoparticles to have “excellent antioxidant capacity,” as they scavenged free radicals. The team said the ABTS+ radical scavenging rate reached 89%, and the DPPH radical scavenging rate reached 49%.

The hemoglobin-PDA nanoparticles also demonstrated antioxidant capacity by suppressing ROS generation. They reduced hydrogen peroxide-induced ROS generation in H9c2 cells.

Furthermore, the hemoglobin-PDA nanoparticles had little effect on blood constituents and cell viability.

The researchers found the nanoparticles had minimal effects on platelet aggregation, hemolysis in red blood cells, and coagulation processes.

And the nanoparticles had no significant cytotoxic effects on human umbilical vein endothelial cells.

The researchers therefore concluded that their hemoglobin-PDA nanoparticles represent “promising progress” for hemoglobin-based oxygen carriers.

The FP suspected contact dermatitis, but also noted that the patient had white material between his fingers and performed a potassium hydroxide (KOH) preparation. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) Under the microscope, the FP found budding yeast and the pseudohyphae of Candida albicans. Candida in the interdigital space is called erosio interdigitalis blastomycetica.

Patients with diabetes are at higher risk for this condition, as are those who perform “wet work.” The FP discussed the importance of hand protection with the patient and ways to better control his diabetes.

Fortunately, the patient had the next 2 days off of work so he was able to begin his treatment while avoiding the irritating environment at work. The FP recommended that the patient purchase over-the-counter clotrimazole cream to apply between his fingers. He also prescribed 0.1% triamcinolone ointment to be applied twice daily and discussed the use of protective gloves with cotton liners whenever possible.

The FP also referred the patient to Dermatology for further evaluation of the suspected contact dermatitis (including patch testing).

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected contact dermatitis, but also noted that the patient had white material between his fingers and performed a potassium hydroxide (KOH) preparation. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) Under the microscope, the FP found budding yeast and the pseudohyphae of Candida albicans. Candida in the interdigital space is called erosio interdigitalis blastomycetica.

Patients with diabetes are at higher risk for this condition, as are those who perform “wet work.” The FP discussed the importance of hand protection with the patient and ways to better control his diabetes.

Fortunately, the patient had the next 2 days off of work so he was able to begin his treatment while avoiding the irritating environment at work. The FP recommended that the patient purchase over-the-counter clotrimazole cream to apply between his fingers. He also prescribed 0.1% triamcinolone ointment to be applied twice daily and discussed the use of protective gloves with cotton liners whenever possible.

The FP also referred the patient to Dermatology for further evaluation of the suspected contact dermatitis (including patch testing).

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

The FP suspected contact dermatitis, but also noted that the patient had white material between his fingers and performed a potassium hydroxide (KOH) preparation. (See a video on how to perform a KOH preparation here: http://www.mdedge.com/jfponline/article/100603/dermatology/koh-preparation.) Under the microscope, the FP found budding yeast and the pseudohyphae of Candida albicans. Candida in the interdigital space is called erosio interdigitalis blastomycetica.

Patients with diabetes are at higher risk for this condition, as are those who perform “wet work.” The FP discussed the importance of hand protection with the patient and ways to better control his diabetes.

Fortunately, the patient had the next 2 days off of work so he was able to begin his treatment while avoiding the irritating environment at work. The FP recommended that the patient purchase over-the-counter clotrimazole cream to apply between his fingers. He also prescribed 0.1% triamcinolone ointment to be applied twice daily and discussed the use of protective gloves with cotton liners whenever possible.

The FP also referred the patient to Dermatology for further evaluation of the suspected contact dermatitis (including patch testing).

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Usatine R. Hand eczema. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:597-602.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com

Shunt occlusion has been a well-documented cause of shunt failure in newborns who have had systemic to pulmonary shunt placement, and little has been known about why shunts occlude. However, researchers have reported in a small retrospective study that higher postoperative hematocrit levels immediately after surgery may be predictors of shunt occlusion.

Reporting in the April 2017 issue of The Journal of Thoracic and Cardiovascular Surgery, Brett R. Anderson, MD, of New York-Presbyterian/Morgan Stanley Children’s Hospital, Columbia University Medical Center in New York, and coauthors, found that every 5-point increase in postoperative hematocrit more than doubled an infant’s odds of having early shunt occlusion (J Thorac Cardiovasc Surg. 2017;153:947-55).

