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Findings may inform design of new treatments for JMML
Image from the Salk Institute
Researchers have used induced pluripotent stem cells (iPSCs) to model juvenile myelomonocytic leukemia (JMML) and gain new insight into the disease.
The team noted that somatic PTPN11 mutations are known to cause JMML, germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML.
With their work, the researchers found that hematopoietic cells differentiated from iPSCs harboring NS/JMML-causing PTPN11 mutations recapitulate the features of JMML.
They described this work in Cell Reports.
“By studying an inherited human cancer syndrome, our study clarified early events in the development of [JMML],” said Bruce D. Gelb, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.
“More than just creating a model of a disease, we were able to prove that mechanisms seen in our model also happen in the bone marrow of people with this kind of leukemia.”
Specifically, the team found that NS/JMML myeloid cells derived from iPSCs demonstrated increased signaling through STAT5 and upregulation of 2 microRNAs—miR-223 and miR-15a.
Likewise, miR-223 and miR-15a were upregulated in 11 of 19 bone marrow samples from patients with JMML harboring PTPN11 mutations.
However, the microRNAs were not upregulated in patients without PTPN11 mutations. And when the researchers reduced miR-223’s function in NS/JMML iPSCs, they observed a normalization of myelogenesis.
“Going into the current study, experts in the field had tended to lump all forms of JMML together, but the new study was able to isolate biological changes specific to hematopoietic cells with PTPN11 mutations, which causes more severe JMML,” Dr Gelb said.
He and his colleagues also found that microRNA target gene expression levels were reduced in the iPSC-derived myeloid cells and in cells from JMML patients with PTPN11 mutations.
“Our results provide further evidence that the severity of this form of leukemia arises from the degree of changes in the gene PTPN11, altering the protein it codes for, SHP-2, and biologic pathways related to it,” Dr Gelb said. “These proteins promise to become a focus of future drug design efforts.” 
Image from the Salk Institute
Researchers have used induced pluripotent stem cells (iPSCs) to model juvenile myelomonocytic leukemia (JMML) and gain new insight into the disease.
The team noted that somatic PTPN11 mutations are known to cause JMML, germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML.
With their work, the researchers found that hematopoietic cells differentiated from iPSCs harboring NS/JMML-causing PTPN11 mutations recapitulate the features of JMML.
They described this work in Cell Reports.
“By studying an inherited human cancer syndrome, our study clarified early events in the development of [JMML],” said Bruce D. Gelb, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.
“More than just creating a model of a disease, we were able to prove that mechanisms seen in our model also happen in the bone marrow of people with this kind of leukemia.”
Specifically, the team found that NS/JMML myeloid cells derived from iPSCs demonstrated increased signaling through STAT5 and upregulation of 2 microRNAs—miR-223 and miR-15a.
Likewise, miR-223 and miR-15a were upregulated in 11 of 19 bone marrow samples from patients with JMML harboring PTPN11 mutations.
However, the microRNAs were not upregulated in patients without PTPN11 mutations. And when the researchers reduced miR-223’s function in NS/JMML iPSCs, they observed a normalization of myelogenesis.
“Going into the current study, experts in the field had tended to lump all forms of JMML together, but the new study was able to isolate biological changes specific to hematopoietic cells with PTPN11 mutations, which causes more severe JMML,” Dr Gelb said.
He and his colleagues also found that microRNA target gene expression levels were reduced in the iPSC-derived myeloid cells and in cells from JMML patients with PTPN11 mutations.
“Our results provide further evidence that the severity of this form of leukemia arises from the degree of changes in the gene PTPN11, altering the protein it codes for, SHP-2, and biologic pathways related to it,” Dr Gelb said. “These proteins promise to become a focus of future drug design efforts.”
Image from the Salk Institute
Researchers have used induced pluripotent stem cells (iPSCs) to model juvenile myelomonocytic leukemia (JMML) and gain new insight into the disease.
The team noted that somatic PTPN11 mutations are known to cause JMML, germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML.
With their work, the researchers found that hematopoietic cells differentiated from iPSCs harboring NS/JMML-causing PTPN11 mutations recapitulate the features of JMML.
They described this work in Cell Reports.
“By studying an inherited human cancer syndrome, our study clarified early events in the development of [JMML],” said Bruce D. Gelb, MD, of the Icahn School of Medicine at Mount Sinai in New York, New York.
“More than just creating a model of a disease, we were able to prove that mechanisms seen in our model also happen in the bone marrow of people with this kind of leukemia.”
Specifically, the team found that NS/JMML myeloid cells derived from iPSCs demonstrated increased signaling through STAT5 and upregulation of 2 microRNAs—miR-223 and miR-15a.
Likewise, miR-223 and miR-15a were upregulated in 11 of 19 bone marrow samples from patients with JMML harboring PTPN11 mutations.
However, the microRNAs were not upregulated in patients without PTPN11 mutations. And when the researchers reduced miR-223’s function in NS/JMML iPSCs, they observed a normalization of myelogenesis.
“Going into the current study, experts in the field had tended to lump all forms of JMML together, but the new study was able to isolate biological changes specific to hematopoietic cells with PTPN11 mutations, which causes more severe JMML,” Dr Gelb said.
He and his colleagues also found that microRNA target gene expression levels were reduced in the iPSC-derived myeloid cells and in cells from JMML patients with PTPN11 mutations.
“Our results provide further evidence that the severity of this form of leukemia arises from the degree of changes in the gene PTPN11, altering the protein it codes for, SHP-2, and biologic pathways related to it,” Dr Gelb said. “These proteins promise to become a focus of future drug design efforts.”
Smartphone use may put patient data at risk
Photo by Daniel Sone
A new survey suggests that doctors and nurses in London are routinely using their own smartphones for patient care.
Investigators say the current lack of data encryption on these devices could result in the inadvertent disclosure of “highly sensitive and confidential data” in the absence of an active organizational strategy on digital security.
The team raised this issue and reported results of the survey in BMJ Innovations.
Mohammad H. Mobasheri, MBBS, of Imperial College London in the UK, and his colleagues wanted to determine how healthcare professionals are using digital technology on the frontline.
So the investigators invited more than 6000 clinical staff at 5 London hospitals of varying sizes to complete a questionnaire on ownership and use of portable devices and mobile health apps in the workplace.
The results are based on the responses of 287 doctors and 564 nurses from different specialties.
About 99% of doctors said they owned a smartphone, and 73.5% owned a tablet. The equivalent figures for nurses were 95.1% and 64.7%, respectively.
When asked about the usefulness of smartphones for carrying out clinical duties, 92.6% of doctors and 53.2% of nurses said these devices were “very useful” or “useful.”
Most doctors (93.8%) used their smartphone while at work to communicate with their colleagues, compared with 28.5% of nurses. About half of the doctors (50.2%) used their smartphone instead of a traditional bleep (page).
About 78% of doctors and 34.8% of nurses said they had downloaded a medical app to their device, with 89.6% of doctors and 67.1% of nurses saying they used these apps as part of their clinical work.
Of those who owned a medical app and used it at work, 41.3% of doctors reported using such an app weekly, and 33% said they used one daily. The equivalent figures for nurses were 42% and 22.3%, respectively.
The apps included drug formularies, medical calculators, and those for disease diagnosis and treatment, reference and education, documentation and drug preparation.
When asked if they had ever sent patient data over their smartphones using SMS, app-based messaging (such as WhatsApp), and picture messaging using their smartphone camera, many respondents said they had done so.
About 65% of doctors had used SMS, 33.1% had used app-based messaging, and 46% had used their phone’s camera and picture messaging to send a photo of a wound or X-ray to a colleague. The corresponding figures for nurses were much lower—13.8%, 5.7%, and 7.4%, respectively.
About 28% of doctors and 3.6% of nurses said they still retained clinical information on their smartphones.
A substantial proportion of respondents said they wanted to be able to use their own devices at work. About 72% of doctors and 37.2% of nurses wanted a secure means of sending patient data to colleagues using their own smartphone.
Fully secure messaging services for smartphones are not yet available in the UK, and the data are unlikely to be encrypted, according to investigators. They therefore urged National Health Service organizations to make sure their staff understands the potential risks of sharing patient information via their unsecured smartphones.
The team said the results of this survey provide strong evidence that healthcare organizations need to develop policies to support the safe and secure use of digital technologies in the workplace.
Photo by Daniel Sone
A new survey suggests that doctors and nurses in London are routinely using their own smartphones for patient care.
Investigators say the current lack of data encryption on these devices could result in the inadvertent disclosure of “highly sensitive and confidential data” in the absence of an active organizational strategy on digital security.
The team raised this issue and reported results of the survey in BMJ Innovations.
Mohammad H. Mobasheri, MBBS, of Imperial College London in the UK, and his colleagues wanted to determine how healthcare professionals are using digital technology on the frontline.
So the investigators invited more than 6000 clinical staff at 5 London hospitals of varying sizes to complete a questionnaire on ownership and use of portable devices and mobile health apps in the workplace.
The results are based on the responses of 287 doctors and 564 nurses from different specialties.
About 99% of doctors said they owned a smartphone, and 73.5% owned a tablet. The equivalent figures for nurses were 95.1% and 64.7%, respectively.
When asked about the usefulness of smartphones for carrying out clinical duties, 92.6% of doctors and 53.2% of nurses said these devices were “very useful” or “useful.”
Most doctors (93.8%) used their smartphone while at work to communicate with their colleagues, compared with 28.5% of nurses. About half of the doctors (50.2%) used their smartphone instead of a traditional bleep (page).
About 78% of doctors and 34.8% of nurses said they had downloaded a medical app to their device, with 89.6% of doctors and 67.1% of nurses saying they used these apps as part of their clinical work.
Of those who owned a medical app and used it at work, 41.3% of doctors reported using such an app weekly, and 33% said they used one daily. The equivalent figures for nurses were 42% and 22.3%, respectively.
The apps included drug formularies, medical calculators, and those for disease diagnosis and treatment, reference and education, documentation and drug preparation.
When asked if they had ever sent patient data over their smartphones using SMS, app-based messaging (such as WhatsApp), and picture messaging using their smartphone camera, many respondents said they had done so.
About 65% of doctors had used SMS, 33.1% had used app-based messaging, and 46% had used their phone’s camera and picture messaging to send a photo of a wound or X-ray to a colleague. The corresponding figures for nurses were much lower—13.8%, 5.7%, and 7.4%, respectively.
About 28% of doctors and 3.6% of nurses said they still retained clinical information on their smartphones.
A substantial proportion of respondents said they wanted to be able to use their own devices at work. About 72% of doctors and 37.2% of nurses wanted a secure means of sending patient data to colleagues using their own smartphone.
Fully secure messaging services for smartphones are not yet available in the UK, and the data are unlikely to be encrypted, according to investigators. They therefore urged National Health Service organizations to make sure their staff understands the potential risks of sharing patient information via their unsecured smartphones.
