User login
Researchers propose new risk groups for NK-AML
NEWPORT BEACH, CALIF. – New research suggests patients with normal karyotype acute myeloid leukemia (NK-AML) can be divided into four risk groups associated with overall survival.
Investigators used machine learning algorithms to study the association between mutations and overall survival in 1,352 patients with NK-AML. The analysis revealed combinations of mutations that could be used to classify NK-AML patients into favorable, intermediate-1, intermediate-2, and unfavorable risk groups.
For example, patients who had NPM1 mutations but wild-type FLT3-ITD and DNMT3A, had a median overall survival of 99.1 months and could be classified as favorable risk. Conversely, patients who had NPM1, FLT3-ITD, and DNMT3A mutations, had a median overall survival of 13.4 months and could be classified as unfavorable risk.
Aziz Nazha, MD, of the Cleveland Clinic, and his colleagues conducted this research and presented the findings at the Acute Leukemia Forum of Hemedicus.
The investigators looked at genomic and clinical data from 1,352 patients with NK-AML. The patients were a median age of 55 years and had a median white blood cell count of 21.3 x 109/L, a median hemoglobin of 9.1 g/dL, and a median platelet count of 61 x 109/L. More than half of patients (57.3%) were male.
The patients were screened for 35 genes that are commonly mutated in AML and other myeloid malignancies. The investigators used machine learning algorithms, including random survival forest and recommender system algorithms, to study the association between mutations and overall survival in an “unbiased” way.
Dr. Nazha said there were a median of three mutations per patient sample, and “there are some competing interests between those mutations to impact the prognosis of the patient.”
The investigators used the mutations and their associations with overall survival to classify patients into the risk groups outlined in the table below.
These findings can improve the risk stratification of NK-AML and may aid physicians in making treatment decisions, according to Dr. Nazha and his colleagues. To move this work forward, the investigators are attempting to develop a personalized model that can make predictions specific to an individual patient based on that patient’s mutation information.
Dr. Nazha reported having no financial disclosures relevant to this research. Other investigators reported relationships with the Munich Leukemia Laboratory.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
NEWPORT BEACH, CALIF. – New research suggests patients with normal karyotype acute myeloid leukemia (NK-AML) can be divided into four risk groups associated with overall survival.
Investigators used machine learning algorithms to study the association between mutations and overall survival in 1,352 patients with NK-AML. The analysis revealed combinations of mutations that could be used to classify NK-AML patients into favorable, intermediate-1, intermediate-2, and unfavorable risk groups.
For example, patients who had NPM1 mutations but wild-type FLT3-ITD and DNMT3A, had a median overall survival of 99.1 months and could be classified as favorable risk. Conversely, patients who had NPM1, FLT3-ITD, and DNMT3A mutations, had a median overall survival of 13.4 months and could be classified as unfavorable risk.
Aziz Nazha, MD, of the Cleveland Clinic, and his colleagues conducted this research and presented the findings at the Acute Leukemia Forum of Hemedicus.
The investigators looked at genomic and clinical data from 1,352 patients with NK-AML. The patients were a median age of 55 years and had a median white blood cell count of 21.3 x 109/L, a median hemoglobin of 9.1 g/dL, and a median platelet count of 61 x 109/L. More than half of patients (57.3%) were male.
The patients were screened for 35 genes that are commonly mutated in AML and other myeloid malignancies. The investigators used machine learning algorithms, including random survival forest and recommender system algorithms, to study the association between mutations and overall survival in an “unbiased” way.
Dr. Nazha said there were a median of three mutations per patient sample, and “there are some competing interests between those mutations to impact the prognosis of the patient.”
The investigators used the mutations and their associations with overall survival to classify patients into the risk groups outlined in the table below.
These findings can improve the risk stratification of NK-AML and may aid physicians in making treatment decisions, according to Dr. Nazha and his colleagues. To move this work forward, the investigators are attempting to develop a personalized model that can make predictions specific to an individual patient based on that patient’s mutation information.
Dr. Nazha reported having no financial disclosures relevant to this research. Other investigators reported relationships with the Munich Leukemia Laboratory.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
NEWPORT BEACH, CALIF. – New research suggests patients with normal karyotype acute myeloid leukemia (NK-AML) can be divided into four risk groups associated with overall survival.
Investigators used machine learning algorithms to study the association between mutations and overall survival in 1,352 patients with NK-AML. The analysis revealed combinations of mutations that could be used to classify NK-AML patients into favorable, intermediate-1, intermediate-2, and unfavorable risk groups.
For example, patients who had NPM1 mutations but wild-type FLT3-ITD and DNMT3A, had a median overall survival of 99.1 months and could be classified as favorable risk. Conversely, patients who had NPM1, FLT3-ITD, and DNMT3A mutations, had a median overall survival of 13.4 months and could be classified as unfavorable risk.
Aziz Nazha, MD, of the Cleveland Clinic, and his colleagues conducted this research and presented the findings at the Acute Leukemia Forum of Hemedicus.
The investigators looked at genomic and clinical data from 1,352 patients with NK-AML. The patients were a median age of 55 years and had a median white blood cell count of 21.3 x 109/L, a median hemoglobin of 9.1 g/dL, and a median platelet count of 61 x 109/L. More than half of patients (57.3%) were male.
The patients were screened for 35 genes that are commonly mutated in AML and other myeloid malignancies. The investigators used machine learning algorithms, including random survival forest and recommender system algorithms, to study the association between mutations and overall survival in an “unbiased” way.
Dr. Nazha said there were a median of three mutations per patient sample, and “there are some competing interests between those mutations to impact the prognosis of the patient.”
The investigators used the mutations and their associations with overall survival to classify patients into the risk groups outlined in the table below.
These findings can improve the risk stratification of NK-AML and may aid physicians in making treatment decisions, according to Dr. Nazha and his colleagues. To move this work forward, the investigators are attempting to develop a personalized model that can make predictions specific to an individual patient based on that patient’s mutation information.
Dr. Nazha reported having no financial disclosures relevant to this research. Other investigators reported relationships with the Munich Leukemia Laboratory.
The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.
REPORTING FROM ALF 2019
Ruzurgi approved for Lambert-Eaton myasthenic syndrome in patients under age 17
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Amifampridine (Ruzurgi) has been approved for the treatment of Lambert-Eaton myasthenic syndrome (LEMS), a rare autoimmune neuromuscular disorder, in patients aged 6 to less than 17 years, according to a statement from the Food and Drug Administration.
The approval is the first for a LEMS treatment specifically for pediatric patients.
“This approval will provide a much-needed treatment option for pediatric patients with LEMS who have significant weakness and fatigue that can often cause great difficulties with daily activities,” Billy Dunn, MD, director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research, said in the statement.
The prevalence of LEMS in pediatric patients is not known, but the overall prevalence of LEMS is estimated to be three per million individuals worldwide, according to the FDA press release.
Use of amifampridine in patients 6 to less than 17 years of age is supported by pharmacokinetic data in adult patients, pharmacokinetic modeling and simulation to identify the dosing regimen in pediatric patients, and safety data from pediatric patients 6 to less than 17 years of age.
A randomized, double-blind, placebo-controlled withdrawal study enrolled 32 adult patients who had taken amifampridine for at least 3 months. The study compared patients continuing on amifampridine with patients switched to placebo. Effectiveness was measured by the degree of change in a test that assessed the time it took the patient to rise from a chair, walk three meters, and return to the chair for three consecutive laps without pause. The patients who continued on amifampridine experienced less impairment compared with those switched to placebo. Effectiveness was also measured with a self-assessment scale for LEMS-related weakness. The scores indicated greater perceived weakening in the patients switched to placebo.
The most common side effects among amifampridine users were paresthesia, abdominal pain, indigestion, dizziness, and nausea. Side effects reported in pediatric patients were similar to those seen in adult patients. Seizures have been observed in patients without a history of seizures. Signs of hypersensitivity reactions include rash, hives, itching, fever, swelling, or trouble breathing.
The FDA granted this application Priority Review and Fast Track designations. Amifampridine also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.
The FDA granted the approval of amifampridine (Ruzurgi) to Jacobus Pharmaceutical Company.
Oropharynx cancer burden is shifting to older men
The burden of the U.S. oropharynx cancer epidemic is shifting toward older adults, finds a population-based cohort study spanning 23 years. As a result, the disease will likely become one predominantly affecting elderly white men over the next decade. In addition, projections suggest that the annual number of new cases will likely rise exponentially.
Historically, the incidence of oropharynx cancer rose rapidly among white men aged younger than 60 years because of human papillomavirus (HPV) infections (J Clin Oncol. 2011;29:4294-301). But given factors such as aging, possible changes in behavior, and vaccination, the current trajectory is unknown.
Investigators led by Joseph E. Tota, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute analyzed Surveillance, Epidemiology, and End Results registry data for 1992-2015 to ascertain whether the increases in oropharynx cancer have continued into recent birth cohorts and to forecast future burden across subgroups.
Results published in the Journal of Clinical Oncology showed that, among white men, oropharynx cancer incidence accelerated among those born during 1927-1939 (by 3.5% per 2-year birth cohort) and during 1939-1955 (by 5.3% per 2-year birth cohort), whereas the pace of increase moderated among those born during 1955-1969 (by 1.7% per 2-year birth cohort).
Given these trends, the investigators forecast that incidence will increase sharply between 2016 and 2029 among older white men aged 65-74 years (from 40.7 to 71.2 per 100,000) and 75-84 years (from 25.7 to 50.1 per 100,000), increase moderately among white men aged 55-64 years (from 40.3 to 52.0 per 100,000), and remain stable among white men aged 45-54 years (at roughly 18 per 100,000).
Taking population growth into account, Dr. Tota and colleagues project a 52% increase in annual number of cases in the United States (from 20,124 to 30,629 between 2016 and 2029), mainly driven by a 127% increase among older adults aged at least 65 years (from 7,976 to 18,072) and a 54% increase among white men (from 14,453 to 22,241). As of 2029, white men older than 65 years will account for approximately 44% of all cases.
“Our results suggest an ebbing of the oropharynx cancer epidemic in younger individuals, exaggeration of the epidemic in older individuals, and a continued exponential increase in the annual number of oropharynx cancers over the next decade,” Dr. Tota and coinvestigators summarized.
The findings have important implications regarding treatment of older patients with oropharynx cancer, they noted. “It is likely that the biology of HPV-positive tumors is similar in younger versus older patients; nonetheless, older patients have poorer survival outcomes because of competing comorbidities, treatment-associated acute and chronic toxicity with chemoradiation, or an inability to receive maximally effective therapies. … Thus, older patients with oropharynx cancer may have different risks and benefits when receiving deintensified regimens than younger patients. The emergence of immunotherapies, whose efficacy may be more age invariant than cytotoxic chemotherapies, could provide a promising treatment avenue for older patients with oropharynx cancer.”