“Beginning in the latter half of 2014, we noticed an increase in the incidence of early shunt occlusions in our neonatal cardiac intensive care unit,” Dr. Anderson and coauthors said. So they conducted a retrospective chart review of 80 infants who had undergone systemic to pulmonary shunt placement from January 2010 to July 2015, hypothesizing that increased hematocrit in the early postoperative period might have caused early shunt occlusion. They investigated the association between the first postoperative hematocrit and early shunt occlusion and in-hospital mortality in these patients.

Five patients (6.3%) experienced early shunt occlusion – that is, within 24 hours of placement (actually, within 10 hours of placement). Overall, 12 infants (15%) experienced shunt occlusion. The physicians at New York-Presbyterian do not administer anticoagulation in these patients during the first 12 hours after shunt placement.

The median initial postoperative hematocrit was 41.7%, with a range of 31.7%-55.8%. The survival analysis the researchers performed found that for every 5 additional percentage points, the hazard ratio for early shunt occlusion was 2.7 (P = .007) and 1.74 for any shunt occlusion (P less than .001). Incidentally, four cases of early shunt occlusion occurred in the later study period after 2014, during which the average first postoperative hematocrit was significantly higher than in the pre-2014 study period, 45.3% vs. 41.5% (P = .21), and the odds of early shunt occlusion were 16 times higher (P less than .001). Dr. Anderson and coauthors said the possible explanation for this variation was a switch to a new point-of-care analyzer in 2013.

With regard to mortality, six infants overall (7.4%) died before discharge, and four (5%) within 30 days of shunt placement. No infants with early shunt occlusion died, although two with late shunt occlusion died. Increased inotrope score and first postoperative arterial oxygen tension were the only factors associated with increased mortality. “No significant association was identified between hematocrit and 30-day mortality,” Dr. Anderson and coauthors said.

In the first 24 hours after surgery, 11 infants (13.8%) received packed red blood cell (PRBC) transfusions, seven (8.8%) received platelets, and four (5%) received fresh frozen plasma/cryoprecipitate. Higher postoperative PRBC transfusion volumes were associated with increased odds of mortality (P = .001), but none of these factors were significantly associated with early shunt occlusion.

Dr. Anderson and coauthors acknowledged that shunt occlusion is a “vexing problem” in infants with cyanotic heart disease. While other researchers studied postoperative hematocrit levels and possible associations with outcomes, including shunt occlusion and mortality, the New York-Presbyterian investigators said this is the first study of the first postoperative hematocrit.

Dr. Anderson and coauthors said their findings raise the question about the ideal perioperative prophylactic antithrombotic therapy in these patients. These researchers initiate aspirin therapy 12 hours after surgery if hemostasis is established.

As a result of this study, Dr. Anderson and coauthors instituted a number of practice changes at their center. They include:

• Cardiac anesthesiologists have been asked not to transfuse shunted neonates with hematocrit level of greater than or equal to 35%, and hematocrits are then immediately repeated when a patient returns to the cardiac ICU.

• Patients with hematocrits greater than or equal to 55% get partial exchange transfusions.

• An individualized approach for patients with lower hematocrits who are more cyanotic than expected. This includes a diagnostic echocardiogram, nitric oxide, oxygen and heparin, escalated inotropic support if necessary and sometimes a cautious approach to transfusions if symptoms do not resolve and an acute shunt occlusion if not likely.

Dr. Anderson and coauthors acknowledged limits to their study, most notably its retrospective nature and a small population at a single center, and that large investigations are needed to validate their findings.

Dr. Anderson disclosed receiving salary support from the National Center for Advancing Translational Sciences. Coauthor Jennifer M. Duchon, MDCM, MPH, receives salary support from the National Institute of Allergy and Infectious Disease. The remaining coauthors had no financial relationships to disclose.

Shunt occlusion has been a well-documented cause of shunt failure in newborns who have had systemic to pulmonary shunt placement, and little has been known about why shunts occlude. However, researchers have reported in a small retrospective study that higher postoperative hematocrit levels immediately after surgery may be predictors of shunt occlusion.

Reporting in the April 2017 issue of The Journal of Thoracic and Cardiovascular Surgery, Brett R. Anderson, MD, of New York-Presbyterian/Morgan Stanley Children’s Hospital, Columbia University Medical Center in New York, and coauthors, found that every 5-point increase in postoperative hematocrit more than doubled an infant’s odds of having early shunt occlusion (J Thorac Cardiovasc Surg. 2017;153:947-55).