The team said the results of this survey provide strong evidence that healthcare organizations need to develop policies to support the safe and secure use of digital technologies in the workplace.
Photo by Daniel Sone
A new survey suggests that doctors and nurses in London are routinely using their own smartphones for patient care.
Investigators say the current lack of data encryption on these devices could result in the inadvertent disclosure of “highly sensitive and confidential data” in the absence of an active organizational strategy on digital security.
The team raised this issue and reported results of the survey in BMJ Innovations.
Mohammad H. Mobasheri, MBBS, of Imperial College London in the UK, and his colleagues wanted to determine how healthcare professionals are using digital technology on the frontline.
So the investigators invited more than 6000 clinical staff at 5 London hospitals of varying sizes to complete a questionnaire on ownership and use of portable devices and mobile health apps in the workplace.
The results are based on the responses of 287 doctors and 564 nurses from different specialties.
About 99% of doctors said they owned a smartphone, and 73.5% owned a tablet. The equivalent figures for nurses were 95.1% and 64.7%, respectively.
When asked about the usefulness of smartphones for carrying out clinical duties, 92.6% of doctors and 53.2% of nurses said these devices were “very useful” or “useful.”
Most doctors (93.8%) used their smartphone while at work to communicate with their colleagues, compared with 28.5% of nurses. About half of the doctors (50.2%) used their smartphone instead of a traditional bleep (page).
About 78% of doctors and 34.8% of nurses said they had downloaded a medical app to their device, with 89.6% of doctors and 67.1% of nurses saying they used these apps as part of their clinical work.
Of those who owned a medical app and used it at work, 41.3% of doctors reported using such an app weekly, and 33% said they used one daily. The equivalent figures for nurses were 42% and 22.3%, respectively.
The apps included drug formularies, medical calculators, and those for disease diagnosis and treatment, reference and education, documentation and drug preparation.
When asked if they had ever sent patient data over their smartphones using SMS, app-based messaging (such as WhatsApp), and picture messaging using their smartphone camera, many respondents said they had done so.
About 65% of doctors had used SMS, 33.1% had used app-based messaging, and 46% had used their phone’s camera and picture messaging to send a photo of a wound or X-ray to a colleague. The corresponding figures for nurses were much lower—13.8%, 5.7%, and 7.4%, respectively.
About 28% of doctors and 3.6% of nurses said they still retained clinical information on their smartphones.
A substantial proportion of respondents said they wanted to be able to use their own devices at work. About 72% of doctors and 37.2% of nurses wanted a secure means of sending patient data to colleagues using their own smartphone.
Fully secure messaging services for smartphones are not yet available in the UK, and the data are unlikely to be encrypted, according to investigators. They therefore urged National Health Service organizations to make sure their staff understands the potential risks of sharing patient information via their unsecured smartphones.
The team said the results of this survey provide strong evidence that healthcare organizations need to develop policies to support the safe and secure use of digital technologies in the workplace.
Endovascular treatment of acute IVC thrombosis found effective
Endovascular treatment of acute thrombosis of the inferior vena cava is safe and effective with excellent short-term results, according to the results of a 10-year retrospective review reported by Dr. Khanjan H. Nagarsheth and his colleagues at the Staten Island University (N.Y.) Hospital.
Dr. Nagarsheth and his colleagues assessed 25 patients (44% men) with a mean age of 50.3 years, who underwent catheter-directed treatment in either the operating room or the angiography suite for acute (existing for less than 2 weeks) symptomatic IVC thrombosis (Annals Vasc Surg. 2015; 29:1373-9).
All patients had a prior history of deep vein thrombosis; 21 patients had an IVC filter at presentation.
Endovascular treatment was successful in all 25 patients. The greater majority of patients (22, 88%) received both catheter-directed thrombolysis (CDT) and pharmacomechanical thrombectomy; the remaining 3 patients received CDT alone.
Significant (greater than 50% luminal gain) angiographic resolution of the venous thromboembolism was achieved in all patients, with 23 (92%) reporting moderate to complete symptomatic improvement immediately after the procedure. At the median follow-up of 54.3 weeks, symptomatic improvement was noted in all patients, and complete symptom resolution was seen in 16 (89%). None of the IVC filters were removed and 67% of patients had a patent IVC at last follow-up.
“An aggressive endovascular approach to treatment of [acute thrombosis of the] IVC is warranted even in the presence of a thrombosed caval filter,” the authors concluded.
The authors did not indicate the existence of any conflicts.
Read the full study online in the Annals of Vascular Surgery.
Endovascular treatment of acute thrombosis of the inferior vena cava is safe and effective with excellent short-term results, according to the results of a 10-year retrospective review reported by Dr. Khanjan H. Nagarsheth and his colleagues at the Staten Island University (N.Y.) Hospital.
Dr. Nagarsheth and his colleagues assessed 25 patients (44% men) with a mean age of 50.3 years, who underwent catheter-directed treatment in either the operating room or the angiography suite for acute (existing for less than 2 weeks) symptomatic IVC thrombosis (Annals Vasc Surg. 2015; 29:1373-9).
All patients had a prior history of deep vein thrombosis; 21 patients had an IVC filter at presentation.
Endovascular treatment was successful in all 25 patients. The greater majority of patients (22, 88%) received both catheter-directed thrombolysis (CDT) and pharmacomechanical thrombectomy; the remaining 3 patients received CDT alone.
Significant (greater than 50% luminal gain) angiographic resolution of the venous thromboembolism was achieved in all patients, with 23 (92%) reporting moderate to complete symptomatic improvement immediately after the procedure. At the median follow-up of 54.3 weeks, symptomatic improvement was noted in all patients, and complete symptom resolution was seen in 16 (89%). None of the IVC filters were removed and 67% of patients had a patent IVC at last follow-up.
“An aggressive endovascular approach to treatment of [acute thrombosis of the] IVC is warranted even in the presence of a thrombosed caval filter,” the authors concluded.
The authors did not indicate the existence of any conflicts.
Read the full study online in the Annals of Vascular Surgery.
Endovascular treatment of acute thrombosis of the inferior vena cava is safe and effective with excellent short-term results, according to the results of a 10-year retrospective review reported by Dr. Khanjan H. Nagarsheth and his colleagues at the Staten Island University (N.Y.) Hospital.
Dr. Nagarsheth and his colleagues assessed 25 patients (44% men) with a mean age of 50.3 years, who underwent catheter-directed treatment in either the operating room or the angiography suite for acute (existing for less than 2 weeks) symptomatic IVC thrombosis (Annals Vasc Surg. 2015; 29:1373-9).
All patients had a prior history of deep vein thrombosis; 21 patients had an IVC filter at presentation.
Endovascular treatment was successful in all 25 patients. The greater majority of patients (22, 88%) received both catheter-directed thrombolysis (CDT) and pharmacomechanical thrombectomy; the remaining 3 patients received CDT alone.
Significant (greater than 50% luminal gain) angiographic resolution of the venous thromboembolism was achieved in all patients, with 23 (92%) reporting moderate to complete symptomatic improvement immediately after the procedure. At the median follow-up of 54.3 weeks, symptomatic improvement was noted in all patients, and complete symptom resolution was seen in 16 (89%). None of the IVC filters were removed and 67% of patients had a patent IVC at last follow-up.
“An aggressive endovascular approach to treatment of [acute thrombosis of the] IVC is warranted even in the presence of a thrombosed caval filter,” the authors concluded.
The authors did not indicate the existence of any conflicts.
Read the full study online in the Annals of Vascular Surgery.
FROM THE ANNALS OF VASCULAR SURGERY
PDT with daylight effective in clearing AKs of the face, scalp
Photodynamic therapy (PDT) using daylight was as effective as PDT with an artificial light source in clearing grade I actinic keratoses (AKs) of the face and scalp after 3 months, but was associated with less pain and less severe side effects in a small Italian study.
In addition, most of the patients preferred the treatment with daylight photodynamic therapy (DL-PDT), reported Dr. Maria Concetta Fargnoli of the University of L’Aquila (Italy) and her associates (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:1926-32).
The prospective intrapatient study compared the effects of DL-PDT with conventional PDT (c-PDT) at 3 months in 35 patients with multiple grade I AKs of the face and scalp in September and October 2013. Patients were treated with c-PDT on one side of the face and DL-PDT on the other side. For c-PDT, light therapy was administered after methyl aminolevulinate (MAL) cream was applied to the treatment area and occluded. For DL-PDT, MAL cream was applied to the treatment area, left uncovered for 30 minutes in the dark; patients then exposed these areas to daylight for 2 hours, between 11 a.m. and 3 p.m., after which the cream was wiped off.
At 3 months, the complete response rate of grade I AKs was 87% for DL-PDT and 91% for c-PDT, which was not a significant difference. It was less effective for grade II and III AKs in the study, though, and at 6 months, the recurrence rate for grade I AKs treated with DL-PDT was higher (17%) than for those treated with c-PDT (12%), with a P value less than .05.
Treatment with DL-PDT was associated with significantly less pain and less severe adverse events, with less erythema, crusting, and pustular eruption 2 days after treatment. In addition, 88% of the patients were more satisfied with DL-PDT, the authors said.
“Our study confirms that DL-PDT using MAL is an effective, safe, and convenient alternative for the treatment of grade I AKs ,” they concluded. “Interestingly, clinical response for AK I was significantly moderated by outdoor temperature, increasing at higher temperatures.”
The authors had no conflicts of interest. Dr. Fargnoli received a research grant from Galderma, Italy, but Galderma played no role in the study, according to the study’s disclosure statement. Galderma manufactures the MAL cream product used in the study.
Photodynamic therapy (PDT) using daylight was as effective as PDT with an artificial light source in clearing grade I actinic keratoses (AKs) of the face and scalp after 3 months, but was associated with less pain and less severe side effects in a small Italian study.
In addition, most of the patients preferred the treatment with daylight photodynamic therapy (DL-PDT), reported Dr. Maria Concetta Fargnoli of the University of L’Aquila (Italy) and her associates (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:1926-32).
The prospective intrapatient study compared the effects of DL-PDT with conventional PDT (c-PDT) at 3 months in 35 patients with multiple grade I AKs of the face and scalp in September and October 2013. Patients were treated with c-PDT on one side of the face and DL-PDT on the other side. For c-PDT, light therapy was administered after methyl aminolevulinate (MAL) cream was applied to the treatment area and occluded. For DL-PDT, MAL cream was applied to the treatment area, left uncovered for 30 minutes in the dark; patients then exposed these areas to daylight for 2 hours, between 11 a.m. and 3 p.m., after which the cream was wiped off.
