Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the LightMix® Zika rRT-PCR Test.

The test, distributed by Roche, is used to detect the Zika virus in EDTA plasma or serum samples.

The LightMix® Zika rRT-PCR Test is intended for use in patients meeting clinical criteria or epidemiological criteria for Zika virus testing according to the US Centers for Disease Control and Prevention.

The test can only be used by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-US laboratories.

About the EUA

The LightMix® Zika rRT-PCR Test has not been FDA-cleared or approved. An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the LightMix® Zika rRT-PCR Test is only authorized for use as long as circumstances exist to justify the authorization of the emergency use of

in vitro diagnostics for the detection of Zika virus under section 564(b)(1) of the Federal Food, Drug & Cosmetic Act, 21 U.S.C.§360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

About the test

The LightMix® Zika rRT-PCR Test is designed to provide qualitative detection of Zika viral RNA in combination with a full process RNA control that monitors all steps from extraction to PCR result.

Nucleic acid extraction is authorized to be performed with Roche’s MagNA Pure Compact Instrument (and Isolation Kit I – Large Volume) or, for laboratories wanting to process a higher number of samples, the MagNA Pure 96 Instrument (and DNA and Viral NA Large Volume Kit) for high-throughput automated extraction.

The test was developed to run on Roche’s LightCycler® 480 Instrument II or cobas z 480 Analyzer. The end-to-end automated process from sample preparation to results for up to 96 samples can be performed in 2.5 hours.

The LightMix® Zika rRT-PCR Test is manufactured by TIB MOLBIOL GmbH and distributed by Roche.

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the LightMix® Zika rRT-PCR Test.

The test, distributed by Roche, is used to detect the Zika virus in EDTA plasma or serum samples.

The LightMix® Zika rRT-PCR Test is intended for use in patients meeting clinical criteria or epidemiological criteria for Zika virus testing according to the US Centers for Disease Control and Prevention.

The test can only be used by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-US laboratories.

About the EUA

The LightMix® Zika rRT-PCR Test has not been FDA-cleared or approved. An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the LightMix® Zika rRT-PCR Test is only authorized for use as long as circumstances exist to justify the authorization of the emergency use of

in vitro diagnostics for the detection of Zika virus under section 564(b)(1) of the Federal Food, Drug & Cosmetic Act, 21 U.S.C.§360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

About the test

The LightMix® Zika rRT-PCR Test is designed to provide qualitative detection of Zika viral RNA in combination with a full process RNA control that monitors all steps from extraction to PCR result.

Nucleic acid extraction is authorized to be performed with Roche’s MagNA Pure Compact Instrument (and Isolation Kit I – Large Volume) or, for laboratories wanting to process a higher number of samples, the MagNA Pure 96 Instrument (and DNA and Viral NA Large Volume Kit) for high-throughput automated extraction.

The test was developed to run on Roche’s LightCycler® 480 Instrument II or cobas z 480 Analyzer. The end-to-end automated process from sample preparation to results for up to 96 samples can be performed in 2.5 hours.

The LightMix® Zika rRT-PCR Test is manufactured by TIB MOLBIOL GmbH and distributed by Roche.

Blood samples

Photo by Graham Colm

The US Food and Drug Administration (FDA) has issued an emergency use authorization (EUA) for the LightMix® Zika rRT-PCR Test.

The test, distributed by Roche, is used to detect the Zika virus in EDTA plasma or serum samples.

The LightMix® Zika rRT-PCR Test is intended for use in patients meeting clinical criteria or epidemiological criteria for Zika virus testing according to the US Centers for Disease Control and Prevention.

The test can only be used by laboratories certified under the Clinical Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, to perform high complexity tests, or by similarly qualified non-US laboratories.

About the EUA

The LightMix® Zika rRT-PCR Test has not been FDA-cleared or approved. An EUA allows for the use of unapproved medical products or unapproved uses of approved medical products in an emergency.

The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

This means the LightMix® Zika rRT-PCR Test is only authorized for use as long as circumstances exist to justify the authorization of the emergency use of

in vitro diagnostics for the detection of Zika virus under section 564(b)(1) of the Federal Food, Drug & Cosmetic Act, 21 U.S.C.§360bbb-3(b)(1), unless the authorization is terminated or revoked sooner.

About the test

The LightMix® Zika rRT-PCR Test is designed to provide qualitative detection of Zika viral RNA in combination with a full process RNA control that monitors all steps from extraction to PCR result.

Nucleic acid extraction is authorized to be performed with Roche’s MagNA Pure Compact Instrument (and Isolation Kit I – Large Volume) or, for laboratories wanting to process a higher number of samples, the MagNA Pure 96 Instrument (and DNA and Viral NA Large Volume Kit) for high-throughput automated extraction.

The test was developed to run on Roche’s LightCycler® 480 Instrument II or cobas z 480 Analyzer. The end-to-end automated process from sample preparation to results for up to 96 samples can be performed in 2.5 hours.

The LightMix® Zika rRT-PCR Test is manufactured by TIB MOLBIOL GmbH and distributed by Roche.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

The factor Xa antidote andexanet achieved effective hemostasis 12 hours after infusion in 79% of patients who had developed serious acute bleeding on factor Xa inhibitor therapy, according to a preliminary analysis of an ongoing study of how reducing anti–factor Xa activity affects clinical hemostatic outcomes.

“The site of bleeding was most often gastrointestinal or intracranial; anti–factor Xa activity was considerably elevated in most patients and, as such, was likely to be a major impediment to clinical hemostasis. The administration of an andexanet bolus and infusion resulted in rapid and substantial reversal of anti–factor Xa activity,” Stuart Connolly, MD, of McMaster University, Hamilton, Ont., and his associates reported at the ESC Congress and in a simultaneously published study (N Engl J Med. 2016 Aug 30. doi: 10.1056/NEJMoa1607887).

Andexanet alfa is a recombinant modified human factor Xa decoy protein that “sharply” reduced plasma levels of unbound factor Xa inhibitors as well as anti-factor Xa activity in healthy older volunteers receiving apixaban or rivaroxaban, the researchers noted. Based on those findings, they designed a prospective, multicenter, single-group, open-label study (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors; ANNEXA-4) of andexanet in patients with potentially life-threatening acute major bleeding related to anticoagulation with a factor Xa inhibitor.