Dr. Tota reported receiving travel, accommodations, and expenses from Merck. The study was supported by the Intramural Research Program of the National Institutes of Health/NCI.
SOURCE: Tota JE et al. J Clin Oncol. 2019 Apr 26. doi: 10.1200/JCO.19.00370.
The burden of the U.S. oropharynx cancer epidemic is shifting toward older adults, finds a population-based cohort study spanning 23 years. As a result, the disease will likely become one predominantly affecting elderly white men over the next decade. In addition, projections suggest that the annual number of new cases will likely rise exponentially.
Historically, the incidence of oropharynx cancer rose rapidly among white men aged younger than 60 years because of human papillomavirus (HPV) infections (J Clin Oncol. 2011;29:4294-301). But given factors such as aging, possible changes in behavior, and vaccination, the current trajectory is unknown.
Investigators led by Joseph E. Tota, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute analyzed Surveillance, Epidemiology, and End Results registry data for 1992-2015 to ascertain whether the increases in oropharynx cancer have continued into recent birth cohorts and to forecast future burden across subgroups.
Results published in the Journal of Clinical Oncology showed that, among white men, oropharynx cancer incidence accelerated among those born during 1927-1939 (by 3.5% per 2-year birth cohort) and during 1939-1955 (by 5.3% per 2-year birth cohort), whereas the pace of increase moderated among those born during 1955-1969 (by 1.7% per 2-year birth cohort).
Given these trends, the investigators forecast that incidence will increase sharply between 2016 and 2029 among older white men aged 65-74 years (from 40.7 to 71.2 per 100,000) and 75-84 years (from 25.7 to 50.1 per 100,000), increase moderately among white men aged 55-64 years (from 40.3 to 52.0 per 100,000), and remain stable among white men aged 45-54 years (at roughly 18 per 100,000).
Taking population growth into account, Dr. Tota and colleagues project a 52% increase in annual number of cases in the United States (from 20,124 to 30,629 between 2016 and 2029), mainly driven by a 127% increase among older adults aged at least 65 years (from 7,976 to 18,072) and a 54% increase among white men (from 14,453 to 22,241). As of 2029, white men older than 65 years will account for approximately 44% of all cases.
“Our results suggest an ebbing of the oropharynx cancer epidemic in younger individuals, exaggeration of the epidemic in older individuals, and a continued exponential increase in the annual number of oropharynx cancers over the next decade,” Dr. Tota and coinvestigators summarized.
The findings have important implications regarding treatment of older patients with oropharynx cancer, they noted. “It is likely that the biology of HPV-positive tumors is similar in younger versus older patients; nonetheless, older patients have poorer survival outcomes because of competing comorbidities, treatment-associated acute and chronic toxicity with chemoradiation, or an inability to receive maximally effective therapies. … Thus, older patients with oropharynx cancer may have different risks and benefits when receiving deintensified regimens than younger patients. The emergence of immunotherapies, whose efficacy may be more age invariant than cytotoxic chemotherapies, could provide a promising treatment avenue for older patients with oropharynx cancer.”
Dr. Tota reported receiving travel, accommodations, and expenses from Merck. The study was supported by the Intramural Research Program of the National Institutes of Health/NCI.
SOURCE: Tota JE et al. J Clin Oncol. 2019 Apr 26. doi: 10.1200/JCO.19.00370.
The burden of the U.S. oropharynx cancer epidemic is shifting toward older adults, finds a population-based cohort study spanning 23 years. As a result, the disease will likely become one predominantly affecting elderly white men over the next decade. In addition, projections suggest that the annual number of new cases will likely rise exponentially.
Historically, the incidence of oropharynx cancer rose rapidly among white men aged younger than 60 years because of human papillomavirus (HPV) infections (J Clin Oncol. 2011;29:4294-301). But given factors such as aging, possible changes in behavior, and vaccination, the current trajectory is unknown.
Investigators led by Joseph E. Tota, PhD, of the division of cancer epidemiology and genetics at the National Cancer Institute analyzed Surveillance, Epidemiology, and End Results registry data for 1992-2015 to ascertain whether the increases in oropharynx cancer have continued into recent birth cohorts and to forecast future burden across subgroups.
Results published in the Journal of Clinical Oncology showed that, among white men, oropharynx cancer incidence accelerated among those born during 1927-1939 (by 3.5% per 2-year birth cohort) and during 1939-1955 (by 5.3% per 2-year birth cohort), whereas the pace of increase moderated among those born during 1955-1969 (by 1.7% per 2-year birth cohort).
Given these trends, the investigators forecast that incidence will increase sharply between 2016 and 2029 among older white men aged 65-74 years (from 40.7 to 71.2 per 100,000) and 75-84 years (from 25.7 to 50.1 per 100,000), increase moderately among white men aged 55-64 years (from 40.3 to 52.0 per 100,000), and remain stable among white men aged 45-54 years (at roughly 18 per 100,000).
Taking population growth into account, Dr. Tota and colleagues project a 52% increase in annual number of cases in the United States (from 20,124 to 30,629 between 2016 and 2029), mainly driven by a 127% increase among older adults aged at least 65 years (from 7,976 to 18,072) and a 54% increase among white men (from 14,453 to 22,241). As of 2029, white men older than 65 years will account for approximately 44% of all cases.
“Our results suggest an ebbing of the oropharynx cancer epidemic in younger individuals, exaggeration of the epidemic in older individuals, and a continued exponential increase in the annual number of oropharynx cancers over the next decade,” Dr. Tota and coinvestigators summarized.
The findings have important implications regarding treatment of older patients with oropharynx cancer, they noted. “It is likely that the biology of HPV-positive tumors is similar in younger versus older patients; nonetheless, older patients have poorer survival outcomes because of competing comorbidities, treatment-associated acute and chronic toxicity with chemoradiation, or an inability to receive maximally effective therapies. … Thus, older patients with oropharynx cancer may have different risks and benefits when receiving deintensified regimens than younger patients. The emergence of immunotherapies, whose efficacy may be more age invariant than cytotoxic chemotherapies, could provide a promising treatment avenue for older patients with oropharynx cancer.”
Dr. Tota reported receiving travel, accommodations, and expenses from Merck. The study was supported by the Intramural Research Program of the National Institutes of Health/NCI.
SOURCE: Tota JE et al. J Clin Oncol. 2019 Apr 26. doi: 10.1200/JCO.19.00370.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
The Poké-sulcus, interchangeable hipsters, and worm PTSD
Gotta catch ‘em all
In a somewhat unsurprising turn of events, researchers have discovered the exact impact that late-1990s Pokémon obsession had on the human brain. Could Bulbasaur and Charmander really change the way your gray matter works? Pikachu says yes.
Researchers scanned the brains of adults who played Pokémon extensively as children (and possibly as not-children, with the advent of Pokémon Go). They found that, in these adults, the occipitotemporal sulcus region of the brain responded more to images of Pokémon – the original 150, of course – than any other type of image.
The researchers compared this result to “novices” (a.k.a. people who had other hobbies) and noted that novice brains did not have a preference for Pokémon.
Basically, the brain of these experienced players has built them an internal Pokédex, fulfilling the dream of every Pokémaster. Ash Ketchum would be proud.
Hipsters don’t all look the same! (Yes, they do)
Slouchy beanie, scruffy beard, maybe a pair of fake spectacles, and definitely flannel – the uniform of the male hipster. Today’s Beatnik-wannabes all praise nonconformism, but what happens when everyone nonconforms the same?
You get an extremely hilarious threat of lawsuit, that’s what.
The MIT Technology Review published an article about the studies from a mathematician from Brandeis University, who examines how information transmission influences the behavior of a population.
He found that, in general, hipsters in a society initially “act randomly but then undergo a phase transition into a synchronized state.” Despite all their best efforts to push against the mainstream, hipsters eventually sync up with one another and conform to each other.
The article was published with a photo of a man in a beanie, beard, and plaid shirt. The publication soon received an email from a man who claimed he was the person in the photo, and he hadn’t given his consent, and he was upset with the article, calling it a “bit of click-bait about why hipsters all look the same.”
The email-writer angrily threatened legal action … until a quick image check showed that he was not, in fact, the man in the stock photo.
The unnamed hipster slunk away to recover in shame, presumably with organic coffee and a Neutral Milk Hotel album on vinyl.
You don’t need a brain to feel fear
PTSD is normally not a laughing matter. It’s a real mental health disorder, and it deserves to be studied. But somehow, a group of researchers from the Hebrew University of Jerusalem found comedy gold researching the disorder by giving PTSD to ... worms.
Specifically, to Caenorhabditis elegans, a workhorse of biological research. In a study published in Current Biology, the researchers starved their hapless test subjects for a day while spraying them with a scent they normally enjoy. The next day, the worms were fed properly, but when exposed to the same scent, the nematodes went into a defensive mode, showing C. elegans is capable of associative memory.
Because C. elegans only has 302 neurons, it was very simple to find which neurons were affecting their memory and genetically engineer future generations whose “fight or flight” impulse could be activated by switching a light on or off.
Obviously, determining which specific neurons carry associative memory has benefit for the potential treatment of PTSD. We have to wonder though, what do the researchers tell people they do for a living? “Ah, yes, I’m conducting very important research: I make small worms afraid of the light.”
Can’t imagine they get invited to too many parties.
Fly the organ-friendly skies
Much like the proverbial stork, a drone flew 2.8 miles over Baltimore during the early-morning hours of April 19 to deliver a precious cargo.
What? No, it was not a baby! Are you nuts?
This drone was, in fact, the first unmanned aircraft to deliver a human donor organ – in this case, a kidney. This next big step for medicine was taken by the team of Joseph Scalea, MD, of the University of Maryland in Baltimore, one of the surgeons who performed the transplant. In earlier test flights, Dr. Scalea’s team was the first to use a drone to transport medical supplies, such as saline and blood tubes, between the launch site and the helipad at the university medical center.
The custom-made drone “needed to meet the rigid medical, technical, and regulatory demands of carrying an unaccompanied deceased donor organ for human transplant.” It has backup propellers, backup motors, dual batteries, and a parachute recovery system, as well as an organ-tracking system, unlike current methods, according to the university.
Our regular reader (Thanks again, Dr Pepper) may remember that LOTME recently reported on San Francisco’s “Poop Patrol” and suggested that the media would hail it as “Uber, but for poop.” Care to take a guess at what Dr. Scalea called his drone?
That right. “Uber for organs.” Sigh. That’s supposed to be our job. No, wait a second!
