Doctor and patient

Photo courtesy of the CDC

In a single-center study, researchers found that educating healthcare providers about the need for venous thromboembolism (VTE) prophylaxis did not ensure that patients received appropriate treatment.

Before the educational program was introduced, 36% of patients who were at risk of VTE were not receiving VTE prophylaxis. After the program, 26% of at-risk patients were not receiving prophylaxis.

The researchers reported these findings in the Canadian Journal of Cardiology.

The team carried out chart reviews of patients in a university-affiliated, tertiary care cardiology center, which included a clinical teaching unit and a coronary care unit.

Audits were conducted 3 and 5 months before the introduction of an educational program on VTE prophylaxis protocol, followed by a second series of audits 3 and 5 months after protocol initiation.

In each set of audits, conducted over 2 months, 3 independent groups consisting of a physician and a nonphysician healthcare provider (nursing, pharmacy) each reviewed the data. Discrepancies were settled by the senior investigators.

In the first set of audits, 173 charts for patients considered at high risk for VTE were evaluated. The second set of audits included 247 patients.

Prior to the educational program, including a guideline-based protocol, 36% of all patients who were considered at risk for VTE did not receive prophylaxis.

Three months after the program was initiated, 21% of patients were still not being treated according to the recommended guidelines, and that percentage rose to 28% at 5 months post-protocol.

“Awareness and education surrounding VTE prophylaxis is challenging in the inpatient teaching unit model due to a number of factors, including the high turnover of senior and junior physicians as well as nursing staff,” said study author Colette Seifer, of the University of Manitoba in Winnipeg, Manitoba, Canada.

“A single time point intervention is unlikely to result in a sustained improvement in VTE prophylaxis rates.”

However, Seifer and her colleagues believe that automated alerts and checklists incorporated into electronic patient records or used via innovative software programs have the potential to improve compliance rates.

Doctor and patient

Photo courtesy of the CDC

In a single-center study, researchers found that educating healthcare providers about the need for venous thromboembolism (VTE) prophylaxis did not ensure that patients received appropriate treatment.

Before the educational program was introduced, 36% of patients who were at risk of VTE were not receiving VTE prophylaxis. After the program, 26% of at-risk patients were not receiving prophylaxis.

The researchers reported these findings in the Canadian Journal of Cardiology.

The team carried out chart reviews of patients in a university-affiliated, tertiary care cardiology center, which included a clinical teaching unit and a coronary care unit.

Audits were conducted 3 and 5 months before the introduction of an educational program on VTE prophylaxis protocol, followed by a second series of audits 3 and 5 months after protocol initiation.

In each set of audits, conducted over 2 months, 3 independent groups consisting of a physician and a nonphysician healthcare provider (nursing, pharmacy) each reviewed the data. Discrepancies were settled by the senior investigators.

In the first set of audits, 173 charts for patients considered at high risk for VTE were evaluated. The second set of audits included 247 patients.

Prior to the educational program, including a guideline-based protocol, 36% of all patients who were considered at risk for VTE did not receive prophylaxis.

Three months after the program was initiated, 21% of patients were still not being treated according to the recommended guidelines, and that percentage rose to 28% at 5 months post-protocol.

“Awareness and education surrounding VTE prophylaxis is challenging in the inpatient teaching unit model due to a number of factors, including the high turnover of senior and junior physicians as well as nursing staff,” said study author Colette Seifer, of the University of Manitoba in Winnipeg, Manitoba, Canada.

“A single time point intervention is unlikely to result in a sustained improvement in VTE prophylaxis rates.”

However, Seifer and her colleagues believe that automated alerts and checklists incorporated into electronic patient records or used via innovative software programs have the potential to improve compliance rates.

Doctor and patient

Photo courtesy of the CDC

In a single-center study, researchers found that educating healthcare providers about the need for venous thromboembolism (VTE) prophylaxis did not ensure that patients received appropriate treatment.

Before the educational program was introduced, 36% of patients who were at risk of VTE were not receiving VTE prophylaxis. After the program, 26% of at-risk patients were not receiving prophylaxis.

The researchers reported these findings in the Canadian Journal of Cardiology.

The team carried out chart reviews of patients in a university-affiliated, tertiary care cardiology center, which included a clinical teaching unit and a coronary care unit.

Audits were conducted 3 and 5 months before the introduction of an educational program on VTE prophylaxis protocol, followed by a second series of audits 3 and 5 months after protocol initiation.

In each set of audits, conducted over 2 months, 3 independent groups consisting of a physician and a nonphysician healthcare provider (nursing, pharmacy) each reviewed the data. Discrepancies were settled by the senior investigators.

In the first set of audits, 173 charts for patients considered at high risk for VTE were evaluated. The second set of audits included 247 patients.

Prior to the educational program, including a guideline-based protocol, 36% of all patients who were considered at risk for VTE did not receive prophylaxis.

Three months after the program was initiated, 21% of patients were still not being treated according to the recommended guidelines, and that percentage rose to 28% at 5 months post-protocol.

“Awareness and education surrounding VTE prophylaxis is challenging in the inpatient teaching unit model due to a number of factors, including the high turnover of senior and junior physicians as well as nursing staff,” said study author Colette Seifer, of the University of Manitoba in Winnipeg, Manitoba, Canada.

“A single time point intervention is unlikely to result in a sustained improvement in VTE prophylaxis rates.”

However, Seifer and her colleagues believe that automated alerts and checklists incorporated into electronic patient records or used via innovative software programs have the potential to improve compliance rates.

Woman praying

Photo by Petr Kratochvil

Three meta-analyses shed new light on the role religion and spirituality play in cancer patients’ mental, social, and physical well-being.

The analyses, published in Cancer, indicate that religion and spirituality have significant associations with patients’ health.

But investigators observed wide variability among studies with regard to how different dimensions of religion and spirituality relate to different aspects of health.

In the first analysis, the investigators focused on physical health. Patients reporting greater overall religiousness and spirituality reported better physical health, greater ability to perform their usual daily tasks, and fewer physical symptoms of cancer and treatment.

“These relationships were particularly strong in patients who experienced greater emotional aspects of religion and spirituality, including a sense of meaning and purpose in life as well as a connection to a source larger than oneself,” said study author Heather Jim, PhD, of the Moffitt Cancer Center in Tampa, Florida.

Dr Jim noted that patients who reported greater cognitive aspects of religion and spirituality, such as the ability to integrate the cancer into their religious or spiritual beliefs, also reported better physical health. However, physical health was not related to behavioral aspects of religion and spiritualty, such as church attendance, prayer, or meditation.

In the second analysis, the investigators examined patients’ mental health. The team discovered that emotional aspects of religion and spirituality were more strongly associated with positive mental health than behavioral or cognitive aspects of religion and spirituality.

“Spiritual well-being was, unsurprisingly, associated with less anxiety, depression, or distress,” said study author John Salsman, PhD, of Wake Forest School of Medicine in Winston-Salem, North Carolina.

“Also, greater levels of spiritual distress and a sense of disconnectedness with God or a religious community was associated with greater psychological distress or poorer emotional well-being.”

The third analysis pertained to social health, or patients’ capacity to retain social roles and relationships in the face of illness.  Religion and spirituality, as well as each of its dimensions, had modest but reliable links with social health.

“When we took a closer look, we found that patients with stronger spiritual well-being, more benign images of God (such as perceptions of a benevolent God rather than an angry or distant God), or stronger beliefs (such as convictions that a personal God can be called upon for assistance) reported better social health,” said study author Allen Sherman, PhD, of the University of Arkansas for Medical Sciences in Little Rock. “In contrast, those who struggled with their faith fared more poorly.”

The investigators believe future research should focus on how relationships between religious or spiritual involvement and health change over time and whether support services designed to enhance particular aspects of religion and spirituality in interested patients might help improve their well-being.

“In addition, some patients struggle with the religious or spiritual significance of their cancer, which is normal,” Dr Jim said. “How they resolve their struggle may impact their health, but more research is needed to better understand and support these patients.”

Woman praying

Photo by Petr Kratochvil

Three meta-analyses shed new light on the role religion and spirituality play in cancer patients’ mental, social, and physical well-being.

The analyses, published in Cancer, indicate that religion and spirituality have significant associations with patients’ health.

But investigators observed wide variability among studies with regard to how different dimensions of religion and spirituality relate to different aspects of health.

In the first analysis, the investigators focused on physical health. Patients reporting greater overall religiousness and spirituality reported better physical health, greater ability to perform their usual daily tasks, and fewer physical symptoms of cancer and treatment.

“These relationships were particularly strong in patients who experienced greater emotional aspects of religion and spirituality, including a sense of meaning and purpose in life as well as a connection to a source larger than oneself,” said study author Heather Jim, PhD, of the Moffitt Cancer Center in Tampa, Florida.

Dr Jim noted that patients who reported greater cognitive aspects of religion and spirituality, such as the ability to integrate the cancer into their religious or spiritual beliefs, also reported better physical health. However, physical health was not related to behavioral aspects of religion and spiritualty, such as church attendance, prayer, or meditation.

In the second analysis, the investigators examined patients’ mental health. The team discovered that emotional aspects of religion and spirituality were more strongly associated with positive mental health than behavioral or cognitive aspects of religion and spirituality.

“Spiritual well-being was, unsurprisingly, associated with less anxiety, depression, or distress,” said study author John Salsman, PhD, of Wake Forest School of Medicine in Winston-Salem, North Carolina.

“Also, greater levels of spiritual distress and a sense of disconnectedness with God or a religious community was associated with greater psychological distress or poorer emotional well-being.”

The third analysis pertained to social health, or patients’ capacity to retain social roles and relationships in the face of illness.  Religion and spirituality, as well as each of its dimensions, had modest but reliable links with social health.

“When we took a closer look, we found that patients with stronger spiritual well-being, more benign images of God (such as perceptions of a benevolent God rather than an angry or distant God), or stronger beliefs (such as convictions that a personal God can be called upon for assistance) reported better social health,” said study author Allen Sherman, PhD, of the University of Arkansas for Medical Sciences in Little Rock. “In contrast, those who struggled with their faith fared more poorly.”

The investigators believe future research should focus on how relationships between religious or spiritual involvement and health change over time and whether support services designed to enhance particular aspects of religion and spirituality in interested patients might help improve their well-being.

“In addition, some patients struggle with the religious or spiritual significance of their cancer, which is normal,” Dr Jim said. “How they resolve their struggle may impact their health, but more research is needed to better understand and support these patients.”

Woman praying

Photo by Petr Kratochvil

Three meta-analyses shed new light on the role religion and spirituality play in cancer patients’ mental, social, and physical well-being.

The analyses, published in Cancer, indicate that religion and spirituality have significant associations with patients’ health.

But investigators observed wide variability among studies with regard to how different dimensions of religion and spirituality relate to different aspects of health.

In the first analysis, the investigators focused on physical health. Patients reporting greater overall religiousness and spirituality reported better physical health, greater ability to perform their usual daily tasks, and fewer physical symptoms of cancer and treatment.

“These relationships were particularly strong in patients who experienced greater emotional aspects of religion and spirituality, including a sense of meaning and purpose in life as well as a connection to a source larger than oneself,” said study author Heather Jim, PhD, of the Moffitt Cancer Center in Tampa, Florida.

Dr Jim noted that patients who reported greater cognitive aspects of religion and spirituality, such as the ability to integrate the cancer into their religious or spiritual beliefs, also reported better physical health. However, physical health was not related to behavioral aspects of religion and spiritualty, such as church attendance, prayer, or meditation.

