NASHVILLE, TENN. – In patients with symptomatic vertebrobasilar disease, low distal flow measured noninvasively predicted a patient’s subsequent risk for stroke in a multicenter, prospective study of 72 patients.

The finding “has implications for investigating interventional or aggressive medical treatments,” which should be aimed at this high-risk subgroup of patients, Dr. Sepideh Amin-Hanjani said at the International Stroke Conference, sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

Patients with “the highest risk for recurrence have the best chance to benefit from intervention,” said Dr. Amin-Hanjani, professor of neurosurgery and codirector of neurovascular surgery at the University of Illinois at Chicago. For the time being, no interventions for vertebrobasilar disease have proven efficacy and safety, but the new finding provides a way to identify the highest risk patients who stand to gain the most from intervention and should serve as the target population for future trials.

The VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) trial enrolled 72 adults at any of five U.S. centers or at one in Canada. Enrolled patients had a recent stroke or transient ischemic attack in their vertebrobasilar territory plus angiographic evidence of at least 50% stenosis in an extra- or intracranial vertebral or basilar artery. All patients underwent quantitative MR angioplasty of their large vertebrobasilar arteries using software, Noninvasive Optimal Vessel Analysis (NOVA), that measures volumetric flow rates through vessels. Eighteen patients (25%) had low distal flow, defined as a greater than 20% reduction in flow, compared with normal, and 54 patients (75%) who had normal flow.

The study’s primary endpoint was an incident ischemic stroke in the vertebrobasilar territory during 12 months of follow-up. During a median follow-up of 23 months, 10 patients had this type of new stroke.

Among the 18 low-flow patients, four (22%) had a primary endpoint after 12 months, and among the 54 normal-flow patients, 2 (4%) had a primary endpoint after 12 months, a statistically significant difference, Dr. Amin-Hanjani reported at the conference.

In a multivariate analysis, low-flow at baseline linked with a significant, ninefold increased risk for incident stroke, compared with normal-flow patients. The location of the blockage – in the basilar region, vertebral region, or both – had no apparent impact on outcome.

About 30% of ischemic strokes occur in the posterior circulation, and about a third of those are caused by vertebrobasilar disease secondary to atherosclerosis. Overall patients who have had strokes of this type face a 10%-15% rate of new stroke annually despite receiving standard medical treatment, Dr. Amin-Hanjani said.

Dr. Amin-Hanjanihas received research grants from GE Healthcare and VasSol, the company that markets the NOVA software used in VERiTAS. A coauthor on the report has a significant ownership interest in VasSol.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – In patients with symptomatic vertebrobasilar disease, low distal flow measured noninvasively predicted a patient’s subsequent risk for stroke in a multicenter, prospective study of 72 patients.

The finding “has implications for investigating interventional or aggressive medical treatments,” which should be aimed at this high-risk subgroup of patients, Dr. Sepideh Amin-Hanjani said at the International Stroke Conference, sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

Patients with “the highest risk for recurrence have the best chance to benefit from intervention,” said Dr. Amin-Hanjani, professor of neurosurgery and codirector of neurovascular surgery at the University of Illinois at Chicago. For the time being, no interventions for vertebrobasilar disease have proven efficacy and safety, but the new finding provides a way to identify the highest risk patients who stand to gain the most from intervention and should serve as the target population for future trials.

The VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) trial enrolled 72 adults at any of five U.S. centers or at one in Canada. Enrolled patients had a recent stroke or transient ischemic attack in their vertebrobasilar territory plus angiographic evidence of at least 50% stenosis in an extra- or intracranial vertebral or basilar artery. All patients underwent quantitative MR angioplasty of their large vertebrobasilar arteries using software, Noninvasive Optimal Vessel Analysis (NOVA), that measures volumetric flow rates through vessels. Eighteen patients (25%) had low distal flow, defined as a greater than 20% reduction in flow, compared with normal, and 54 patients (75%) who had normal flow.