This interim report from the ongoing study included 67 patients with data available by June 17, 2016. Participants averaged 77 years of age and were receiving a factor Xa inhibtor because of atrial fibrillation, venous thromboembolism, or both. All patients received a bolus of andexanet for 15 to 30 minutes followed by a 2-hour infusion. Based on previous studies, the researchers used a 400-mg bolus of andexanet followed by a 480-mg infusion when patients had last taken their factor Xa inhibitor more than 7 hours before, and a higher 800-mg bolus followed by a 960-mg infusion when patients had taken their anticoagulant more recently. Bleeding and hemostasis were evaluated based on serial CT or MRI scans of patients with intracranial hemorrhage and corrected hemoglobin and hematocrit levels at 12 hours for patients with gastrointestinal and other nonvisible bleeding.

Among 47 patients in the primary efficacy analysis, 37 (79%) achieved excellent or good hemostasis (95% confidence interval, 64% to 89%), including 81% of patients on rivaroxaban and 75% of patients on enoxaparin, the researchers reported. “The rates of excellent or good efficacy were 84% for gastrointestinal bleeding and 80% for intracranial bleeding, rates that were consistent for other subgroups that were examined,” they said. Among the five patients (10%) with the most residual anti–factor Xa activity, all had received the lower andexanet dose. Four had received rivaroxaban while one had received apixaban.

The safety population included all 67 patients, none of whom developed infusion reactions or antibodies to factors X, Xa, or andexanet. After 30 days of follow-up, 12 patients (18%) had experienced one or more thrombotic events, including deep vein thrombosis (seven patients), stroke (five patients), myocardial infarction (one patient), and pulmonary embolism (one patient). One-third of these events occurred within 3 days of receiving andexanet, while the rest occurred by day 30. A total of 10 patients (15%) died, and six deaths were from cardiovascular causes. “A controlled study would be required to assess whether the frequency of these events exceeded that expected in patients at increased risk for thrombotic events,” the researchers commented.

Portola Pharmaceuticals makes andexanet alfa and funded the study. Dr. Connolly disclosed ties to Bayer, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, CSL Behring, Octapharma, and Boehringer Ingelheim outside the submitted work.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Invasive coronary therapies deserve credit for the decade-long decline in mortality among patients hospitalized with NSTEMI in the United Kingdom, Marlous Hall, PhD, said at the annual meeting of the European Society of Cardiology.

All-cause mortality improved approximately 3.2% per year in NSTEMI cases during a recent 10-year period, and most of that reduction (88%) was attributed to an increase in guideline-indicated treatment using coronary angiography, PCI, and CABG. Appropriate pharmacologic therapies also accounted for a significant though much smaller portion (10%) of that improvement, said Dr. Hall of the University of Leeds (England) Institute of Cardiovascular and Metabolic Medicine.

Dr. Hall’s findings were presented at the meeting and simultaneously published online Aug. 30 in JAMA (JAMA 2016 Aug 30. doi: 10.1001/jama.2016.1076).

NSTEMI-related deaths have declined globally in recent years, but the underlying reasons have been unclear. Some experts expressed concern that this reduction may not be a real treatment effect but may actually represent the expansion of treatment to a much lower-risk population. This concern worsened after the introduction of a higher-sensitivity troponin assay that identifies milder cases of acute coronary syndrome, Dr. Hall noted.

He and his associates examined this issue by analyzing data in a nationwide ACS registry that tracks patients treated at all 247 hospitals in England and Wales. They focused on time trends in 30-day and 180-day mortality among 389,057 adults treated for NSTEMI in 2003-2013. The median patient age was 72.7 years. Study participants were followed for a median of 2.3 years after diagnosis.

This patient population had a high rate of comorbidities including hypertension, current or former smoking, diabetes, angina, and previous MI. Most patients had an intermediate-to-high cardiac risk score. There were 37,236 deaths.

As expected, all-cause mortality declined over time, at an average of 3.2% per year. In particular, in-hospital mortality decreased from 10.9% in 2003 to 5.0% in 2013.

Only a small portion of this decline could be attributed to lower patient risk at diagnosis. The single most important variable accounting for reduced mortality was the appropriate, guideline-indicated use of invasive therapies. It was estimated that coronary angiography, PCI, and CABG contributed approximately 88% to the improvement in patient survival and that appropriate, guideline-indicated use of pharmacologic therapies contributed approximately 10%.

In a further analysis of the data, “use of an invasive coronary strategy was associated with a relative decrease in mortality of 46.1%. Furthermore, the estimate of the indirect contribution associated with an invasive coronary strategy through the provision of [comprehensive] cardiac rehabilitation was small (3.6%),” Dr. Hall said.

He cautioned that the study results should not be interpreted to mean that medical therapies are unimportant. “In our cohort, aspirin, P2Y12 inhibitors, beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor-blockers, and statins each had a significant association with improved survival,” Dr. Hall said.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Off-hours presentation to the hospital with STEMI did not affect PCI outcomes in the international prospective randomized CHAMPION PHOENIX trial.

The newer findings are reassuring and, in contrast with findings from several previous retrospective registry–based studies, suggest that presenting to the hospital at night or on weekends or holidays is no more hazardous than presenting during regular working hours, Senthil Selvaraj, MD, said in a presentation at the annual congress of the European Society of Cardiology. The results may reflect global quality improvement measures in STEMI care.

In the study, which was simultaneously published in Journal of the American College of Cardiology, researchers assessed the outcomes of 1,992 patients with STEMI participating in a large, industry-sponsored clinical trial. The primary efficacy outcome – a combination of all-cause mortality, MI, stent thrombosis, or ischemia-driven revascularization at 48 hours – was no different between patients who presented at 7 a.m. through 7 p.m. Monday through Friday than in those who presented during off hours (RR, 1.00), said Dr. Selvaraj of Brigham and Women’s Hospital Heart & Vascular Center, Boston.

There also was no difference between the two study groups in the primary safety outcome, which was moderate to severe bleeding events.

PCI yielded consistent benefits regardless of the timing of patient presentation, Dr. Selvaraj said.

CHAMPION PHOENIX was sponsored by the Medicines Company.

Nikesh Ardeshna, MD

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

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

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

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

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

Diagnosis: partial epilepsy with and without secondary generalization.

Questions and Discussion:

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

Nikesh Ardeshna, MD

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

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

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

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

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

Diagnosis: partial epilepsy with and without secondary generalization.