Okay, here’s one: “organ droner.”
Gotta catch ‘em all
In a somewhat unsurprising turn of events, researchers have discovered the exact impact that late-1990s Pokémon obsession had on the human brain. Could Bulbasaur and Charmander really change the way your gray matter works? Pikachu says yes.
Researchers scanned the brains of adults who played Pokémon extensively as children (and possibly as not-children, with the advent of Pokémon Go). They found that, in these adults, the occipitotemporal sulcus region of the brain responded more to images of Pokémon – the original 150, of course – than any other type of image.
The researchers compared this result to “novices” (a.k.a. people who had other hobbies) and noted that novice brains did not have a preference for Pokémon.
Basically, the brain of these experienced players has built them an internal Pokédex, fulfilling the dream of every Pokémaster. Ash Ketchum would be proud.
Hipsters don’t all look the same! (Yes, they do)
Slouchy beanie, scruffy beard, maybe a pair of fake spectacles, and definitely flannel – the uniform of the male hipster. Today’s Beatnik-wannabes all praise nonconformism, but what happens when everyone nonconforms the same?
You get an extremely hilarious threat of lawsuit, that’s what.
The MIT Technology Review published an article about the studies from a mathematician from Brandeis University, who examines how information transmission influences the behavior of a population.
He found that, in general, hipsters in a society initially “act randomly but then undergo a phase transition into a synchronized state.” Despite all their best efforts to push against the mainstream, hipsters eventually sync up with one another and conform to each other.
The article was published with a photo of a man in a beanie, beard, and plaid shirt. The publication soon received an email from a man who claimed he was the person in the photo, and he hadn’t given his consent, and he was upset with the article, calling it a “bit of click-bait about why hipsters all look the same.”
The email-writer angrily threatened legal action … until a quick image check showed that he was not, in fact, the man in the stock photo.
The unnamed hipster slunk away to recover in shame, presumably with organic coffee and a Neutral Milk Hotel album on vinyl.
You don’t need a brain to feel fear
PTSD is normally not a laughing matter. It’s a real mental health disorder, and it deserves to be studied. But somehow, a group of researchers from the Hebrew University of Jerusalem found comedy gold researching the disorder by giving PTSD to ... worms.
Specifically, to Caenorhabditis elegans, a workhorse of biological research. In a study published in Current Biology, the researchers starved their hapless test subjects for a day while spraying them with a scent they normally enjoy. The next day, the worms were fed properly, but when exposed to the same scent, the nematodes went into a defensive mode, showing C. elegans is capable of associative memory.
Because C. elegans only has 302 neurons, it was very simple to find which neurons were affecting their memory and genetically engineer future generations whose “fight or flight” impulse could be activated by switching a light on or off.
Obviously, determining which specific neurons carry associative memory has benefit for the potential treatment of PTSD. We have to wonder though, what do the researchers tell people they do for a living? “Ah, yes, I’m conducting very important research: I make small worms afraid of the light.”
Can’t imagine they get invited to too many parties.
Fly the organ-friendly skies
Much like the proverbial stork, a drone flew 2.8 miles over Baltimore during the early-morning hours of April 19 to deliver a precious cargo.
What? No, it was not a baby! Are you nuts?
This drone was, in fact, the first unmanned aircraft to deliver a human donor organ – in this case, a kidney. This next big step for medicine was taken by the team of Joseph Scalea, MD, of the University of Maryland in Baltimore, one of the surgeons who performed the transplant. In earlier test flights, Dr. Scalea’s team was the first to use a drone to transport medical supplies, such as saline and blood tubes, between the launch site and the helipad at the university medical center.
The custom-made drone “needed to meet the rigid medical, technical, and regulatory demands of carrying an unaccompanied deceased donor organ for human transplant.” It has backup propellers, backup motors, dual batteries, and a parachute recovery system, as well as an organ-tracking system, unlike current methods, according to the university.
Our regular reader (Thanks again, Dr Pepper) may remember that LOTME recently reported on San Francisco’s “Poop Patrol” and suggested that the media would hail it as “Uber, but for poop.” Care to take a guess at what Dr. Scalea called his drone?
That right. “Uber for organs.” Sigh. That’s supposed to be our job. No, wait a second!
Okay, here’s one: “organ droner.”
Gotta catch ‘em all
In a somewhat unsurprising turn of events, researchers have discovered the exact impact that late-1990s Pokémon obsession had on the human brain. Could Bulbasaur and Charmander really change the way your gray matter works? Pikachu says yes.
Researchers scanned the brains of adults who played Pokémon extensively as children (and possibly as not-children, with the advent of Pokémon Go). They found that, in these adults, the occipitotemporal sulcus region of the brain responded more to images of Pokémon – the original 150, of course – than any other type of image.
The researchers compared this result to “novices” (a.k.a. people who had other hobbies) and noted that novice brains did not have a preference for Pokémon.
Basically, the brain of these experienced players has built them an internal Pokédex, fulfilling the dream of every Pokémaster. Ash Ketchum would be proud.
Hipsters don’t all look the same! (Yes, they do)
Slouchy beanie, scruffy beard, maybe a pair of fake spectacles, and definitely flannel – the uniform of the male hipster. Today’s Beatnik-wannabes all praise nonconformism, but what happens when everyone nonconforms the same?
You get an extremely hilarious threat of lawsuit, that’s what.
The MIT Technology Review published an article about the studies from a mathematician from Brandeis University, who examines how information transmission influences the behavior of a population.
He found that, in general, hipsters in a society initially “act randomly but then undergo a phase transition into a synchronized state.” Despite all their best efforts to push against the mainstream, hipsters eventually sync up with one another and conform to each other.
The article was published with a photo of a man in a beanie, beard, and plaid shirt. The publication soon received an email from a man who claimed he was the person in the photo, and he hadn’t given his consent, and he was upset with the article, calling it a “bit of click-bait about why hipsters all look the same.”
The email-writer angrily threatened legal action … until a quick image check showed that he was not, in fact, the man in the stock photo.
The unnamed hipster slunk away to recover in shame, presumably with organic coffee and a Neutral Milk Hotel album on vinyl.
You don’t need a brain to feel fear
PTSD is normally not a laughing matter. It’s a real mental health disorder, and it deserves to be studied. But somehow, a group of researchers from the Hebrew University of Jerusalem found comedy gold researching the disorder by giving PTSD to ... worms.
Specifically, to Caenorhabditis elegans, a workhorse of biological research. In a study published in Current Biology, the researchers starved their hapless test subjects for a day while spraying them with a scent they normally enjoy. The next day, the worms were fed properly, but when exposed to the same scent, the nematodes went into a defensive mode, showing C. elegans is capable of associative memory.
Because C. elegans only has 302 neurons, it was very simple to find which neurons were affecting their memory and genetically engineer future generations whose “fight or flight” impulse could be activated by switching a light on or off.
Obviously, determining which specific neurons carry associative memory has benefit for the potential treatment of PTSD. We have to wonder though, what do the researchers tell people they do for a living? “Ah, yes, I’m conducting very important research: I make small worms afraid of the light.”
Can’t imagine they get invited to too many parties.
Fly the organ-friendly skies
Much like the proverbial stork, a drone flew 2.8 miles over Baltimore during the early-morning hours of April 19 to deliver a precious cargo.
What? No, it was not a baby! Are you nuts?
This drone was, in fact, the first unmanned aircraft to deliver a human donor organ – in this case, a kidney. This next big step for medicine was taken by the team of Joseph Scalea, MD, of the University of Maryland in Baltimore, one of the surgeons who performed the transplant. In earlier test flights, Dr. Scalea’s team was the first to use a drone to transport medical supplies, such as saline and blood tubes, between the launch site and the helipad at the university medical center.
The custom-made drone “needed to meet the rigid medical, technical, and regulatory demands of carrying an unaccompanied deceased donor organ for human transplant.” It has backup propellers, backup motors, dual batteries, and a parachute recovery system, as well as an organ-tracking system, unlike current methods, according to the university.
Our regular reader (Thanks again, Dr Pepper) may remember that LOTME recently reported on San Francisco’s “Poop Patrol” and suggested that the media would hail it as “Uber, but for poop.” Care to take a guess at what Dr. Scalea called his drone?
That right. “Uber for organs.” Sigh. That’s supposed to be our job. No, wait a second!
Okay, here’s one: “organ droner.”
AACE 2019: Top takeaways from Yehuda Handelsman and Paul Jellinger
in a video interview at the meeting.
Dr. Handelsman, medical director of the Metabolic Institute of America, in Tarzana, Calif., summarized the top take-home messages from a premeeting symposium he chaired on diabetes, cardiovascular disease (CVD), and lipid management in high-risk patients. Dr. Jellinger, professor of clinical medicine on the voluntary faculty at the University of Miami Miller School of Medicine, looked at management aspects and therapy goals based on a comparison of the lipid guideline from the American College of Cardiology and the American Heart Association with that from the AACE. Other highlights from the symposium included expert analysis of the CREDENCE trial results on canagliflozin for improving renal outcomes in patients with type 2 diabetes, advice on the management of heart failure in diabetes, and recommendations on managing hyperglycemia.
Dr. Jellinger and Dr. Handelsman, who are members of the editorial advisory board of Clinical Endocrinology News, highlighted the emergence of anabolic treatments for osteoporosis, in particular the sclerostin-neutralizing monoclonal antibody, romosozumab. The therapy was recently approved for the treatment of postmenopausal osteoporosis and is unique in that it both promotes bone formation and reduces resorption. They also noted the switch away from previous practice to now using an anabolic drug first, then going to an antiresorptive therapy, rather than the other way around.
They discussed the keynote address by social media guru, Kevin Pho, MD; a debate that centered on the merits of the American Diabetes Association’s guideline for treating diabetes versus that from the AACE; a presentation on sustained remission of type 2 diabetes with a very low calorie diet; and a report on encouraging findings with an experimental drug for Graves eye disease.
in a video interview at the meeting.
Dr. Handelsman, medical director of the Metabolic Institute of America, in Tarzana, Calif., summarized the top take-home messages from a premeeting symposium he chaired on diabetes, cardiovascular disease (CVD), and lipid management in high-risk patients. Dr. Jellinger, professor of clinical medicine on the voluntary faculty at the University of Miami Miller School of Medicine, looked at management aspects and therapy goals based on a comparison of the lipid guideline from the American College of Cardiology and the American Heart Association with that from the AACE. Other highlights from the symposium included expert analysis of the CREDENCE trial results on canagliflozin for improving renal outcomes in patients with type 2 diabetes, advice on the management of heart failure in diabetes, and recommendations on managing hyperglycemia.