The study’s primary endpoint was an incident ischemic stroke in the vertebrobasilar territory during 12 months of follow-up. During a median follow-up of 23 months, 10 patients had this type of new stroke.

Among the 18 low-flow patients, four (22%) had a primary endpoint after 12 months, and among the 54 normal-flow patients, 2 (4%) had a primary endpoint after 12 months, a statistically significant difference, Dr. Amin-Hanjani reported at the conference.

In a multivariate analysis, low-flow at baseline linked with a significant, ninefold increased risk for incident stroke, compared with normal-flow patients. The location of the blockage – in the basilar region, vertebral region, or both – had no apparent impact on outcome.

About 30% of ischemic strokes occur in the posterior circulation, and about a third of those are caused by vertebrobasilar disease secondary to atherosclerosis. Overall patients who have had strokes of this type face a 10%-15% rate of new stroke annually despite receiving standard medical treatment, Dr. Amin-Hanjani said.

Dr. Amin-Hanjanihas received research grants from GE Healthcare and VasSol, the company that markets the NOVA software used in VERiTAS. A coauthor on the report has a significant ownership interest in VasSol.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – In patients with symptomatic vertebrobasilar disease, low distal flow measured noninvasively predicted a patient’s subsequent risk for stroke in a multicenter, prospective study of 72 patients.

The finding “has implications for investigating interventional or aggressive medical treatments,” which should be aimed at this high-risk subgroup of patients, Dr. Sepideh Amin-Hanjani said at the International Stroke Conference, sponsored by the American Heart Association.

Mitchel L. Zoler/Frontline Medical News

Patients with “the highest risk for recurrence have the best chance to benefit from intervention,” said Dr. Amin-Hanjani, professor of neurosurgery and codirector of neurovascular surgery at the University of Illinois at Chicago. For the time being, no interventions for vertebrobasilar disease have proven efficacy and safety, but the new finding provides a way to identify the highest risk patients who stand to gain the most from intervention and should serve as the target population for future trials.

The VERiTAS (Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke) trial enrolled 72 adults at any of five U.S. centers or at one in Canada. Enrolled patients had a recent stroke or transient ischemic attack in their vertebrobasilar territory plus angiographic evidence of at least 50% stenosis in an extra- or intracranial vertebral or basilar artery. All patients underwent quantitative MR angioplasty of their large vertebrobasilar arteries using software, Noninvasive Optimal Vessel Analysis (NOVA), that measures volumetric flow rates through vessels. Eighteen patients (25%) had low distal flow, defined as a greater than 20% reduction in flow, compared with normal, and 54 patients (75%) who had normal flow.

The study’s primary endpoint was an incident ischemic stroke in the vertebrobasilar territory during 12 months of follow-up. During a median follow-up of 23 months, 10 patients had this type of new stroke.

Among the 18 low-flow patients, four (22%) had a primary endpoint after 12 months, and among the 54 normal-flow patients, 2 (4%) had a primary endpoint after 12 months, a statistically significant difference, Dr. Amin-Hanjani reported at the conference.

In a multivariate analysis, low-flow at baseline linked with a significant, ninefold increased risk for incident stroke, compared with normal-flow patients. The location of the blockage – in the basilar region, vertebral region, or both – had no apparent impact on outcome.

About 30% of ischemic strokes occur in the posterior circulation, and about a third of those are caused by vertebrobasilar disease secondary to atherosclerosis. Overall patients who have had strokes of this type face a 10%-15% rate of new stroke annually despite receiving standard medical treatment, Dr. Amin-Hanjani said.

Dr. Amin-Hanjanihas received research grants from GE Healthcare and VasSol, the company that markets the NOVA software used in VERiTAS. A coauthor on the report has a significant ownership interest in VasSol.

[email protected]

On Twitter @mitchelzoler

The pathogenesis of respiratory infections such as acute otitis media (AOM), sinusitis, and pneumonia involves complex interactions among bacteria, respiratory viruses, and host immune responses.