At 3 months, the complete response rate of grade I AKs was 87% for DL-PDT and 91% for c-PDT, which was not a significant difference. It was less effective for grade II and III AKs in the study, though, and at 6 months, the recurrence rate for grade I AKs treated with DL-PDT was higher (17%) than for those treated with c-PDT (12%), with a P value less than .05.
Treatment with DL-PDT was associated with significantly less pain and less severe adverse events, with less erythema, crusting, and pustular eruption 2 days after treatment. In addition, 88% of the patients were more satisfied with DL-PDT, the authors said.
“Our study confirms that DL-PDT using MAL is an effective, safe, and convenient alternative for the treatment of grade I AKs ,” they concluded. “Interestingly, clinical response for AK I was significantly moderated by outdoor temperature, increasing at higher temperatures.”
The authors had no conflicts of interest. Dr. Fargnoli received a research grant from Galderma, Italy, but Galderma played no role in the study, according to the study’s disclosure statement. Galderma manufactures the MAL cream product used in the study.
Photodynamic therapy (PDT) using daylight was as effective as PDT with an artificial light source in clearing grade I actinic keratoses (AKs) of the face and scalp after 3 months, but was associated with less pain and less severe side effects in a small Italian study.
In addition, most of the patients preferred the treatment with daylight photodynamic therapy (DL-PDT), reported Dr. Maria Concetta Fargnoli of the University of L’Aquila (Italy) and her associates (J Eur Acad Dermatol Venereol. 2015 Oct;29[10]:1926-32).
The prospective intrapatient study compared the effects of DL-PDT with conventional PDT (c-PDT) at 3 months in 35 patients with multiple grade I AKs of the face and scalp in September and October 2013. Patients were treated with c-PDT on one side of the face and DL-PDT on the other side. For c-PDT, light therapy was administered after methyl aminolevulinate (MAL) cream was applied to the treatment area and occluded. For DL-PDT, MAL cream was applied to the treatment area, left uncovered for 30 minutes in the dark; patients then exposed these areas to daylight for 2 hours, between 11 a.m. and 3 p.m., after which the cream was wiped off.
At 3 months, the complete response rate of grade I AKs was 87% for DL-PDT and 91% for c-PDT, which was not a significant difference. It was less effective for grade II and III AKs in the study, though, and at 6 months, the recurrence rate for grade I AKs treated with DL-PDT was higher (17%) than for those treated with c-PDT (12%), with a P value less than .05.
Treatment with DL-PDT was associated with significantly less pain and less severe adverse events, with less erythema, crusting, and pustular eruption 2 days after treatment. In addition, 88% of the patients were more satisfied with DL-PDT, the authors said.
“Our study confirms that DL-PDT using MAL is an effective, safe, and convenient alternative for the treatment of grade I AKs ,” they concluded. “Interestingly, clinical response for AK I was significantly moderated by outdoor temperature, increasing at higher temperatures.”
The authors had no conflicts of interest. Dr. Fargnoli received a research grant from Galderma, Italy, but Galderma played no role in the study, according to the study’s disclosure statement. Galderma manufactures the MAL cream product used in the study.
FROM THE JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
Key clinical point: Photodynamic therapy using daylight was as effective as PDT with an artificial light source in clearing grade I actinic keratoses of the face and scalp after 3 months, but was associated with less pain and less severe side effects, and was more acceptable to patients.
Major finding: At 3 months, the complete response rate of grade I AKs treated with daylight photodynamic therapy was 87% vs. 91% among those treated with conventional PDT (P = .16).
Data source: A prospective intrapatient, left-right study compared the effects of daylight PDT with methyl aminolevulinate cream and conventional PDT at 3 months in 35 patients with grade I AKs. c-PDT was also combined with application of the MAL cream.
Disclosures: The authors had no financial conflicts of interest. Dr. Fargnoli received a research grant from Galderma, Italy, but Galderma played no role in the study, according to the study’s disclosure statement. Galderma manufactures the MAL cream product used in the study.
Does psychiatric treatment prevent suicide?
Over the past 2 decades, more and more people have been treated with antidepressant medications. In the same period of time, suicide rates have gone up – not down. To those of us who treat patients, this fact is both surprising and perplexing. It seems that suicidal thoughts are a common feature of major depression, and when the depressive symptoms abate with treatment, the suicidal thoughts dissipate. Intuitively, it seems that treating depression on a larger scale should prevent suicides, but we still don’t know that conclusively.
According to the National Health and Nutrition Examination Survey (NHANES), 11% percent of Americans over the age of 12 are taking an antidepressant medication. In women aged 40-59, this number is 23%. Of those taking antidepressants, only one-third have seen a mental health professional in the past 12 months. What also is striking is that for people surveyed with symptoms of severe depression, only one-third were on medication.
In 2013, just over 40,000 Americans died of suicide. From 2000 to 2013, the suicide rate per 100,000 Americans has steadily increased from 10.4 to 12.6 per 100,000 people. While we know that people with psychiatric illnesses have higher rates of suicide compared with the general population, what we don’t know is whether the people dying are the same people who are getting treatment.
Thinking about this gets very difficult. It has been estimated that 90% of those who die of suicide have suffered from a mental illness. This figure includes those who were treated, untreated, and previously treated, but the studies have methodologic inconsistencies and that 90% estimate may not be accurate. Certainly, however, people die of suicide for reasons that have nothing to do with psychiatric illness, and we do know that impulsive responses to distressing circumstances are a factor, especially when a lethal method is easily available.
Several studies have shown that antidepressant use, particularly in older adults, may be associated with a decrease in suicidality. The studies often combine suicide attempts and completions. The issues with younger patients are more complicated, and in recent weeks, the reanalysis of the 2001 Paxil 329 study has again raised issues about the safety of certain antidepressants in children and adolescents. The data for all these studies are both confusing and contradictory, and are not easy to examine or interpret.
We also don’t know what role psychotherapy plays. A study done at Johns Hopkins Bloomberg School of Public Health looked at the follow-up for 65,000 people in Denmark who had attempted suicide and found that the rates for completed suicide dropped if the patient received a short course of psychosocial therapy at a suicide prevention center. But again, this study looked at a select group of people who had already attempted suicide.
I began to think it might help to ask these questions in a closed system where patients could be tallied with regard to requests for treatment, what type of treatment was provided, and even access to autopsy results. The U.S. Department of Veterans Affairs seemed to be a source where such answers might be found. It has been reported that 22 veterans a day die by suicide, and many veterans get their care in VA facilities, with VA pharmacy benefits, and treatment effects can, in theory, be studied.
Hoping to get a better sense of the relationship between treatment and suicide, I met with Robert Bossarte, Ph.D., director of the Epidemiology Program in the VA’s Office of Public Health. His career has been focused on suicide prevention.
The first thing Dr. Bossarte did was dissuade me of the idea that the VA is a closed system. Not all veterans receive lifelong benefits from the VA, and the formulas for determining who is entitled to what benefits, and for how long, is rather complicated. Dr. Bossarte also noted that some patients go outside of the system for their care.
“What we do know is that among those who have used VA services in the previous year, about 2,000 veterans a year die from suicide. It’s been hovering around that for the past decade,” Dr. Bossarte explained, again emphasizing that many veterans do not receive care at VA facilities. “We published a report in 2012 where we estimated 22 veterans a day die by suicide and that caught fire, but it is purely an estimate. The truth is we have no idea what the real count is, because until we began working on the Suicide Data Repository there was no national register of veteran mortality and there has been no way for us to know.”
Dr. Bossarte anticipates that the VA will have the data necessary to calculate more accurate statistics by the end of the year. “More than 70% of veteran suicide are in people over age 50; but the rates are going up most among the youngest.”
A notable drop in veteran suicide rates for those who used services occurred between 2001 and 2003, and that decrease remains unexplained; it preceded later changes in mental health services and enhanced suicide prevention programs. Dr. Bossarte also pointed out that just under half of veterans who die from suicide have no mental health diagnosis, despite yearly screening to identify people who may be suffering from posttraumatic stress disorder, alcohol-related disorders, and depression.
“The attention on veteran suicide started around 2007,” Dr. Bossarte explained. “Mark Kaplan published a study using publicly available mortality data; those who reported they were veterans were twice as likely to die of suicide as those who were not.”
While this sparked interest in veteran suicide, it’s important to note that a replication of that study in 2012 by Matthew Miller did not have the same findings.
“Then, in 2008, for the first time in recent history,” Dr. Bossarte continued, “the suicide rate among active duty military personnel exceeded that of the general population. Traditionally, rates of suicide in this population have been 40%-50% lower than in the general population. The increased rate was seen primarily in the Army and Marines. Serious mental illness may make people ineligible for military service, as can violent and disruptive behavior – things that are associated with suicide – so you tended to get a healthier population in the military.”
Dr. Bossarte noted that there was conjecture that increased suicide rates among active military might be related to more waivers that allowed people to enlist who would not ordinarily be eligible, and/or to higher rates of deployment. He went on to talk about Army STARRS (Army Study to Assess Risk and Resilience in Servicemembers).
“STARRS devoted $50 million over 5 years to the largest suicide study and did not find an effect of waivers. They did report a higher suicide rate among those who were deployed, however. But then Tim Bullman in my office looked at suicide rates 7 years after separation from service, and he reported a higher suicide rate among those who were never deployed.” The VA studies, I quickly realized, were also confusing and contradictory.
The VA has greatly expanded its mental health and suicide prevention services. For veterans overall, suicide rates have stabilized, but they have not decreased. For those veterans with psychiatric disorders, however, the suicide rates have gone down.
“When you ask ‘does treatment matter?’ it’s so hard to disentangle psychotherapy from pharmacotherapy. Over the past decade, we’ve seen a significant decrease in the suicide rate among those veterans with mental health disorders. We’ve looked at suicide rates every way you can think of. One thing we do know is that the better the relationship with the clinician, the lower the suicide risk.”
We talked about the role of hospitalization in preventing suicide, and Dr. Bossarte noted that the highest risk for suicide is immediately following hospital discharge.
“We are looking at people hospitalized after their first-ever suicide attempts and rates of mortality, including suicidal behavior, for 1 year after discharge. In very preliminary findings, we didn’t see any difference in the outcome for either all-cause mortality or repeat suicide attempts in those who were hospitalized, compared to those who were not. We don’t yet know about completed suicide.”
I left my discussion with Dr. Bossarte with more questions than answers. We have reason to believe that treatment helps, but we still don’t know which treatments help which people, and we do know that treatment doesn’t prevent suicide in every patient. In a culture where “treatment” has come to be equated with “prescribing” and is often based on a checklist of symptoms done by a primary care clinician, one might wonder if combining psychotherapy and medication – an increasingly rare offering – might have a better outcome. Simply put, for a problem that prematurely takes more than 40,000 lives a year, we know much too little.
Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).