Questions and Discussion:

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

Nikesh Ardeshna, MD

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

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

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

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

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

Diagnosis: partial epilepsy with and without secondary generalization.

Questions and Discussion:

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

The European Society of Clinical Microbiology and Infectious Diseases has updated its clinical guideline for diagnosing Clostridium difficile infection, according to a report in Clinical Microbiology and Infection.

“Our aim is to not only improve diagnosis of C. difficile infection, but also to standardize the diagnostic process across Europe to allow for improved surveillance of the disease,” Ed J. Kuijper, MD, of the Centre for Infectious Diseases, Leiden (the Netherlands) University Medical Centre and lead investigator for the new guideline, said in a press statement.

CDC/Jennifer Hulsey

The Society released its first guideline regarding C. difficile diagnosis in 2009, but it required revision because many new diagnostic tests have become commercially available since then. The updated guideline focuses on diagnosing patients of all ages with diarrhea who are suspected of having C. difficile infection and is intended for use by medical microbiologists, gastroenterologists, infectious disease specialists, and infection control practitioners, said Monique J.T. Crobach, MD, who is also of Leiden University and is first author of the guideline, and her associates (Clin Microbiol Infect. 2016;22:S63-81).

They performed a comprehensive meta-analysis of 56 studies that compared 24 commercially available diagnostic assays against either of the current “gold standard” tests, the cell cytotoxicity neutralization assay or the toxigenic culture. Forty-one of these studies were published after 2009. Based on their findings, Dr. Crobach and her associates formulated 16 recommendations and suggestions, noting the quality of evidence supporting each one.

The updated guideline strongly recommends against using any single diagnostic assay to diagnose C. difficile infection, regardless of the technology on which it is based. Instead, diagnosis should rest on clinical signs and symptoms together with a two-step algorithm starting with either a nucleic acid amplification test or a glutamate dehydrogenase enzyme immunoassay. Samples with positive results on this initial test should be tested further with a toxin A/B enzyme immunoassay.

An alternative algorithm is to initially test samples with both a glutamate dehydrogenase and a toxin A/B enzyme immunoassay. The guideline spells out what actions to take in the event of concordant positive results, concordant negative results, or discordant results.

Testing for C. difficile should not be limited to samples with a specific request from a physician. All unformed stool samples from patients aged 3 years and older should be tested for the organism. In contrast, formed stool samples shouldn’t be tested for C. difficile unless the patient has paralytic ileus.

The guideline also addresses repeat testing. Performing a repeat test after an initial negative result during the same diarrheal episode may be useful in selected cases with ongoing clinical suspicion during an epidemic situation, or even in cases with high clinical suspicion during endemic situations. But repeat testing after an initial positive result generally is not recommended. Repeat testing to assess whether the patient is cured is definitely not recommended.

However, the decision to treat patients for C. difficile infection is a clinical one and may be justified even if all laboratory results are negative, Dr. Crobach and her associates noted.

The European Society of Clinical Microbiology and Infectious Diseases has updated its clinical guideline for diagnosing Clostridium difficile infection, according to a report in Clinical Microbiology and Infection.

“Our aim is to not only improve diagnosis of C. difficile infection, but also to standardize the diagnostic process across Europe to allow for improved surveillance of the disease,” Ed J. Kuijper, MD, of the Centre for Infectious Diseases, Leiden (the Netherlands) University Medical Centre and lead investigator for the new guideline, said in a press statement.

CDC/Jennifer Hulsey

The Society released its first guideline regarding C. difficile diagnosis in 2009, but it required revision because many new diagnostic tests have become commercially available since then. The updated guideline focuses on diagnosing patients of all ages with diarrhea who are suspected of having C. difficile infection and is intended for use by medical microbiologists, gastroenterologists, infectious disease specialists, and infection control practitioners, said Monique J.T. Crobach, MD, who is also of Leiden University and is first author of the guideline, and her associates (Clin Microbiol Infect. 2016;22:S63-81).

They performed a comprehensive meta-analysis of 56 studies that compared 24 commercially available diagnostic assays against either of the current “gold standard” tests, the cell cytotoxicity neutralization assay or the toxigenic culture. Forty-one of these studies were published after 2009. Based on their findings, Dr. Crobach and her associates formulated 16 recommendations and suggestions, noting the quality of evidence supporting each one.

The updated guideline strongly recommends against using any single diagnostic assay to diagnose C. difficile infection, regardless of the technology on which it is based. Instead, diagnosis should rest on clinical signs and symptoms together with a two-step algorithm starting with either a nucleic acid amplification test or a glutamate dehydrogenase enzyme immunoassay. Samples with positive results on this initial test should be tested further with a toxin A/B enzyme immunoassay.

An alternative algorithm is to initially test samples with both a glutamate dehydrogenase and a toxin A/B enzyme immunoassay. The guideline spells out what actions to take in the event of concordant positive results, concordant negative results, or discordant results.

Testing for C. difficile should not be limited to samples with a specific request from a physician. All unformed stool samples from patients aged 3 years and older should be tested for the organism. In contrast, formed stool samples shouldn’t be tested for C. difficile unless the patient has paralytic ileus.

The guideline also addresses repeat testing. Performing a repeat test after an initial negative result during the same diarrheal episode may be useful in selected cases with ongoing clinical suspicion during an epidemic situation, or even in cases with high clinical suspicion during endemic situations. But repeat testing after an initial positive result generally is not recommended. Repeat testing to assess whether the patient is cured is definitely not recommended.

However, the decision to treat patients for C. difficile infection is a clinical one and may be justified even if all laboratory results are negative, Dr. Crobach and her associates noted.

The European Society of Clinical Microbiology and Infectious Diseases has updated its clinical guideline for diagnosing Clostridium difficile infection, according to a report in Clinical Microbiology and Infection.

“Our aim is to not only improve diagnosis of C. difficile infection, but also to standardize the diagnostic process across Europe to allow for improved surveillance of the disease,” Ed J. Kuijper, MD, of the Centre for Infectious Diseases, Leiden (the Netherlands) University Medical Centre and lead investigator for the new guideline, said in a press statement.

CDC/Jennifer Hulsey

The Society released its first guideline regarding C. difficile diagnosis in 2009, but it required revision because many new diagnostic tests have become commercially available since then. The updated guideline focuses on diagnosing patients of all ages with diarrhea who are suspected of having C. difficile infection and is intended for use by medical microbiologists, gastroenterologists, infectious disease specialists, and infection control practitioners, said Monique J.T. Crobach, MD, who is also of Leiden University and is first author of the guideline, and her associates (Clin Microbiol Infect. 2016;22:S63-81).