“Beginning in the latter half of 2014, we noticed an increase in the incidence of early shunt occlusions in our neonatal cardiac intensive care unit,” Dr. Anderson and coauthors said. So they conducted a retrospective chart review of 80 infants who had undergone systemic to pulmonary shunt placement from January 2010 to July 2015, hypothesizing that increased hematocrit in the early postoperative period might have caused early shunt occlusion. They investigated the association between the first postoperative hematocrit and early shunt occlusion and in-hospital mortality in these patients.

Five patients (6.3%) experienced early shunt occlusion – that is, within 24 hours of placement (actually, within 10 hours of placement). Overall, 12 infants (15%) experienced shunt occlusion. The physicians at New York-Presbyterian do not administer anticoagulation in these patients during the first 12 hours after shunt placement.

The median initial postoperative hematocrit was 41.7%, with a range of 31.7%-55.8%. The survival analysis the researchers performed found that for every 5 additional percentage points, the hazard ratio for early shunt occlusion was 2.7 (P = .007) and 1.74 for any shunt occlusion (P less than .001). Incidentally, four cases of early shunt occlusion occurred in the later study period after 2014, during which the average first postoperative hematocrit was significantly higher than in the pre-2014 study period, 45.3% vs. 41.5% (P = .21), and the odds of early shunt occlusion were 16 times higher (P less than .001). Dr. Anderson and coauthors said the possible explanation for this variation was a switch to a new point-of-care analyzer in 2013.

With regard to mortality, six infants overall (7.4%) died before discharge, and four (5%) within 30 days of shunt placement. No infants with early shunt occlusion died, although two with late shunt occlusion died. Increased inotrope score and first postoperative arterial oxygen tension were the only factors associated with increased mortality. “No significant association was identified between hematocrit and 30-day mortality,” Dr. Anderson and coauthors said.

In the first 24 hours after surgery, 11 infants (13.8%) received packed red blood cell (PRBC) transfusions, seven (8.8%) received platelets, and four (5%) received fresh frozen plasma/cryoprecipitate. Higher postoperative PRBC transfusion volumes were associated with increased odds of mortality (P = .001), but none of these factors were significantly associated with early shunt occlusion.

Dr. Anderson and coauthors acknowledged that shunt occlusion is a “vexing problem” in infants with cyanotic heart disease. While other researchers studied postoperative hematocrit levels and possible associations with outcomes, including shunt occlusion and mortality, the New York-Presbyterian investigators said this is the first study of the first postoperative hematocrit.

Dr. Anderson and coauthors said their findings raise the question about the ideal perioperative prophylactic antithrombotic therapy in these patients. These researchers initiate aspirin therapy 12 hours after surgery if hemostasis is established.

As a result of this study, Dr. Anderson and coauthors instituted a number of practice changes at their center. They include:

• Cardiac anesthesiologists have been asked not to transfuse shunted neonates with hematocrit level of greater than or equal to 35%, and hematocrits are then immediately repeated when a patient returns to the cardiac ICU.

• Patients with hematocrits greater than or equal to 55% get partial exchange transfusions.

• An individualized approach for patients with lower hematocrits who are more cyanotic than expected. This includes a diagnostic echocardiogram, nitric oxide, oxygen and heparin, escalated inotropic support if necessary and sometimes a cautious approach to transfusions if symptoms do not resolve and an acute shunt occlusion if not likely.

Dr. Anderson and coauthors acknowledged limits to their study, most notably its retrospective nature and a small population at a single center, and that large investigations are needed to validate their findings.

Dr. Anderson disclosed receiving salary support from the National Center for Advancing Translational Sciences. Coauthor Jennifer M. Duchon, MDCM, MPH, receives salary support from the National Institute of Allergy and Infectious Disease. The remaining coauthors had no financial relationships to disclose.

Shunt occlusion has been a well-documented cause of shunt failure in newborns who have had systemic to pulmonary shunt placement, and little has been known about why shunts occlude. However, researchers have reported in a small retrospective study that higher postoperative hematocrit levels immediately after surgery may be predictors of shunt occlusion.