Over the past 2 decades, more and more people have been treated with antidepressant medications. In the same period of time, suicide rates have gone up – not down. To those of us who treat patients, this fact is both surprising and perplexing. It seems that suicidal thoughts are a common feature of major depression, and when the depressive symptoms abate with treatment, the suicidal thoughts dissipate. Intuitively, it seems that treating depression on a larger scale should prevent suicides, but we still don’t know that conclusively.
According to the National Health and Nutrition Examination Survey (NHANES), 11% percent of Americans over the age of 12 are taking an antidepressant medication. In women aged 40-59, this number is 23%. Of those taking antidepressants, only one-third have seen a mental health professional in the past 12 months. What also is striking is that for people surveyed with symptoms of severe depression, only one-third were on medication.
In 2013, just over 40,000 Americans died of suicide. From 2000 to 2013, the suicide rate per 100,000 Americans has steadily increased from 10.4 to 12.6 per 100,000 people. While we know that people with psychiatric illnesses have higher rates of suicide compared with the general population, what we don’t know is whether the people dying are the same people who are getting treatment.
Thinking about this gets very difficult. It has been estimated that 90% of those who die of suicide have suffered from a mental illness. This figure includes those who were treated, untreated, and previously treated, but the studies have methodologic inconsistencies and that 90% estimate may not be accurate. Certainly, however, people die of suicide for reasons that have nothing to do with psychiatric illness, and we do know that impulsive responses to distressing circumstances are a factor, especially when a lethal method is easily available.
Several studies have shown that antidepressant use, particularly in older adults, may be associated with a decrease in suicidality. The studies often combine suicide attempts and completions. The issues with younger patients are more complicated, and in recent weeks, the reanalysis of the 2001 Paxil 329 study has again raised issues about the safety of certain antidepressants in children and adolescents. The data for all these studies are both confusing and contradictory, and are not easy to examine or interpret.
We also don’t know what role psychotherapy plays. A study done at Johns Hopkins Bloomberg School of Public Health looked at the follow-up for 65,000 people in Denmark who had attempted suicide and found that the rates for completed suicide dropped if the patient received a short course of psychosocial therapy at a suicide prevention center. But again, this study looked at a select group of people who had already attempted suicide.
I began to think it might help to ask these questions in a closed system where patients could be tallied with regard to requests for treatment, what type of treatment was provided, and even access to autopsy results. The U.S. Department of Veterans Affairs seemed to be a source where such answers might be found. It has been reported that 22 veterans a day die by suicide, and many veterans get their care in VA facilities, with VA pharmacy benefits, and treatment effects can, in theory, be studied.
Hoping to get a better sense of the relationship between treatment and suicide, I met with Robert Bossarte, Ph.D., director of the Epidemiology Program in the VA’s Office of Public Health. His career has been focused on suicide prevention.
The first thing Dr. Bossarte did was dissuade me of the idea that the VA is a closed system. Not all veterans receive lifelong benefits from the VA, and the formulas for determining who is entitled to what benefits, and for how long, is rather complicated. Dr. Bossarte also noted that some patients go outside of the system for their care.
“What we do know is that among those who have used VA services in the previous year, about 2,000 veterans a year die from suicide. It’s been hovering around that for the past decade,” Dr. Bossarte explained, again emphasizing that many veterans do not receive care at VA facilities. “We published a report in 2012 where we estimated 22 veterans a day die by suicide and that caught fire, but it is purely an estimate. The truth is we have no idea what the real count is, because until we began working on the Suicide Data Repository there was no national register of veteran mortality and there has been no way for us to know.”
Dr. Bossarte anticipates that the VA will have the data necessary to calculate more accurate statistics by the end of the year. “More than 70% of veteran suicide are in people over age 50; but the rates are going up most among the youngest.”
A notable drop in veteran suicide rates for those who used services occurred between 2001 and 2003, and that decrease remains unexplained; it preceded later changes in mental health services and enhanced suicide prevention programs. Dr. Bossarte also pointed out that just under half of veterans who die from suicide have no mental health diagnosis, despite yearly screening to identify people who may be suffering from posttraumatic stress disorder, alcohol-related disorders, and depression.
“The attention on veteran suicide started around 2007,” Dr. Bossarte explained. “Mark Kaplan published a study using publicly available mortality data; those who reported they were veterans were twice as likely to die of suicide as those who were not.”
While this sparked interest in veteran suicide, it’s important to note that a replication of that study in 2012 by Matthew Miller did not have the same findings.
“Then, in 2008, for the first time in recent history,” Dr. Bossarte continued, “the suicide rate among active duty military personnel exceeded that of the general population. Traditionally, rates of suicide in this population have been 40%-50% lower than in the general population. The increased rate was seen primarily in the Army and Marines. Serious mental illness may make people ineligible for military service, as can violent and disruptive behavior – things that are associated with suicide – so you tended to get a healthier population in the military.”
Dr. Bossarte noted that there was conjecture that increased suicide rates among active military might be related to more waivers that allowed people to enlist who would not ordinarily be eligible, and/or to higher rates of deployment. He went on to talk about Army STARRS (Army Study to Assess Risk and Resilience in Servicemembers).
“STARRS devoted $50 million over 5 years to the largest suicide study and did not find an effect of waivers. They did report a higher suicide rate among those who were deployed, however. But then Tim Bullman in my office looked at suicide rates 7 years after separation from service, and he reported a higher suicide rate among those who were never deployed.” The VA studies, I quickly realized, were also confusing and contradictory.
The VA has greatly expanded its mental health and suicide prevention services. For veterans overall, suicide rates have stabilized, but they have not decreased. For those veterans with psychiatric disorders, however, the suicide rates have gone down.
“When you ask ‘does treatment matter?’ it’s so hard to disentangle psychotherapy from pharmacotherapy. Over the past decade, we’ve seen a significant decrease in the suicide rate among those veterans with mental health disorders. We’ve looked at suicide rates every way you can think of. One thing we do know is that the better the relationship with the clinician, the lower the suicide risk.”
We talked about the role of hospitalization in preventing suicide, and Dr. Bossarte noted that the highest risk for suicide is immediately following hospital discharge.
“We are looking at people hospitalized after their first-ever suicide attempts and rates of mortality, including suicidal behavior, for 1 year after discharge. In very preliminary findings, we didn’t see any difference in the outcome for either all-cause mortality or repeat suicide attempts in those who were hospitalized, compared to those who were not. We don’t yet know about completed suicide.”
I left my discussion with Dr. Bossarte with more questions than answers. We have reason to believe that treatment helps, but we still don’t know which treatments help which people, and we do know that treatment doesn’t prevent suicide in every patient. In a culture where “treatment” has come to be equated with “prescribing” and is often based on a checklist of symptoms done by a primary care clinician, one might wonder if combining psychotherapy and medication – an increasingly rare offering – might have a better outcome. Simply put, for a problem that prematurely takes more than 40,000 lives a year, we know much too little.
Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).
Over the past 2 decades, more and more people have been treated with antidepressant medications. In the same period of time, suicide rates have gone up – not down. To those of us who treat patients, this fact is both surprising and perplexing. It seems that suicidal thoughts are a common feature of major depression, and when the depressive symptoms abate with treatment, the suicidal thoughts dissipate. Intuitively, it seems that treating depression on a larger scale should prevent suicides, but we still don’t know that conclusively.
According to the National Health and Nutrition Examination Survey (NHANES), 11% percent of Americans over the age of 12 are taking an antidepressant medication. In women aged 40-59, this number is 23%. Of those taking antidepressants, only one-third have seen a mental health professional in the past 12 months. What also is striking is that for people surveyed with symptoms of severe depression, only one-third were on medication.
In 2013, just over 40,000 Americans died of suicide. From 2000 to 2013, the suicide rate per 100,000 Americans has steadily increased from 10.4 to 12.6 per 100,000 people. While we know that people with psychiatric illnesses have higher rates of suicide compared with the general population, what we don’t know is whether the people dying are the same people who are getting treatment.
Thinking about this gets very difficult. It has been estimated that 90% of those who die of suicide have suffered from a mental illness. This figure includes those who were treated, untreated, and previously treated, but the studies have methodologic inconsistencies and that 90% estimate may not be accurate. Certainly, however, people die of suicide for reasons that have nothing to do with psychiatric illness, and we do know that impulsive responses to distressing circumstances are a factor, especially when a lethal method is easily available.
Several studies have shown that antidepressant use, particularly in older adults, may be associated with a decrease in suicidality. The studies often combine suicide attempts and completions. The issues with younger patients are more complicated, and in recent weeks, the reanalysis of the 2001 Paxil 329 study has again raised issues about the safety of certain antidepressants in children and adolescents. The data for all these studies are both confusing and contradictory, and are not easy to examine or interpret.
We also don’t know what role psychotherapy plays. A study done at Johns Hopkins Bloomberg School of Public Health looked at the follow-up for 65,000 people in Denmark who had attempted suicide and found that the rates for completed suicide dropped if the patient received a short course of psychosocial therapy at a suicide prevention center. But again, this study looked at a select group of people who had already attempted suicide.
I began to think it might help to ask these questions in a closed system where patients could be tallied with regard to requests for treatment, what type of treatment was provided, and even access to autopsy results. The U.S. Department of Veterans Affairs seemed to be a source where such answers might be found. It has been reported that 22 veterans a day die by suicide, and many veterans get their care in VA facilities, with VA pharmacy benefits, and treatment effects can, in theory, be studied.
Hoping to get a better sense of the relationship between treatment and suicide, I met with Robert Bossarte, Ph.D., director of the Epidemiology Program in the VA’s Office of Public Health. His career has been focused on suicide prevention.
The first thing Dr. Bossarte did was dissuade me of the idea that the VA is a closed system. Not all veterans receive lifelong benefits from the VA, and the formulas for determining who is entitled to what benefits, and for how long, is rather complicated. Dr. Bossarte also noted that some patients go outside of the system for their care.
“What we do know is that among those who have used VA services in the previous year, about 2,000 veterans a year die from suicide. It’s been hovering around that for the past decade,” Dr. Bossarte explained, again emphasizing that many veterans do not receive care at VA facilities. “We published a report in 2012 where we estimated 22 veterans a day die by suicide and that caught fire, but it is purely an estimate. The truth is we have no idea what the real count is, because until we began working on the Suicide Data Repository there was no national register of veteran mortality and there has been no way for us to know.”
Dr. Bossarte anticipates that the VA will have the data necessary to calculate more accurate statistics by the end of the year. “More than 70% of veteran suicide are in people over age 50; but the rates are going up most among the youngest.”
A notable drop in veteran suicide rates for those who used services occurred between 2001 and 2003, and that decrease remains unexplained; it preceded later changes in mental health services and enhanced suicide prevention programs. Dr. Bossarte also pointed out that just under half of veterans who die from suicide have no mental health diagnosis, despite yearly screening to identify people who may be suffering from posttraumatic stress disorder, alcohol-related disorders, and depression.