My clinical and laboratory group and others have described respiratory infections as resulting from the growth of a single otopathogen, such as Streptococcus pneumoniae (Spn), nontypeable Haemophilus influenzae (NTHi), or Moraxella catarrhalis (Mcat) in the nasopharynx (NP) followed by ascension to the middle ear, sinuses, or descent to the lungs. Recent research from my group and others has resulted in a shift from a single pathogen focus toward consideration of respiratory infections as a polymicrobial disease. Bacterial and viral interactions are critical in respiratory infection pathogenesis. Commensal bacteria can alter virulence of bacterial pathogens and interfere with antibiotic treatment.

The traditional view of the immune system is that it is an assembly of human tissues, cells, and molecules that work to eliminate pathogens. Recent discoveries indicate that commensals play a central role in regulating human immune responses. Thus, the key questions in the field are:

1) How do members of the NP microbiome and innate immune responses maintain health in young children over time?

2) Do specific deleterious members of the NP microbiome alter host innate immune responses in a manner that predisposes to respiratory infections?

3) How does the microbiome and innate response in the NP differ when recovery, relapse of infection, or persistent infection occurs?

Virtually all young children are colonized by Spn, NTHi, or Mcat during the first 3 years of life. My group and others have shown that competitive interactions among bacteria influence whether these potential pathogens successfully colonize and cause respiratory infections. Recent studies have demonstrated that hundreds of different bacterial species colonize the upper respiratory tract. Diverse communities have been shown to be more stable and resistant to invasion by foreign species. Data from cross-sectional studies demonstrate that specific commensals, including Dolosigranulum, Corynebacterium, and Lactococcus, are associated with decreased risk of respiratory infections. Prior studies have been limited by the use of culture-based methods or have been cross sectional in design. Therefore, the optimal levels of diversity and NP commensals critical for maintaining health in the upper respiratory tract of children are currently unknown and under study by my group and others. Studies that utilize high-throughput culture-independent molecular detection methods are now used to identify optimal levels of diversity and commensal members of the microbiome critical for maintaining health homeostasis.

The innate immune system constitutes the first line of defense against respiratory pathogen colonization and respiratory virus infection. It relies on pattern recognition receptors on innate immune cells to detect evolutionarily conserved pathogen-associated molecular patterns expressed on pathogen surfaces. Toll-like receptors (TLRs) are crucial in the innate immune response; TLR 3, 7, and 8 recognize respiratory infection-associated viral pathogens. TLR2, 4, and 5 recognize respiratory infection-associated bacterial pathogens, and TLR9 and TLR13 recognize both viral and bacterial pathogens. The activation of TLRs triggers signaling cascades and regulates the expression of a wide range of cytokines leading to antimicrobial and inflammatory responses. Cytokines (there are dozens) associated with the pathogenesis, development, severity, and clinical outcomes of respiratory infections identify hypotheses that our group is exploring to expand our understanding of how innate responses might be manipulated to favor the child host. Importantly, it has already been shown that cytokine profiles differ in the NP depending on the number and type of bacteria and viruses involved.

My group recently has shown that serum IL-10 levels are significantly higher in AOM from Spn than are the levels associated with NTHi and Mcat, suggesting use of detection of this cytokine as a serum biomarker. Others have shown that the levels of IL-1-beta, TNF-alpha, IL-6, IL-8, IL-10, and IL-17a in middle ear fluids from children with recurrent AOM correlate significantly with higher bacterial load (and worse disease). Previous studies on cytokine responses associated with AOM have focused on limited numbers of cytokines and have not examined any relationship with commensals of the NP microbiome. Moreover, the subset of children who experience excessively frequent respiratory infections likely have disturbances in their microbiome (made worse with antibiotics) and innate immune response. Because of our growing knowledge about the microbiome and innate immune response, I see a compelling need to assess interactions of the NP microbiome and innate immune responses in children that are associated with sustained health and control of respiratory infections.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said the work was supported by a National Institutes of Health grant, and he had no relevant conflicts of interest. E-mail him at [email protected].