They performed a comprehensive meta-analysis of 56 studies that compared 24 commercially available diagnostic assays against either of the current “gold standard” tests, the cell cytotoxicity neutralization assay or the toxigenic culture. Forty-one of these studies were published after 2009. Based on their findings, Dr. Crobach and her associates formulated 16 recommendations and suggestions, noting the quality of evidence supporting each one.

The updated guideline strongly recommends against using any single diagnostic assay to diagnose C. difficile infection, regardless of the technology on which it is based. Instead, diagnosis should rest on clinical signs and symptoms together with a two-step algorithm starting with either a nucleic acid amplification test or a glutamate dehydrogenase enzyme immunoassay. Samples with positive results on this initial test should be tested further with a toxin A/B enzyme immunoassay.

An alternative algorithm is to initially test samples with both a glutamate dehydrogenase and a toxin A/B enzyme immunoassay. The guideline spells out what actions to take in the event of concordant positive results, concordant negative results, or discordant results.

Testing for C. difficile should not be limited to samples with a specific request from a physician. All unformed stool samples from patients aged 3 years and older should be tested for the organism. In contrast, formed stool samples shouldn’t be tested for C. difficile unless the patient has paralytic ileus.

The guideline also addresses repeat testing. Performing a repeat test after an initial negative result during the same diarrheal episode may be useful in selected cases with ongoing clinical suspicion during an epidemic situation, or even in cases with high clinical suspicion during endemic situations. But repeat testing after an initial positive result generally is not recommended. Repeat testing to assess whether the patient is cured is definitely not recommended.

However, the decision to treat patients for C. difficile infection is a clinical one and may be justified even if all laboratory results are negative, Dr. Crobach and her associates noted.

The platysma muscle has been widely studied in its course through the cervical region in an attempt to develop more effective surgical approaches for rejuvenation. As a person ages, the platysma muscle becomes thinner, less defined, and ptotic, which results in the clinical appearance of a sagging neck that prompts patients to undergo neck-lift procedures. However, little is known about the course of the platysma in the mid and lower face and the implications on facial aging.

Bae et al (Plast Reconstr Surg. 2016;138:365-371) performed a cadaveric dissection of the facial portion of the platysma muscle to delineate the morphology and extension of the muscle in the mid and lower face. Thirty-four adult hemifaces were dissected. The demographics were broken down by age (mean, 71.4 years; range, 41–93 years), gender (29 men; 5 women), and ethnicity (14 Korean; 20 Thai). The extension of the platysma was documented according to a grid the authors created. The grid was divided along 3 horizontal lines (H1–H3) and 3 vertical lines (V1–V3). The intersection of these lines created a grid that was comprised of 3×3 squares and was labeled superior (S1–S3), middle (M1–M3), and inferior (I1–I3). H1 was a line drawn horizontally from the tragus to the lateral orbit, H2 was a line from the earlobe to the nasal ala, and H3 was a line from the angle of the mandible to the corner of the mouth.

The extension pattern of the facial portion of the platysma muscle was classified into patterns: A (n=3; S1–S2, M1–M3, and I1-I3 were covered by the muscle), B-1 (n=20; M1–M3, I1–I3), B-2 (n=9; M1–M2, I1–I3), and C (n=2; I1-I3).

The platysma muscle is divided into anterior and posterior portions. The anterior platysma ascends superiorly and medially in the face to interdigitate with the depressor anguli oris and the depressor labii inferioris muscles. The morphology pattern of the posterior platysma varied and was classified into 1 of 3 patterns: straight (n=13), straight-curved (n=18), and curved (n=3). The straight pattern showed platysma fibers that travel parallel to the mandibular malar line and head toward the zygomaticus major or the orbicularis oculi muscles. The straight-curved type has fibers that travel straight from the neck to the face but then curve, heading toward the risorius, zygomaticus major, or orbicularis oculi muscle depending on the extent of the platysma muscle in the area. The curved type has fibers that run parallel to the zygomaticus arch and interdigitate with the orbicularis oculi muscle and either the risorius or zygomaticus major muscle.

What’s the issue?

For many years, the cervical platysma muscle was studied and surgical approaches were modified to enhance results. The authors of this study have taken the study of the platysma muscle further to delineate its course through the face. Knowledge of the various pathways of the muscle can help us determine the most natural direction to resuspend ptotic facial tissue during surgery and minimally invasive procedures such as thread-lifting. The most salient points include: (1) the lower one-third of the masseter muscle is covered by the platysma, and (2) straight-curved was the most common morphology type, suggesting that the vector for repositioning the platysma muscle is vertical.

Although Bae et al do not discuss the use of botulinum toxin (BTX) in the treatment of the platysma, the results of this study further support the importance of BTX to the lower face. We can look back at more than 14 years of cosmetic use of BTX for the glabella and see the reduced number of brow-lift surgeries nationwide. Although the preventative effects of BTX on brow depression still need to be scientifically proven, it may behoove us to think preventatively on the use of BTX in the platysma to minimize ptosis of the lower face and neck. The results of this anatomic study support the importance of tailoring the approach to the dynamic lines caused by the platysma muscle in each patient to address jowls and neck bands. Have you been offering lower face BTX treatments to patients in an effort to reduce lower face aging?

We want to know your views! Tell us what you think.

The platysma muscle has been widely studied in its course through the cervical region in an attempt to develop more effective surgical approaches for rejuvenation. As a person ages, the platysma muscle becomes thinner, less defined, and ptotic, which results in the clinical appearance of a sagging neck that prompts patients to undergo neck-lift procedures. However, little is known about the course of the platysma in the mid and lower face and the implications on facial aging.

Bae et al (Plast Reconstr Surg. 2016;138:365-371) performed a cadaveric dissection of the facial portion of the platysma muscle to delineate the morphology and extension of the muscle in the mid and lower face. Thirty-four adult hemifaces were dissected. The demographics were broken down by age (mean, 71.4 years; range, 41–93 years), gender (29 men; 5 women), and ethnicity (14 Korean; 20 Thai). The extension of the platysma was documented according to a grid the authors created. The grid was divided along 3 horizontal lines (H1–H3) and 3 vertical lines (V1–V3). The intersection of these lines created a grid that was comprised of 3×3 squares and was labeled superior (S1–S3), middle (M1–M3), and inferior (I1–I3). H1 was a line drawn horizontally from the tragus to the lateral orbit, H2 was a line from the earlobe to the nasal ala, and H3 was a line from the angle of the mandible to the corner of the mouth.