Dr. Jellinger and Dr. Handelsman, who are members of the editorial advisory board of Clinical Endocrinology News, highlighted the emergence of anabolic treatments for osteoporosis, in particular the sclerostin-neutralizing monoclonal antibody, romosozumab. The therapy was recently approved for the treatment of postmenopausal osteoporosis and is unique in that it both promotes bone formation and reduces resorption. They also noted the switch away from previous practice to now using an anabolic drug first, then going to an antiresorptive therapy, rather than the other way around.
They discussed the keynote address by social media guru, Kevin Pho, MD; a debate that centered on the merits of the American Diabetes Association’s guideline for treating diabetes versus that from the AACE; a presentation on sustained remission of type 2 diabetes with a very low calorie diet; and a report on encouraging findings with an experimental drug for Graves eye disease.
in a video interview at the meeting.
Dr. Handelsman, medical director of the Metabolic Institute of America, in Tarzana, Calif., summarized the top take-home messages from a premeeting symposium he chaired on diabetes, cardiovascular disease (CVD), and lipid management in high-risk patients. Dr. Jellinger, professor of clinical medicine on the voluntary faculty at the University of Miami Miller School of Medicine, looked at management aspects and therapy goals based on a comparison of the lipid guideline from the American College of Cardiology and the American Heart Association with that from the AACE. Other highlights from the symposium included expert analysis of the CREDENCE trial results on canagliflozin for improving renal outcomes in patients with type 2 diabetes, advice on the management of heart failure in diabetes, and recommendations on managing hyperglycemia.
Dr. Jellinger and Dr. Handelsman, who are members of the editorial advisory board of Clinical Endocrinology News, highlighted the emergence of anabolic treatments for osteoporosis, in particular the sclerostin-neutralizing monoclonal antibody, romosozumab. The therapy was recently approved for the treatment of postmenopausal osteoporosis and is unique in that it both promotes bone formation and reduces resorption. They also noted the switch away from previous practice to now using an anabolic drug first, then going to an antiresorptive therapy, rather than the other way around.
They discussed the keynote address by social media guru, Kevin Pho, MD; a debate that centered on the merits of the American Diabetes Association’s guideline for treating diabetes versus that from the AACE; a presentation on sustained remission of type 2 diabetes with a very low calorie diet; and a report on encouraging findings with an experimental drug for Graves eye disease.
REPORTING FROM AACE 2019
Clock gene disruption might underlie IBD
Clock gene disruption may contribute to inflammatory bowel disease (IBD), and medical therapy might improve both gene expression and disease activity, suggest the results of a first-in-kind study.
Expression levels of five clock genes were significantly lower in inflamed intestinal mucosa from young, newly diagnosed, untreated patients with IBD, compared with intestinal mucosa from controls (P less than .05), wrote Yael Weintraub, MD, of Sourasky Tel-Aviv (Israel) Medical Center and associates in Clinical Gastroenterology and Hepatology. Uninflamed intestinal mucosa and peripheral white blood cells from patients also had significantly less clock gene mRNA, compared with corresponding samples from controls (P less than .05), which suggests that circadian clock disruption factors into the pathogenesis of IBD, the investigators said.
Sleep disturbances and shift work are significant risk factors for IBD and for disease flare. This prospective, 32-participant study assessed sleep patterns and mRNA expression levels for six genes associated with the circadian clock. Validated questionnaires found no significant differences in sleep timing, duration, tendency to snore, and “morningness” versus “eveningness” between patients and controls. However, patients tended to go to bed later and to rise later on weeknights than did controls (P = .08 and .06, respectively). This difference was more pronounced in patients with ulcerative colitis, compared with those with Crohn’s disease, the researchers noted.
In an adjusted analysis, five clock genes (CLOCK, BMAL1, CRY1, CRY2, and PER1) showed 3- to 66-fold lower expression in samples of inflamed intestinal mucosa from patients, compared with intestinal mucosa from controls. Expression of a sixth clock gene (PER2) also was lower but did not reach statistical significance. “Interestingly, noninflamed tissue obtained from IBD patients showed a similar significant reduction in clock gene expression, except for PER2, which showed threefold induction (P less than .001) compared to controls,” the researchers said.
Clock genes were expressed at lower levels in peripheral white blood cells from patients versus controls, and this disparity correlated with higher fecal calprotectin (but not C-reactive protein) levels. “The reduction in clock gene expression was more pronounced in ulcerative colitis compared to Crohn’s disease patients,” the researchers noted. Patients with ulcerative colitis had significantly reduced expression of all six clock genes, compared with controls, whereas patients with Crohn’s disease only had significantly reduced expression of CLOCK.
All 14 patients in the study had newly diagnosed, treatment-naive, endoscopically confirmed IBD. Most were in their early to mid-teens, and eight had Crohn’s disease, five had ulcerative colitis, and one had unclassified IBD. Endoscopic severity was usually mild or moderate. The 18 controls had negative endoscopy and histopathology findings but otherwise resembled patients in terms of age, body mass index, and sex distribution. Both patients and controls were recruited from the same tertiary care center.
“Importantly, a follow-up of a cohort of the IBD patients treated with 5-aminosalicylic acid (5-ASA) or anti-tumor necrosis factor (anti-TNF) revealed that their clinical score improved as well as their clock gene expression,” the investigators wrote. They called for “further research, clarifying the association between the circadian clock and IBD at the genetic and molecular levels, as well as interventional studies investigating the effect of circadian alterations on IBD therapy and course.”
The researchers did not report external funding sources. They reported having no conflicts of interest.
SOURCE: Weintraub Y et al. Clin Gastroenterol Hepatol. 2019 April 10. doi: 10.1016/j.cgh.2019.04.013.
Clock gene disruption may contribute to inflammatory bowel disease (IBD), and medical therapy might improve both gene expression and disease activity, suggest the results of a first-in-kind study.
Expression levels of five clock genes were significantly lower in inflamed intestinal mucosa from young, newly diagnosed, untreated patients with IBD, compared with intestinal mucosa from controls (P less than .05), wrote Yael Weintraub, MD, of Sourasky Tel-Aviv (Israel) Medical Center and associates in Clinical Gastroenterology and Hepatology. Uninflamed intestinal mucosa and peripheral white blood cells from patients also had significantly less clock gene mRNA, compared with corresponding samples from controls (P less than .05), which suggests that circadian clock disruption factors into the pathogenesis of IBD, the investigators said.
Sleep disturbances and shift work are significant risk factors for IBD and for disease flare. This prospective, 32-participant study assessed sleep patterns and mRNA expression levels for six genes associated with the circadian clock. Validated questionnaires found no significant differences in sleep timing, duration, tendency to snore, and “morningness” versus “eveningness” between patients and controls. However, patients tended to go to bed later and to rise later on weeknights than did controls (P = .08 and .06, respectively). This difference was more pronounced in patients with ulcerative colitis, compared with those with Crohn’s disease, the researchers noted.
In an adjusted analysis, five clock genes (CLOCK, BMAL1, CRY1, CRY2, and PER1) showed 3- to 66-fold lower expression in samples of inflamed intestinal mucosa from patients, compared with intestinal mucosa from controls. Expression of a sixth clock gene (PER2) also was lower but did not reach statistical significance. “Interestingly, noninflamed tissue obtained from IBD patients showed a similar significant reduction in clock gene expression, except for PER2, which showed threefold induction (P less than .001) compared to controls,” the researchers said.
Clock genes were expressed at lower levels in peripheral white blood cells from patients versus controls, and this disparity correlated with higher fecal calprotectin (but not C-reactive protein) levels. “The reduction in clock gene expression was more pronounced in ulcerative colitis compared to Crohn’s disease patients,” the researchers noted. Patients with ulcerative colitis had significantly reduced expression of all six clock genes, compared with controls, whereas patients with Crohn’s disease only had significantly reduced expression of CLOCK.
All 14 patients in the study had newly diagnosed, treatment-naive, endoscopically confirmed IBD. Most were in their early to mid-teens, and eight had Crohn’s disease, five had ulcerative colitis, and one had unclassified IBD. Endoscopic severity was usually mild or moderate. The 18 controls had negative endoscopy and histopathology findings but otherwise resembled patients in terms of age, body mass index, and sex distribution. Both patients and controls were recruited from the same tertiary care center.
“Importantly, a follow-up of a cohort of the IBD patients treated with 5-aminosalicylic acid (5-ASA) or anti-tumor necrosis factor (anti-TNF) revealed that their clinical score improved as well as their clock gene expression,” the investigators wrote. They called for “further research, clarifying the association between the circadian clock and IBD at the genetic and molecular levels, as well as interventional studies investigating the effect of circadian alterations on IBD therapy and course.”
The researchers did not report external funding sources. They reported having no conflicts of interest.
SOURCE: Weintraub Y et al. Clin Gastroenterol Hepatol. 2019 April 10. doi: 10.1016/j.cgh.2019.04.013.
Clock gene disruption may contribute to inflammatory bowel disease (IBD), and medical therapy might improve both gene expression and disease activity, suggest the results of a first-in-kind study.
Expression levels of five clock genes were significantly lower in inflamed intestinal mucosa from young, newly diagnosed, untreated patients with IBD, compared with intestinal mucosa from controls (P less than .05), wrote Yael Weintraub, MD, of Sourasky Tel-Aviv (Israel) Medical Center and associates in Clinical Gastroenterology and Hepatology. Uninflamed intestinal mucosa and peripheral white blood cells from patients also had significantly less clock gene mRNA, compared with corresponding samples from controls (P less than .05), which suggests that circadian clock disruption factors into the pathogenesis of IBD, the investigators said.
Sleep disturbances and shift work are significant risk factors for IBD and for disease flare. This prospective, 32-participant study assessed sleep patterns and mRNA expression levels for six genes associated with the circadian clock. Validated questionnaires found no significant differences in sleep timing, duration, tendency to snore, and “morningness” versus “eveningness” between patients and controls. However, patients tended to go to bed later and to rise later on weeknights than did controls (P = .08 and .06, respectively). This difference was more pronounced in patients with ulcerative colitis, compared with those with Crohn’s disease, the researchers noted.
In an adjusted analysis, five clock genes (CLOCK, BMAL1, CRY1, CRY2, and PER1) showed 3- to 66-fold lower expression in samples of inflamed intestinal mucosa from patients, compared with intestinal mucosa from controls. Expression of a sixth clock gene (PER2) also was lower but did not reach statistical significance. “Interestingly, noninflamed tissue obtained from IBD patients showed a similar significant reduction in clock gene expression, except for PER2, which showed threefold induction (P less than .001) compared to controls,” the researchers said.