In the second analysis, the investigators examined patients’ mental health. The team discovered that emotional aspects of religion and spirituality were more strongly associated with positive mental health than behavioral or cognitive aspects of religion and spirituality.

“Spiritual well-being was, unsurprisingly, associated with less anxiety, depression, or distress,” said study author John Salsman, PhD, of Wake Forest School of Medicine in Winston-Salem, North Carolina.

“Also, greater levels of spiritual distress and a sense of disconnectedness with God or a religious community was associated with greater psychological distress or poorer emotional well-being.”

The third analysis pertained to social health, or patients’ capacity to retain social roles and relationships in the face of illness.  Religion and spirituality, as well as each of its dimensions, had modest but reliable links with social health.

“When we took a closer look, we found that patients with stronger spiritual well-being, more benign images of God (such as perceptions of a benevolent God rather than an angry or distant God), or stronger beliefs (such as convictions that a personal God can be called upon for assistance) reported better social health,” said study author Allen Sherman, PhD, of the University of Arkansas for Medical Sciences in Little Rock. “In contrast, those who struggled with their faith fared more poorly.”

The investigators believe future research should focus on how relationships between religious or spiritual involvement and health change over time and whether support services designed to enhance particular aspects of religion and spirituality in interested patients might help improve their well-being.

“In addition, some patients struggle with the religious or spiritual significance of their cancer, which is normal,” Dr Jim said. “How they resolve their struggle may impact their health, but more research is needed to better understand and support these patients.”

SAN ANTONIO – Despite mounting evidence that blood cultures don’t contribute to the care of immunocompetent children admitted to the hospital with uncomplicated skin and soft tissue infections (SSTIs), they continue to be performed routinely in some hospitals, according to a study presented at the Pediatric Hospital Medicine 2015 meeting.

Current practice guidelines recommend against routine use of blood cultures in uncomplicated SSTIs (Clin Infect Dis. 2014;59(2):e10-52).

(c) CDC/Janice Haney Carr

A 2013 study of children admitted for uncomplicated SSTIs (n = 482) found no positive blood cultures in the cohort, and cultures were also associated with a significantly longer length of stay. More than half of those children, however, had received antibiotics before their blood cultures, leaving open the possibility that some negative results were the result of treatment with antibiotics (Pediatrics. 2013;132(3):454-9).

Dr. Claudette Gonzalez and her colleagues at Nicklaus Children’s Hospital, Miami, presented findings from a study that used a cohort of otherwise healthy infants and children (n = 176) admitted from the emergency department with uncomplicated SSTIs.

Dr. Gonzalez and her associates sought to strengthen the evidence against routine use of cultures by excluding children who had received antibiotics within 2 weeks of presenting to the hospital.Dr. Gonzalez noted that, despite guidelines, blood cultures remained a routine part of the workup at her hospital, with 66% of the study sample receiving cultures (n = 116). Of febrile patients, 80% received cultures; of nonfebrile patients, 59% received cultures. Patients who had a blood culture drawn were significantly more likely to have had fever (P < .01). They also were more likely to have higher white blood cell and C-reactive protein (CRP) counts (P > .05 for both), but despite this, the rate of positive blood cultures was still less than 1%.

Of the 116 blood cultures drawn, 5 grew contaminants and only 1 was a true positive, for methicillin-susceptible Staphylococcus aureus (MSSA).

The study, unlike most previous studies, enrolled patients younger than 1 year of age (n = 28), but Dr. Gonzalez said that “we don’t have a big enough sample to really make conclusions about that age group.” Also in contrast to some previous studies, Dr. Gonzalez and her associates did not find a statistically significant difference in length of stay between the patients who had received cultures and those that did not (mean 3.62 vs. 3.4 days, P > .05).The one patient in the study with true bacteremia was a 1.4-year-old child presenting with no fever, cellulitis of hands and feet, no lymphangitis, and a white blood count of 8.5 × 10³/L and a CRP of less than 0.5 mg/dL. “The WBC count was within normal range and the CRP was not elevated, so you wouldn’t have necessarily picked this kid out to say he needs a blood culture,” Dr. Gonzalez said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Still, she said, the study strengthens the evidence base against use of blood cultures in this population. “For children 1 year and older I think it’s very clear,” she said. The investigators are now proceeding with an implementation study to determine whether guidance against routine blood cultures should be put into practice at their institution.

Although the initial study revealed that 66% of children with uncomplicated SSTIs were receiving cultures, preliminary unpublished results show “it’s now at about 44%,” she said, following education of residents, fellows, and ED clinicians.

In addition to communicating with the ED to reduce use of blood cultures in this population, Dr. Gonzalez said, “we’re getting guidelines plugged into our order set in the [electronic medical record], so that’s a second reminder not to draw blood cultures. And we’re measuring to see if our rates improve further.”

Dr. Gonzalez received no outside funding for her study and disclosed no conflicts of interest.

SAN ANTONIO – Despite mounting evidence that blood cultures don’t contribute to the care of immunocompetent children admitted to the hospital with uncomplicated skin and soft tissue infections (SSTIs), they continue to be performed routinely in some hospitals, according to a study presented at the Pediatric Hospital Medicine 2015 meeting.

Current practice guidelines recommend against routine use of blood cultures in uncomplicated SSTIs (Clin Infect Dis. 2014;59(2):e10-52).

(c) CDC/Janice Haney Carr

A 2013 study of children admitted for uncomplicated SSTIs (n = 482) found no positive blood cultures in the cohort, and cultures were also associated with a significantly longer length of stay. More than half of those children, however, had received antibiotics before their blood cultures, leaving open the possibility that some negative results were the result of treatment with antibiotics (Pediatrics. 2013;132(3):454-9).

Dr. Claudette Gonzalez and her colleagues at Nicklaus Children’s Hospital, Miami, presented findings from a study that used a cohort of otherwise healthy infants and children (n = 176) admitted from the emergency department with uncomplicated SSTIs.

Dr. Gonzalez and her associates sought to strengthen the evidence against routine use of cultures by excluding children who had received antibiotics within 2 weeks of presenting to the hospital.Dr. Gonzalez noted that, despite guidelines, blood cultures remained a routine part of the workup at her hospital, with 66% of the study sample receiving cultures (n = 116). Of febrile patients, 80% received cultures; of nonfebrile patients, 59% received cultures. Patients who had a blood culture drawn were significantly more likely to have had fever (P < .01). They also were more likely to have higher white blood cell and C-reactive protein (CRP) counts (P > .05 for both), but despite this, the rate of positive blood cultures was still less than 1%.

Of the 116 blood cultures drawn, 5 grew contaminants and only 1 was a true positive, for methicillin-susceptible Staphylococcus aureus (MSSA).

The study, unlike most previous studies, enrolled patients younger than 1 year of age (n = 28), but Dr. Gonzalez said that “we don’t have a big enough sample to really make conclusions about that age group.” Also in contrast to some previous studies, Dr. Gonzalez and her associates did not find a statistically significant difference in length of stay between the patients who had received cultures and those that did not (mean 3.62 vs. 3.4 days, P > .05).The one patient in the study with true bacteremia was a 1.4-year-old child presenting with no fever, cellulitis of hands and feet, no lymphangitis, and a white blood count of 8.5 × 10³/L and a CRP of less than 0.5 mg/dL. “The WBC count was within normal range and the CRP was not elevated, so you wouldn’t have necessarily picked this kid out to say he needs a blood culture,” Dr. Gonzalez said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Still, she said, the study strengthens the evidence base against use of blood cultures in this population. “For children 1 year and older I think it’s very clear,” she said. The investigators are now proceeding with an implementation study to determine whether guidance against routine blood cultures should be put into practice at their institution.

Although the initial study revealed that 66% of children with uncomplicated SSTIs were receiving cultures, preliminary unpublished results show “it’s now at about 44%,” she said, following education of residents, fellows, and ED clinicians.

In addition to communicating with the ED to reduce use of blood cultures in this population, Dr. Gonzalez said, “we’re getting guidelines plugged into our order set in the [electronic medical record], so that’s a second reminder not to draw blood cultures. And we’re measuring to see if our rates improve further.”

Dr. Gonzalez received no outside funding for her study and disclosed no conflicts of interest.

SAN ANTONIO – Despite mounting evidence that blood cultures don’t contribute to the care of immunocompetent children admitted to the hospital with uncomplicated skin and soft tissue infections (SSTIs), they continue to be performed routinely in some hospitals, according to a study presented at the Pediatric Hospital Medicine 2015 meeting.

Current practice guidelines recommend against routine use of blood cultures in uncomplicated SSTIs (Clin Infect Dis. 2014;59(2):e10-52).

(c) CDC/Janice Haney Carr

A 2013 study of children admitted for uncomplicated SSTIs (n = 482) found no positive blood cultures in the cohort, and cultures were also associated with a significantly longer length of stay. More than half of those children, however, had received antibiotics before their blood cultures, leaving open the possibility that some negative results were the result of treatment with antibiotics (Pediatrics. 2013;132(3):454-9).

Dr. Claudette Gonzalez and her colleagues at Nicklaus Children’s Hospital, Miami, presented findings from a study that used a cohort of otherwise healthy infants and children (n = 176) admitted from the emergency department with uncomplicated SSTIs.

Dr. Gonzalez and her associates sought to strengthen the evidence against routine use of cultures by excluding children who had received antibiotics within 2 weeks of presenting to the hospital.Dr. Gonzalez noted that, despite guidelines, blood cultures remained a routine part of the workup at her hospital, with 66% of the study sample receiving cultures (n = 116). Of febrile patients, 80% received cultures; of nonfebrile patients, 59% received cultures. Patients who had a blood culture drawn were significantly more likely to have had fever (P < .01). They also were more likely to have higher white blood cell and C-reactive protein (CRP) counts (P > .05 for both), but despite this, the rate of positive blood cultures was still less than 1%.

Of the 116 blood cultures drawn, 5 grew contaminants and only 1 was a true positive, for methicillin-susceptible Staphylococcus aureus (MSSA).

The study, unlike most previous studies, enrolled patients younger than 1 year of age (n = 28), but Dr. Gonzalez said that “we don’t have a big enough sample to really make conclusions about that age group.” Also in contrast to some previous studies, Dr. Gonzalez and her associates did not find a statistically significant difference in length of stay between the patients who had received cultures and those that did not (mean 3.62 vs. 3.4 days, P > .05).The one patient in the study with true bacteremia was a 1.4-year-old child presenting with no fever, cellulitis of hands and feet, no lymphangitis, and a white blood count of 8.5 × 10³/L and a CRP of less than 0.5 mg/dL. “The WBC count was within normal range and the CRP was not elevated, so you wouldn’t have necessarily picked this kid out to say he needs a blood culture,” Dr. Gonzalez said at the meeting, which was sponsored by the Society of Hospital Medicine, the American Academy of Pediatrics, the AAP Section on Hospital Medicine, and the Academic Pediatric Association.

Still, she said, the study strengthens the evidence base against use of blood cultures in this population. “For children 1 year and older I think it’s very clear,” she said. The investigators are now proceeding with an implementation study to determine whether guidance against routine blood cultures should be put into practice at their institution.

Although the initial study revealed that 66% of children with uncomplicated SSTIs were receiving cultures, preliminary unpublished results show “it’s now at about 44%,” she said, following education of residents, fellows, and ED clinicians.

In addition to communicating with the ED to reduce use of blood cultures in this population, Dr. Gonzalez said, “we’re getting guidelines plugged into our order set in the [electronic medical record], so that’s a second reminder not to draw blood cultures. And we’re measuring to see if our rates improve further.”

Dr. Gonzalez received no outside funding for her study and disclosed no conflicts of interest.