Reporting in the April 2017 issue of The Journal of Thoracic and Cardiovascular Surgery, Brett R. Anderson, MD, of New York-Presbyterian/Morgan Stanley Children’s Hospital, Columbia University Medical Center in New York, and coauthors, found that every 5-point increase in postoperative hematocrit more than doubled an infant’s odds of having early shunt occlusion (J Thorac Cardiovasc Surg. 2017;153:947-55).

“Beginning in the latter half of 2014, we noticed an increase in the incidence of early shunt occlusions in our neonatal cardiac intensive care unit,” Dr. Anderson and coauthors said. So they conducted a retrospective chart review of 80 infants who had undergone systemic to pulmonary shunt placement from January 2010 to July 2015, hypothesizing that increased hematocrit in the early postoperative period might have caused early shunt occlusion. They investigated the association between the first postoperative hematocrit and early shunt occlusion and in-hospital mortality in these patients.

Five patients (6.3%) experienced early shunt occlusion – that is, within 24 hours of placement (actually, within 10 hours of placement). Overall, 12 infants (15%) experienced shunt occlusion. The physicians at New York-Presbyterian do not administer anticoagulation in these patients during the first 12 hours after shunt placement.

The median initial postoperative hematocrit was 41.7%, with a range of 31.7%-55.8%. The survival analysis the researchers performed found that for every 5 additional percentage points, the hazard ratio for early shunt occlusion was 2.7 (P = .007) and 1.74 for any shunt occlusion (P less than .001). Incidentally, four cases of early shunt occlusion occurred in the later study period after 2014, during which the average first postoperative hematocrit was significantly higher than in the pre-2014 study period, 45.3% vs. 41.5% (P = .21), and the odds of early shunt occlusion were 16 times higher (P less than .001). Dr. Anderson and coauthors said the possible explanation for this variation was a switch to a new point-of-care analyzer in 2013.

With regard to mortality, six infants overall (7.4%) died before discharge, and four (5%) within 30 days of shunt placement. No infants with early shunt occlusion died, although two with late shunt occlusion died. Increased inotrope score and first postoperative arterial oxygen tension were the only factors associated with increased mortality. “No significant association was identified between hematocrit and 30-day mortality,” Dr. Anderson and coauthors said.

In the first 24 hours after surgery, 11 infants (13.8%) received packed red blood cell (PRBC) transfusions, seven (8.8%) received platelets, and four (5%) received fresh frozen plasma/cryoprecipitate. Higher postoperative PRBC transfusion volumes were associated with increased odds of mortality (P = .001), but none of these factors were significantly associated with early shunt occlusion.

Dr. Anderson and coauthors acknowledged that shunt occlusion is a “vexing problem” in infants with cyanotic heart disease. While other researchers studied postoperative hematocrit levels and possible associations with outcomes, including shunt occlusion and mortality, the New York-Presbyterian investigators said this is the first study of the first postoperative hematocrit.

Dr. Anderson and coauthors said their findings raise the question about the ideal perioperative prophylactic antithrombotic therapy in these patients. These researchers initiate aspirin therapy 12 hours after surgery if hemostasis is established.

As a result of this study, Dr. Anderson and coauthors instituted a number of practice changes at their center. They include:

• Cardiac anesthesiologists have been asked not to transfuse shunted neonates with hematocrit level of greater than or equal to 35%, and hematocrits are then immediately repeated when a patient returns to the cardiac ICU.

• Patients with hematocrits greater than or equal to 55% get partial exchange transfusions.

• An individualized approach for patients with lower hematocrits who are more cyanotic than expected. This includes a diagnostic echocardiogram, nitric oxide, oxygen and heparin, escalated inotropic support if necessary and sometimes a cautious approach to transfusions if symptoms do not resolve and an acute shunt occlusion if not likely.

Dr. Anderson and coauthors acknowledged limits to their study, most notably its retrospective nature and a small population at a single center, and that large investigations are needed to validate their findings.

Dr. Anderson disclosed receiving salary support from the National Center for Advancing Translational Sciences. Coauthor Jennifer M. Duchon, MDCM, MPH, receives salary support from the National Institute of Allergy and Infectious Disease. The remaining coauthors had no financial relationships to disclose.

A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.

However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).

For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.

A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.

However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).

For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.

A short course of prednisolone may help rheumatologists differentiate between patients with rheumatoid arthritis and osteoarthritis, a proof of concept study shows.

However, the investigators caution that a positive response to the 3-day steroid course does not confirm a diagnosis of rheumatoid arthritis (RA).