Clock genes were expressed at lower levels in peripheral white blood cells from patients versus controls, and this disparity correlated with higher fecal calprotectin (but not C-reactive protein) levels. “The reduction in clock gene expression was more pronounced in ulcerative colitis compared to Crohn’s disease patients,” the researchers noted. Patients with ulcerative colitis had significantly reduced expression of all six clock genes, compared with controls, whereas patients with Crohn’s disease only had significantly reduced expression of CLOCK.
All 14 patients in the study had newly diagnosed, treatment-naive, endoscopically confirmed IBD. Most were in their early to mid-teens, and eight had Crohn’s disease, five had ulcerative colitis, and one had unclassified IBD. Endoscopic severity was usually mild or moderate. The 18 controls had negative endoscopy and histopathology findings but otherwise resembled patients in terms of age, body mass index, and sex distribution. Both patients and controls were recruited from the same tertiary care center.
“Importantly, a follow-up of a cohort of the IBD patients treated with 5-aminosalicylic acid (5-ASA) or anti-tumor necrosis factor (anti-TNF) revealed that their clinical score improved as well as their clock gene expression,” the investigators wrote. They called for “further research, clarifying the association between the circadian clock and IBD at the genetic and molecular levels, as well as interventional studies investigating the effect of circadian alterations on IBD therapy and course.”
The researchers did not report external funding sources. They reported having no conflicts of interest.
SOURCE: Weintraub Y et al. Clin Gastroenterol Hepatol. 2019 April 10. doi: 10.1016/j.cgh.2019.04.013.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Quick Byte: Hope for HF patients
A new device shows promise for heart failure patients, according to a recent study.
In a trial, 614 patients with severe heart failure were randomly assigned to receive standard medical treatment and a MitraClip, which helps repair the damaged mitral valve, or to receive medical treatment alone.
Among those who received only medical treatment, 151 were hospitalized for heart failure in the ensuing 2 years and 61 died. Among those who got the device, 92 were hospitalized for heart failure during the same period and 28 died.
Reference
1. Kolata G. Tiny Device is a ‘Huge Advance’ for Treatment of Severe Heart Failure. New York Times. Sept 23, 2018. https://www.nytimes.com/2018/09/23/health/heart-failure-valve-repair-microclip.html. Accessed Oct 10, 2018.
A new device shows promise for heart failure patients, according to a recent study.
In a trial, 614 patients with severe heart failure were randomly assigned to receive standard medical treatment and a MitraClip, which helps repair the damaged mitral valve, or to receive medical treatment alone.
Among those who received only medical treatment, 151 were hospitalized for heart failure in the ensuing 2 years and 61 died. Among those who got the device, 92 were hospitalized for heart failure during the same period and 28 died.
Reference
1. Kolata G. Tiny Device is a ‘Huge Advance’ for Treatment of Severe Heart Failure. New York Times. Sept 23, 2018. https://www.nytimes.com/2018/09/23/health/heart-failure-valve-repair-microclip.html. Accessed Oct 10, 2018.
A new device shows promise for heart failure patients, according to a recent study.
In a trial, 614 patients with severe heart failure were randomly assigned to receive standard medical treatment and a MitraClip, which helps repair the damaged mitral valve, or to receive medical treatment alone.
Among those who received only medical treatment, 151 were hospitalized for heart failure in the ensuing 2 years and 61 died. Among those who got the device, 92 were hospitalized for heart failure during the same period and 28 died.
Reference
1. Kolata G. Tiny Device is a ‘Huge Advance’ for Treatment of Severe Heart Failure. New York Times. Sept 23, 2018. https://www.nytimes.com/2018/09/23/health/heart-failure-valve-repair-microclip.html. Accessed Oct 10, 2018.
Netherton Syndrome: An Atypical Presentation
To the Editor:
Netherton syndrome (NS) is a rare autosomal-recessive ichthyosiform disease.1 The incidence is estimated to be 1 in 200,000 individuals.2 Netherton syndrome presents with generalized erythroderma and scaling, characteristic hair shaft abnormalities, and dysregulation of the immune system. Treatment is largely symptomatic and includes fragrance-free emollients, keratolytics, tretinoin, and corticosteroids, either alone or in combination. We report a case of NS in a man with congenital erythroderma, pili torti, and elevated IgE levels.
A 23-year-old man presented with generalized scaly skin that was present since birth. He was the first child born of nonconsanguineous parents. His medical history was suggestive of atopic diatheses such as allergic rhinitis and recurrent urticaria. The patient was of thin build and had widespread erythematous, annular, and polycyclic scaly lesions (Figure 1A), some with characteristic double-edged scale (Figure 1B). The skin was dry due to anhidrosis that was present since birth. Flexural lichenification was present at the cubital fossa of both arms. Scalp hairs were easily pluckable and had generalized thinning of hair density. Hair mount examination showed characteristic features of both trichorrhexis invaginata (Figure 2A) and pili torti (Figure 2B).
hair shaft known as bamboo hair or trichorrhexis invaginata. B, Features of pili torti; the hair
shaft twisted at irregular intervals.
Potassium hydroxide mount from a lesion was negative for fungal elements. Complete hematologic workup showed moderate anemia at 8.0 g/dL (reference range, 8.0–10.9 g/dL) and peripheral eosinophilia at 12% (reference range, 0%–6%). His IgE level was markedly elevated at6331 IU/mL (reference range, 150–1000 IU/mL) when tested with fully automated bidirectionally interfaced chemiluminescent immunoassay. Histopathologic examination of a lesion biopsy showed psoriasiform epidermal hyperplasia, papillomatosis, and acanthosis, consistent with ichthyosis linearis circumflexa (ILC)(Figure 3). Clinicopathologic correlation led to a diagnosis of ILC, trichorrhexis invaginata/pili torti, and atopic diathesis, which is a constellation of disorders related to NS.
We prescribed oral acitretin 25 mg once daily and instructed the patient to apply petroleum jelly; however, the patient returned after 2 weeks due to aggravation of the skin condition with increased scaling and redness. Because the patient showed signs of acute skin failure and erythroderma, we stopped acitretin treatment and managed his condition conservatively with the application of petroleum jelly.
Netherton syndrome is caused by mutation of the SPINK5 gene, serine protease inhibitor Kazal type 5; the corresponding gene is located on the long arm of chromosome 5.3 The gene encodes a serine protease inhibitor proprotein LEKTI (lymphoepithelial Kazal type inhibitor).4 The product of the gene is thought to be necessary for epidermal cell growth and differentiation. The classic clinical triad of NS includes ichthyosiform dermatosis with double-edged scale, hair shaft abnormalities, and atopy or elevated IgE levels.5 Generalized (congenital) erythroderma usually becomes evident at birth or shortly thereafter. Half of patients develop lesions of ILC on the trunk and limbs during childhood.6 A typical ILC lesion is characterized by an erythematous scaly patch that may be annular or polycyclic with double-edged scale at the advancing border. The ability to sweat is impaired, which may cause episodes of hyperpyrexia, especially during humid weather. Patients with hyperpyrexia may be incorrectly diagnosed with bacterial infection and treated with antipyretic drugs or a prolonged course of antibiotics. Trichorrhexis invaginata, also referred to as bamboo hair or ball-and-socket defect, is the pathognomonic hair shaft abnormality seen in NS.7 Other hair shaft abnormalities in this syndrome include trichorrhexis nodosa and pili torti.8 Our patient had hair shaft abnormalities of trichorrhexis invaginata and pili torti, which are rare findings. The third component of this syndrome is atopy, which generally manifests as angioedema, urticaria, allergic rhinitis, peripheral eosinophilia, atopic dermatitis–like skin lesions, asthma, and elevated IgE levels.9
Treatment with emollients, topical steroids, tacrolimus, and psoralen plus UVA does not elicit a satisfactory response. The Table highlights the clinical features and management of NS.
Generally, systemic retinoid therapy is helpful in cases of erythrodermic ichthyosis, but a unique feature of NS is that erythroderma may worsen with systemic retinoid therapy, as retinoids aggravate atopic dermatitis by worsening existing xerosis.4 Our case highlights the rare association of trichorrhexis invaginata with pili torti as well as acitretin treatment worsening our patient’s condition. This paradoxical effect of retinoid therapy further confirmed the diagnosis of NS.
- Suhaila O, Muzhirah A. Netherton syndrome: a case report. Malaysian J Pediatr Child Health. 2010;16:26.
- Emre S, Metin A, Demirseren D, et al. Two siblings with Netherton syndrome. Turk J Med Sci. 2010;40:819-823.
- Chavanas S, Bodemer C, Rochat A, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25:141-142.
- Judge MR, Mclean WH, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, et al, eds. Rook’s Textbook of Dermatology. 8th ed. Singapore: Wiley-Blackwell; 2010:19.1-19.122.
- Greene SL, Muller SA. Netherton’s syndrome. report of a case and review of the literature. J Am Acad Dermatol. 1985;13:329-337.
- Khan I-U, Chaudhary R. Netherton’s syndrome, an uncommon genodermatosis. J Pakistan Assoc Dermatol. 2006;16.
- Boskabadi H, Maamouri G, Mafinejad S. Netherton syndrome, a case report and review of literature. Iran J Pediatr. 2013;23:611-612.
- Hurwitz S. Hereditary skin disorders: the genodermatoses. In: Hurwitz, ed. Clinical Pediatric Dermatology. Philadelphia, PA: WB Saunders; 1993:173.
- Judge MR, McLean WH, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, et al, eds. Rook’s Textbook of Dermatology. 7th ed. Vol 2. Oxford, England: Blackwell Science; 2004:34.35.
To the Editor:
Netherton syndrome (NS) is a rare autosomal-recessive ichthyosiform disease.1 The incidence is estimated to be 1 in 200,000 individuals.2 Netherton syndrome presents with generalized erythroderma and scaling, characteristic hair shaft abnormalities, and dysregulation of the immune system. Treatment is largely symptomatic and includes fragrance-free emollients, keratolytics, tretinoin, and corticosteroids, either alone or in combination. We report a case of NS in a man with congenital erythroderma, pili torti, and elevated IgE levels.
A 23-year-old man presented with generalized scaly skin that was present since birth. He was the first child born of nonconsanguineous parents. His medical history was suggestive of atopic diatheses such as allergic rhinitis and recurrent urticaria. The patient was of thin build and had widespread erythematous, annular, and polycyclic scaly lesions (Figure 1A), some with characteristic double-edged scale (Figure 1B). The skin was dry due to anhidrosis that was present since birth. Flexural lichenification was present at the cubital fossa of both arms. Scalp hairs were easily pluckable and had generalized thinning of hair density. Hair mount examination showed characteristic features of both trichorrhexis invaginata (Figure 2A) and pili torti (Figure 2B).
hair shaft known as bamboo hair or trichorrhexis invaginata. B, Features of pili torti; the hair
shaft twisted at irregular intervals.