Genome testing

Photo courtesy of NIGMS

Investigators say they have identified mutations that cause Fanconi anemia and, in the process, gained new insight into interstrand crosslink (ICL) repair.

The researchers studied two patients who had Fanconi anemia with no known genetic cause.

Genomic sequencing revealed that one patient had a mutation in RAD51, and the other had mutations in UBE2T.

These genes—and others linked to Fanconi anemia in previous studies—contribute to ICL repair, which fixes a misplaced attachment between two strands of DNA.

Caused by chemical agents, ICLs block the replication of DNA, making it impossible for cells to accurately copy their genomes as they divide. The ICL repair process uses multiple enzymes that cut away the connection between the DNA strands, freeing them up and allowing the cells to grow.

The genome is at constant risk of forming ICLs, and defects in the ICL repair pathway can produce a constellation of symptoms associated with Fanconi anemia—a predisposition to cancer, bone marrow failure, infertility, and developmental defects.

Via two different studies, Agata Smogorzewska, MD, PhD, of The Rockefeller University in New York, New York, and her colleagues unearthed new discoveries relating to the disease and the pathway.

“Our work began, as it often does, with samples and histories from patients,” Dr Smogorzewska said. “In these cases, we had two patients who each represented a sort of mystery. They had symptoms of Fanconi anemia but no genetic cause yet identified.”

With the RAD51 research, which was published in Molecular Cell, the investigators set out to determine the cause of the Fanconi anemia-like symptoms in a girl in the university’s International Fanconi Anemia Registry.

When they sequenced the protein-coding genes in her genome, the researchers found a mutation in one of two copies of the RAD51 gene.

The RAD1 protein was already known to be important for another DNA repair process—homologous recombination, in which a missing section of DNA is replaced using its sister strand as a template. Homologous recombination is thought to be used during the last step of ICL repair, after the crosslink has been cut.

Because only one copy of the RAD51 gene was partially defective, the patient’s cells could still perform homologous recombination but not ICL repair.

To show that the defective copy of the RAD51 gene was indeed responsible for the patient’s symptoms, the investigators genetically engineered the girl’s own cells to remove the defect, which restored their ability to fix ICLs.

Further experiments on the patient’s cells led the researchers to suspect that RAD51 plays a role outside of homologous recombination, by tamping down the activity of two enzymes that degrade the DNA at the ICL. When RAD51 is defective, these enzymes—DNA2 and WRN—become overly destructive.

With the UBE2T study, published in Cell Reports, the investigators analyzed genomic data from another patient in the International Fanconi Anemia Registry.

They found compound heterozygous mutations in UBE2T—a large genomic deletion in the paternally derived allele and a large duplication in the maternally derived allele.

While it was already known that UBE2T is involved in activating ICL repair, the researchers said the discovery that these mutations could produce Fanconi anemia revealed that UBE2T is an irreplaceable player in the pathway.

“Although we have discovered new causes for this devastating but very rare genetic disease, the implications of this work go much further,” Dr Smogorzewska said.

“By identifying new disruptions to this repair pathway, we can better understand the mechanisms of an event that is crucial to every cell division—a process that occurs constantly within the human body throughout a lifetime.”

Genome testing

Photo courtesy of NIGMS

Investigators say they have identified mutations that cause Fanconi anemia and, in the process, gained new insight into interstrand crosslink (ICL) repair.

The researchers studied two patients who had Fanconi anemia with no known genetic cause.

Genomic sequencing revealed that one patient had a mutation in RAD51, and the other had mutations in UBE2T.

These genes—and others linked to Fanconi anemia in previous studies—contribute to ICL repair, which fixes a misplaced attachment between two strands of DNA.

Caused by chemical agents, ICLs block the replication of DNA, making it impossible for cells to accurately copy their genomes as they divide. The ICL repair process uses multiple enzymes that cut away the connection between the DNA strands, freeing them up and allowing the cells to grow.

The genome is at constant risk of forming ICLs, and defects in the ICL repair pathway can produce a constellation of symptoms associated with Fanconi anemia—a predisposition to cancer, bone marrow failure, infertility, and developmental defects.

Via two different studies, Agata Smogorzewska, MD, PhD, of The Rockefeller University in New York, New York, and her colleagues unearthed new discoveries relating to the disease and the pathway.

“Our work began, as it often does, with samples and histories from patients,” Dr Smogorzewska said. “In these cases, we had two patients who each represented a sort of mystery. They had symptoms of Fanconi anemia but no genetic cause yet identified.”

With the RAD51 research, which was published in Molecular Cell, the investigators set out to determine the cause of the Fanconi anemia-like symptoms in a girl in the university’s International Fanconi Anemia Registry.

When they sequenced the protein-coding genes in her genome, the researchers found a mutation in one of two copies of the RAD51 gene.

The RAD1 protein was already known to be important for another DNA repair process—homologous recombination, in which a missing section of DNA is replaced using its sister strand as a template. Homologous recombination is thought to be used during the last step of ICL repair, after the crosslink has been cut.

Because only one copy of the RAD51 gene was partially defective, the patient’s cells could still perform homologous recombination but not ICL repair.

To show that the defective copy of the RAD51 gene was indeed responsible for the patient’s symptoms, the investigators genetically engineered the girl’s own cells to remove the defect, which restored their ability to fix ICLs.

Further experiments on the patient’s cells led the researchers to suspect that RAD51 plays a role outside of homologous recombination, by tamping down the activity of two enzymes that degrade the DNA at the ICL. When RAD51 is defective, these enzymes—DNA2 and WRN—become overly destructive.

With the UBE2T study, published in Cell Reports, the investigators analyzed genomic data from another patient in the International Fanconi Anemia Registry.

They found compound heterozygous mutations in UBE2T—a large genomic deletion in the paternally derived allele and a large duplication in the maternally derived allele.

While it was already known that UBE2T is involved in activating ICL repair, the researchers said the discovery that these mutations could produce Fanconi anemia revealed that UBE2T is an irreplaceable player in the pathway.

“Although we have discovered new causes for this devastating but very rare genetic disease, the implications of this work go much further,” Dr Smogorzewska said.

“By identifying new disruptions to this repair pathway, we can better understand the mechanisms of an event that is crucial to every cell division—a process that occurs constantly within the human body throughout a lifetime.”

Genome testing

Photo courtesy of NIGMS

Investigators say they have identified mutations that cause Fanconi anemia and, in the process, gained new insight into interstrand crosslink (ICL) repair.

The researchers studied two patients who had Fanconi anemia with no known genetic cause.

Genomic sequencing revealed that one patient had a mutation in RAD51, and the other had mutations in UBE2T.

These genes—and others linked to Fanconi anemia in previous studies—contribute to ICL repair, which fixes a misplaced attachment between two strands of DNA.

Caused by chemical agents, ICLs block the replication of DNA, making it impossible for cells to accurately copy their genomes as they divide. The ICL repair process uses multiple enzymes that cut away the connection between the DNA strands, freeing them up and allowing the cells to grow.

The genome is at constant risk of forming ICLs, and defects in the ICL repair pathway can produce a constellation of symptoms associated with Fanconi anemia—a predisposition to cancer, bone marrow failure, infertility, and developmental defects.

Via two different studies, Agata Smogorzewska, MD, PhD, of The Rockefeller University in New York, New York, and her colleagues unearthed new discoveries relating to the disease and the pathway.

“Our work began, as it often does, with samples and histories from patients,” Dr Smogorzewska said. “In these cases, we had two patients who each represented a sort of mystery. They had symptoms of Fanconi anemia but no genetic cause yet identified.”

With the RAD51 research, which was published in Molecular Cell, the investigators set out to determine the cause of the Fanconi anemia-like symptoms in a girl in the university’s International Fanconi Anemia Registry.

When they sequenced the protein-coding genes in her genome, the researchers found a mutation in one of two copies of the RAD51 gene.

The RAD1 protein was already known to be important for another DNA repair process—homologous recombination, in which a missing section of DNA is replaced using its sister strand as a template. Homologous recombination is thought to be used during the last step of ICL repair, after the crosslink has been cut.

Because only one copy of the RAD51 gene was partially defective, the patient’s cells could still perform homologous recombination but not ICL repair.

To show that the defective copy of the RAD51 gene was indeed responsible for the patient’s symptoms, the investigators genetically engineered the girl’s own cells to remove the defect, which restored their ability to fix ICLs.

Further experiments on the patient’s cells led the researchers to suspect that RAD51 plays a role outside of homologous recombination, by tamping down the activity of two enzymes that degrade the DNA at the ICL. When RAD51 is defective, these enzymes—DNA2 and WRN—become overly destructive.

With the UBE2T study, published in Cell Reports, the investigators analyzed genomic data from another patient in the International Fanconi Anemia Registry.

They found compound heterozygous mutations in UBE2T—a large genomic deletion in the paternally derived allele and a large duplication in the maternally derived allele.

While it was already known that UBE2T is involved in activating ICL repair, the researchers said the discovery that these mutations could produce Fanconi anemia revealed that UBE2T is an irreplaceable player in the pathway.

“Although we have discovered new causes for this devastating but very rare genetic disease, the implications of this work go much further,” Dr Smogorzewska said.

“By identifying new disruptions to this repair pathway, we can better understand the mechanisms of an event that is crucial to every cell division—a process that occurs constantly within the human body throughout a lifetime.”

In patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), the Lymph2Cx assay was able to separate the cohort into groups with significantly different outcomes based on cell of origin (COO), investigators reported online in the Journal of Clinical Oncology.

In pairwise multivariable analyses, COO was associated with outcomes that were independent of International Prognostic Index score (IPI) and MYC/BCL2 immunohistochemistry (IHC).

©Kativ/iStockphoto

Gene expression profiling of DLBCL has provided classification into two distinct subtypes: germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Using the cell of origin classification can define subgroups with distinct biology ad pathogenesis, as well as identify patient groups with different outcomes after treatment. Improvements in technology have allowed for the use of formalin-fixed paraffin-embedded tissue (FFPET) biopsies for more reliable gene expression profiling.

“The size of the study cohort allowed exploration of the prognostic value of COO in comparison with other prognostic tools,” wrote Dr. David W. Scott of the British Columbia Cancer Agency, Vancouver, and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2014.60.2383).“Although the IPI remains the most powerful tool for risk stratification, COO assignment provides additional prognostic information, particularly evident in the intermediate IPI score group,” the authors noted.

The consistency and reproducibility of COO assignment using the Lymph2Cx assay was evaluated in a large patient cohort treated with R-CHOP therapy, and the relationship between COO, MYC/BCL2 dual expression, and IPI score with respect to defining prognosis in patients with DLBCL was also investigated.

Reproducibility of COO assignment using the Lymph2Cx assay was tested using repeated sampling within tumor biopsies and changes in reagent lots, and concordance of COO calls across the two reagent lots was 100%.

The COO was then determined in 344 patients with de novo DLBCL who were treated with R-CHOP at a single center. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays, and the median follow-up of living patients was 6.5 years (range, 0.75-13.2 years).

COO was a prognostic biomarker in the patient cohort. Those with activated B-cell–like DLBCL had significantly inferior outcomes as compared to patients with germinal center B-cell–like DLBCL (log-rank P less than .001 for time to progression, progression-free survival, disease-specific survival, and overall survival).

When reviewing the relationship between COO, IPI score, and MYC/BCL2 IHC, pairwise multivariable analyses demonstrated that the prognostic impact of COO is independent of IPI score. The prognostic value added by COO was most notable when patients with intermediate IPI scores were evaluated (ABC vs. GCB: 5-year time to progression, 53% v 74%; log-rank P = .003).