For many years, rheumatologists have been using short courses of prednisolone in unclear clinical situations to differentiate between inflammatory and non-inflammatory arthritis, according to the investigators led by Uta Kiltz, MD, from Rheumazentrum Ruhrgebiet, Herne, Germany.

WASHINGTON – Orbital atherectomy (OA) was associated with a lower risk of in-hospital mortality than rotational atherectomy (RA) in female, obese, and elderly study groups, according to data from a prospective observational study.

Each procedure was employed to treat coronary artery calcifications (CAC) in the elderly and the obese prior to percutaneous interventions (PCI).

The data comparing OA with RA in these populations were drawn from the Clinical Outcomes of Atherectomy Prior to PCI (COAP) study, for which Perwaiz M. Meraj, MD, director of structural heart and peripheral vascular disease at the North Shore-LIJ Hospital, Manhasset, N.Y., served as the senior author.

Each set of data, as well as a third set of data comparing OA to RA in female patients, was presented separately at CRT 2017, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

In the comparison of OA to RA in the elderly, a substudy known as COAP-75, the focus was on patients 75 years of age or older who underwent either OA or RA to remove calcified coronary lesions within the context of PCI. As with the obese and female subgroups, the elderly patients in this study were drawn from 35,590 patients who underwent PCI at one of five tertiary care hospitals in a recent 5-year period.

Of the 310 elderly patients undergoing atherectomy, 117 were treated with OA and 193 with RA. The median lesion lengths and diameters were not significantly different between the two groups. Although OA was less likely to be performed through femoral access (53% vs. 68.9%; P = .005), no other measured differences in procedure were significant, with one exception: Fluoroscopy exposure was of shorter duration in the OA, versus the RA, arm (24.0 minutes vs. 29.4 minutes; P = .005).

On univariate analysis, the lower rate of in-hospital deaths for OA did not reach statistical significance (0% vs. 1.55%; P = .176), but the difference was significant on multivariate-adjusted analysis (P = .034).

There were also higher numerical rates of perforation, tamponade, heart failure, and red blood cell transfusion in the RA group, versus the OA group, but only the latter was significant (P = .002) on multivariate-adjusted analysis.

In contrast, there was a higher rate of MI among those treated with OA, rather than RA (17.1% vs. 13.5%), which was not significant on univariate analysis (P = .573) but did reach significance on adjusted-multivariate analysis (P = .008).

Overall, the authors suggested that both OA and RA are safe procedures, but the mortality reduction suggests a potential relative advantage for OA.

Similar conclusions were reached in the substudy of patients with obesity, called COAP-BMI. In that study, 222 patients were evaluated, of which 91 were treated with OA and 131 were treated with RA.

In-hospital mortality was 0% in the group treated with OA, compared with 3.05% in the group treated with RA (P = .004). The rate of in-hospital major adverse cardiovascular events was also significantly lower in the OA group (15.4% vs. 16.3%; P = .007).

“The rate of secondary outcomes for myocardial infarction and stroke were similar between groups, as were individual procedural safety endpoints, including dissection, perforation, tamponade, or heart failure,” reported Evan Shlofmitz, MD, a cardiology fellow at Northwell Health, Manhasset, N.Y., who collaborated with Dr. Meraj and presented the data at the meeting.

As with the study in the elderly, for which Dr. Shlofmitz was also a coauthor, the study in the obese is the first to compare OA and RA, he noted.

In a third substudy, called COAP-Female, OA and RA were compared in 247 women with CAC who were undergoing PCI.

Again, in-hospital mortality rates were higher in those treated with RA, compared with OA, but the difference was not significant (0.79% vs. 0%; P = .254). There were also no significant differences in any secondary outcomes, including MI, or in any procedural complications, such as rates of dissection, perforation, or major bleeding.

The only significant difference identified in the study was a lower fluoroscopy time in those treated with OA relative to RA (21.3 minutes vs. 27.6 minutes; P = .001).

Although fluoroscopy time was not a primary endpoint, “a reduction in radiation exposure has important ramifications for both patients and operators,” Dr. Shlofmitz noted. He suggested that objective data on outcomes in females is needed, because this group has been “severely underrepresented in atherectomy trials.”

Overall, the substudies reinforce a large body of evidence that atherectomy is safe and effective for achieving revascularization in patients undergoing PCI who have CAC, Dr. Shlofmitz concluded. However, the significant mortality advantage for OA relative to RA in the elderly and the obese suggests that the approaches may not be interchangeable.