“The attention on veteran suicide started around 2007,” Dr. Bossarte explained. “Mark Kaplan published a study using publicly available mortality data; those who reported they were veterans were twice as likely to die of suicide as those who were not.”
While this sparked interest in veteran suicide, it’s important to note that a replication of that study in 2012 by Matthew Miller did not have the same findings.
“Then, in 2008, for the first time in recent history,” Dr. Bossarte continued, “the suicide rate among active duty military personnel exceeded that of the general population. Traditionally, rates of suicide in this population have been 40%-50% lower than in the general population. The increased rate was seen primarily in the Army and Marines. Serious mental illness may make people ineligible for military service, as can violent and disruptive behavior – things that are associated with suicide – so you tended to get a healthier population in the military.”
Dr. Bossarte noted that there was conjecture that increased suicide rates among active military might be related to more waivers that allowed people to enlist who would not ordinarily be eligible, and/or to higher rates of deployment. He went on to talk about Army STARRS (Army Study to Assess Risk and Resilience in Servicemembers).
“STARRS devoted $50 million over 5 years to the largest suicide study and did not find an effect of waivers. They did report a higher suicide rate among those who were deployed, however. But then Tim Bullman in my office looked at suicide rates 7 years after separation from service, and he reported a higher suicide rate among those who were never deployed.” The VA studies, I quickly realized, were also confusing and contradictory.
The VA has greatly expanded its mental health and suicide prevention services. For veterans overall, suicide rates have stabilized, but they have not decreased. For those veterans with psychiatric disorders, however, the suicide rates have gone down.
“When you ask ‘does treatment matter?’ it’s so hard to disentangle psychotherapy from pharmacotherapy. Over the past decade, we’ve seen a significant decrease in the suicide rate among those veterans with mental health disorders. We’ve looked at suicide rates every way you can think of. One thing we do know is that the better the relationship with the clinician, the lower the suicide risk.”
We talked about the role of hospitalization in preventing suicide, and Dr. Bossarte noted that the highest risk for suicide is immediately following hospital discharge.
“We are looking at people hospitalized after their first-ever suicide attempts and rates of mortality, including suicidal behavior, for 1 year after discharge. In very preliminary findings, we didn’t see any difference in the outcome for either all-cause mortality or repeat suicide attempts in those who were hospitalized, compared to those who were not. We don’t yet know about completed suicide.”
I left my discussion with Dr. Bossarte with more questions than answers. We have reason to believe that treatment helps, but we still don’t know which treatments help which people, and we do know that treatment doesn’t prevent suicide in every patient. In a culture where “treatment” has come to be equated with “prescribing” and is often based on a checklist of symptoms done by a primary care clinician, one might wonder if combining psychotherapy and medication – an increasingly rare offering – might have a better outcome. Simply put, for a problem that prematurely takes more than 40,000 lives a year, we know much too little.
Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).
ESC model predicts recurrent VTE risk
Recurrent venous thromboembolism was significantly associated with a higher European Society of Cardiology (ESC) pulmonary embolism score. This association was independent of other factors such as age, sex, and body mass index, according to a long-term, prospective follow-up study of 627 patients with a first episode of pulmonary embolism.
In addition, unprovoked PE and varicose veins of the lower limbs also increased recurrence risk, while longer anticoagulation treatment reduced it (Intnl J Cardiol. 2016;202:275-81).
Dr. Shuai Zhang of the Beijing Institute of Respiratory Medicine and coauthors categorized their patients into three groups according to the ESC risk stratification model (Eur Heart J. 2008;29:2276-315). These were low-, intermediate-, and high-risk groups. Of the 627 patients, 84 had suspected VTE recurrence, 68 of whom had this confirmed by imaging diagnosis and were designated as the recurrent group. The 1-, 2-, and 5-year cumulative incidences of recurrent VTE were 4.5%. 7.3%, and 13.9%, respectively.
The researchers compared the 68 recurrent to the 559 nonrecurrent patients; all patients had had a first episode of PE.
Compared with nonrecurrent VTE patients, the recurrent group had significantly more high-risk and intermediate-risk patients, and the high-risk and intermediate-risk patients overall had significantly more cumulative recurrent events than the low-risk group. Multivariate analysis confirmed the association between higher risk in ESC stratification and VTE recurrence independent of age, sex, and body mass index.
Based on these results, the authors stated that, “The severity of disease should be considered in determining the initial treatment and duration of follow-up anticoagulation.”
“These finding support the notion that optimized therapy based on risk stratification is valuable while treating PE patients,” they concluded.
The authors reported having no conflicts of interest.
Read the full study online in the International Journal of Cardiology.
Recurrent venous thromboembolism was significantly associated with a higher European Society of Cardiology (ESC) pulmonary embolism score. This association was independent of other factors such as age, sex, and body mass index, according to a long-term, prospective follow-up study of 627 patients with a first episode of pulmonary embolism.
In addition, unprovoked PE and varicose veins of the lower limbs also increased recurrence risk, while longer anticoagulation treatment reduced it (Intnl J Cardiol. 2016;202:275-81).
Dr. Shuai Zhang of the Beijing Institute of Respiratory Medicine and coauthors categorized their patients into three groups according to the ESC risk stratification model (Eur Heart J. 2008;29:2276-315). These were low-, intermediate-, and high-risk groups. Of the 627 patients, 84 had suspected VTE recurrence, 68 of whom had this confirmed by imaging diagnosis and were designated as the recurrent group. The 1-, 2-, and 5-year cumulative incidences of recurrent VTE were 4.5%. 7.3%, and 13.9%, respectively.
The researchers compared the 68 recurrent to the 559 nonrecurrent patients; all patients had had a first episode of PE.
Compared with nonrecurrent VTE patients, the recurrent group had significantly more high-risk and intermediate-risk patients, and the high-risk and intermediate-risk patients overall had significantly more cumulative recurrent events than the low-risk group. Multivariate analysis confirmed the association between higher risk in ESC stratification and VTE recurrence independent of age, sex, and body mass index.
Based on these results, the authors stated that, “The severity of disease should be considered in determining the initial treatment and duration of follow-up anticoagulation.”
“These finding support the notion that optimized therapy based on risk stratification is valuable while treating PE patients,” they concluded.
The authors reported having no conflicts of interest.
Read the full study online in the International Journal of Cardiology.
Recurrent venous thromboembolism was significantly associated with a higher European Society of Cardiology (ESC) pulmonary embolism score. This association was independent of other factors such as age, sex, and body mass index, according to a long-term, prospective follow-up study of 627 patients with a first episode of pulmonary embolism.
In addition, unprovoked PE and varicose veins of the lower limbs also increased recurrence risk, while longer anticoagulation treatment reduced it (Intnl J Cardiol. 2016;202:275-81).
Dr. Shuai Zhang of the Beijing Institute of Respiratory Medicine and coauthors categorized their patients into three groups according to the ESC risk stratification model (Eur Heart J. 2008;29:2276-315). These were low-, intermediate-, and high-risk groups. Of the 627 patients, 84 had suspected VTE recurrence, 68 of whom had this confirmed by imaging diagnosis and were designated as the recurrent group. The 1-, 2-, and 5-year cumulative incidences of recurrent VTE were 4.5%. 7.3%, and 13.9%, respectively.
The researchers compared the 68 recurrent to the 559 nonrecurrent patients; all patients had had a first episode of PE.
Compared with nonrecurrent VTE patients, the recurrent group had significantly more high-risk and intermediate-risk patients, and the high-risk and intermediate-risk patients overall had significantly more cumulative recurrent events than the low-risk group. Multivariate analysis confirmed the association between higher risk in ESC stratification and VTE recurrence independent of age, sex, and body mass index.
Based on these results, the authors stated that, “The severity of disease should be considered in determining the initial treatment and duration of follow-up anticoagulation.”
“These finding support the notion that optimized therapy based on risk stratification is valuable while treating PE patients,” they concluded.
The authors reported having no conflicts of interest.
Read the full study online in the International Journal of Cardiology.
FROM THE INTERNATIONAL JOURNAL OF CARDIOLOGY
Webcast: How to use the CDC's online tools to manage complex cases in contraception
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Staphylococcal Scalded Skin Syndrome in Pregnancy
To the Editor:
Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering disorder mediated by Staphylococcus aureus exfoliative toxins (ETs).1 It is rare in adults, but when diagnosed, it is often associated with renal failure, immunodeficiency, or overwhelming staphylococcal infection.2 We present a unique case of a pregnant woman with chronic atopic dermatitis (AD) who developed SSSS.
A 21-year-old gravida 3, para 2, aborta 0pregnant woman (29 weeks’ gestation) with a history of chronic AD who was hospitalized with facial edema, purulent ocular discharge, and substantial worsening of AD presented for a dermatology consultation. Her AD was previously managed with topical steroids but had been complicated by multiple methicillin-resistant Staphylococcus aureus (MRSA) infections. On physical examination, she had substantial periorbital edema with purulent discharge from both eyes (Figure 1A), perioral crust with radial fissures (Figure 2A), and mild generalized facial swelling and desquamation (Figure 3). However, the oral cavity was not involved. She had diffuse desquamation in addition to chronic lichenified plaques of the arms, legs, and trunk and SSSS was clinically diagnosed. Cultures of conjunctival discharge were positive for MRSA. The patient was treated with intravenous vancomycin and had a full recovery (Figures 1B and 2B). She delivered a healthy newborn with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, at 36 weeks and 6 days’ gestation by cesarean delivery; however, her postoperative care was complicated by preeclampsia, which was treated with magnesium sulfate. The newborn showed no evidence of infection or blistering at birth or during the hospital stay.
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Figure 1. Periorbital edema with purulent ocular discharge before (A) and after (B) treatment. | Figure 2. Perioral desquamation and radial fissuring before (A) and after (B) treatment. |
Staphylococcal scalded skin syndrome is a superficial blistering disorder that ranges in severity from localized blisters to generalized exfoliation.1 Exfoliative toxin is the major virulence factor responsible for SSSS. Exfoliative toxin is a serine protease that targets desmoglein 1, resulting in intraepidermal separation of keratinocytes.3 Two serologically distinct exfoliative toxins—ETA and ETB—have been associated with human disease.4 Although ETA is encoded on a phage genome, ETB is encoded on a large plasmid.3 Initially it was thought that only strains of S aureus carrying lytic group II phages were responsible for ET production; however, it is now accepted that all phage groups are capable of producing ET and causing SSSS.1
Staphylococcal scalded skin syndrome is most common in infants and children and rare in adults. Although it has been occasionally described in otherwise healthy adults,5 it is most often diagnosed in patients with renal failure (decreased toxin excretion), immunodeficiency (lack of antibodies against toxins), and overwhelming staphylococcal infection (excessive toxin).2 Mortality in treated children is low, but it can reach almost 60% in adults1; therefore, defining risk factors that may aid in early diagnosis are exceedingly important.