Both COO and MYC/BCL2 IHC identified high-risk groups that were similar in size (32% vs. 31%) with comparable outcomes (5-year time to progression, 51% vs. 51%). In pairwise multivariable analyses that included COO and MYC/BCL2 IHC as variables, COO remained significant, thus showing that COO had prognostic power “beyond that conferred merely by enrichment of MYC-positive/BCL2-positive patient cases of the ABC subtype,” wrote the authors.

When COO, IPI, and MYC/BCL2 IHC were all included in multivariable analyses, COO remained significantly associated with time to progression and progression-free survival.

“We anticipate that over the next few years, with the emergence of agents with selective activity in ABC or GCB DLBCL, the determination of COO will become part of the foundation for optimal patient care,” the authors concluded.

In patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), the Lymph2Cx assay was able to separate the cohort into groups with significantly different outcomes based on cell of origin (COO), investigators reported online in the Journal of Clinical Oncology.

In pairwise multivariable analyses, COO was associated with outcomes that were independent of International Prognostic Index score (IPI) and MYC/BCL2 immunohistochemistry (IHC).

©Kativ/iStockphoto

Gene expression profiling of DLBCL has provided classification into two distinct subtypes: germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Using the cell of origin classification can define subgroups with distinct biology ad pathogenesis, as well as identify patient groups with different outcomes after treatment. Improvements in technology have allowed for the use of formalin-fixed paraffin-embedded tissue (FFPET) biopsies for more reliable gene expression profiling.

“The size of the study cohort allowed exploration of the prognostic value of COO in comparison with other prognostic tools,” wrote Dr. David W. Scott of the British Columbia Cancer Agency, Vancouver, and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2014.60.2383).“Although the IPI remains the most powerful tool for risk stratification, COO assignment provides additional prognostic information, particularly evident in the intermediate IPI score group,” the authors noted.

The consistency and reproducibility of COO assignment using the Lymph2Cx assay was evaluated in a large patient cohort treated with R-CHOP therapy, and the relationship between COO, MYC/BCL2 dual expression, and IPI score with respect to defining prognosis in patients with DLBCL was also investigated.

Reproducibility of COO assignment using the Lymph2Cx assay was tested using repeated sampling within tumor biopsies and changes in reagent lots, and concordance of COO calls across the two reagent lots was 100%.

The COO was then determined in 344 patients with de novo DLBCL who were treated with R-CHOP at a single center. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays, and the median follow-up of living patients was 6.5 years (range, 0.75-13.2 years).

COO was a prognostic biomarker in the patient cohort. Those with activated B-cell–like DLBCL had significantly inferior outcomes as compared to patients with germinal center B-cell–like DLBCL (log-rank P less than .001 for time to progression, progression-free survival, disease-specific survival, and overall survival).

When reviewing the relationship between COO, IPI score, and MYC/BCL2 IHC, pairwise multivariable analyses demonstrated that the prognostic impact of COO is independent of IPI score. The prognostic value added by COO was most notable when patients with intermediate IPI scores were evaluated (ABC vs. GCB: 5-year time to progression, 53% v 74%; log-rank P = .003).

Both COO and MYC/BCL2 IHC identified high-risk groups that were similar in size (32% vs. 31%) with comparable outcomes (5-year time to progression, 51% vs. 51%). In pairwise multivariable analyses that included COO and MYC/BCL2 IHC as variables, COO remained significant, thus showing that COO had prognostic power “beyond that conferred merely by enrichment of MYC-positive/BCL2-positive patient cases of the ABC subtype,” wrote the authors.

When COO, IPI, and MYC/BCL2 IHC were all included in multivariable analyses, COO remained significantly associated with time to progression and progression-free survival.

“We anticipate that over the next few years, with the emergence of agents with selective activity in ABC or GCB DLBCL, the determination of COO will become part of the foundation for optimal patient care,” the authors concluded.

In patients with diffuse large B-cell lymphoma (DLBCL) treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), the Lymph2Cx assay was able to separate the cohort into groups with significantly different outcomes based on cell of origin (COO), investigators reported online in the Journal of Clinical Oncology.

In pairwise multivariable analyses, COO was associated with outcomes that were independent of International Prognostic Index score (IPI) and MYC/BCL2 immunohistochemistry (IHC).

©Kativ/iStockphoto

Gene expression profiling of DLBCL has provided classification into two distinct subtypes: germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Using the cell of origin classification can define subgroups with distinct biology ad pathogenesis, as well as identify patient groups with different outcomes after treatment. Improvements in technology have allowed for the use of formalin-fixed paraffin-embedded tissue (FFPET) biopsies for more reliable gene expression profiling.

“The size of the study cohort allowed exploration of the prognostic value of COO in comparison with other prognostic tools,” wrote Dr. David W. Scott of the British Columbia Cancer Agency, Vancouver, and his colleagues (J Clin Oncol. 2015 Aug 3. doi: 10.1200/JCO.2014.60.2383).“Although the IPI remains the most powerful tool for risk stratification, COO assignment provides additional prognostic information, particularly evident in the intermediate IPI score group,” the authors noted.

The consistency and reproducibility of COO assignment using the Lymph2Cx assay was evaluated in a large patient cohort treated with R-CHOP therapy, and the relationship between COO, MYC/BCL2 dual expression, and IPI score with respect to defining prognosis in patients with DLBCL was also investigated.

Reproducibility of COO assignment using the Lymph2Cx assay was tested using repeated sampling within tumor biopsies and changes in reagent lots, and concordance of COO calls across the two reagent lots was 100%.

The COO was then determined in 344 patients with de novo DLBCL who were treated with R-CHOP at a single center. MYC and BCL2 protein expression was assessed using immunohistochemistry on tissue microarrays, and the median follow-up of living patients was 6.5 years (range, 0.75-13.2 years).

COO was a prognostic biomarker in the patient cohort. Those with activated B-cell–like DLBCL had significantly inferior outcomes as compared to patients with germinal center B-cell–like DLBCL (log-rank P less than .001 for time to progression, progression-free survival, disease-specific survival, and overall survival).

When reviewing the relationship between COO, IPI score, and MYC/BCL2 IHC, pairwise multivariable analyses demonstrated that the prognostic impact of COO is independent of IPI score. The prognostic value added by COO was most notable when patients with intermediate IPI scores were evaluated (ABC vs. GCB: 5-year time to progression, 53% v 74%; log-rank P = .003).

Both COO and MYC/BCL2 IHC identified high-risk groups that were similar in size (32% vs. 31%) with comparable outcomes (5-year time to progression, 51% vs. 51%). In pairwise multivariable analyses that included COO and MYC/BCL2 IHC as variables, COO remained significant, thus showing that COO had prognostic power “beyond that conferred merely by enrichment of MYC-positive/BCL2-positive patient cases of the ABC subtype,” wrote the authors.

When COO, IPI, and MYC/BCL2 IHC were all included in multivariable analyses, COO remained significantly associated with time to progression and progression-free survival.

“We anticipate that over the next few years, with the emergence of agents with selective activity in ABC or GCB DLBCL, the determination of COO will become part of the foundation for optimal patient care,” the authors concluded.

Camellia sinensis, an evergreen tree belonging to the Theaceae family and used by human beings for approximately 4,000 years, is the source of the beverage tea, which is popular throughout the world, especially in Asia.¹ Of the four main true teas (that is, derived from the tea plant C. sinensis), green and white are unfermented, black tea is fermented, and oolong tea is semifermented.^2,3

Polyphenols, many of which act as strong antioxidants, are a diverse family of thousands of chemical substances found in plants. Theaflavins are black tea polyphenols with well-documented tumor-suppressing activity.⁴ In fact, they are thought to be the primary constituents of black tea responsible for conferring chemoprotection against cancer.⁵ Black tea, through oral administration and topical application, has been shown in the laboratory setting to protect skin from UV-induced erythema, premature aging, and cancer.⁶

Halder et al. have found that theaflavins and thearubigins, another key class of black tea polyphenols, can suppress A431 (human epidermoid carcinoma) and A375 (human malignant melanoma) cell proliferation without adversely impacting normal human epidermal keratinocytes. The researchers concluded that theaflavins and thearubigins appear to impart chemopreventive activity via cell cycle arrest and promotion of apoptosis in human skin cancer cells through a mitochondrial death cascade.⁷

In a 2005 English-language literature review, Thornfeldt cited green and black tea, as well as pomegranate, as the only ingredients supported by clinical trial evidence for effectiveness in treating extrinsic aging.²

Oral administration findings in animals and humans

Phyzome/Wikimedia Commons/CC BY-SA 3.0

More than 2 decades ago, Wang et al. found that the effects of orally administered black tea were comparable to those of green tea in suppressing UVB-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SKH-1 mice.⁸

In 1997, Lu et al. found that orally administered black tea inhibited the proliferation of skin tumors and enhanced apoptosis in nonmalignant and malignant skin tumors in female CD-1 mice with tumors initiated by the application of DMBA and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).⁹ Record et al. reported in 1998 that black tea may confer greater protection than green tea against simulated solar irradiation.¹⁰

Hakim and Harris conducted a population-based case-control study in 2001 to assess the effects of the consumption of citrus peel and black tea on squamous cell skin cancer. They found that participants who reported intake of hot black tea and citrus peel had a significant reduction in the risk of squamous cell carcinoma. Further, they concluded that hot black tea and citrus peel displayed independent potential protection against SCC.¹¹

Two years earlier, Zhao et al. used cultured keratinocytes and mouse and human skin to evaluate the effect of both orally and topically administered standardized black tea extract and its two major polyphenolic subfractions against UVB-induced photodamage. Topical pretreatment with the extract on SKH-1 hairless mice significantly lowered the incidence and severity of erythema and diminished skinfold thickness, compared with UVB-exposed nontreated mice. The black tea extract was similarly effective in human subjects. UVB-induced inflammation in murine as well as human skin also was reduced when the standardized extract was administered 5 minutes after UVB exposure. The investigators suggested that their findings indicated that black tea extracts have the capacity to mitigate UVB-generated erythema in human and murine skin.¹²

In 2011, George et al. assessed the chemopreventive effects of topical resveratrol and oral black tea polyphenols in blocking skin carcinogenesis in a two-stage mouse model initiated and promoted by DMBA and TPA, respectively. The combined treatment was found to reduce tumor incidence by approximately 89% (resveratrol alone, approximately 67%; black tea polyphenols alone, approximately 75%). Tumor volume and number also were significantly diminished by the synergistic combination, which, histologically, was noted for suppressing cellular proliferation and inducing apoptosis. The investigators concluded that oral black tea polyphenols combined with topical resveratrol exert greater chemopreventive activity than either compound alone and warrant study in trials for treating skin and other cancers.¹³

Animal studies on topical application

In 1997, Katiyar et al. investigated the anti-inflammatory effects of topically applied black tea polyphenols, primarily theaflavin gallates and (-)-epigallocatechin-3-gallate (EGCG), against TPA-induced inflammatory responses in murine skin. Significant inhibition against TPA-promoted induction of epidermal edema, hyperplasia, leukocyte infiltration, and proinflammatory cytokine expression was rendered by the preapplication of black tea polyphenols prior to TPA exposure. The investigators concluded that black tea polyphenols may be effective against human cutaneous inflammatory responses.¹⁴

Just over a decade later, Patel et al. investigated the in vivo antitumor-promoting effects of the most plentiful polymeric black tea polyphenols (thearubigins) in mice exposed to tumor-initiating DMBA and tumor-promoting TPA over a 40-week period. Pretreatment with topical thearubigins resulted in antipromoting effects in terms of latency, multiplicity, and incidence of skin papillomas. The black tea polyphenols also were found to reduce TPA-induced cell proliferation and epidermal cell apoptosis. The researchers attributed the protective effects of these compounds to their inhibitory impact on TPA-induced cellular proliferation.¹⁵