The pathogenesis of respiratory infections such as acute otitis media (AOM), sinusitis, and pneumonia involves complex interactions among bacteria, respiratory viruses, and host immune responses.

My clinical and laboratory group and others have described respiratory infections as resulting from the growth of a single otopathogen, such as Streptococcus pneumoniae (Spn), nontypeable Haemophilus influenzae (NTHi), or Moraxella catarrhalis (Mcat) in the nasopharynx (NP) followed by ascension to the middle ear, sinuses, or descent to the lungs. Recent research from my group and others has resulted in a shift from a single pathogen focus toward consideration of respiratory infections as a polymicrobial disease. Bacterial and viral interactions are critical in respiratory infection pathogenesis. Commensal bacteria can alter virulence of bacterial pathogens and interfere with antibiotic treatment.

The traditional view of the immune system is that it is an assembly of human tissues, cells, and molecules that work to eliminate pathogens. Recent discoveries indicate that commensals play a central role in regulating human immune responses. Thus, the key questions in the field are:

1) How do members of the NP microbiome and innate immune responses maintain health in young children over time?

2) Do specific deleterious members of the NP microbiome alter host innate immune responses in a manner that predisposes to respiratory infections?

3) How does the microbiome and innate response in the NP differ when recovery, relapse of infection, or persistent infection occurs?

Virtually all young children are colonized by Spn, NTHi, or Mcat during the first 3 years of life. My group and others have shown that competitive interactions among bacteria influence whether these potential pathogens successfully colonize and cause respiratory infections. Recent studies have demonstrated that hundreds of different bacterial species colonize the upper respiratory tract. Diverse communities have been shown to be more stable and resistant to invasion by foreign species. Data from cross-sectional studies demonstrate that specific commensals, including Dolosigranulum, Corynebacterium, and Lactococcus, are associated with decreased risk of respiratory infections. Prior studies have been limited by the use of culture-based methods or have been cross sectional in design. Therefore, the optimal levels of diversity and NP commensals critical for maintaining health in the upper respiratory tract of children are currently unknown and under study by my group and others. Studies that utilize high-throughput culture-independent molecular detection methods are now used to identify optimal levels of diversity and commensal members of the microbiome critical for maintaining health homeostasis.

The innate immune system constitutes the first line of defense against respiratory pathogen colonization and respiratory virus infection. It relies on pattern recognition receptors on innate immune cells to detect evolutionarily conserved pathogen-associated molecular patterns expressed on pathogen surfaces. Toll-like receptors (TLRs) are crucial in the innate immune response; TLR 3, 7, and 8 recognize respiratory infection-associated viral pathogens. TLR2, 4, and 5 recognize respiratory infection-associated bacterial pathogens, and TLR9 and TLR13 recognize both viral and bacterial pathogens. The activation of TLRs triggers signaling cascades and regulates the expression of a wide range of cytokines leading to antimicrobial and inflammatory responses. Cytokines (there are dozens) associated with the pathogenesis, development, severity, and clinical outcomes of respiratory infections identify hypotheses that our group is exploring to expand our understanding of how innate responses might be manipulated to favor the child host. Importantly, it has already been shown that cytokine profiles differ in the NP depending on the number and type of bacteria and viruses involved.

My group recently has shown that serum IL-10 levels are significantly higher in AOM from Spn than are the levels associated with NTHi and Mcat, suggesting use of detection of this cytokine as a serum biomarker. Others have shown that the levels of IL-1-beta, TNF-alpha, IL-6, IL-8, IL-10, and IL-17a in middle ear fluids from children with recurrent AOM correlate significantly with higher bacterial load (and worse disease). Previous studies on cytokine responses associated with AOM have focused on limited numbers of cytokines and have not examined any relationship with commensals of the NP microbiome. Moreover, the subset of children who experience excessively frequent respiratory infections likely have disturbances in their microbiome (made worse with antibiotics) and innate immune response. Because of our growing knowledge about the microbiome and innate immune response, I see a compelling need to assess interactions of the NP microbiome and innate immune responses in children that are associated with sustained health and control of respiratory infections.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said the work was supported by a National Institutes of Health grant, and he had no relevant conflicts of interest. E-mail him at [email protected].