The extension pattern of the facial portion of the platysma muscle was classified into patterns: A (n=3; S1–S2, M1–M3, and I1-I3 were covered by the muscle), B-1 (n=20; M1–M3, I1–I3), B-2 (n=9; M1–M2, I1–I3), and C (n=2; I1-I3).

The platysma muscle is divided into anterior and posterior portions. The anterior platysma ascends superiorly and medially in the face to interdigitate with the depressor anguli oris and the depressor labii inferioris muscles. The morphology pattern of the posterior platysma varied and was classified into 1 of 3 patterns: straight (n=13), straight-curved (n=18), and curved (n=3). The straight pattern showed platysma fibers that travel parallel to the mandibular malar line and head toward the zygomaticus major or the orbicularis oculi muscles. The straight-curved type has fibers that travel straight from the neck to the face but then curve, heading toward the risorius, zygomaticus major, or orbicularis oculi muscle depending on the extent of the platysma muscle in the area. The curved type has fibers that run parallel to the zygomaticus arch and interdigitate with the orbicularis oculi muscle and either the risorius or zygomaticus major muscle.

What’s the issue?

For many years, the cervical platysma muscle was studied and surgical approaches were modified to enhance results. The authors of this study have taken the study of the platysma muscle further to delineate its course through the face. Knowledge of the various pathways of the muscle can help us determine the most natural direction to resuspend ptotic facial tissue during surgery and minimally invasive procedures such as thread-lifting. The most salient points include: (1) the lower one-third of the masseter muscle is covered by the platysma, and (2) straight-curved was the most common morphology type, suggesting that the vector for repositioning the platysma muscle is vertical.

Although Bae et al do not discuss the use of botulinum toxin (BTX) in the treatment of the platysma, the results of this study further support the importance of BTX to the lower face. We can look back at more than 14 years of cosmetic use of BTX for the glabella and see the reduced number of brow-lift surgeries nationwide. Although the preventative effects of BTX on brow depression still need to be scientifically proven, it may behoove us to think preventatively on the use of BTX in the platysma to minimize ptosis of the lower face and neck. The results of this anatomic study support the importance of tailoring the approach to the dynamic lines caused by the platysma muscle in each patient to address jowls and neck bands. Have you been offering lower face BTX treatments to patients in an effort to reduce lower face aging?

We want to know your views! Tell us what you think.

The platysma muscle has been widely studied in its course through the cervical region in an attempt to develop more effective surgical approaches for rejuvenation. As a person ages, the platysma muscle becomes thinner, less defined, and ptotic, which results in the clinical appearance of a sagging neck that prompts patients to undergo neck-lift procedures. However, little is known about the course of the platysma in the mid and lower face and the implications on facial aging.

Bae et al (Plast Reconstr Surg. 2016;138:365-371) performed a cadaveric dissection of the facial portion of the platysma muscle to delineate the morphology and extension of the muscle in the mid and lower face. Thirty-four adult hemifaces were dissected. The demographics were broken down by age (mean, 71.4 years; range, 41–93 years), gender (29 men; 5 women), and ethnicity (14 Korean; 20 Thai). The extension of the platysma was documented according to a grid the authors created. The grid was divided along 3 horizontal lines (H1–H3) and 3 vertical lines (V1–V3). The intersection of these lines created a grid that was comprised of 3×3 squares and was labeled superior (S1–S3), middle (M1–M3), and inferior (I1–I3). H1 was a line drawn horizontally from the tragus to the lateral orbit, H2 was a line from the earlobe to the nasal ala, and H3 was a line from the angle of the mandible to the corner of the mouth.

The extension pattern of the facial portion of the platysma muscle was classified into patterns: A (n=3; S1–S2, M1–M3, and I1-I3 were covered by the muscle), B-1 (n=20; M1–M3, I1–I3), B-2 (n=9; M1–M2, I1–I3), and C (n=2; I1-I3).

The platysma muscle is divided into anterior and posterior portions. The anterior platysma ascends superiorly and medially in the face to interdigitate with the depressor anguli oris and the depressor labii inferioris muscles. The morphology pattern of the posterior platysma varied and was classified into 1 of 3 patterns: straight (n=13), straight-curved (n=18), and curved (n=3). The straight pattern showed platysma fibers that travel parallel to the mandibular malar line and head toward the zygomaticus major or the orbicularis oculi muscles. The straight-curved type has fibers that travel straight from the neck to the face but then curve, heading toward the risorius, zygomaticus major, or orbicularis oculi muscle depending on the extent of the platysma muscle in the area. The curved type has fibers that run parallel to the zygomaticus arch and interdigitate with the orbicularis oculi muscle and either the risorius or zygomaticus major muscle.

What’s the issue?

For many years, the cervical platysma muscle was studied and surgical approaches were modified to enhance results. The authors of this study have taken the study of the platysma muscle further to delineate its course through the face. Knowledge of the various pathways of the muscle can help us determine the most natural direction to resuspend ptotic facial tissue during surgery and minimally invasive procedures such as thread-lifting. The most salient points include: (1) the lower one-third of the masseter muscle is covered by the platysma, and (2) straight-curved was the most common morphology type, suggesting that the vector for repositioning the platysma muscle is vertical.

Although Bae et al do not discuss the use of botulinum toxin (BTX) in the treatment of the platysma, the results of this study further support the importance of BTX to the lower face. We can look back at more than 14 years of cosmetic use of BTX for the glabella and see the reduced number of brow-lift surgeries nationwide. Although the preventative effects of BTX on brow depression still need to be scientifically proven, it may behoove us to think preventatively on the use of BTX in the platysma to minimize ptosis of the lower face and neck. The results of this anatomic study support the importance of tailoring the approach to the dynamic lines caused by the platysma muscle in each patient to address jowls and neck bands. Have you been offering lower face BTX treatments to patients in an effort to reduce lower face aging?

We want to know your views! Tell us what you think.

HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.

A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.

“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).

It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.

Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.

Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.

After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.

Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.

In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).

In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).

Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).

Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).