In 2011, Choi and Kim assessed the whitening effect of black tea water extract topically applied twice daily (6 days a week for 4 weeks) to UVB-induced hyperpigmented spots on the backs of brown guinea pigs. Treatment was divided into control (UVB and saline), vehicle control (UVB, propylene glycol, ethanol, and water), positive control (UVB and 2% hydroquinone), and two experimental groups (UVB and 1% black tea; UVB and 2% black tea). The investigators observed that the hyperpigmented spots treated with hydroquinone and black tea were clearly lighter than those treated by the control or vehicle-control groups. Histologic examination revealed that melanin pigmentation, melanocyte proliferation, and melanin production were significantly diminished in the groups treated with hydroquinone and both concentrations of black tea. The authors concluded that black tea suppresses melanocyte proliferation and melanosome synthesis in vivo, thus displaying the capacity to whiten skin in brown guinea pigs.¹⁶

In 2013, Yeh et al. found in nude mouse skin in vitro that niosomes appear to be feasible as a delivery vehicle for the dermal administration of black tea extracts as a sunscreen agent.¹

Topical studies in humans

Building on findings 3 years earlier¹⁸, Türkoglu et al., in 2010, assessed the photoprotective effects of dermal gels produced from green and black tea aqueous extracts tested in vivo in the forearms of six volunteers exposed to artificial UV light (200-400 nm). In addition to the green tea and black tea gels, a 0.3% caffeine gel, a carbomer gel base, and a control were tested. The investigators reported no eruptions of UV-induced erythema in any of the black and green tea gel sites, but erythema was present to varying degrees at the areas treated with caffeine gel, carbomer gel, and control. The investigators concluded that the black and green tea extracts exhibited potent UV absorbance and that the formulated gels were effective in protecting the skin against UV-induced erythema. Further, the investigators suggested that these agents have the potential to protect against other harm caused by UV radiation, including photoaging.¹⁹

Conclusion

Though not as widely investigated as green tea, the therapeutic potential of black tea is of great interest. Although an abundance of laboratory evidence has emerged, clinical evidence is sparse. Nevertheless, laboratory data suggest the potential uses of black tea in the dermatologic realm and justify more human trials.

References

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. Dermatol. Surg. 2005;31(7 Pt 2):873-80.

3. Oxid Med Cell Longev. 2012:2012:560682.

4. J Environ Pathol Toxicol Oncol. 2010;29(1):55-68.

5. Mol Carcinog. 2000 Jul;28(3):148-55.

6. Am J Clin Dermatol. 2010;11(4):247-67.

7. Carcinogenesis. 2008 Jan;29(1):129-38.

8. Cancer Res. 1994 Jul 1;54(13):3428-35.

9. Carcinogenesis. 1997 Nov;18(11):2163-9.

10. Mutat Res. 1998 Nov 9;422(1):191-9.

11. BMC Dermatol. 2001;1:3.

12. Photochem Photobiol. 1999 Oct;70(4):637-44.

13. PLoS One. 2011;6(8):e23395.

14. Carcinogenesis. 1997 Oct;18(10):1911-6.

15. Cell Prolif. 2008 Jun;41(3):532-53.

16. Toxicol Res. 2011 Sep;27(3):153-60.

17. Int J Dermatol. 2013 Feb;52(2):239-45.

18. Int J Cosmet Sci. 2007 Dec;29(6):437-42.

19. Drug Discov Ther. 2010 Oct;4(5):362-7.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Camellia sinensis, an evergreen tree belonging to the Theaceae family and used by human beings for approximately 4,000 years, is the source of the beverage tea, which is popular throughout the world, especially in Asia.¹ Of the four main true teas (that is, derived from the tea plant C. sinensis), green and white are unfermented, black tea is fermented, and oolong tea is semifermented.^2,3

Polyphenols, many of which act as strong antioxidants, are a diverse family of thousands of chemical substances found in plants. Theaflavins are black tea polyphenols with well-documented tumor-suppressing activity.⁴ In fact, they are thought to be the primary constituents of black tea responsible for conferring chemoprotection against cancer.⁵ Black tea, through oral administration and topical application, has been shown in the laboratory setting to protect skin from UV-induced erythema, premature aging, and cancer.⁶

Halder et al. have found that theaflavins and thearubigins, another key class of black tea polyphenols, can suppress A431 (human epidermoid carcinoma) and A375 (human malignant melanoma) cell proliferation without adversely impacting normal human epidermal keratinocytes. The researchers concluded that theaflavins and thearubigins appear to impart chemopreventive activity via cell cycle arrest and promotion of apoptosis in human skin cancer cells through a mitochondrial death cascade.⁷

In a 2005 English-language literature review, Thornfeldt cited green and black tea, as well as pomegranate, as the only ingredients supported by clinical trial evidence for effectiveness in treating extrinsic aging.²

Oral administration findings in animals and humans

Phyzome/Wikimedia Commons/CC BY-SA 3.0

More than 2 decades ago, Wang et al. found that the effects of orally administered black tea were comparable to those of green tea in suppressing UVB-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SKH-1 mice.⁸

In 1997, Lu et al. found that orally administered black tea inhibited the proliferation of skin tumors and enhanced apoptosis in nonmalignant and malignant skin tumors in female CD-1 mice with tumors initiated by the application of DMBA and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).⁹ Record et al. reported in 1998 that black tea may confer greater protection than green tea against simulated solar irradiation.¹⁰

Hakim and Harris conducted a population-based case-control study in 2001 to assess the effects of the consumption of citrus peel and black tea on squamous cell skin cancer. They found that participants who reported intake of hot black tea and citrus peel had a significant reduction in the risk of squamous cell carcinoma. Further, they concluded that hot black tea and citrus peel displayed independent potential protection against SCC.¹¹

Two years earlier, Zhao et al. used cultured keratinocytes and mouse and human skin to evaluate the effect of both orally and topically administered standardized black tea extract and its two major polyphenolic subfractions against UVB-induced photodamage. Topical pretreatment with the extract on SKH-1 hairless mice significantly lowered the incidence and severity of erythema and diminished skinfold thickness, compared with UVB-exposed nontreated mice. The black tea extract was similarly effective in human subjects. UVB-induced inflammation in murine as well as human skin also was reduced when the standardized extract was administered 5 minutes after UVB exposure. The investigators suggested that their findings indicated that black tea extracts have the capacity to mitigate UVB-generated erythema in human and murine skin.¹²

In 2011, George et al. assessed the chemopreventive effects of topical resveratrol and oral black tea polyphenols in blocking skin carcinogenesis in a two-stage mouse model initiated and promoted by DMBA and TPA, respectively. The combined treatment was found to reduce tumor incidence by approximately 89% (resveratrol alone, approximately 67%; black tea polyphenols alone, approximately 75%). Tumor volume and number also were significantly diminished by the synergistic combination, which, histologically, was noted for suppressing cellular proliferation and inducing apoptosis. The investigators concluded that oral black tea polyphenols combined with topical resveratrol exert greater chemopreventive activity than either compound alone and warrant study in trials for treating skin and other cancers.¹³

Animal studies on topical application

In 1997, Katiyar et al. investigated the anti-inflammatory effects of topically applied black tea polyphenols, primarily theaflavin gallates and (-)-epigallocatechin-3-gallate (EGCG), against TPA-induced inflammatory responses in murine skin. Significant inhibition against TPA-promoted induction of epidermal edema, hyperplasia, leukocyte infiltration, and proinflammatory cytokine expression was rendered by the preapplication of black tea polyphenols prior to TPA exposure. The investigators concluded that black tea polyphenols may be effective against human cutaneous inflammatory responses.¹⁴

Just over a decade later, Patel et al. investigated the in vivo antitumor-promoting effects of the most plentiful polymeric black tea polyphenols (thearubigins) in mice exposed to tumor-initiating DMBA and tumor-promoting TPA over a 40-week period. Pretreatment with topical thearubigins resulted in antipromoting effects in terms of latency, multiplicity, and incidence of skin papillomas. The black tea polyphenols also were found to reduce TPA-induced cell proliferation and epidermal cell apoptosis. The researchers attributed the protective effects of these compounds to their inhibitory impact on TPA-induced cellular proliferation.¹⁵

In 2011, Choi and Kim assessed the whitening effect of black tea water extract topically applied twice daily (6 days a week for 4 weeks) to UVB-induced hyperpigmented spots on the backs of brown guinea pigs. Treatment was divided into control (UVB and saline), vehicle control (UVB, propylene glycol, ethanol, and water), positive control (UVB and 2% hydroquinone), and two experimental groups (UVB and 1% black tea; UVB and 2% black tea). The investigators observed that the hyperpigmented spots treated with hydroquinone and black tea were clearly lighter than those treated by the control or vehicle-control groups. Histologic examination revealed that melanin pigmentation, melanocyte proliferation, and melanin production were significantly diminished in the groups treated with hydroquinone and both concentrations of black tea. The authors concluded that black tea suppresses melanocyte proliferation and melanosome synthesis in vivo, thus displaying the capacity to whiten skin in brown guinea pigs.¹⁶

In 2013, Yeh et al. found in nude mouse skin in vitro that niosomes appear to be feasible as a delivery vehicle for the dermal administration of black tea extracts as a sunscreen agent.¹

Topical studies in humans

Building on findings 3 years earlier¹⁸, Türkoglu et al., in 2010, assessed the photoprotective effects of dermal gels produced from green and black tea aqueous extracts tested in vivo in the forearms of six volunteers exposed to artificial UV light (200-400 nm). In addition to the green tea and black tea gels, a 0.3% caffeine gel, a carbomer gel base, and a control were tested. The investigators reported no eruptions of UV-induced erythema in any of the black and green tea gel sites, but erythema was present to varying degrees at the areas treated with caffeine gel, carbomer gel, and control. The investigators concluded that the black and green tea extracts exhibited potent UV absorbance and that the formulated gels were effective in protecting the skin against UV-induced erythema. Further, the investigators suggested that these agents have the potential to protect against other harm caused by UV radiation, including photoaging.¹⁹

Conclusion

Though not as widely investigated as green tea, the therapeutic potential of black tea is of great interest. Although an abundance of laboratory evidence has emerged, clinical evidence is sparse. Nevertheless, laboratory data suggest the potential uses of black tea in the dermatologic realm and justify more human trials.

References

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. Dermatol. Surg. 2005;31(7 Pt 2):873-80.