We believe that both our patient’s history of AD and her pregnancy contributed to the development of SSSS. The patient had a history of multiple MRSA infections prior to this hospitalization, suggesting MRSA colonization, which is a common complication of AD with more than 75% of AD patients colonized with S aureus.6 Additionally, S aureus superantigen stimulation can result in the loss of regulatory T cells’ natural immunosuppression. Regulatory T cells are remarkably increased in patients with AD; therefore, the inflammatory response to S aureus is likely amplified in an atopic patient, as there is more native immunosuppressive capacity to be affected.4 Furthermore, we believe that pregnancy and its associated immunomodulation is a risk for SSSS. Immune changes in pregnancy are still not well understood; however, it is known that there are alterations to allow symbiosis between the mother and fetus. Anti-ET IgG antibodies are thought to play an important role in protecting against SSSS. Historically, studies on serum immunoglobulin levels during pregnancy have had conflicting findings. They have shown that IgG is either unchanged or decreased, while IgA, IgE, and IgM can be increased, decreased, or unchanged.7 In a study of immunoglobulins in pregnancy, Bahna et al7 showed that IgE is unchanged over the course of pregnancy, but their analysis did not address IgG levels. If IgG levels in fact decrease during pregnancy, the mother could be at risk for SSSS due to her inability to neutralize toxins. Even if total IgG levels remain unchanged, it is possible that specific antitoxin antibodies are decreased. Additionally, there is a documented suppression and alteration in T-cell response to prevent fetal rejection during pregnancy.8 Adult SSSS has been documented several times in human immunodeficiency virus–positive patients, suggesting there may be some association between T-cell suppression and SSSS susceptibility.9 Interestingly, pregnancy, similar to AD, results in an increase in immunosuppressive T cells,10 which, if deactivated by superantigens, could potentially contribute to an increased inflammatory response. All of these immune system alterations likely leave the mother vulnerable to toxin-mediated events such as SSSS.
We believe this case highlights the importance of considering SSSS in both atopic and pregnant patients with desquamating eruptions. In the case of pregnant patients, it is important to consider the risks and benefits of any medical treatments for both the mother and infant. Vancomycin is a pregnancy category B drug and was chosen for its known effectiveness and safety in pregnancy. One study compared 10 babies with mothers who were treated with vancomycin during the second and third trimesters for MRSA to 20 babies with mothers who did not receive vancomycin and did not find an increased risk for sensorineural hearing loss or nephrotoxicity.11 There is no known increased risk for preeclampsia with vancomycin, but some studies have suggested that maternal infection independently increases the risk for preeclampsia.12 Other treatment options were not as safe as vancomycin in this case: doxycycline is contraindicated (pregnancy category D) due to the potential for staining of deciduous teeth and skeletal growth impairment, trimethoprim-sulfamethoxazole is a pregnancy category D drug during the third trimester due to the risk of kernicterus, and linezolid is a pregnancy category C drug.13
1. Ladhani S. Recent developments in staphylococcal scalded skin syndrome. Clin Microbiol Infect. 2001;7:301-307.
2. Ladhani S, Joannou CL, Lochrie DP, et al. Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev. 1999;12:224-242.
3. Kato F, Kadomoto N, Iwamoto Y, et al. Regulatory mechanism for exfoliative toxin production in Staphylococcus aureus. Infect Immun. 2011;79:1660-1670.
4. Iwatsuki K, Yamasaki O, Morizane S, et al. Staphylococcal cutaneous infections: invasion, evasion and aggression. J Dermatol Sci. 2006;42:203-214.
5. Opal SM, Johnson-Winegar AD, Cross AS. Staphylococcal scalded skin syndrome in two immunocompetent adults caused by exfoliation B-producing Staphylococcus aureus. J Clin Microbiol. 1988;26:1283-1286.
6. Hill SE, Yung A, Rademaker M. Prevalence of Staphylococcus aureus and antibiotic resistance in children with atopic dermatitis: a New Zealand experience. Australas J Dermatol. 2011;52:27-31.
7. Bahna SL, Woo CK, Manuel PV, et al. Serum total IgE level during pregnancy and postpartum. Allergol Immunopathol (Madr). 2011;39:291-294.
8. Poole JA, Claman HN. Immunology of pregnancy: implications for the mother. Clin Rev Allergy Immunol. 2004;26:161-170.
9. Farrell AM, Ross JS, Umasankar S, et al. Staphylococcal scalded skin syndrome in an HIV-1 seropositive man. Br J Dermatol. 1996;134:962-965.
10. Somerset DA, Zheng Y, Kilby MD, et al. Normal human pregnancy is associated with an elevation in the immune suppressive CD251 CD41 regulatory T-cell subset. Immunology. 2004;112:38-43.
11. Reyes MP, Ostrea EM Jr, Carbinian AE, et al. Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant? Am J Obstet Gynecol. 1989;161:977-981.
12. Rustveldt LO, Kelsey SF, Sharma, R. Associations between maternal infections and preeclampsia: a systemic review of epidemiologic studies. Matern Child Health J. 2008;12: 223-242.
13. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. Vol 2. 2nd ed. Barcelona, Spain: Elsevier Limited; 2008.
To the Editor:
Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering disorder mediated by Staphylococcus aureus exfoliative toxins (ETs).1 It is rare in adults, but when diagnosed, it is often associated with renal failure, immunodeficiency, or overwhelming staphylococcal infection.2 We present a unique case of a pregnant woman with chronic atopic dermatitis (AD) who developed SSSS.
A 21-year-old gravida 3, para 2, aborta 0pregnant woman (29 weeks’ gestation) with a history of chronic AD who was hospitalized with facial edema, purulent ocular discharge, and substantial worsening of AD presented for a dermatology consultation. Her AD was previously managed with topical steroids but had been complicated by multiple methicillin-resistant Staphylococcus aureus (MRSA) infections. On physical examination, she had substantial periorbital edema with purulent discharge from both eyes (Figure 1A), perioral crust with radial fissures (Figure 2A), and mild generalized facial swelling and desquamation (Figure 3). However, the oral cavity was not involved. She had diffuse desquamation in addition to chronic lichenified plaques of the arms, legs, and trunk and SSSS was clinically diagnosed. Cultures of conjunctival discharge were positive for MRSA. The patient was treated with intravenous vancomycin and had a full recovery (Figures 1B and 2B). She delivered a healthy newborn with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, at 36 weeks and 6 days’ gestation by cesarean delivery; however, her postoperative care was complicated by preeclampsia, which was treated with magnesium sulfate. The newborn showed no evidence of infection or blistering at birth or during the hospital stay.
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Figure 1. Periorbital edema with purulent ocular discharge before (A) and after (B) treatment. | Figure 2. Perioral desquamation and radial fissuring before (A) and after (B) treatment. |
Staphylococcal scalded skin syndrome is a superficial blistering disorder that ranges in severity from localized blisters to generalized exfoliation.1 Exfoliative toxin is the major virulence factor responsible for SSSS. Exfoliative toxin is a serine protease that targets desmoglein 1, resulting in intraepidermal separation of keratinocytes.3 Two serologically distinct exfoliative toxins—ETA and ETB—have been associated with human disease.4 Although ETA is encoded on a phage genome, ETB is encoded on a large plasmid.3 Initially it was thought that only strains of S aureus carrying lytic group II phages were responsible for ET production; however, it is now accepted that all phage groups are capable of producing ET and causing SSSS.1
Staphylococcal scalded skin syndrome is most common in infants and children and rare in adults. Although it has been occasionally described in otherwise healthy adults,5 it is most often diagnosed in patients with renal failure (decreased toxin excretion), immunodeficiency (lack of antibodies against toxins), and overwhelming staphylococcal infection (excessive toxin).2 Mortality in treated children is low, but it can reach almost 60% in adults1; therefore, defining risk factors that may aid in early diagnosis are exceedingly important.
We believe that both our patient’s history of AD and her pregnancy contributed to the development of SSSS. The patient had a history of multiple MRSA infections prior to this hospitalization, suggesting MRSA colonization, which is a common complication of AD with more than 75% of AD patients colonized with S aureus.6 Additionally, S aureus superantigen stimulation can result in the loss of regulatory T cells’ natural immunosuppression. Regulatory T cells are remarkably increased in patients with AD; therefore, the inflammatory response to S aureus is likely amplified in an atopic patient, as there is more native immunosuppressive capacity to be affected.4 Furthermore, we believe that pregnancy and its associated immunomodulation is a risk for SSSS. Immune changes in pregnancy are still not well understood; however, it is known that there are alterations to allow symbiosis between the mother and fetus. Anti-ET IgG antibodies are thought to play an important role in protecting against SSSS. Historically, studies on serum immunoglobulin levels during pregnancy have had conflicting findings. They have shown that IgG is either unchanged or decreased, while IgA, IgE, and IgM can be increased, decreased, or unchanged.7 In a study of immunoglobulins in pregnancy, Bahna et al7 showed that IgE is unchanged over the course of pregnancy, but their analysis did not address IgG levels. If IgG levels in fact decrease during pregnancy, the mother could be at risk for SSSS due to her inability to neutralize toxins. Even if total IgG levels remain unchanged, it is possible that specific antitoxin antibodies are decreased. Additionally, there is a documented suppression and alteration in T-cell response to prevent fetal rejection during pregnancy.8 Adult SSSS has been documented several times in human immunodeficiency virus–positive patients, suggesting there may be some association between T-cell suppression and SSSS susceptibility.9 Interestingly, pregnancy, similar to AD, results in an increase in immunosuppressive T cells,10 which, if deactivated by superantigens, could potentially contribute to an increased inflammatory response. All of these immune system alterations likely leave the mother vulnerable to toxin-mediated events such as SSSS.
We believe this case highlights the importance of considering SSSS in both atopic and pregnant patients with desquamating eruptions. In the case of pregnant patients, it is important to consider the risks and benefits of any medical treatments for both the mother and infant. Vancomycin is a pregnancy category B drug and was chosen for its known effectiveness and safety in pregnancy. One study compared 10 babies with mothers who were treated with vancomycin during the second and third trimesters for MRSA to 20 babies with mothers who did not receive vancomycin and did not find an increased risk for sensorineural hearing loss or nephrotoxicity.11 There is no known increased risk for preeclampsia with vancomycin, but some studies have suggested that maternal infection independently increases the risk for preeclampsia.12 Other treatment options were not as safe as vancomycin in this case: doxycycline is contraindicated (pregnancy category D) due to the potential for staining of deciduous teeth and skeletal growth impairment, trimethoprim-sulfamethoxazole is a pregnancy category D drug during the third trimester due to the risk of kernicterus, and linezolid is a pregnancy category C drug.13
To the Editor:
Staphylococcal scalded skin syndrome (SSSS) is a superficial blistering disorder mediated by Staphylococcus aureus exfoliative toxins (ETs).1 It is rare in adults, but when diagnosed, it is often associated with renal failure, immunodeficiency, or overwhelming staphylococcal infection.2 We present a unique case of a pregnant woman with chronic atopic dermatitis (AD) who developed SSSS.