Dr. Shlofmitz reported no financial relationships to disclose.

WASHINGTON – Orbital atherectomy (OA) was associated with a lower risk of in-hospital mortality than rotational atherectomy (RA) in female, obese, and elderly study groups, according to data from a prospective observational study.

Each procedure was employed to treat coronary artery calcifications (CAC) in the elderly and the obese prior to percutaneous interventions (PCI).

The data comparing OA with RA in these populations were drawn from the Clinical Outcomes of Atherectomy Prior to PCI (COAP) study, for which Perwaiz M. Meraj, MD, director of structural heart and peripheral vascular disease at the North Shore-LIJ Hospital, Manhasset, N.Y., served as the senior author.

Each set of data, as well as a third set of data comparing OA to RA in female patients, was presented separately at CRT 2017, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

In the comparison of OA to RA in the elderly, a substudy known as COAP-75, the focus was on patients 75 years of age or older who underwent either OA or RA to remove calcified coronary lesions within the context of PCI. As with the obese and female subgroups, the elderly patients in this study were drawn from 35,590 patients who underwent PCI at one of five tertiary care hospitals in a recent 5-year period.

Of the 310 elderly patients undergoing atherectomy, 117 were treated with OA and 193 with RA. The median lesion lengths and diameters were not significantly different between the two groups. Although OA was less likely to be performed through femoral access (53% vs. 68.9%; P = .005), no other measured differences in procedure were significant, with one exception: Fluoroscopy exposure was of shorter duration in the OA, versus the RA, arm (24.0 minutes vs. 29.4 minutes; P = .005).

On univariate analysis, the lower rate of in-hospital deaths for OA did not reach statistical significance (0% vs. 1.55%; P = .176), but the difference was significant on multivariate-adjusted analysis (P = .034).

There were also higher numerical rates of perforation, tamponade, heart failure, and red blood cell transfusion in the RA group, versus the OA group, but only the latter was significant (P = .002) on multivariate-adjusted analysis.

In contrast, there was a higher rate of MI among those treated with OA, rather than RA (17.1% vs. 13.5%), which was not significant on univariate analysis (P = .573) but did reach significance on adjusted-multivariate analysis (P = .008).

Overall, the authors suggested that both OA and RA are safe procedures, but the mortality reduction suggests a potential relative advantage for OA.

Similar conclusions were reached in the substudy of patients with obesity, called COAP-BMI. In that study, 222 patients were evaluated, of which 91 were treated with OA and 131 were treated with RA.

In-hospital mortality was 0% in the group treated with OA, compared with 3.05% in the group treated with RA (P = .004). The rate of in-hospital major adverse cardiovascular events was also significantly lower in the OA group (15.4% vs. 16.3%; P = .007).

“The rate of secondary outcomes for myocardial infarction and stroke were similar between groups, as were individual procedural safety endpoints, including dissection, perforation, tamponade, or heart failure,” reported Evan Shlofmitz, MD, a cardiology fellow at Northwell Health, Manhasset, N.Y., who collaborated with Dr. Meraj and presented the data at the meeting.

As with the study in the elderly, for which Dr. Shlofmitz was also a coauthor, the study in the obese is the first to compare OA and RA, he noted.

In a third substudy, called COAP-Female, OA and RA were compared in 247 women with CAC who were undergoing PCI.

Again, in-hospital mortality rates were higher in those treated with RA, compared with OA, but the difference was not significant (0.79% vs. 0%; P = .254). There were also no significant differences in any secondary outcomes, including MI, or in any procedural complications, such as rates of dissection, perforation, or major bleeding.

The only significant difference identified in the study was a lower fluoroscopy time in those treated with OA relative to RA (21.3 minutes vs. 27.6 minutes; P = .001).

Although fluoroscopy time was not a primary endpoint, “a reduction in radiation exposure has important ramifications for both patients and operators,” Dr. Shlofmitz noted. He suggested that objective data on outcomes in females is needed, because this group has been “severely underrepresented in atherectomy trials.”

Overall, the substudies reinforce a large body of evidence that atherectomy is safe and effective for achieving revascularization in patients undergoing PCI who have CAC, Dr. Shlofmitz concluded. However, the significant mortality advantage for OA relative to RA in the elderly and the obese suggests that the approaches may not be interchangeable.

Dr. Shlofmitz reported no financial relationships to disclose.