3. Oxid Med Cell Longev. 2012:2012:560682.

4. J Environ Pathol Toxicol Oncol. 2010;29(1):55-68.

5. Mol Carcinog. 2000 Jul;28(3):148-55.

6. Am J Clin Dermatol. 2010;11(4):247-67.

7. Carcinogenesis. 2008 Jan;29(1):129-38.

8. Cancer Res. 1994 Jul 1;54(13):3428-35.

9. Carcinogenesis. 1997 Nov;18(11):2163-9.

10. Mutat Res. 1998 Nov 9;422(1):191-9.

11. BMC Dermatol. 2001;1:3.

12. Photochem Photobiol. 1999 Oct;70(4):637-44.

13. PLoS One. 2011;6(8):e23395.

14. Carcinogenesis. 1997 Oct;18(10):1911-6.

15. Cell Prolif. 2008 Jun;41(3):532-53.

16. Toxicol Res. 2011 Sep;27(3):153-60.

17. Int J Dermatol. 2013 Feb;52(2):239-45.

18. Int J Cosmet Sci. 2007 Dec;29(6):437-42.

19. Drug Discov Ther. 2010 Oct;4(5):362-7.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Camellia sinensis, an evergreen tree belonging to the Theaceae family and used by human beings for approximately 4,000 years, is the source of the beverage tea, which is popular throughout the world, especially in Asia.¹ Of the four main true teas (that is, derived from the tea plant C. sinensis), green and white are unfermented, black tea is fermented, and oolong tea is semifermented.^2,3

Polyphenols, many of which act as strong antioxidants, are a diverse family of thousands of chemical substances found in plants. Theaflavins are black tea polyphenols with well-documented tumor-suppressing activity.⁴ In fact, they are thought to be the primary constituents of black tea responsible for conferring chemoprotection against cancer.⁵ Black tea, through oral administration and topical application, has been shown in the laboratory setting to protect skin from UV-induced erythema, premature aging, and cancer.⁶

Halder et al. have found that theaflavins and thearubigins, another key class of black tea polyphenols, can suppress A431 (human epidermoid carcinoma) and A375 (human malignant melanoma) cell proliferation without adversely impacting normal human epidermal keratinocytes. The researchers concluded that theaflavins and thearubigins appear to impart chemopreventive activity via cell cycle arrest and promotion of apoptosis in human skin cancer cells through a mitochondrial death cascade.⁷

In a 2005 English-language literature review, Thornfeldt cited green and black tea, as well as pomegranate, as the only ingredients supported by clinical trial evidence for effectiveness in treating extrinsic aging.²

Oral administration findings in animals and humans

Phyzome/Wikimedia Commons/CC BY-SA 3.0

More than 2 decades ago, Wang et al. found that the effects of orally administered black tea were comparable to those of green tea in suppressing UVB-induced skin carcinogenesis in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SKH-1 mice.⁸

In 1997, Lu et al. found that orally administered black tea inhibited the proliferation of skin tumors and enhanced apoptosis in nonmalignant and malignant skin tumors in female CD-1 mice with tumors initiated by the application of DMBA and promoted with 12-O-tetradecanoylphorbol-13-acetate (TPA).⁹ Record et al. reported in 1998 that black tea may confer greater protection than green tea against simulated solar irradiation.¹⁰

Hakim and Harris conducted a population-based case-control study in 2001 to assess the effects of the consumption of citrus peel and black tea on squamous cell skin cancer. They found that participants who reported intake of hot black tea and citrus peel had a significant reduction in the risk of squamous cell carcinoma. Further, they concluded that hot black tea and citrus peel displayed independent potential protection against SCC.¹¹

Two years earlier, Zhao et al. used cultured keratinocytes and mouse and human skin to evaluate the effect of both orally and topically administered standardized black tea extract and its two major polyphenolic subfractions against UVB-induced photodamage. Topical pretreatment with the extract on SKH-1 hairless mice significantly lowered the incidence and severity of erythema and diminished skinfold thickness, compared with UVB-exposed nontreated mice. The black tea extract was similarly effective in human subjects. UVB-induced inflammation in murine as well as human skin also was reduced when the standardized extract was administered 5 minutes after UVB exposure. The investigators suggested that their findings indicated that black tea extracts have the capacity to mitigate UVB-generated erythema in human and murine skin.¹²

In 2011, George et al. assessed the chemopreventive effects of topical resveratrol and oral black tea polyphenols in blocking skin carcinogenesis in a two-stage mouse model initiated and promoted by DMBA and TPA, respectively. The combined treatment was found to reduce tumor incidence by approximately 89% (resveratrol alone, approximately 67%; black tea polyphenols alone, approximately 75%). Tumor volume and number also were significantly diminished by the synergistic combination, which, histologically, was noted for suppressing cellular proliferation and inducing apoptosis. The investigators concluded that oral black tea polyphenols combined with topical resveratrol exert greater chemopreventive activity than either compound alone and warrant study in trials for treating skin and other cancers.¹³

Animal studies on topical application

In 1997, Katiyar et al. investigated the anti-inflammatory effects of topically applied black tea polyphenols, primarily theaflavin gallates and (-)-epigallocatechin-3-gallate (EGCG), against TPA-induced inflammatory responses in murine skin. Significant inhibition against TPA-promoted induction of epidermal edema, hyperplasia, leukocyte infiltration, and proinflammatory cytokine expression was rendered by the preapplication of black tea polyphenols prior to TPA exposure. The investigators concluded that black tea polyphenols may be effective against human cutaneous inflammatory responses.¹⁴

Just over a decade later, Patel et al. investigated the in vivo antitumor-promoting effects of the most plentiful polymeric black tea polyphenols (thearubigins) in mice exposed to tumor-initiating DMBA and tumor-promoting TPA over a 40-week period. Pretreatment with topical thearubigins resulted in antipromoting effects in terms of latency, multiplicity, and incidence of skin papillomas. The black tea polyphenols also were found to reduce TPA-induced cell proliferation and epidermal cell apoptosis. The researchers attributed the protective effects of these compounds to their inhibitory impact on TPA-induced cellular proliferation.¹⁵

In 2011, Choi and Kim assessed the whitening effect of black tea water extract topically applied twice daily (6 days a week for 4 weeks) to UVB-induced hyperpigmented spots on the backs of brown guinea pigs. Treatment was divided into control (UVB and saline), vehicle control (UVB, propylene glycol, ethanol, and water), positive control (UVB and 2% hydroquinone), and two experimental groups (UVB and 1% black tea; UVB and 2% black tea). The investigators observed that the hyperpigmented spots treated with hydroquinone and black tea were clearly lighter than those treated by the control or vehicle-control groups. Histologic examination revealed that melanin pigmentation, melanocyte proliferation, and melanin production were significantly diminished in the groups treated with hydroquinone and both concentrations of black tea. The authors concluded that black tea suppresses melanocyte proliferation and melanosome synthesis in vivo, thus displaying the capacity to whiten skin in brown guinea pigs.¹⁶

In 2013, Yeh et al. found in nude mouse skin in vitro that niosomes appear to be feasible as a delivery vehicle for the dermal administration of black tea extracts as a sunscreen agent.¹

Topical studies in humans

Building on findings 3 years earlier¹⁸, Türkoglu et al., in 2010, assessed the photoprotective effects of dermal gels produced from green and black tea aqueous extracts tested in vivo in the forearms of six volunteers exposed to artificial UV light (200-400 nm). In addition to the green tea and black tea gels, a 0.3% caffeine gel, a carbomer gel base, and a control were tested. The investigators reported no eruptions of UV-induced erythema in any of the black and green tea gel sites, but erythema was present to varying degrees at the areas treated with caffeine gel, carbomer gel, and control. The investigators concluded that the black and green tea extracts exhibited potent UV absorbance and that the formulated gels were effective in protecting the skin against UV-induced erythema. Further, the investigators suggested that these agents have the potential to protect against other harm caused by UV radiation, including photoaging.¹⁹

Conclusion

Though not as widely investigated as green tea, the therapeutic potential of black tea is of great interest. Although an abundance of laboratory evidence has emerged, clinical evidence is sparse. Nevertheless, laboratory data suggest the potential uses of black tea in the dermatologic realm and justify more human trials.

References

1. Cancer Lett. 1997 Mar 19;114(1-2):315-7.

2. Dermatol. Surg. 2005;31(7 Pt 2):873-80.

3. Oxid Med Cell Longev. 2012:2012:560682.

4. J Environ Pathol Toxicol Oncol. 2010;29(1):55-68.

5. Mol Carcinog. 2000 Jul;28(3):148-55.

6. Am J Clin Dermatol. 2010;11(4):247-67.

7. Carcinogenesis. 2008 Jan;29(1):129-38.

8. Cancer Res. 1994 Jul 1;54(13):3428-35.

9. Carcinogenesis. 1997 Nov;18(11):2163-9.

10. Mutat Res. 1998 Nov 9;422(1):191-9.

11. BMC Dermatol. 2001;1:3.

12. Photochem Photobiol. 1999 Oct;70(4):637-44.

13. PLoS One. 2011;6(8):e23395.

14. Carcinogenesis. 1997 Oct;18(10):1911-6.

15. Cell Prolif. 2008 Jun;41(3):532-53.

16. Toxicol Res. 2011 Sep;27(3):153-60.

17. Int J Dermatol. 2013 Feb;52(2):239-45.

18. Int J Cosmet Sci. 2007 Dec;29(6):437-42.

19. Drug Discov Ther. 2010 Oct;4(5):362-7.

Dr. Baumann is chief executive officer of the Baumann Cosmetic & Research Institute in the Design District in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote the textbook “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and a book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). She has contributed to the Cosmeceutical Critique column in Dermatology News since January 2001. Her latest book, “Cosmeceuticals and Cosmetic Ingredients,” was published in November 2014. Dr. Baumann has received funding for clinical grants from Allergan, Aveeno, Avon Products, Evolus, Galderma, GlaxoSmithKline, Kythera Biopharmaceuticals, Mary Kay, Medicis Pharmaceuticals, Neutrogena, Philosophy, Topix Pharmaceuticals, and Unilever.

Plasmodium parasite

infecting an RBC

Image courtesy of St. Jude

Children’s Research Hospital

Luminol, the compound detectives spray at crime scenes to find trace amounts of blood, can help kill malaria parasites, according to preclinical research published in eLife.

Luminol glows blue when it encounters the hemoglobin in red blood cells (RBCs), and researchers have found they can trick malaria-infected RBCs into

building up a volatile chemical stockpile that can be set off by luminol’s glow.

To achieve this, the researchers exposed infected RBCs to an amino acid known as 5-aminolevulinic acid (ALA), luminol, and 4-iodophenol (a small-molecule that enhances the intensity and duration of luminol chemiluminescence).

This triggered buildup of the chemical, protoporphyrin IX (PPIX), which effectively killed the parasites. When the team substituted artemisinin for 4-iodophenol, they observed similar results.

“The light that luminol emits is enhanced by the antimalarial drug artemisinin,” said study author Daniel Goldberg, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“We think these agents could be combined to form an innovative treatment for malaria.”

The researchers believe this type of therapy would have an advantage over current malaria treatments, which have become less effective as the parasite mutates. That is because the new approach targets proteins made by human RBCs, which the parasite can’t mutate.

To uncover this approach, Dr Goldberg and his colleagues worked with human RBCs infected with Plasmodium falciparum. The team wanted to better understand how the parasite gets hold of heme, which is essential to the parasite’s survival.

They found that P falciparum opens an unnatural channel on the surface of RBCs. When the researchers put ALA (an ingredient of heme) into a solution containing infected RBCs, ALA entered the cells through the channel and started the heme-making process.

This led to a buildup of PPIX. When exposed to luminol and 4-iodophenol, PPIX emitted free radicals. This potently inhibited parasite growth, according to the researchers. And microscopic examination revealed widespread parasite death.

The ALA/luminol/4-iodophenol combination also worked in a parasite line that was resistant to antifolate and quinolone antibiotics, as well as one with a kelch-13 protein mutation, which confers artemisinin tolerance.

The researchers then wanted to determine if artemisinin would enhance their strategy. So they incubated malaria-infected RBCs with ALA, luminol, and/or sub-therapeutic doses of dihydroartemisinin.

Each of the components alone or 2 of them together had little effect, but all 3 in combination successfully ablated parasite growth.

The researchers are now planning to test this treatment approach in vivo.

“All of these agents—the amino acid, the luminol, and artemisinin—have been cleared for use in humans individually, so we are optimistic that they won’t present any safety problems together,” Dr Goldberg said. “This could be a promising new treatment for a devastating disease.”