Potassium hydroxide mount from a lesion was negative for fungal elements. Complete hematologic workup showed moderate anemia at 8.0 g/dL (reference range, 8.0–10.9 g/dL) and peripheral eosinophilia at 12% (reference range, 0%–6%). His IgE level was markedly elevated at6331 IU/mL (reference range, 150–1000 IU/mL) when tested with fully automated bidirectionally interfaced chemiluminescent immunoassay. Histopathologic examination of a lesion biopsy showed psoriasiform epidermal hyperplasia, papillomatosis, and acanthosis, consistent with ichthyosis linearis circumflexa (ILC)(Figure 3). Clinicopathologic correlation led to a diagnosis of ILC, trichorrhexis invaginata/pili torti, and atopic diathesis, which is a constellation of disorders related to NS.
We prescribed oral acitretin 25 mg once daily and instructed the patient to apply petroleum jelly; however, the patient returned after 2 weeks due to aggravation of the skin condition with increased scaling and redness. Because the patient showed signs of acute skin failure and erythroderma, we stopped acitretin treatment and managed his condition conservatively with the application of petroleum jelly.
Netherton syndrome is caused by mutation of the SPINK5 gene, serine protease inhibitor Kazal type 5; the corresponding gene is located on the long arm of chromosome 5.3 The gene encodes a serine protease inhibitor proprotein LEKTI (lymphoepithelial Kazal type inhibitor).4 The product of the gene is thought to be necessary for epidermal cell growth and differentiation. The classic clinical triad of NS includes ichthyosiform dermatosis with double-edged scale, hair shaft abnormalities, and atopy or elevated IgE levels.5 Generalized (congenital) erythroderma usually becomes evident at birth or shortly thereafter. Half of patients develop lesions of ILC on the trunk and limbs during childhood.6 A typical ILC lesion is characterized by an erythematous scaly patch that may be annular or polycyclic with double-edged scale at the advancing border. The ability to sweat is impaired, which may cause episodes of hyperpyrexia, especially during humid weather. Patients with hyperpyrexia may be incorrectly diagnosed with bacterial infection and treated with antipyretic drugs or a prolonged course of antibiotics. Trichorrhexis invaginata, also referred to as bamboo hair or ball-and-socket defect, is the pathognomonic hair shaft abnormality seen in NS.7 Other hair shaft abnormalities in this syndrome include trichorrhexis nodosa and pili torti.8 Our patient had hair shaft abnormalities of trichorrhexis invaginata and pili torti, which are rare findings. The third component of this syndrome is atopy, which generally manifests as angioedema, urticaria, allergic rhinitis, peripheral eosinophilia, atopic dermatitis–like skin lesions, asthma, and elevated IgE levels.9
Treatment with emollients, topical steroids, tacrolimus, and psoralen plus UVA does not elicit a satisfactory response. The Table highlights the clinical features and management of NS.
Generally, systemic retinoid therapy is helpful in cases of erythrodermic ichthyosis, but a unique feature of NS is that erythroderma may worsen with systemic retinoid therapy, as retinoids aggravate atopic dermatitis by worsening existing xerosis.4 Our case highlights the rare association of trichorrhexis invaginata with pili torti as well as acitretin treatment worsening our patient’s condition. This paradoxical effect of retinoid therapy further confirmed the diagnosis of NS.
To the Editor:
Netherton syndrome (NS) is a rare autosomal-recessive ichthyosiform disease.1 The incidence is estimated to be 1 in 200,000 individuals.2 Netherton syndrome presents with generalized erythroderma and scaling, characteristic hair shaft abnormalities, and dysregulation of the immune system. Treatment is largely symptomatic and includes fragrance-free emollients, keratolytics, tretinoin, and corticosteroids, either alone or in combination. We report a case of NS in a man with congenital erythroderma, pili torti, and elevated IgE levels.
A 23-year-old man presented with generalized scaly skin that was present since birth. He was the first child born of nonconsanguineous parents. His medical history was suggestive of atopic diatheses such as allergic rhinitis and recurrent urticaria. The patient was of thin build and had widespread erythematous, annular, and polycyclic scaly lesions (Figure 1A), some with characteristic double-edged scale (Figure 1B). The skin was dry due to anhidrosis that was present since birth. Flexural lichenification was present at the cubital fossa of both arms. Scalp hairs were easily pluckable and had generalized thinning of hair density. Hair mount examination showed characteristic features of both trichorrhexis invaginata (Figure 2A) and pili torti (Figure 2B).
hair shaft known as bamboo hair or trichorrhexis invaginata. B, Features of pili torti; the hair
shaft twisted at irregular intervals.
Potassium hydroxide mount from a lesion was negative for fungal elements. Complete hematologic workup showed moderate anemia at 8.0 g/dL (reference range, 8.0–10.9 g/dL) and peripheral eosinophilia at 12% (reference range, 0%–6%). His IgE level was markedly elevated at6331 IU/mL (reference range, 150–1000 IU/mL) when tested with fully automated bidirectionally interfaced chemiluminescent immunoassay. Histopathologic examination of a lesion biopsy showed psoriasiform epidermal hyperplasia, papillomatosis, and acanthosis, consistent with ichthyosis linearis circumflexa (ILC)(Figure 3). Clinicopathologic correlation led to a diagnosis of ILC, trichorrhexis invaginata/pili torti, and atopic diathesis, which is a constellation of disorders related to NS.
We prescribed oral acitretin 25 mg once daily and instructed the patient to apply petroleum jelly; however, the patient returned after 2 weeks due to aggravation of the skin condition with increased scaling and redness. Because the patient showed signs of acute skin failure and erythroderma, we stopped acitretin treatment and managed his condition conservatively with the application of petroleum jelly.
Netherton syndrome is caused by mutation of the SPINK5 gene, serine protease inhibitor Kazal type 5; the corresponding gene is located on the long arm of chromosome 5.3 The gene encodes a serine protease inhibitor proprotein LEKTI (lymphoepithelial Kazal type inhibitor).4 The product of the gene is thought to be necessary for epidermal cell growth and differentiation. The classic clinical triad of NS includes ichthyosiform dermatosis with double-edged scale, hair shaft abnormalities, and atopy or elevated IgE levels.5 Generalized (congenital) erythroderma usually becomes evident at birth or shortly thereafter. Half of patients develop lesions of ILC on the trunk and limbs during childhood.6 A typical ILC lesion is characterized by an erythematous scaly patch that may be annular or polycyclic with double-edged scale at the advancing border. The ability to sweat is impaired, which may cause episodes of hyperpyrexia, especially during humid weather. Patients with hyperpyrexia may be incorrectly diagnosed with bacterial infection and treated with antipyretic drugs or a prolonged course of antibiotics. Trichorrhexis invaginata, also referred to as bamboo hair or ball-and-socket defect, is the pathognomonic hair shaft abnormality seen in NS.7 Other hair shaft abnormalities in this syndrome include trichorrhexis nodosa and pili torti.8 Our patient had hair shaft abnormalities of trichorrhexis invaginata and pili torti, which are rare findings. The third component of this syndrome is atopy, which generally manifests as angioedema, urticaria, allergic rhinitis, peripheral eosinophilia, atopic dermatitis–like skin lesions, asthma, and elevated IgE levels.9
Treatment with emollients, topical steroids, tacrolimus, and psoralen plus UVA does not elicit a satisfactory response. The Table highlights the clinical features and management of NS.
Generally, systemic retinoid therapy is helpful in cases of erythrodermic ichthyosis, but a unique feature of NS is that erythroderma may worsen with systemic retinoid therapy, as retinoids aggravate atopic dermatitis by worsening existing xerosis.4 Our case highlights the rare association of trichorrhexis invaginata with pili torti as well as acitretin treatment worsening our patient’s condition. This paradoxical effect of retinoid therapy further confirmed the diagnosis of NS.
- Suhaila O, Muzhirah A. Netherton syndrome: a case report. Malaysian J Pediatr Child Health. 2010;16:26.
- Emre S, Metin A, Demirseren D, et al. Two siblings with Netherton syndrome. Turk J Med Sci. 2010;40:819-823.
- Chavanas S, Bodemer C, Rochat A, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25:141-142.
- Judge MR, Mclean WH, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, et al, eds. Rook’s Textbook of Dermatology. 8th ed. Singapore: Wiley-Blackwell; 2010:19.1-19.122.
- Greene SL, Muller SA. Netherton’s syndrome. report of a case and review of the literature. J Am Acad Dermatol. 1985;13:329-337.
- Khan I-U, Chaudhary R. Netherton’s syndrome, an uncommon genodermatosis. J Pakistan Assoc Dermatol. 2006;16.
- Boskabadi H, Maamouri G, Mafinejad S. Netherton syndrome, a case report and review of literature. Iran J Pediatr. 2013;23:611-612.
- Hurwitz S. Hereditary skin disorders: the genodermatoses. In: Hurwitz, ed. Clinical Pediatric Dermatology. Philadelphia, PA: WB Saunders; 1993:173.
- Judge MR, McLean WH, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, et al, eds. Rook’s Textbook of Dermatology. 7th ed. Vol 2. Oxford, England: Blackwell Science; 2004:34.35.
- Suhaila O, Muzhirah A. Netherton syndrome: a case report. Malaysian J Pediatr Child Health. 2010;16:26.
- Emre S, Metin A, Demirseren D, et al. Two siblings with Netherton syndrome. Turk J Med Sci. 2010;40:819-823.
- Chavanas S, Bodemer C, Rochat A, et al. Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome. Nat Genet. 2000;25:141-142.
- Judge MR, Mclean WH, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, et al, eds. Rook’s Textbook of Dermatology. 8th ed. Singapore: Wiley-Blackwell; 2010:19.1-19.122.
- Greene SL, Muller SA. Netherton’s syndrome. report of a case and review of the literature. J Am Acad Dermatol. 1985;13:329-337.
- Khan I-U, Chaudhary R. Netherton’s syndrome, an uncommon genodermatosis. J Pakistan Assoc Dermatol. 2006;16.
- Boskabadi H, Maamouri G, Mafinejad S. Netherton syndrome, a case report and review of literature. Iran J Pediatr. 2013;23:611-612.
- Hurwitz S. Hereditary skin disorders: the genodermatoses. In: Hurwitz, ed. Clinical Pediatric Dermatology. Philadelphia, PA: WB Saunders; 1993:173.