The pathogenesis of respiratory infections such as acute otitis media (AOM), sinusitis, and pneumonia involves complex interactions among bacteria, respiratory viruses, and host immune responses.

My clinical and laboratory group and others have described respiratory infections as resulting from the growth of a single otopathogen, such as Streptococcus pneumoniae (Spn), nontypeable Haemophilus influenzae (NTHi), or Moraxella catarrhalis (Mcat) in the nasopharynx (NP) followed by ascension to the middle ear, sinuses, or descent to the lungs. Recent research from my group and others has resulted in a shift from a single pathogen focus toward consideration of respiratory infections as a polymicrobial disease. Bacterial and viral interactions are critical in respiratory infection pathogenesis. Commensal bacteria can alter virulence of bacterial pathogens and interfere with antibiotic treatment.

The traditional view of the immune system is that it is an assembly of human tissues, cells, and molecules that work to eliminate pathogens. Recent discoveries indicate that commensals play a central role in regulating human immune responses. Thus, the key questions in the field are:

1) How do members of the NP microbiome and innate immune responses maintain health in young children over time?

2) Do specific deleterious members of the NP microbiome alter host innate immune responses in a manner that predisposes to respiratory infections?

3) How does the microbiome and innate response in the NP differ when recovery, relapse of infection, or persistent infection occurs?

Virtually all young children are colonized by Spn, NTHi, or Mcat during the first 3 years of life. My group and others have shown that competitive interactions among bacteria influence whether these potential pathogens successfully colonize and cause respiratory infections. Recent studies have demonstrated that hundreds of different bacterial species colonize the upper respiratory tract. Diverse communities have been shown to be more stable and resistant to invasion by foreign species. Data from cross-sectional studies demonstrate that specific commensals, including Dolosigranulum, Corynebacterium, and Lactococcus, are associated with decreased risk of respiratory infections. Prior studies have been limited by the use of culture-based methods or have been cross sectional in design. Therefore, the optimal levels of diversity and NP commensals critical for maintaining health in the upper respiratory tract of children are currently unknown and under study by my group and others. Studies that utilize high-throughput culture-independent molecular detection methods are now used to identify optimal levels of diversity and commensal members of the microbiome critical for maintaining health homeostasis.

The innate immune system constitutes the first line of defense against respiratory pathogen colonization and respiratory virus infection. It relies on pattern recognition receptors on innate immune cells to detect evolutionarily conserved pathogen-associated molecular patterns expressed on pathogen surfaces. Toll-like receptors (TLRs) are crucial in the innate immune response; TLR 3, 7, and 8 recognize respiratory infection-associated viral pathogens. TLR2, 4, and 5 recognize respiratory infection-associated bacterial pathogens, and TLR9 and TLR13 recognize both viral and bacterial pathogens. The activation of TLRs triggers signaling cascades and regulates the expression of a wide range of cytokines leading to antimicrobial and inflammatory responses. Cytokines (there are dozens) associated with the pathogenesis, development, severity, and clinical outcomes of respiratory infections identify hypotheses that our group is exploring to expand our understanding of how innate responses might be manipulated to favor the child host. Importantly, it has already been shown that cytokine profiles differ in the NP depending on the number and type of bacteria and viruses involved.

My group recently has shown that serum IL-10 levels are significantly higher in AOM from Spn than are the levels associated with NTHi and Mcat, suggesting use of detection of this cytokine as a serum biomarker. Others have shown that the levels of IL-1-beta, TNF-alpha, IL-6, IL-8, IL-10, and IL-17a in middle ear fluids from children with recurrent AOM correlate significantly with higher bacterial load (and worse disease). Previous studies on cytokine responses associated with AOM have focused on limited numbers of cytokines and have not examined any relationship with commensals of the NP microbiome. Moreover, the subset of children who experience excessively frequent respiratory infections likely have disturbances in their microbiome (made worse with antibiotics) and innate immune response. Because of our growing knowledge about the microbiome and innate immune response, I see a compelling need to assess interactions of the NP microbiome and innate immune responses in children that are associated with sustained health and control of respiratory infections.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero said the work was supported by a National Institutes of Health grant, and he had no relevant conflicts of interest. E-mail him at [email protected].