“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.

HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.

A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.

“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).

It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.

Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.

Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.

After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.

Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.

In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).

In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).

Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).

Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).

“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.

HIV-infected women with cervical cancer have significantly lower survival rates than women with cervical cancer who are not infected, investigators found.

A study of 348 women with invasive cervical cancer in Botswana, a nation with robust and wide-reaching HIV prevention and antiretroviral therapy (ART) programs, showed that women who had HIV infections had a twofold greater risk for death within 3 years than women without HIV, reported Scott Dryden-Peterson, MD, from the Brigham and Women’s Hospital and Harvard TH Chan School of Public Health in Boston, and his colleagues.

“Even in the context of good access to and use of ART, HIV infection more than doubled the risk of death among women who received curative guideline-concordant therapy. Competing mortality from HIV-associated infections seemed to contribute minimally to the excess risk of death; rather, earlier oncologic progression among women with HIV seemed to account for the excess mortality,” they wrote (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.9613).

It is well known that HIV infection significantly increases the risk of cervical cancer, with HIV-infected women having a sixfold greater risk for the malignancy than women in the general population, the investigators stated.

Whether HIV has a detrimental effect on cervical cancer–specific survival was unclear, however, prompting them to investigate the question in a cohort of 348 women, 231 of whom were infected with HIV, 96 of whom were free of infection, and 21 of whom had unknown HIV status.

Of the women with HIV, 189 (81.8%) had started on ART before their cancers were diagnosed, and had been on therapy for a median of 4.8 years. Most of the HIV-infected women had CD4 cell counts that fell in the moderate or mildly immunosuppressed range (median 397 cells per microliter). Of this group, only 24 had CD4 counts below 200, the threshold for a diagnosis of AIDS.

After a median follow-up of 19.7 months, 157 participants had died, including 117 women with HIV infections and 40 without infections.

Three-year survival, the primary outcome, was 35% for women with HIV, compared with 48% for uninfected women.

In an analysis adjusted for age, cancer stage, CD4 cell counts, duration of ART, radiation dose received and treatment intent (curative or palliative), the hazard ratio for death among women with HIV was 1.95 (P = .007).

In an analysis restricted to women who received therapy with curative intent, the HR was 2.35 (P = .002), and an analysis restricted to women who received therapy with curative intent that adhered to clinical guidelines showed that the HR for death among HIV-infected women was 2.65 (P = .037).

Of note, the detrimental effect of HIV on survival was highest among women with stage I (HR, 4.03) and stage II (HR, 2.44) cancers, compared with stages III or IV (P = .035).

Among women with CD4 cell counts below 250, the HR for death was 2.75. This risk diminished with increasing cell counts, but remained significantly higher among women with near-normal counts (350 to 500 cells/microliter; HR, 1.87; significant according to confidence intervals).

“Advanced stage and poor treatment completion contributed to high mortality overall,” the investigators wrote.

Extramedullary disease is common in newly diagnosed acute myeloid leukemia, and frequently occurs in at least two sites, but is not an independent prognostic factor for overall survival, according to an analysis of 11 clinical trials.

“Importantly, the presence of extramedullary disease should not affect the choice of post-remission therapy,” concluded Dr. Chezi Ganzel of Shaare Zedek Medical Center, Jerusalem, Israel, together with his associates on behalf of the ECOG-ACRIN Cancer Research Group.

Extramedullary disease was found in anywhere from 2% to 30% of AML patients in past studies, and its prognostic impact was “unfavorable in some reports, but not in others,” the investigators noted. To help clarify the issue, they studied patients aged 15 years and up with newly diagnosed AML from 11 clinical trials conducted between 1980 and 2008. The initial study population included 3,522 patients, of which 282 were excluded for having promyelocytic leukemia (168 patients), leukemia that was not AML (29 patieints), no baseline assessment of extramedullary disease (41 patients), no survival data (20 patients), or no eligibility for retrospective central review (24 patients). That left 3,240 patients, of whom 769 (24%) had extramedullary disease. The most commonly involved sites included the lymph nodes (about 12% of patients), spleen (7%), liver (5%), skin (5%), and gingiva (4%). Only 1% of patients had detectable central nervous system involvement. Most (65%) of patients had one site of extramedullary disease, while 21% had two sites, and the rest had more extensive involvement (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.1305).

Rates of complete remission were 59.7% overall, 59% among patients with extramedullary disease, and 60% among patients without extramedullary disease, the investigators said. Just as the presence of extramedullary disease did not significantly affect the likelihood of complete remission, nor did any specific site of extramedullary disease, although there was a non-significant trend toward lower rates of complete remission among patients with splenic or gingival involvement.

The median overall survival for the cohort was 1 year. Univariate analyses linked the presence of any extramedullary disease (P = .005) and involvement of the skin (P = .002), spleen (P less than .001), and liver (P less than .001) with shorter overall survival. However, none of these relationships held up in a multivariable analysis that accounted for other significant prognostic factors, including earlier year of registration, older age, high white blood cell count, low platelet count, poor performance status, high cytogenetic risk status, and not achieving a complete remission, said the researchers.“It is possible that individual sites of extramedullary disease are, in fact, associated with poorer prognosis [but that] these patients also have other unfavorable prognostic factors, such as high white blood cell count and unfavorable cytogenetics,” the researchers commented.

Based on this large study, treatment decisions “should be made on the basis of recognized AML prognostic factors, irrespective of the presence of extramedullary disease,” they concluded.

The National Institutes of Health supported the work. Dr. Ganzel had no disclosures.

Extramedullary disease is common in newly diagnosed acute myeloid leukemia, and frequently occurs in at least two sites, but is not an independent prognostic factor for overall survival, according to an analysis of 11 clinical trials.

“Importantly, the presence of extramedullary disease should not affect the choice of post-remission therapy,” concluded Dr. Chezi Ganzel of Shaare Zedek Medical Center, Jerusalem, Israel, together with his associates on behalf of the ECOG-ACRIN Cancer Research Group.