A 21-year-old gravida 3, para 2, aborta 0pregnant woman (29 weeks’ gestation) with a history of chronic AD who was hospitalized with facial edema, purulent ocular discharge, and substantial worsening of AD presented for a dermatology consultation. Her AD was previously managed with topical steroids but had been complicated by multiple methicillin-resistant Staphylococcus aureus (MRSA) infections. On physical examination, she had substantial periorbital edema with purulent discharge from both eyes (Figure 1A), perioral crust with radial fissures (Figure 2A), and mild generalized facial swelling and desquamation (Figure 3). However, the oral cavity was not involved. She had diffuse desquamation in addition to chronic lichenified plaques of the arms, legs, and trunk and SSSS was clinically diagnosed. Cultures of conjunctival discharge were positive for MRSA. The patient was treated with intravenous vancomycin and had a full recovery (Figures 1B and 2B). She delivered a healthy newborn with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively, at 36 weeks and 6 days’ gestation by cesarean delivery; however, her postoperative care was complicated by preeclampsia, which was treated with magnesium sulfate. The newborn showed no evidence of infection or blistering at birth or during the hospital stay.
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| ||
Figure 1. Periorbital edema with purulent ocular discharge before (A) and after (B) treatment. | Figure 2. Perioral desquamation and radial fissuring before (A) and after (B) treatment. |
Staphylococcal scalded skin syndrome is a superficial blistering disorder that ranges in severity from localized blisters to generalized exfoliation.1 Exfoliative toxin is the major virulence factor responsible for SSSS. Exfoliative toxin is a serine protease that targets desmoglein 1, resulting in intraepidermal separation of keratinocytes.3 Two serologically distinct exfoliative toxins—ETA and ETB—have been associated with human disease.4 Although ETA is encoded on a phage genome, ETB is encoded on a large plasmid.3 Initially it was thought that only strains of S aureus carrying lytic group II phages were responsible for ET production; however, it is now accepted that all phage groups are capable of producing ET and causing SSSS.1
Staphylococcal scalded skin syndrome is most common in infants and children and rare in adults. Although it has been occasionally described in otherwise healthy adults,5 it is most often diagnosed in patients with renal failure (decreased toxin excretion), immunodeficiency (lack of antibodies against toxins), and overwhelming staphylococcal infection (excessive toxin).2 Mortality in treated children is low, but it can reach almost 60% in adults1; therefore, defining risk factors that may aid in early diagnosis are exceedingly important.
We believe that both our patient’s history of AD and her pregnancy contributed to the development of SSSS. The patient had a history of multiple MRSA infections prior to this hospitalization, suggesting MRSA colonization, which is a common complication of AD with more than 75% of AD patients colonized with S aureus.6 Additionally, S aureus superantigen stimulation can result in the loss of regulatory T cells’ natural immunosuppression. Regulatory T cells are remarkably increased in patients with AD; therefore, the inflammatory response to S aureus is likely amplified in an atopic patient, as there is more native immunosuppressive capacity to be affected.4 Furthermore, we believe that pregnancy and its associated immunomodulation is a risk for SSSS. Immune changes in pregnancy are still not well understood; however, it is known that there are alterations to allow symbiosis between the mother and fetus. Anti-ET IgG antibodies are thought to play an important role in protecting against SSSS. Historically, studies on serum immunoglobulin levels during pregnancy have had conflicting findings. They have shown that IgG is either unchanged or decreased, while IgA, IgE, and IgM can be increased, decreased, or unchanged.7 In a study of immunoglobulins in pregnancy, Bahna et al7 showed that IgE is unchanged over the course of pregnancy, but their analysis did not address IgG levels. If IgG levels in fact decrease during pregnancy, the mother could be at risk for SSSS due to her inability to neutralize toxins. Even if total IgG levels remain unchanged, it is possible that specific antitoxin antibodies are decreased. Additionally, there is a documented suppression and alteration in T-cell response to prevent fetal rejection during pregnancy.8 Adult SSSS has been documented several times in human immunodeficiency virus–positive patients, suggesting there may be some association between T-cell suppression and SSSS susceptibility.9 Interestingly, pregnancy, similar to AD, results in an increase in immunosuppressive T cells,10 which, if deactivated by superantigens, could potentially contribute to an increased inflammatory response. All of these immune system alterations likely leave the mother vulnerable to toxin-mediated events such as SSSS.
We believe this case highlights the importance of considering SSSS in both atopic and pregnant patients with desquamating eruptions. In the case of pregnant patients, it is important to consider the risks and benefits of any medical treatments for both the mother and infant. Vancomycin is a pregnancy category B drug and was chosen for its known effectiveness and safety in pregnancy. One study compared 10 babies with mothers who were treated with vancomycin during the second and third trimesters for MRSA to 20 babies with mothers who did not receive vancomycin and did not find an increased risk for sensorineural hearing loss or nephrotoxicity.11 There is no known increased risk for preeclampsia with vancomycin, but some studies have suggested that maternal infection independently increases the risk for preeclampsia.12 Other treatment options were not as safe as vancomycin in this case: doxycycline is contraindicated (pregnancy category D) due to the potential for staining of deciduous teeth and skeletal growth impairment, trimethoprim-sulfamethoxazole is a pregnancy category D drug during the third trimester due to the risk of kernicterus, and linezolid is a pregnancy category C drug.13
1. Ladhani S. Recent developments in staphylococcal scalded skin syndrome. Clin Microbiol Infect. 2001;7:301-307.
2. Ladhani S, Joannou CL, Lochrie DP, et al. Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev. 1999;12:224-242.
3. Kato F, Kadomoto N, Iwamoto Y, et al. Regulatory mechanism for exfoliative toxin production in Staphylococcus aureus. Infect Immun. 2011;79:1660-1670.
4. Iwatsuki K, Yamasaki O, Morizane S, et al. Staphylococcal cutaneous infections: invasion, evasion and aggression. J Dermatol Sci. 2006;42:203-214.
5. Opal SM, Johnson-Winegar AD, Cross AS. Staphylococcal scalded skin syndrome in two immunocompetent adults caused by exfoliation B-producing Staphylococcus aureus. J Clin Microbiol. 1988;26:1283-1286.
6. Hill SE, Yung A, Rademaker M. Prevalence of Staphylococcus aureus and antibiotic resistance in children with atopic dermatitis: a New Zealand experience. Australas J Dermatol. 2011;52:27-31.
7. Bahna SL, Woo CK, Manuel PV, et al. Serum total IgE level during pregnancy and postpartum. Allergol Immunopathol (Madr). 2011;39:291-294.
8. Poole JA, Claman HN. Immunology of pregnancy: implications for the mother. Clin Rev Allergy Immunol. 2004;26:161-170.
9. Farrell AM, Ross JS, Umasankar S, et al. Staphylococcal scalded skin syndrome in an HIV-1 seropositive man. Br J Dermatol. 1996;134:962-965.
10. Somerset DA, Zheng Y, Kilby MD, et al. Normal human pregnancy is associated with an elevation in the immune suppressive CD251 CD41 regulatory T-cell subset. Immunology. 2004;112:38-43.
11. Reyes MP, Ostrea EM Jr, Carbinian AE, et al. Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant? Am J Obstet Gynecol. 1989;161:977-981.
12. Rustveldt LO, Kelsey SF, Sharma, R. Associations between maternal infections and preeclampsia: a systemic review of epidemiologic studies. Matern Child Health J. 2008;12: 223-242.
13. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. Vol 2. 2nd ed. Barcelona, Spain: Elsevier Limited; 2008.
1. Ladhani S. Recent developments in staphylococcal scalded skin syndrome. Clin Microbiol Infect. 2001;7:301-307.
2. Ladhani S, Joannou CL, Lochrie DP, et al. Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev. 1999;12:224-242.
3. Kato F, Kadomoto N, Iwamoto Y, et al. Regulatory mechanism for exfoliative toxin production in Staphylococcus aureus. Infect Immun. 2011;79:1660-1670.
4. Iwatsuki K, Yamasaki O, Morizane S, et al. Staphylococcal cutaneous infections: invasion, evasion and aggression. J Dermatol Sci. 2006;42:203-214.
5. Opal SM, Johnson-Winegar AD, Cross AS. Staphylococcal scalded skin syndrome in two immunocompetent adults caused by exfoliation B-producing Staphylococcus aureus. J Clin Microbiol. 1988;26:1283-1286.
6. Hill SE, Yung A, Rademaker M. Prevalence of Staphylococcus aureus and antibiotic resistance in children with atopic dermatitis: a New Zealand experience. Australas J Dermatol. 2011;52:27-31.
7. Bahna SL, Woo CK, Manuel PV, et al. Serum total IgE level during pregnancy and postpartum. Allergol Immunopathol (Madr). 2011;39:291-294.
8. Poole JA, Claman HN. Immunology of pregnancy: implications for the mother. Clin Rev Allergy Immunol. 2004;26:161-170.
9. Farrell AM, Ross JS, Umasankar S, et al. Staphylococcal scalded skin syndrome in an HIV-1 seropositive man. Br J Dermatol. 1996;134:962-965.
10. Somerset DA, Zheng Y, Kilby MD, et al. Normal human pregnancy is associated with an elevation in the immune suppressive CD251 CD41 regulatory T-cell subset. Immunology. 2004;112:38-43.
11. Reyes MP, Ostrea EM Jr, Carbinian AE, et al. Vancomycin during pregnancy: does it cause hearing loss or nephrotoxicity in the infant? Am J Obstet Gynecol. 1989;161:977-981.
12. Rustveldt LO, Kelsey SF, Sharma, R. Associations between maternal infections and preeclampsia: a systemic review of epidemiologic studies. Matern Child Health J. 2008;12: 223-242.
13. Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. Vol 2. 2nd ed. Barcelona, Spain: Elsevier Limited; 2008.
IgA increase linked to fewer infections in CLL patients on ibrutinib
Increases in IgA levels were associated with a reduced risk of infections in 84 chronic lymphocytic leukemia (CLL) patients participating in a trial of ibrutinib 420 mg once daily.
After 28 months of ibrutinib treatment, 69 (82%) patients had developed 177 infections. Lower rates of infections were found in those who experienced an IgA increase of at least 50% from their baseline values (P = .03), reported Dr. Clare Sun of the hematology branch of the National Heart, Lung and Blood Institute in Bethesda, Md., and her associates.