WASHINGTON – Orbital atherectomy (OA) was associated with a lower risk of in-hospital mortality than rotational atherectomy (RA) in female, obese, and elderly study groups, according to data from a prospective observational study.

Each procedure was employed to treat coronary artery calcifications (CAC) in the elderly and the obese prior to percutaneous interventions (PCI).

The data comparing OA with RA in these populations were drawn from the Clinical Outcomes of Atherectomy Prior to PCI (COAP) study, for which Perwaiz M. Meraj, MD, director of structural heart and peripheral vascular disease at the North Shore-LIJ Hospital, Manhasset, N.Y., served as the senior author.

Each set of data, as well as a third set of data comparing OA to RA in female patients, was presented separately at CRT 2017, sponsored by the Cardiovascular Research Institute at Washington Hospital Center.

In the comparison of OA to RA in the elderly, a substudy known as COAP-75, the focus was on patients 75 years of age or older who underwent either OA or RA to remove calcified coronary lesions within the context of PCI. As with the obese and female subgroups, the elderly patients in this study were drawn from 35,590 patients who underwent PCI at one of five tertiary care hospitals in a recent 5-year period.

Of the 310 elderly patients undergoing atherectomy, 117 were treated with OA and 193 with RA. The median lesion lengths and diameters were not significantly different between the two groups. Although OA was less likely to be performed through femoral access (53% vs. 68.9%; P = .005), no other measured differences in procedure were significant, with one exception: Fluoroscopy exposure was of shorter duration in the OA, versus the RA, arm (24.0 minutes vs. 29.4 minutes; P = .005).

On univariate analysis, the lower rate of in-hospital deaths for OA did not reach statistical significance (0% vs. 1.55%; P = .176), but the difference was significant on multivariate-adjusted analysis (P = .034).

There were also higher numerical rates of perforation, tamponade, heart failure, and red blood cell transfusion in the RA group, versus the OA group, but only the latter was significant (P = .002) on multivariate-adjusted analysis.

In contrast, there was a higher rate of MI among those treated with OA, rather than RA (17.1% vs. 13.5%), which was not significant on univariate analysis (P = .573) but did reach significance on adjusted-multivariate analysis (P = .008).

Overall, the authors suggested that both OA and RA are safe procedures, but the mortality reduction suggests a potential relative advantage for OA.

Similar conclusions were reached in the substudy of patients with obesity, called COAP-BMI. In that study, 222 patients were evaluated, of which 91 were treated with OA and 131 were treated with RA.

In-hospital mortality was 0% in the group treated with OA, compared with 3.05% in the group treated with RA (P = .004). The rate of in-hospital major adverse cardiovascular events was also significantly lower in the OA group (15.4% vs. 16.3%; P = .007).

“The rate of secondary outcomes for myocardial infarction and stroke were similar between groups, as were individual procedural safety endpoints, including dissection, perforation, tamponade, or heart failure,” reported Evan Shlofmitz, MD, a cardiology fellow at Northwell Health, Manhasset, N.Y., who collaborated with Dr. Meraj and presented the data at the meeting.

As with the study in the elderly, for which Dr. Shlofmitz was also a coauthor, the study in the obese is the first to compare OA and RA, he noted.

In a third substudy, called COAP-Female, OA and RA were compared in 247 women with CAC who were undergoing PCI.

Again, in-hospital mortality rates were higher in those treated with RA, compared with OA, but the difference was not significant (0.79% vs. 0%; P = .254). There were also no significant differences in any secondary outcomes, including MI, or in any procedural complications, such as rates of dissection, perforation, or major bleeding.

The only significant difference identified in the study was a lower fluoroscopy time in those treated with OA relative to RA (21.3 minutes vs. 27.6 minutes; P = .001).

Although fluoroscopy time was not a primary endpoint, “a reduction in radiation exposure has important ramifications for both patients and operators,” Dr. Shlofmitz noted. He suggested that objective data on outcomes in females is needed, because this group has been “severely underrepresented in atherectomy trials.”

Overall, the substudies reinforce a large body of evidence that atherectomy is safe and effective for achieving revascularization in patients undergoing PCI who have CAC, Dr. Shlofmitz concluded. However, the significant mortality advantage for OA relative to RA in the elderly and the obese suggests that the approaches may not be interchangeable.

Dr. Shlofmitz reported no financial relationships to disclose.