- Judge MR, McLean WH, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, et al, eds. Rook’s Textbook of Dermatology. 7th ed. Vol 2. Oxford, England: Blackwell Science; 2004:34.35.
Practice Points
- Netherton syndrome is characterized by generalized erythroderma and scaling, hair shaft abnormalities, and dysregulation of the immune system.
- Treatment is largely symptomatic and includes fragrance-free emollients, keratolytics, tretinoin, and corticosteroids, either alone or in combination.
Adult-Onset Asymmetrical Lipomatosis
To the Editor:
An 85-year-old woman presented with extra growth of subcutaneous fat at the left anterior infradiaphragm that expanded circumferentially to the left back over the last 4 years. Two years prior to the current presentation, the left thigh became visibly thicker than the right. Diffuse subtle lipomatosis affecting the ipsilateral face, neck, arms, calf, and foot was noted at that time. Additionally, the patient had hyperlipidemia, gastroesophageal reflux disease, osteoporosis, and scoliosis, all beginning in her late 60s. She reported no alcohol or tobacco use and was taking rosuvastatin, esomeprazole, calcium, vitamin D, and glucosamine. There was no reported family history of asymmetric growth or bony deformities, and her children were healthy.
On physical examination, the lipomatosis affected the entire left side, most prominently around the abdomen, back, and thighs. The affected side was nontender and nonpruritic; there was no atrophy of the unaffected side (Figure). Maximum thigh circumference was 55.1 cm on the affected side and 52.6 cm on the unaffected side. There were no differences in power, reflex, or sensation between the 2 sides, and no hyperhidrosis or vascular malformations were present. Laboratory investigations, including complete blood cell count, complete metabolic panel, lipids, and thyroid-stimulating and sex hormone panels all were within reference range.
Enzi et al1 reported 2 women who developed asymmetrical lipomatosis between the ages of 13 and 20 years. Acquired asymmetrical lipomatosis should be differentiated from the asymmetrical overgrowth diagnosed in neonates and infants.
Proteus syndrome (PS) is a progressive disease involving a combination of overgrowth in a mosaic distribution, connective tissue and epidermal nevi, ovarian cysts, parotid gland tumor, dysregulated adipose tissue, lymphovascular malformation, and certain facial phenotypes.2,3 The average age of onset is 6 to 18 months, and half of cases present at birth.3,4 Hemihyperplasia-multiple lipomatosis syndrome (HHML) describes a mild and nonprogressive variant that does not satisfy the diagnostic criteria of PS; it typically is diagnosed at birth.5 One case of mild and delayed-onset PS was described in a woman who started developing signs at 15 years of age.6 In comparison, asymmetrical lipomatosis and scoliosis were the only abnormal clinical signs present in our patient, and the lipomatosis developed diffusely, as opposed to the typical mosaic distribution found in PS and HHML. Scoliosis can be found in PS and HHML secondary to hemihypertrophy of vertebra or infiltrative intraspinal lipomatosis.7,8 Our patient’s scoliosis was diagnosed more than 10 years prior to the onset of lipomatosis, likely representing degenerative joint disease.9
Prior reported cases of asymmetrical lipomatosis did not describe treatment.1 Ultrasound-guided or conventional liposuction and lipectomy are mainstream therapies for multiple symmetrical lipomatosis, an acquired lipomatosis typically affecting alcoholics in the fourth decade of life. However, recurrence rates are high for surgical treatment of unencapsulated lipomatosis, likely due to incomplete removal of the adipose tissue.10 Alternative treatments found in case reports, including oral salbutamol, mesotherapy using phosphatidylcholine, and fenofibrate (200 mg/d), require further study.11-13 Our patient was not aesthetically bothered by her lipomatosis; therefore, imaging and treatment options were not pursued. In conclusion, we report a patient with acquired asymmetrical lipomatosis with onset in late adulthood, unique from the existing syndromes of asymmetrical hemihyperplasia.1,14
- Enzi G, Digito M, Enzi GB, et al. Asymmetrical lipomatosis: report of two cases. Postgrad Med J. 1985;61:797-800.
- Biesecker LG, Happle R, Mulliken JB, et al. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet. 1999;84:389-395.
- Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet. 2006;14:1151-1157.
- Cohen MM Jr. Proteus syndrome: an update. Am J Med Genet C Semin Med Genet. 2005;137C:38-52.
- Biesecker LG, Peters KF, Darling TN, et al. Clinical differentiation between Proteus syndrome and hemihyperplasia: description of a distinct form of hemihyperplasia. Am J Med Genet. 1998;79:311-318.
- Luo S, Feng Y, Zheng Y, et al. Mild and delayed-onset Proteus syndrome. Eur J Dermatol. 2007;17:172-173.
- Takebayashi T, Yamashita T, Yokogushi K, et al. Scoliosis in Proteus syndrome: case report. Spine. 2001;26:E395-E398.
- Schulte TL, Liljenqvist U, Görgens H, et al. Hemihyperplasia-multiple lipomatosis syndrome (HHML): a challenge in spinal care. Acta Orthop Belg. 2008;74:714-719.
- Robin GC, Span Y, Steinberg R, et al. Scoliosis in the elderly: a follow-up study. Spine. 1982;7:355-359.
- Brea-García B, Cameselle-Teijeiro J, Couto-González I, et al. Madelung’s disease: comorbidities, fatty mass distribution, and response to treatment of 22 patients. Aesthet Plast Surg. 2013;37:409-416.
- Hasegawa T, Matsukura T, Ikeda S. Mesotherapy for benign symmetric lipomatosis. Aesthet Plast Surg. 2010;34:153-156.
- Zeitler H, Ulrich-Merzenich G, Richter DF, et al. Multiple benign symmetric lipomatosis—a differential diagnosis of obesity. is there a rationale for fibrate treatment? Obes Surg. 2008;18:1354-1356.
- Leung N, Gaer J, Beggs D, et al. Multiple symmetric lipomatosis (Launois‐Bensaude syndrome): effect of oral salbutamol. Clin Endocrinol. 1987;27:601-606.
- Craiglow BG, Ko CJ, Antaya RJ. Two cases of hemihyperplasia-multiple lipomatosis syndrome and review of asymmetric hemihyperplasia syndromes. Pediatr Dermatol. 2014;31:507-510.
To the Editor:
An 85-year-old woman presented with extra growth of subcutaneous fat at the left anterior infradiaphragm that expanded circumferentially to the left back over the last 4 years. Two years prior to the current presentation, the left thigh became visibly thicker than the right. Diffuse subtle lipomatosis affecting the ipsilateral face, neck, arms, calf, and foot was noted at that time. Additionally, the patient had hyperlipidemia, gastroesophageal reflux disease, osteoporosis, and scoliosis, all beginning in her late 60s. She reported no alcohol or tobacco use and was taking rosuvastatin, esomeprazole, calcium, vitamin D, and glucosamine. There was no reported family history of asymmetric growth or bony deformities, and her children were healthy.
On physical examination, the lipomatosis affected the entire left side, most prominently around the abdomen, back, and thighs. The affected side was nontender and nonpruritic; there was no atrophy of the unaffected side (Figure). Maximum thigh circumference was 55.1 cm on the affected side and 52.6 cm on the unaffected side. There were no differences in power, reflex, or sensation between the 2 sides, and no hyperhidrosis or vascular malformations were present. Laboratory investigations, including complete blood cell count, complete metabolic panel, lipids, and thyroid-stimulating and sex hormone panels all were within reference range.
Enzi et al1 reported 2 women who developed asymmetrical lipomatosis between the ages of 13 and 20 years. Acquired asymmetrical lipomatosis should be differentiated from the asymmetrical overgrowth diagnosed in neonates and infants.
Proteus syndrome (PS) is a progressive disease involving a combination of overgrowth in a mosaic distribution, connective tissue and epidermal nevi, ovarian cysts, parotid gland tumor, dysregulated adipose tissue, lymphovascular malformation, and certain facial phenotypes.2,3 The average age of onset is 6 to 18 months, and half of cases present at birth.3,4 Hemihyperplasia-multiple lipomatosis syndrome (HHML) describes a mild and nonprogressive variant that does not satisfy the diagnostic criteria of PS; it typically is diagnosed at birth.5 One case of mild and delayed-onset PS was described in a woman who started developing signs at 15 years of age.6 In comparison, asymmetrical lipomatosis and scoliosis were the only abnormal clinical signs present in our patient, and the lipomatosis developed diffusely, as opposed to the typical mosaic distribution found in PS and HHML. Scoliosis can be found in PS and HHML secondary to hemihypertrophy of vertebra or infiltrative intraspinal lipomatosis.7,8 Our patient’s scoliosis was diagnosed more than 10 years prior to the onset of lipomatosis, likely representing degenerative joint disease.9
Prior reported cases of asymmetrical lipomatosis did not describe treatment.1 Ultrasound-guided or conventional liposuction and lipectomy are mainstream therapies for multiple symmetrical lipomatosis, an acquired lipomatosis typically affecting alcoholics in the fourth decade of life. However, recurrence rates are high for surgical treatment of unencapsulated lipomatosis, likely due to incomplete removal of the adipose tissue.10 Alternative treatments found in case reports, including oral salbutamol, mesotherapy using phosphatidylcholine, and fenofibrate (200 mg/d), require further study.11-13 Our patient was not aesthetically bothered by her lipomatosis; therefore, imaging and treatment options were not pursued. In conclusion, we report a patient with acquired asymmetrical lipomatosis with onset in late adulthood, unique from the existing syndromes of asymmetrical hemihyperplasia.1,14
To the Editor:
An 85-year-old woman presented with extra growth of subcutaneous fat at the left anterior infradiaphragm that expanded circumferentially to the left back over the last 4 years. Two years prior to the current presentation, the left thigh became visibly thicker than the right. Diffuse subtle lipomatosis affecting the ipsilateral face, neck, arms, calf, and foot was noted at that time. Additionally, the patient had hyperlipidemia, gastroesophageal reflux disease, osteoporosis, and scoliosis, all beginning in her late 60s. She reported no alcohol or tobacco use and was taking rosuvastatin, esomeprazole, calcium, vitamin D, and glucosamine. There was no reported family history of asymmetric growth or bony deformities, and her children were healthy.
On physical examination, the lipomatosis affected the entire left side, most prominently around the abdomen, back, and thighs. The affected side was nontender and nonpruritic; there was no atrophy of the unaffected side (Figure). Maximum thigh circumference was 55.1 cm on the affected side and 52.6 cm on the unaffected side. There were no differences in power, reflex, or sensation between the 2 sides, and no hyperhidrosis or vascular malformations were present. Laboratory investigations, including complete blood cell count, complete metabolic panel, lipids, and thyroid-stimulating and sex hormone panels all were within reference range.