Perhaps one of the biggest ways in which I’ve evolved as a doctor over the 4.5 years I’ve been in private practice is that I am not so shy about ordering tests anymore.

My point is illustrated by the case of a lovely lady I met when I was starting out in practice who complained of being in pain all the time. She was referred to me for a very low titer antinuclear antibody and a barely positive rheumatoid factor. She’d had a very long history of severe depression and anxiety. She clearly connected her symptoms to having stopped her antidepressants. She attributed her dry mouth to her benzodiazepine. I told her that I thought she had fibromyalgia and that, as she herself pointed out, it was probably related to her emotional health. We talked about the lack of any real pharmacologic treatment for the illness. We addressed self-care: that she needed to sleep better, exercise more, and treat her depression.

Three years later she came back to me with hand swelling, hypergammaglobulinemia, renal tubular acidosis, this time with significantly higher ANA and RF titers, and hypocomplementemia. You guessed it; she has Sjögren’s syndrome.

Seeing patients 40 hours a week has been incredibly challenging but also incredibly rewarding. While the large number of cases that I’ve seen has sharpened my clinical eye, it has also broadened my differential diagnoses and improved my knowledge of when it will be helpful to order more tests.

It used to be that I was extremely conservative about ordering tests. This comes from having gone to med school in the Philippines, where each test was paid for by the patient out of pocket and GDP per capita is $2,765 (compared with $53,041 for the United States) and minimum wage is less than 2 dollars a day. Every CBC has to count. If a professor asked you why you were ordering a test, “to establish a baseline” was an unacceptable reason. When I started residency here, I was incredulous that the admitted patients got a CBC and chem-7 daily. This seemed like a huge and unjustifiable waste to me.

Today, I am not so uptight. Of course, I am still extremely thoughtful about ordering tests. I do not order tests without knowing what I am looking for, or how the result will affect management. But I also recognize that there is a non-zero probability that what I suspect is fibromyalgia is something else, something with a different prognosis, better or worse, something that needs to be managed and monitored differently.

After all, “clinical judgment” does not mean relying on the history and physical exam alone. Good clinical judgment requires medical knowledge, informed by experience, supplemented by test results, and complemented by an open, inquisitive mind.

Dr. Chan practices rheumatology in Pawtucket, R.I.

Perhaps one of the biggest ways in which I’ve evolved as a doctor over the 4.5 years I’ve been in private practice is that I am not so shy about ordering tests anymore.

My point is illustrated by the case of a lovely lady I met when I was starting out in practice who complained of being in pain all the time. She was referred to me for a very low titer antinuclear antibody and a barely positive rheumatoid factor. She’d had a very long history of severe depression and anxiety. She clearly connected her symptoms to having stopped her antidepressants. She attributed her dry mouth to her benzodiazepine. I told her that I thought she had fibromyalgia and that, as she herself pointed out, it was probably related to her emotional health. We talked about the lack of any real pharmacologic treatment for the illness. We addressed self-care: that she needed to sleep better, exercise more, and treat her depression.

Three years later she came back to me with hand swelling, hypergammaglobulinemia, renal tubular acidosis, this time with significantly higher ANA and RF titers, and hypocomplementemia. You guessed it; she has Sjögren’s syndrome.

Seeing patients 40 hours a week has been incredibly challenging but also incredibly rewarding. While the large number of cases that I’ve seen has sharpened my clinical eye, it has also broadened my differential diagnoses and improved my knowledge of when it will be helpful to order more tests.