Extramedullary disease was found in anywhere from 2% to 30% of AML patients in past studies, and its prognostic impact was “unfavorable in some reports, but not in others,” the investigators noted. To help clarify the issue, they studied patients aged 15 years and up with newly diagnosed AML from 11 clinical trials conducted between 1980 and 2008. The initial study population included 3,522 patients, of which 282 were excluded for having promyelocytic leukemia (168 patients), leukemia that was not AML (29 patieints), no baseline assessment of extramedullary disease (41 patients), no survival data (20 patients), or no eligibility for retrospective central review (24 patients). That left 3,240 patients, of whom 769 (24%) had extramedullary disease. The most commonly involved sites included the lymph nodes (about 12% of patients), spleen (7%), liver (5%), skin (5%), and gingiva (4%). Only 1% of patients had detectable central nervous system involvement. Most (65%) of patients had one site of extramedullary disease, while 21% had two sites, and the rest had more extensive involvement (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.1305).

Rates of complete remission were 59.7% overall, 59% among patients with extramedullary disease, and 60% among patients without extramedullary disease, the investigators said. Just as the presence of extramedullary disease did not significantly affect the likelihood of complete remission, nor did any specific site of extramedullary disease, although there was a non-significant trend toward lower rates of complete remission among patients with splenic or gingival involvement.

The median overall survival for the cohort was 1 year. Univariate analyses linked the presence of any extramedullary disease (P = .005) and involvement of the skin (P = .002), spleen (P less than .001), and liver (P less than .001) with shorter overall survival. However, none of these relationships held up in a multivariable analysis that accounted for other significant prognostic factors, including earlier year of registration, older age, high white blood cell count, low platelet count, poor performance status, high cytogenetic risk status, and not achieving a complete remission, said the researchers.“It is possible that individual sites of extramedullary disease are, in fact, associated with poorer prognosis [but that] these patients also have other unfavorable prognostic factors, such as high white blood cell count and unfavorable cytogenetics,” the researchers commented.

Based on this large study, treatment decisions “should be made on the basis of recognized AML prognostic factors, irrespective of the presence of extramedullary disease,” they concluded.

The National Institutes of Health supported the work. Dr. Ganzel had no disclosures.

Extramedullary disease is common in newly diagnosed acute myeloid leukemia, and frequently occurs in at least two sites, but is not an independent prognostic factor for overall survival, according to an analysis of 11 clinical trials.

“Importantly, the presence of extramedullary disease should not affect the choice of post-remission therapy,” concluded Dr. Chezi Ganzel of Shaare Zedek Medical Center, Jerusalem, Israel, together with his associates on behalf of the ECOG-ACRIN Cancer Research Group.

Extramedullary disease was found in anywhere from 2% to 30% of AML patients in past studies, and its prognostic impact was “unfavorable in some reports, but not in others,” the investigators noted. To help clarify the issue, they studied patients aged 15 years and up with newly diagnosed AML from 11 clinical trials conducted between 1980 and 2008. The initial study population included 3,522 patients, of which 282 were excluded for having promyelocytic leukemia (168 patients), leukemia that was not AML (29 patieints), no baseline assessment of extramedullary disease (41 patients), no survival data (20 patients), or no eligibility for retrospective central review (24 patients). That left 3,240 patients, of whom 769 (24%) had extramedullary disease. The most commonly involved sites included the lymph nodes (about 12% of patients), spleen (7%), liver (5%), skin (5%), and gingiva (4%). Only 1% of patients had detectable central nervous system involvement. Most (65%) of patients had one site of extramedullary disease, while 21% had two sites, and the rest had more extensive involvement (J Clin Oncol. 2016 Aug 29. doi: 10.1200/JCO.2016.67.1305).

Rates of complete remission were 59.7% overall, 59% among patients with extramedullary disease, and 60% among patients without extramedullary disease, the investigators said. Just as the presence of extramedullary disease did not significantly affect the likelihood of complete remission, nor did any specific site of extramedullary disease, although there was a non-significant trend toward lower rates of complete remission among patients with splenic or gingival involvement.

The median overall survival for the cohort was 1 year. Univariate analyses linked the presence of any extramedullary disease (P = .005) and involvement of the skin (P = .002), spleen (P less than .001), and liver (P less than .001) with shorter overall survival. However, none of these relationships held up in a multivariable analysis that accounted for other significant prognostic factors, including earlier year of registration, older age, high white blood cell count, low platelet count, poor performance status, high cytogenetic risk status, and not achieving a complete remission, said the researchers.“It is possible that individual sites of extramedullary disease are, in fact, associated with poorer prognosis [but that] these patients also have other unfavorable prognostic factors, such as high white blood cell count and unfavorable cytogenetics,” the researchers commented.

Based on this large study, treatment decisions “should be made on the basis of recognized AML prognostic factors, irrespective of the presence of extramedullary disease,” they concluded.

The National Institutes of Health supported the work. Dr. Ganzel had no disclosures.

The presence or absence of minimal residual disease predicted progression-free and, to a lesser degree, overall survival among chronic lymphocytic leukemia (CLL) patients who achieved complete or partial remission with six courses of chemoimmunotherapy, based on two randomized phase III trials.

These findings underscore the value of measuring minimal residual disease (MRD) in patients who respond to a defined period of CLL therapy, Dr. Gabor Kovacs of the University of Cologne (Germany) and his associates wrote Aug. 29 in the Journal of Clinical Oncology.

The investigators examined the predictive value of measuring MRD in peripheral blood by using four-color flow cytometry at a threshold of 10^-4 by analyzing data from 554 adult CLL patients who achieved complete or partial remission during two phase III trials – one (CLL8) comparing fludarabine and cyclophosphamide with fludarabine, cyclophosphamide, and rituximab (FCR) and a second (CLL10) comparing FCR with bendamustine plus rituximab (J Clin Oncol. 2016 Aug 29. doi:10.1200/JCO.2016.67.1305).

The median progression-free survival (PFS) after the end of treatment was 61 months for the 34% (186 patients) who attained MRD-negative complete remission (CR), 54 months for the 29% of patients who attained MRD-negative partial remission (PR), 35 months for the 7% of patients who attained MRD-positive CR, and 21 months for the 30% of patients who attained MRD-positive PR. Progression-free survival did not differ significantly between MRD-negative CR and MRD-negative PR patients, but was significantly longer for MRD-negative PR patients than for MRD-positive CR patients (P = .048).

Progression-free survival was even more distinct for MRD-positive CR patients, compared with those who attained MRD-positive PR (P = .002). Overall survival was significantly shorter only when patients had MRD-positive PR rather than MRD-negative CR (72 months vs. not reached, P = .001).