Plasmodium parasite

infecting an RBC

Image courtesy of St. Jude

Children’s Research Hospital

Luminol, the compound detectives spray at crime scenes to find trace amounts of blood, can help kill malaria parasites, according to preclinical research published in eLife.

Luminol glows blue when it encounters the hemoglobin in red blood cells (RBCs), and researchers have found they can trick malaria-infected RBCs into

building up a volatile chemical stockpile that can be set off by luminol’s glow.

To achieve this, the researchers exposed infected RBCs to an amino acid known as 5-aminolevulinic acid (ALA), luminol, and 4-iodophenol (a small-molecule that enhances the intensity and duration of luminol chemiluminescence).

This triggered buildup of the chemical, protoporphyrin IX (PPIX), which effectively killed the parasites. When the team substituted artemisinin for 4-iodophenol, they observed similar results.

“The light that luminol emits is enhanced by the antimalarial drug artemisinin,” said study author Daniel Goldberg, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“We think these agents could be combined to form an innovative treatment for malaria.”

The researchers believe this type of therapy would have an advantage over current malaria treatments, which have become less effective as the parasite mutates. That is because the new approach targets proteins made by human RBCs, which the parasite can’t mutate.

To uncover this approach, Dr Goldberg and his colleagues worked with human RBCs infected with Plasmodium falciparum. The team wanted to better understand how the parasite gets hold of heme, which is essential to the parasite’s survival.

They found that P falciparum opens an unnatural channel on the surface of RBCs. When the researchers put ALA (an ingredient of heme) into a solution containing infected RBCs, ALA entered the cells through the channel and started the heme-making process.

This led to a buildup of PPIX. When exposed to luminol and 4-iodophenol, PPIX emitted free radicals. This potently inhibited parasite growth, according to the researchers. And microscopic examination revealed widespread parasite death.

The ALA/luminol/4-iodophenol combination also worked in a parasite line that was resistant to antifolate and quinolone antibiotics, as well as one with a kelch-13 protein mutation, which confers artemisinin tolerance.

The researchers then wanted to determine if artemisinin would enhance their strategy. So they incubated malaria-infected RBCs with ALA, luminol, and/or sub-therapeutic doses of dihydroartemisinin.

Each of the components alone or 2 of them together had little effect, but all 3 in combination successfully ablated parasite growth.

The researchers are now planning to test this treatment approach in vivo.

“All of these agents—the amino acid, the luminol, and artemisinin—have been cleared for use in humans individually, so we are optimistic that they won’t present any safety problems together,” Dr Goldberg said. “This could be a promising new treatment for a devastating disease.”

Plasmodium parasite

infecting an RBC

Image courtesy of St. Jude

Children’s Research Hospital

Luminol, the compound detectives spray at crime scenes to find trace amounts of blood, can help kill malaria parasites, according to preclinical research published in eLife.

Luminol glows blue when it encounters the hemoglobin in red blood cells (RBCs), and researchers have found they can trick malaria-infected RBCs into

building up a volatile chemical stockpile that can be set off by luminol’s glow.

To achieve this, the researchers exposed infected RBCs to an amino acid known as 5-aminolevulinic acid (ALA), luminol, and 4-iodophenol (a small-molecule that enhances the intensity and duration of luminol chemiluminescence).

This triggered buildup of the chemical, protoporphyrin IX (PPIX), which effectively killed the parasites. When the team substituted artemisinin for 4-iodophenol, they observed similar results.

“The light that luminol emits is enhanced by the antimalarial drug artemisinin,” said study author Daniel Goldberg, MD, PhD, of the Washington University School of Medicine in St Louis, Missouri.

“We think these agents could be combined to form an innovative treatment for malaria.”

The researchers believe this type of therapy would have an advantage over current malaria treatments, which have become less effective as the parasite mutates. That is because the new approach targets proteins made by human RBCs, which the parasite can’t mutate.

To uncover this approach, Dr Goldberg and his colleagues worked with human RBCs infected with Plasmodium falciparum. The team wanted to better understand how the parasite gets hold of heme, which is essential to the parasite’s survival.

They found that P falciparum opens an unnatural channel on the surface of RBCs. When the researchers put ALA (an ingredient of heme) into a solution containing infected RBCs, ALA entered the cells through the channel and started the heme-making process.

This led to a buildup of PPIX. When exposed to luminol and 4-iodophenol, PPIX emitted free radicals. This potently inhibited parasite growth, according to the researchers. And microscopic examination revealed widespread parasite death.

The ALA/luminol/4-iodophenol combination also worked in a parasite line that was resistant to antifolate and quinolone antibiotics, as well as one with a kelch-13 protein mutation, which confers artemisinin tolerance.

The researchers then wanted to determine if artemisinin would enhance their strategy. So they incubated malaria-infected RBCs with ALA, luminol, and/or sub-therapeutic doses of dihydroartemisinin.

Each of the components alone or 2 of them together had little effect, but all 3 in combination successfully ablated parasite growth.

The researchers are now planning to test this treatment approach in vivo.

“All of these agents—the amino acid, the luminol, and artemisinin—have been cleared for use in humans individually, so we are optimistic that they won’t present any safety problems together,” Dr Goldberg said. “This could be a promising new treatment for a devastating disease.”

Vascular Surgery has evolved to balance clinical medicine, open and minimally invasive surgical interventions, and innovation into a unique career where technological advancement is constantly pushing the boundaries of what is possible in surgical capabilities.

Being awed and inspired by the Vascular Surgery specialty, we have put together the 6Ps for pursuing a career in Vascular Surgery in the spirit of the notorious 6Ps for acute limb ischemia.

1. Patients: Vascular patients are a unique and complex population of patients burdened with numerous comorbidities. Approaching and managing vascular patients requires a good understanding of preoperative medical assessment, risk factor modification, and clinical medicine. Moreover, the nature of vascular disease allows vascular surgeons to develop longstanding relationships with their patients and their families, and follow them through numerous stages of their illness and recovery.

2. Procedures: Performing vascular surgery is a delicate and exhilarating experience operating on arteries, veins, and lymphatics virtually in every part of the body, from the neck, chest, abdomen, and upper and lower limbs. We perform complex procedures from minimally invasive routes to intricate open procedures. Vascular surgeons offer lifesaving, limb-salvaging and quality of life-improving procedures on a daily basis.

3. Problem solving: As medical students and residents can appreciate in vascular teaching rounds, there is never one answer to a clinical situation. Each particular case may be considered through multiple approaches – open surgery, endovascular surgery, hybrid surgery, or medical management. Strikingly, within each category there are further numerous options to consider. Trying to develop the solutions and clinical judgment around a case is what makes this specialty tantalizing. 4. People: Vascular surgeons are the nicest group of surgeons we have ever worked with (there might be a large bias in this statement). They are passionate about their specialty, dedicated to patient care, enthusiastic to teach students, and always easily approachable. We have both been fortunate to be mentored by vascular surgeons and as such decided to pursue careers in this extremely patient-centered field. Given that it is a small community, it truly feels like you are part of the vascular family.

5. Potential: Technology is advancing at an extraordinarily fast pace and the vascular community fosters innovation from preventative strategies, new imaging modalities, and new graft designs just to name a few. The big question is, where will the vascular specialty be in 10 years? And our belief is that it depends on the limits of our imagination. We need to challenge conventional thinking with courage and imagination, bringing innovation to the health care platform.

And finally, one should pursue a career in vascular surgery because it is simply ...

6. Pretty awesome.

As the frontiers of science and technology push forward, so too do the ideas, creativity, and innovation of talented people. Our hope is to be at that cutting edge leading the development of improved medical care and surgical delivery as vascular surgeons.

Vascular Surgery has evolved to balance clinical medicine, open and minimally invasive surgical interventions, and innovation into a unique career where technological advancement is constantly pushing the boundaries of what is possible in surgical capabilities.

Being awed and inspired by the Vascular Surgery specialty, we have put together the 6Ps for pursuing a career in Vascular Surgery in the spirit of the notorious 6Ps for acute limb ischemia.

1. Patients: Vascular patients are a unique and complex population of patients burdened with numerous comorbidities. Approaching and managing vascular patients requires a good understanding of preoperative medical assessment, risk factor modification, and clinical medicine. Moreover, the nature of vascular disease allows vascular surgeons to develop longstanding relationships with their patients and their families, and follow them through numerous stages of their illness and recovery.

2. Procedures: Performing vascular surgery is a delicate and exhilarating experience operating on arteries, veins, and lymphatics virtually in every part of the body, from the neck, chest, abdomen, and upper and lower limbs. We perform complex procedures from minimally invasive routes to intricate open procedures. Vascular surgeons offer lifesaving, limb-salvaging and quality of life-improving procedures on a daily basis.

3. Problem solving: As medical students and residents can appreciate in vascular teaching rounds, there is never one answer to a clinical situation. Each particular case may be considered through multiple approaches – open surgery, endovascular surgery, hybrid surgery, or medical management. Strikingly, within each category there are further numerous options to consider. Trying to develop the solutions and clinical judgment around a case is what makes this specialty tantalizing. 4. People: Vascular surgeons are the nicest group of surgeons we have ever worked with (there might be a large bias in this statement). They are passionate about their specialty, dedicated to patient care, enthusiastic to teach students, and always easily approachable. We have both been fortunate to be mentored by vascular surgeons and as such decided to pursue careers in this extremely patient-centered field. Given that it is a small community, it truly feels like you are part of the vascular family.

5. Potential: Technology is advancing at an extraordinarily fast pace and the vascular community fosters innovation from preventative strategies, new imaging modalities, and new graft designs just to name a few. The big question is, where will the vascular specialty be in 10 years? And our belief is that it depends on the limits of our imagination. We need to challenge conventional thinking with courage and imagination, bringing innovation to the health care platform.

And finally, one should pursue a career in vascular surgery because it is simply ...

6. Pretty awesome.

As the frontiers of science and technology push forward, so too do the ideas, creativity, and innovation of talented people. Our hope is to be at that cutting edge leading the development of improved medical care and surgical delivery as vascular surgeons.

Vascular Surgery has evolved to balance clinical medicine, open and minimally invasive surgical interventions, and innovation into a unique career where technological advancement is constantly pushing the boundaries of what is possible in surgical capabilities.

Being awed and inspired by the Vascular Surgery specialty, we have put together the 6Ps for pursuing a career in Vascular Surgery in the spirit of the notorious 6Ps for acute limb ischemia.

1. Patients: Vascular patients are a unique and complex population of patients burdened with numerous comorbidities. Approaching and managing vascular patients requires a good understanding of preoperative medical assessment, risk factor modification, and clinical medicine. Moreover, the nature of vascular disease allows vascular surgeons to develop longstanding relationships with their patients and their families, and follow them through numerous stages of their illness and recovery.

2. Procedures: Performing vascular surgery is a delicate and exhilarating experience operating on arteries, veins, and lymphatics virtually in every part of the body, from the neck, chest, abdomen, and upper and lower limbs. We perform complex procedures from minimally invasive routes to intricate open procedures. Vascular surgeons offer lifesaving, limb-salvaging and quality of life-improving procedures on a daily basis.

3. Problem solving: As medical students and residents can appreciate in vascular teaching rounds, there is never one answer to a clinical situation. Each particular case may be considered through multiple approaches – open surgery, endovascular surgery, hybrid surgery, or medical management. Strikingly, within each category there are further numerous options to consider. Trying to develop the solutions and clinical judgment around a case is what makes this specialty tantalizing. 4. People: Vascular surgeons are the nicest group of surgeons we have ever worked with (there might be a large bias in this statement). They are passionate about their specialty, dedicated to patient care, enthusiastic to teach students, and always easily approachable. We have both been fortunate to be mentored by vascular surgeons and as such decided to pursue careers in this extremely patient-centered field. Given that it is a small community, it truly feels like you are part of the vascular family.