At baseline, the patients’ median IgA value was 0.47 g/L; after 6 months of treatment with ibrutinib, the median IgA value was 0.74 g/L. The levels of IgA continued to rise in the next 12 months (n = 43, median increase of 45%, P less than 0001), and patients’ IgA levels at 24 months also were greater than their baseline levels (n = 28, median increase of 64%, P less than .0001).
Using serum-free light chain measures to distinguish clonal and normal B cells, researchers also found recovery of normal B cells and increases in B-cell precursors in bone marrow and in normal B cells in the peripheral blood. This growth, however, was not large enough to raise the majority of patients’ normal B cells to normal levels.
The findings suggest “ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL,” Dr. Sun and her associates wrote. “The rapidity of increase in IgA suggests that pre-existing antibody-producing cells may be secreting more immunoglobulins, whilst CLL cells, which impair immunoglobulin production, are removed by ibrutinib.”
The patients also had a decline in IgG levels, however, which did not appear to have an adverse impact. The patients’ IgG levels remained stable during the first 6 months of treatment, but by 12 months they had decreased (n = 35, median reduction of 4%, P < .0006), falling further at 24 months (n = 21, median reduction of 23%, P < .0001).
Because ibrutinib may be given indefinitely, extended follow-up is needed to determine the immunologic consequences of prolonged Bruton’s tyrosine kinase inhibition, the researchers wrote.
Read the full study in Blood (2015. doi: 10.1182/blood-2015-04-639203).
Increases in IgA levels were associated with a reduced risk of infections in 84 chronic lymphocytic leukemia (CLL) patients participating in a trial of ibrutinib 420 mg once daily.
After 28 months of ibrutinib treatment, 69 (82%) patients had developed 177 infections. Lower rates of infections were found in those who experienced an IgA increase of at least 50% from their baseline values (P = .03), reported Dr. Clare Sun of the hematology branch of the National Heart, Lung and Blood Institute in Bethesda, Md., and her associates.
At baseline, the patients’ median IgA value was 0.47 g/L; after 6 months of treatment with ibrutinib, the median IgA value was 0.74 g/L. The levels of IgA continued to rise in the next 12 months (n = 43, median increase of 45%, P less than 0001), and patients’ IgA levels at 24 months also were greater than their baseline levels (n = 28, median increase of 64%, P less than .0001).
Using serum-free light chain measures to distinguish clonal and normal B cells, researchers also found recovery of normal B cells and increases in B-cell precursors in bone marrow and in normal B cells in the peripheral blood. This growth, however, was not large enough to raise the majority of patients’ normal B cells to normal levels.
The findings suggest “ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL,” Dr. Sun and her associates wrote. “The rapidity of increase in IgA suggests that pre-existing antibody-producing cells may be secreting more immunoglobulins, whilst CLL cells, which impair immunoglobulin production, are removed by ibrutinib.”
The patients also had a decline in IgG levels, however, which did not appear to have an adverse impact. The patients’ IgG levels remained stable during the first 6 months of treatment, but by 12 months they had decreased (n = 35, median reduction of 4%, P < .0006), falling further at 24 months (n = 21, median reduction of 23%, P < .0001).
Because ibrutinib may be given indefinitely, extended follow-up is needed to determine the immunologic consequences of prolonged Bruton’s tyrosine kinase inhibition, the researchers wrote.
Read the full study in Blood (2015. doi: 10.1182/blood-2015-04-639203).
Increases in IgA levels were associated with a reduced risk of infections in 84 chronic lymphocytic leukemia (CLL) patients participating in a trial of ibrutinib 420 mg once daily.
After 28 months of ibrutinib treatment, 69 (82%) patients had developed 177 infections. Lower rates of infections were found in those who experienced an IgA increase of at least 50% from their baseline values (P = .03), reported Dr. Clare Sun of the hematology branch of the National Heart, Lung and Blood Institute in Bethesda, Md., and her associates.
At baseline, the patients’ median IgA value was 0.47 g/L; after 6 months of treatment with ibrutinib, the median IgA value was 0.74 g/L. The levels of IgA continued to rise in the next 12 months (n = 43, median increase of 45%, P less than 0001), and patients’ IgA levels at 24 months also were greater than their baseline levels (n = 28, median increase of 64%, P less than .0001).
Using serum-free light chain measures to distinguish clonal and normal B cells, researchers also found recovery of normal B cells and increases in B-cell precursors in bone marrow and in normal B cells in the peripheral blood. This growth, however, was not large enough to raise the majority of patients’ normal B cells to normal levels.
The findings suggest “ibrutinib allows for a clinically meaningful recovery of humoral immune function in patients with CLL,” Dr. Sun and her associates wrote. “The rapidity of increase in IgA suggests that pre-existing antibody-producing cells may be secreting more immunoglobulins, whilst CLL cells, which impair immunoglobulin production, are removed by ibrutinib.”
The patients also had a decline in IgG levels, however, which did not appear to have an adverse impact. The patients’ IgG levels remained stable during the first 6 months of treatment, but by 12 months they had decreased (n = 35, median reduction of 4%, P < .0006), falling further at 24 months (n = 21, median reduction of 23%, P < .0001).
Because ibrutinib may be given indefinitely, extended follow-up is needed to determine the immunologic consequences of prolonged Bruton’s tyrosine kinase inhibition, the researchers wrote.
Read the full study in Blood (2015. doi: 10.1182/blood-2015-04-639203).
FROM BLOOD
JAK inhibitors could treat Sézary syndrome, team says
Photo courtesy of NIGMS
Patients with Sézary syndrome (SS) may have a more complex array of genetic mutations than we thought, according to a paper published in Nature Communications.
Investigators uncovered a genomic landscape that, they believe, can be used to design personalized treatment regimens for SS patients.
In particular, the team found mutations in the JAK/STAT pathway and discovered that JAK-mutated SS cells are sensitive to JAK inhibitors.
To conduct this research, the investigators sequenced SS patient samples using 3 different approaches. They performed whole-genome sequencing (n=6), whole-exome sequencing (n=66), and array comparative genomic hybridization-based copy-number analysis (n=80).
“We basically found chromosomal chaos in all of our samples,” said study author Kojo Elenitoba-Johnson, MD, of the University of Pennsylvania in Philadelphia.
“We did not expect the degree of genetic complexity that we found in our study.”
The investigators identified previously unknown, recurrent, loss-of-function mutations that target genes regulating epigenetic pathways.
One of these targets is ARID1A, and the team found that loss-of-function mutations and/or deletions in ARID1A occurred in more than 40% of the SS genome studied.
The investigators also identified gain-of-function mutations in PLCG1, JAK1, JAK3, STAT3, and STAT5B.
And in preliminary drug-mutation matching studies, JAK1-mutated SS cells were sensitive to JAK inhibitors.
“With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,” Dr Elenitoba-Johnson said. “But this is just the start. These results highlight the genetic vulnerabilities that we can use in designing precision medicine therapies.”
Now, the investigators want to develop a molecular taxonomy for mutations in SS patients. Using the sequencing technology they used in this study, the team hopes to pinpoint the exact mistakes in each patient’s SS-related genes.
From this, the investigators hope to identify distinct subsets of the disease and stratify patients for precision therapy based on their mutations and the inhibitors available for those mutations.
Photo courtesy of NIGMS
Patients with Sézary syndrome (SS) may have a more complex array of genetic mutations than we thought, according to a paper published in Nature Communications.
Investigators uncovered a genomic landscape that, they believe, can be used to design personalized treatment regimens for SS patients.
In particular, the team found mutations in the JAK/STAT pathway and discovered that JAK-mutated SS cells are sensitive to JAK inhibitors.
To conduct this research, the investigators sequenced SS patient samples using 3 different approaches. They performed whole-genome sequencing (n=6), whole-exome sequencing (n=66), and array comparative genomic hybridization-based copy-number analysis (n=80).
“We basically found chromosomal chaos in all of our samples,” said study author Kojo Elenitoba-Johnson, MD, of the University of Pennsylvania in Philadelphia.
“We did not expect the degree of genetic complexity that we found in our study.”
The investigators identified previously unknown, recurrent, loss-of-function mutations that target genes regulating epigenetic pathways.
One of these targets is ARID1A, and the team found that loss-of-function mutations and/or deletions in ARID1A occurred in more than 40% of the SS genome studied.
The investigators also identified gain-of-function mutations in PLCG1, JAK1, JAK3, STAT3, and STAT5B.
And in preliminary drug-mutation matching studies, JAK1-mutated SS cells were sensitive to JAK inhibitors.
“With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,” Dr Elenitoba-Johnson said. “But this is just the start. These results highlight the genetic vulnerabilities that we can use in designing precision medicine therapies.”
Now, the investigators want to develop a molecular taxonomy for mutations in SS patients. Using the sequencing technology they used in this study, the team hopes to pinpoint the exact mistakes in each patient’s SS-related genes.
From this, the investigators hope to identify distinct subsets of the disease and stratify patients for precision therapy based on their mutations and the inhibitors available for those mutations.
Photo courtesy of NIGMS
Patients with Sézary syndrome (SS) may have a more complex array of genetic mutations than we thought, according to a paper published in Nature Communications.
Investigators uncovered a genomic landscape that, they believe, can be used to design personalized treatment regimens for SS patients.
In particular, the team found mutations in the JAK/STAT pathway and discovered that JAK-mutated SS cells are sensitive to JAK inhibitors.
To conduct this research, the investigators sequenced SS patient samples using 3 different approaches. They performed whole-genome sequencing (n=6), whole-exome sequencing (n=66), and array comparative genomic hybridization-based copy-number analysis (n=80).
“We basically found chromosomal chaos in all of our samples,” said study author Kojo Elenitoba-Johnson, MD, of the University of Pennsylvania in Philadelphia.
“We did not expect the degree of genetic complexity that we found in our study.”
The investigators identified previously unknown, recurrent, loss-of-function mutations that target genes regulating epigenetic pathways.
One of these targets is ARID1A, and the team found that loss-of-function mutations and/or deletions in ARID1A occurred in more than 40% of the SS genome studied.
The investigators also identified gain-of-function mutations in PLCG1, JAK1, JAK3, STAT3, and STAT5B.
And in preliminary drug-mutation matching studies, JAK1-mutated SS cells were sensitive to JAK inhibitors.
“With knowledge like this, we can design clinical trials using JAK inhibitors for SS patients based on their JAK mutations,” Dr Elenitoba-Johnson said. “But this is just the start. These results highlight the genetic vulnerabilities that we can use in designing precision medicine therapies.”
Now, the investigators want to develop a molecular taxonomy for mutations in SS patients. Using the sequencing technology they used in this study, the team hopes to pinpoint the exact mistakes in each patient’s SS-related genes.
From this, the investigators hope to identify distinct subsets of the disease and stratify patients for precision therapy based on their mutations and the inhibitors available for those mutations.