Enzi et al1 reported 2 women who developed asymmetrical lipomatosis between the ages of 13 and 20 years. Acquired asymmetrical lipomatosis should be differentiated from the asymmetrical overgrowth diagnosed in neonates and infants.
Proteus syndrome (PS) is a progressive disease involving a combination of overgrowth in a mosaic distribution, connective tissue and epidermal nevi, ovarian cysts, parotid gland tumor, dysregulated adipose tissue, lymphovascular malformation, and certain facial phenotypes.2,3 The average age of onset is 6 to 18 months, and half of cases present at birth.3,4 Hemihyperplasia-multiple lipomatosis syndrome (HHML) describes a mild and nonprogressive variant that does not satisfy the diagnostic criteria of PS; it typically is diagnosed at birth.5 One case of mild and delayed-onset PS was described in a woman who started developing signs at 15 years of age.6 In comparison, asymmetrical lipomatosis and scoliosis were the only abnormal clinical signs present in our patient, and the lipomatosis developed diffusely, as opposed to the typical mosaic distribution found in PS and HHML. Scoliosis can be found in PS and HHML secondary to hemihypertrophy of vertebra or infiltrative intraspinal lipomatosis.7,8 Our patient’s scoliosis was diagnosed more than 10 years prior to the onset of lipomatosis, likely representing degenerative joint disease.9
Prior reported cases of asymmetrical lipomatosis did not describe treatment.1 Ultrasound-guided or conventional liposuction and lipectomy are mainstream therapies for multiple symmetrical lipomatosis, an acquired lipomatosis typically affecting alcoholics in the fourth decade of life. However, recurrence rates are high for surgical treatment of unencapsulated lipomatosis, likely due to incomplete removal of the adipose tissue.10 Alternative treatments found in case reports, including oral salbutamol, mesotherapy using phosphatidylcholine, and fenofibrate (200 mg/d), require further study.11-13 Our patient was not aesthetically bothered by her lipomatosis; therefore, imaging and treatment options were not pursued. In conclusion, we report a patient with acquired asymmetrical lipomatosis with onset in late adulthood, unique from the existing syndromes of asymmetrical hemihyperplasia.1,14
- Enzi G, Digito M, Enzi GB, et al. Asymmetrical lipomatosis: report of two cases. Postgrad Med J. 1985;61:797-800.
- Biesecker LG, Happle R, Mulliken JB, et al. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet. 1999;84:389-395.
- Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet. 2006;14:1151-1157.
- Cohen MM Jr. Proteus syndrome: an update. Am J Med Genet C Semin Med Genet. 2005;137C:38-52.
- Biesecker LG, Peters KF, Darling TN, et al. Clinical differentiation between Proteus syndrome and hemihyperplasia: description of a distinct form of hemihyperplasia. Am J Med Genet. 1998;79:311-318.
- Luo S, Feng Y, Zheng Y, et al. Mild and delayed-onset Proteus syndrome. Eur J Dermatol. 2007;17:172-173.
- Takebayashi T, Yamashita T, Yokogushi K, et al. Scoliosis in Proteus syndrome: case report. Spine. 2001;26:E395-E398.
- Schulte TL, Liljenqvist U, Görgens H, et al. Hemihyperplasia-multiple lipomatosis syndrome (HHML): a challenge in spinal care. Acta Orthop Belg. 2008;74:714-719.
- Robin GC, Span Y, Steinberg R, et al. Scoliosis in the elderly: a follow-up study. Spine. 1982;7:355-359.
- Brea-García B, Cameselle-Teijeiro J, Couto-González I, et al. Madelung’s disease: comorbidities, fatty mass distribution, and response to treatment of 22 patients. Aesthet Plast Surg. 2013;37:409-416.
- Hasegawa T, Matsukura T, Ikeda S. Mesotherapy for benign symmetric lipomatosis. Aesthet Plast Surg. 2010;34:153-156.
- Zeitler H, Ulrich-Merzenich G, Richter DF, et al. Multiple benign symmetric lipomatosis—a differential diagnosis of obesity. is there a rationale for fibrate treatment? Obes Surg. 2008;18:1354-1356.
- Leung N, Gaer J, Beggs D, et al. Multiple symmetric lipomatosis (Launois‐Bensaude syndrome): effect of oral salbutamol. Clin Endocrinol. 1987;27:601-606.
- Craiglow BG, Ko CJ, Antaya RJ. Two cases of hemihyperplasia-multiple lipomatosis syndrome and review of asymmetric hemihyperplasia syndromes. Pediatr Dermatol. 2014;31:507-510.
- Enzi G, Digito M, Enzi GB, et al. Asymmetrical lipomatosis: report of two cases. Postgrad Med J. 1985;61:797-800.
- Biesecker LG, Happle R, Mulliken JB, et al. Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet. 1999;84:389-395.
- Biesecker L. The challenges of Proteus syndrome: diagnosis and management. Eur J Hum Genet. 2006;14:1151-1157.
- Cohen MM Jr. Proteus syndrome: an update. Am J Med Genet C Semin Med Genet. 2005;137C:38-52.
- Biesecker LG, Peters KF, Darling TN, et al. Clinical differentiation between Proteus syndrome and hemihyperplasia: description of a distinct form of hemihyperplasia. Am J Med Genet. 1998;79:311-318.
- Luo S, Feng Y, Zheng Y, et al. Mild and delayed-onset Proteus syndrome. Eur J Dermatol. 2007;17:172-173.
- Takebayashi T, Yamashita T, Yokogushi K, et al. Scoliosis in Proteus syndrome: case report. Spine. 2001;26:E395-E398.
- Schulte TL, Liljenqvist U, Görgens H, et al. Hemihyperplasia-multiple lipomatosis syndrome (HHML): a challenge in spinal care. Acta Orthop Belg. 2008;74:714-719.
- Robin GC, Span Y, Steinberg R, et al. Scoliosis in the elderly: a follow-up study. Spine. 1982;7:355-359.
- Brea-García B, Cameselle-Teijeiro J, Couto-González I, et al. Madelung’s disease: comorbidities, fatty mass distribution, and response to treatment of 22 patients. Aesthet Plast Surg. 2013;37:409-416.
- Hasegawa T, Matsukura T, Ikeda S. Mesotherapy for benign symmetric lipomatosis. Aesthet Plast Surg. 2010;34:153-156.
- Zeitler H, Ulrich-Merzenich G, Richter DF, et al. Multiple benign symmetric lipomatosis—a differential diagnosis of obesity. is there a rationale for fibrate treatment? Obes Surg. 2008;18:1354-1356.
- Leung N, Gaer J, Beggs D, et al. Multiple symmetric lipomatosis (Launois‐Bensaude syndrome): effect of oral salbutamol. Clin Endocrinol. 1987;27:601-606.
- Craiglow BG, Ko CJ, Antaya RJ. Two cases of hemihyperplasia-multiple lipomatosis syndrome and review of asymmetric hemihyperplasia syndromes. Pediatr Dermatol. 2014;31:507-510.
Practice Points
- Acquired asymmetrical lipomatosis is a rare condition that can develop at any age; it should be differentiated from existing syndromes of asymmetrical hemihyperplasia.
- Acquired asymmetrical lipomatosis is a clinical diagnosis with no laboratory changes. If the patient is clinically stable and asymptomatic, no further investigation or management is required.
DOPPS participation associated with lower HCV rates in dialysis patients
Dialysis patients are commonly infected with hepatitis C virus (HCV), and such infections are associated with increased morbidity and mortality. A team of international researchers assessed trends in the prevalence, incidence, and risk factors for HCV infection among more than 82,000 dialysis patients as defined by a documented diagnosis or antibody positivity using the Dialysis Outcomes and Practice Patterns Study.
They found that overall, among prevalent hemodialysis patients, HCV prevalence was nearly 10% during 2012-2015. The prevalence ranged from a low of 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. However, the prevalence of HCV decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had initiated dialysis within less than 4 months.
The incidence of . Although most units reported no seroconversions, 10% of units experienced three or more cases over a median of 1.1 years.
The researchers also found that high HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates.
“Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population,” wrote Michel Jadoul, MD, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, and colleagues.
Their report, sponsored by Merck, appeared in Kidney International. A number of the authors reported being speakers or consultants for a variety of pharmaceutical companies; two of the authors are employees of Merck. Support for the ongoing DOPPS Program is provided without restriction on publications.
SOURCE: Jadoul M et al. Kidney Int. 2019;95:939-47.
Dialysis patients are commonly infected with hepatitis C virus (HCV), and such infections are associated with increased morbidity and mortality. A team of international researchers assessed trends in the prevalence, incidence, and risk factors for HCV infection among more than 82,000 dialysis patients as defined by a documented diagnosis or antibody positivity using the Dialysis Outcomes and Practice Patterns Study.
They found that overall, among prevalent hemodialysis patients, HCV prevalence was nearly 10% during 2012-2015. The prevalence ranged from a low of 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. However, the prevalence of HCV decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had initiated dialysis within less than 4 months.
The incidence of . Although most units reported no seroconversions, 10% of units experienced three or more cases over a median of 1.1 years.
The researchers also found that high HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates.
“Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population,” wrote Michel Jadoul, MD, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, and colleagues.
Their report, sponsored by Merck, appeared in Kidney International. A number of the authors reported being speakers or consultants for a variety of pharmaceutical companies; two of the authors are employees of Merck. Support for the ongoing DOPPS Program is provided without restriction on publications.
SOURCE: Jadoul M et al. Kidney Int. 2019;95:939-47.
Dialysis patients are commonly infected with hepatitis C virus (HCV), and such infections are associated with increased morbidity and mortality. A team of international researchers assessed trends in the prevalence, incidence, and risk factors for HCV infection among more than 82,000 dialysis patients as defined by a documented diagnosis or antibody positivity using the Dialysis Outcomes and Practice Patterns Study.
They found that overall, among prevalent hemodialysis patients, HCV prevalence was nearly 10% during 2012-2015. The prevalence ranged from a low of 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. However, the prevalence of HCV decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had initiated dialysis within less than 4 months.
The incidence of . Although most units reported no seroconversions, 10% of units experienced three or more cases over a median of 1.1 years.
The researchers also found that high HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates.
“Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population,” wrote Michel Jadoul, MD, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, and colleagues.
Their report, sponsored by Merck, appeared in Kidney International. A number of the authors reported being speakers or consultants for a variety of pharmaceutical companies; two of the authors are employees of Merck. Support for the ongoing DOPPS Program is provided without restriction on publications.
SOURCE: Jadoul M et al. Kidney Int. 2019;95:939-47.
FROM KIDNEY INTERNATIONAL