Among the MRD-negative PR patients, 16% had only residual lymphadenopathy, 11% had only bone marrow involvement, 48% had only splenomegaly, and 25% had more than one organ system affected, the researchers noted. Importantly, PFS for MRD-negative PR with residual splenomegaly (63 months) was similar to that for MRD-negative CR (61 months, P = .354).

In contrast, patients with MRD-negative PR and residual lymphadenopathy had shorter PFS than did MRD-negative CR patients (31 months, P = .001). “We hypothesize that residual splenomegaly after chemoimmunotherapy often represents tissue that does not contribute to a subsequent clinical progression,” the researchers commented.

They also noted an important caveat – their findings are only valid for patients who received a defined period of CLL treatment followed by observation (without maintenance), not for patients who are treated indefinitely until progression.

The CLL8 and CLL10 trials were funded by Roche, Mundipharma, and the German Federal Ministry of Education and Research. Dr. Kavocs disclosed support for travel, accommodations, and expenses from Roche and Celgene.

The presence or absence of minimal residual disease predicted progression-free and, to a lesser degree, overall survival among chronic lymphocytic leukemia (CLL) patients who achieved complete or partial remission with six courses of chemoimmunotherapy, based on two randomized phase III trials.

These findings underscore the value of measuring minimal residual disease (MRD) in patients who respond to a defined period of CLL therapy, Dr. Gabor Kovacs of the University of Cologne (Germany) and his associates wrote Aug. 29 in the Journal of Clinical Oncology.

The investigators examined the predictive value of measuring MRD in peripheral blood by using four-color flow cytometry at a threshold of 10^-4 by analyzing data from 554 adult CLL patients who achieved complete or partial remission during two phase III trials – one (CLL8) comparing fludarabine and cyclophosphamide with fludarabine, cyclophosphamide, and rituximab (FCR) and a second (CLL10) comparing FCR with bendamustine plus rituximab (J Clin Oncol. 2016 Aug 29. doi:10.1200/JCO.2016.67.1305).

The median progression-free survival (PFS) after the end of treatment was 61 months for the 34% (186 patients) who attained MRD-negative complete remission (CR), 54 months for the 29% of patients who attained MRD-negative partial remission (PR), 35 months for the 7% of patients who attained MRD-positive CR, and 21 months for the 30% of patients who attained MRD-positive PR. Progression-free survival did not differ significantly between MRD-negative CR and MRD-negative PR patients, but was significantly longer for MRD-negative PR patients than for MRD-positive CR patients (P = .048).

Progression-free survival was even more distinct for MRD-positive CR patients, compared with those who attained MRD-positive PR (P = .002). Overall survival was significantly shorter only when patients had MRD-positive PR rather than MRD-negative CR (72 months vs. not reached, P = .001).

Among the MRD-negative PR patients, 16% had only residual lymphadenopathy, 11% had only bone marrow involvement, 48% had only splenomegaly, and 25% had more than one organ system affected, the researchers noted. Importantly, PFS for MRD-negative PR with residual splenomegaly (63 months) was similar to that for MRD-negative CR (61 months, P = .354).

In contrast, patients with MRD-negative PR and residual lymphadenopathy had shorter PFS than did MRD-negative CR patients (31 months, P = .001). “We hypothesize that residual splenomegaly after chemoimmunotherapy often represents tissue that does not contribute to a subsequent clinical progression,” the researchers commented.

They also noted an important caveat – their findings are only valid for patients who received a defined period of CLL treatment followed by observation (without maintenance), not for patients who are treated indefinitely until progression.

The CLL8 and CLL10 trials were funded by Roche, Mundipharma, and the German Federal Ministry of Education and Research. Dr. Kavocs disclosed support for travel, accommodations, and expenses from Roche and Celgene.

The presence or absence of minimal residual disease predicted progression-free and, to a lesser degree, overall survival among chronic lymphocytic leukemia (CLL) patients who achieved complete or partial remission with six courses of chemoimmunotherapy, based on two randomized phase III trials.

These findings underscore the value of measuring minimal residual disease (MRD) in patients who respond to a defined period of CLL therapy, Dr. Gabor Kovacs of the University of Cologne (Germany) and his associates wrote Aug. 29 in the Journal of Clinical Oncology.

The investigators examined the predictive value of measuring MRD in peripheral blood by using four-color flow cytometry at a threshold of 10^-4 by analyzing data from 554 adult CLL patients who achieved complete or partial remission during two phase III trials – one (CLL8) comparing fludarabine and cyclophosphamide with fludarabine, cyclophosphamide, and rituximab (FCR) and a second (CLL10) comparing FCR with bendamustine plus rituximab (J Clin Oncol. 2016 Aug 29. doi:10.1200/JCO.2016.67.1305).

The median progression-free survival (PFS) after the end of treatment was 61 months for the 34% (186 patients) who attained MRD-negative complete remission (CR), 54 months for the 29% of patients who attained MRD-negative partial remission (PR), 35 months for the 7% of patients who attained MRD-positive CR, and 21 months for the 30% of patients who attained MRD-positive PR. Progression-free survival did not differ significantly between MRD-negative CR and MRD-negative PR patients, but was significantly longer for MRD-negative PR patients than for MRD-positive CR patients (P = .048).

Progression-free survival was even more distinct for MRD-positive CR patients, compared with those who attained MRD-positive PR (P = .002). Overall survival was significantly shorter only when patients had MRD-positive PR rather than MRD-negative CR (72 months vs. not reached, P = .001).

Among the MRD-negative PR patients, 16% had only residual lymphadenopathy, 11% had only bone marrow involvement, 48% had only splenomegaly, and 25% had more than one organ system affected, the researchers noted. Importantly, PFS for MRD-negative PR with residual splenomegaly (63 months) was similar to that for MRD-negative CR (61 months, P = .354).

In contrast, patients with MRD-negative PR and residual lymphadenopathy had shorter PFS than did MRD-negative CR patients (31 months, P = .001). “We hypothesize that residual splenomegaly after chemoimmunotherapy often represents tissue that does not contribute to a subsequent clinical progression,” the researchers commented.

They also noted an important caveat – their findings are only valid for patients who received a defined period of CLL treatment followed by observation (without maintenance), not for patients who are treated indefinitely until progression.

The CLL8 and CLL10 trials were funded by Roche, Mundipharma, and the German Federal Ministry of Education and Research. Dr. Kavocs disclosed support for travel, accommodations, and expenses from Roche and Celgene.