5. Potential: Technology is advancing at an extraordinarily fast pace and the vascular community fosters innovation from preventative strategies, new imaging modalities, and new graft designs just to name a few. The big question is, where will the vascular specialty be in 10 years? And our belief is that it depends on the limits of our imagination. We need to challenge conventional thinking with courage and imagination, bringing innovation to the health care platform.

And finally, one should pursue a career in vascular surgery because it is simply ...

6. Pretty awesome.

As the frontiers of science and technology push forward, so too do the ideas, creativity, and innovation of talented people. Our hope is to be at that cutting edge leading the development of improved medical care and surgical delivery as vascular surgeons.

Adding a mechanical suction technique to local thrombolysis to break up and remove blood clots reduced postthrombotic syndrome (PTS) after deep vein thrombosis (DVT) without causing increased complications, according to a small retrospective study.

Dr. Chun-Yang Huang of the National Yang Ming University (Taipei, Taiwan) and colleagues examined patients diagnosed with acute proximal lower limb DVT. Patients received either thrombolysis alone via a catheter-directed thrombolysis (CDT), or percutaneous mechanical thrombectomy (PMT) by a combination of pharmacologic thrombolysis and suction; both techniques were accompanied by systemic anticoagulation. Though both treatment groups fared well during treatment and for the 12-month follow-up period, the PMT group had a significantly lower incidence of PTS 1 year after treatment (Ann. Vascular Surg. 2015. doi: 10.1016/j.avsg.2015.01.014).

For those with DVT, parenteral anticoagulation prevents propagation of the clot and minimizes risk of pulmonary embolism (PE); however, anticoagulation does not accelerate dissolution of the existing clot. According to study authors, 30%-40% of those with proximal leg DVTs will go on to develop PTS, with the prolonged distal venous stasis from an undisturbed clot causing loss of valvular competence and resultant chronic venous insufficiency. PTS can involve leg swelling, discomfort, skin changes, and ulceration, with significant impact on quality of life and health care costs.

Techniques such as CDT and PMT can increase the rate of clot dissolution, thus restoring patency sooner and minimizing risk for PTS. However, these methods also can carry increased risk of bleeding and infection, considerations that must be balanced against potential benefit.

Investigators reviewed records for 39 patients who were diagnosed with ultrasound- or CT-confirmed acute proximal lower limb DVT and received either CDT or PMT during the period from November 2010 to November 2013. Patients were not randomized to treatment arms but were assigned using clinical judgment and patient preference. During the 12-month follow-up, three participants died of malignancy and two were lost to follow-up. Analysis was completed for the remaining 34 patients.

Overall, patient characteristics did not differ significantly between groups, with mean ages of 62.75 for the PMT group (n = 16) and 64.17 for the CDT group (n = 18). In all, 13/34 participants were female. Patients in both treatment groups fared well, with no 30-day mortality, and no episodes of major bleeding, PE, or renal failure. Ten patients in the PMT group and six in the CDT group required stenting of the common iliac vein to maintain patency, a nonsignificant difference. Just one participant in the CDE group experienced a minor bleeding event.

Turning to outcomes, study authors assessed postprocedure patency, finding improved patency for both procedures (P less than .001 for both, compared with preoperation patency scores), with no significant difference between the two groups post procedure. Thrombus scores were also significantly better for both treatment arms post procedure (P less than .001). Clot burden tended to improve more rapidly over the 12-month follow-up period for the PMT group, though the difference between groups was just short of statistically significant.

At 12 months, though the amount of venous reflux did not differ significantly between groups, those who had received PMT had significantly fewer signs and symptoms of PTS. This assessment used the Villalta scale, a standardized assessment and scoring system for PTS, where higher numbers indicate worse PTS. The PMT group’s Villalta score was 2.06 +/–2.95, compared with 5.06 +/–4.07 for the CDT group (P = .030).

Study limitations included the small study size, retrospective study design, and lack of randomization. Acknowledging these limitations, Dr. Huang and coauthors called for larger, multicenter, randomized controlled studies of PMT. The personal and economic costs of PTS, they argue, warrant exploring whether PMT may help minimize total thrombolysis dose, reduce hospital stays, and decrease costs while minimizing the risks of chronic venous insufficiency post DVT.

Dr. Huang and coauthors reported no conflicts of interest.

Adding a mechanical suction technique to local thrombolysis to break up and remove blood clots reduced postthrombotic syndrome (PTS) after deep vein thrombosis (DVT) without causing increased complications, according to a small retrospective study.

Dr. Chun-Yang Huang of the National Yang Ming University (Taipei, Taiwan) and colleagues examined patients diagnosed with acute proximal lower limb DVT. Patients received either thrombolysis alone via a catheter-directed thrombolysis (CDT), or percutaneous mechanical thrombectomy (PMT) by a combination of pharmacologic thrombolysis and suction; both techniques were accompanied by systemic anticoagulation. Though both treatment groups fared well during treatment and for the 12-month follow-up period, the PMT group had a significantly lower incidence of PTS 1 year after treatment (Ann. Vascular Surg. 2015. doi: 10.1016/j.avsg.2015.01.014).

For those with DVT, parenteral anticoagulation prevents propagation of the clot and minimizes risk of pulmonary embolism (PE); however, anticoagulation does not accelerate dissolution of the existing clot. According to study authors, 30%-40% of those with proximal leg DVTs will go on to develop PTS, with the prolonged distal venous stasis from an undisturbed clot causing loss of valvular competence and resultant chronic venous insufficiency. PTS can involve leg swelling, discomfort, skin changes, and ulceration, with significant impact on quality of life and health care costs.

Techniques such as CDT and PMT can increase the rate of clot dissolution, thus restoring patency sooner and minimizing risk for PTS. However, these methods also can carry increased risk of bleeding and infection, considerations that must be balanced against potential benefit.

Investigators reviewed records for 39 patients who were diagnosed with ultrasound- or CT-confirmed acute proximal lower limb DVT and received either CDT or PMT during the period from November 2010 to November 2013. Patients were not randomized to treatment arms but were assigned using clinical judgment and patient preference. During the 12-month follow-up, three participants died of malignancy and two were lost to follow-up. Analysis was completed for the remaining 34 patients.

Overall, patient characteristics did not differ significantly between groups, with mean ages of 62.75 for the PMT group (n = 16) and 64.17 for the CDT group (n = 18). In all, 13/34 participants were female. Patients in both treatment groups fared well, with no 30-day mortality, and no episodes of major bleeding, PE, or renal failure. Ten patients in the PMT group and six in the CDT group required stenting of the common iliac vein to maintain patency, a nonsignificant difference. Just one participant in the CDE group experienced a minor bleeding event.

Turning to outcomes, study authors assessed postprocedure patency, finding improved patency for both procedures (P less than .001 for both, compared with preoperation patency scores), with no significant difference between the two groups post procedure. Thrombus scores were also significantly better for both treatment arms post procedure (P less than .001). Clot burden tended to improve more rapidly over the 12-month follow-up period for the PMT group, though the difference between groups was just short of statistically significant.

At 12 months, though the amount of venous reflux did not differ significantly between groups, those who had received PMT had significantly fewer signs and symptoms of PTS. This assessment used the Villalta scale, a standardized assessment and scoring system for PTS, where higher numbers indicate worse PTS. The PMT group’s Villalta score was 2.06 +/–2.95, compared with 5.06 +/–4.07 for the CDT group (P = .030).

Study limitations included the small study size, retrospective study design, and lack of randomization. Acknowledging these limitations, Dr. Huang and coauthors called for larger, multicenter, randomized controlled studies of PMT. The personal and economic costs of PTS, they argue, warrant exploring whether PMT may help minimize total thrombolysis dose, reduce hospital stays, and decrease costs while minimizing the risks of chronic venous insufficiency post DVT.

Dr. Huang and coauthors reported no conflicts of interest.

Adding a mechanical suction technique to local thrombolysis to break up and remove blood clots reduced postthrombotic syndrome (PTS) after deep vein thrombosis (DVT) without causing increased complications, according to a small retrospective study.

Dr. Chun-Yang Huang of the National Yang Ming University (Taipei, Taiwan) and colleagues examined patients diagnosed with acute proximal lower limb DVT. Patients received either thrombolysis alone via a catheter-directed thrombolysis (CDT), or percutaneous mechanical thrombectomy (PMT) by a combination of pharmacologic thrombolysis and suction; both techniques were accompanied by systemic anticoagulation. Though both treatment groups fared well during treatment and for the 12-month follow-up period, the PMT group had a significantly lower incidence of PTS 1 year after treatment (Ann. Vascular Surg. 2015. doi: 10.1016/j.avsg.2015.01.014).

For those with DVT, parenteral anticoagulation prevents propagation of the clot and minimizes risk of pulmonary embolism (PE); however, anticoagulation does not accelerate dissolution of the existing clot. According to study authors, 30%-40% of those with proximal leg DVTs will go on to develop PTS, with the prolonged distal venous stasis from an undisturbed clot causing loss of valvular competence and resultant chronic venous insufficiency. PTS can involve leg swelling, discomfort, skin changes, and ulceration, with significant impact on quality of life and health care costs.

Techniques such as CDT and PMT can increase the rate of clot dissolution, thus restoring patency sooner and minimizing risk for PTS. However, these methods also can carry increased risk of bleeding and infection, considerations that must be balanced against potential benefit.

Investigators reviewed records for 39 patients who were diagnosed with ultrasound- or CT-confirmed acute proximal lower limb DVT and received either CDT or PMT during the period from November 2010 to November 2013. Patients were not randomized to treatment arms but were assigned using clinical judgment and patient preference. During the 12-month follow-up, three participants died of malignancy and two were lost to follow-up. Analysis was completed for the remaining 34 patients.

Overall, patient characteristics did not differ significantly between groups, with mean ages of 62.75 for the PMT group (n = 16) and 64.17 for the CDT group (n = 18). In all, 13/34 participants were female. Patients in both treatment groups fared well, with no 30-day mortality, and no episodes of major bleeding, PE, or renal failure. Ten patients in the PMT group and six in the CDT group required stenting of the common iliac vein to maintain patency, a nonsignificant difference. Just one participant in the CDE group experienced a minor bleeding event.

Turning to outcomes, study authors assessed postprocedure patency, finding improved patency for both procedures (P less than .001 for both, compared with preoperation patency scores), with no significant difference between the two groups post procedure. Thrombus scores were also significantly better for both treatment arms post procedure (P less than .001). Clot burden tended to improve more rapidly over the 12-month follow-up period for the PMT group, though the difference between groups was just short of statistically significant.

At 12 months, though the amount of venous reflux did not differ significantly between groups, those who had received PMT had significantly fewer signs and symptoms of PTS. This assessment used the Villalta scale, a standardized assessment and scoring system for PTS, where higher numbers indicate worse PTS. The PMT group’s Villalta score was 2.06 +/–2.95, compared with 5.06 +/–4.07 for the CDT group (P = .030).

Study limitations included the small study size, retrospective study design, and lack of randomization. Acknowledging these limitations, Dr. Huang and coauthors called for larger, multicenter, randomized controlled studies of PMT. The personal and economic costs of PTS, they argue, warrant exploring whether PMT may help minimize total thrombolysis dose, reduce hospital stays, and decrease costs while minimizing the risks of chronic venous insufficiency post DVT.

Dr. Huang and coauthors reported no conflicts of interest.