It used to be that I was extremely conservative about ordering tests. This comes from having gone to med school in the Philippines, where each test was paid for by the patient out of pocket and GDP per capita is $2,765 (compared with $53,041 for the United States) and minimum wage is less than 2 dollars a day. Every CBC has to count. If a professor asked you why you were ordering a test, “to establish a baseline” was an unacceptable reason. When I started residency here, I was incredulous that the admitted patients got a CBC and chem-7 daily. This seemed like a huge and unjustifiable waste to me.

Today, I am not so uptight. Of course, I am still extremely thoughtful about ordering tests. I do not order tests without knowing what I am looking for, or how the result will affect management. But I also recognize that there is a non-zero probability that what I suspect is fibromyalgia is something else, something with a different prognosis, better or worse, something that needs to be managed and monitored differently.

After all, “clinical judgment” does not mean relying on the history and physical exam alone. Good clinical judgment requires medical knowledge, informed by experience, supplemented by test results, and complemented by an open, inquisitive mind.

Dr. Chan practices rheumatology in Pawtucket, R.I.

Perhaps one of the biggest ways in which I’ve evolved as a doctor over the 4.5 years I’ve been in private practice is that I am not so shy about ordering tests anymore.

My point is illustrated by the case of a lovely lady I met when I was starting out in practice who complained of being in pain all the time. She was referred to me for a very low titer antinuclear antibody and a barely positive rheumatoid factor. She’d had a very long history of severe depression and anxiety. She clearly connected her symptoms to having stopped her antidepressants. She attributed her dry mouth to her benzodiazepine. I told her that I thought she had fibromyalgia and that, as she herself pointed out, it was probably related to her emotional health. We talked about the lack of any real pharmacologic treatment for the illness. We addressed self-care: that she needed to sleep better, exercise more, and treat her depression.

Three years later she came back to me with hand swelling, hypergammaglobulinemia, renal tubular acidosis, this time with significantly higher ANA and RF titers, and hypocomplementemia. You guessed it; she has Sjögren’s syndrome.

Seeing patients 40 hours a week has been incredibly challenging but also incredibly rewarding. While the large number of cases that I’ve seen has sharpened my clinical eye, it has also broadened my differential diagnoses and improved my knowledge of when it will be helpful to order more tests.

It used to be that I was extremely conservative about ordering tests. This comes from having gone to med school in the Philippines, where each test was paid for by the patient out of pocket and GDP per capita is $2,765 (compared with $53,041 for the United States) and minimum wage is less than 2 dollars a day. Every CBC has to count. If a professor asked you why you were ordering a test, “to establish a baseline” was an unacceptable reason. When I started residency here, I was incredulous that the admitted patients got a CBC and chem-7 daily. This seemed like a huge and unjustifiable waste to me.

Today, I am not so uptight. Of course, I am still extremely thoughtful about ordering tests. I do not order tests without knowing what I am looking for, or how the result will affect management. But I also recognize that there is a non-zero probability that what I suspect is fibromyalgia is something else, something with a different prognosis, better or worse, something that needs to be managed and monitored differently.

After all, “clinical judgment” does not mean relying on the history and physical exam alone. Good clinical judgment requires medical knowledge, informed by experience, supplemented by test results, and complemented by an open, inquisitive mind.

Dr. Chan practices rheumatology in Pawtucket, R.I.

A month ago, a 33-year-old woman noticed skin changes on her arms and face. The affected areas have recently begun to itch and burn—particularly, the patient notes, since she spent an extended period in the sun over the weekend. She has used an antifungal cream (nystatin) on the rash, to no avail.

The patient denies joint pain, fever, and malaise. She has a sister with multiple sclerosis, but her family history is otherwise unremarkable. The patient’s only medication is oral contraceptives, which she has taken since the birth of her first and only child last year.

EXAMINATION
The patient is afebrile and in no particular distress. A florid red rash covers both cheeks, sparing the nose entirely. The margins are somewhat indurated and redder than the clearing centers. The follicular orifices are somewhat patulous, and a fine scale covers the affected areas of the face. The lateral brachial and triceps (sun-exposed) areas of both arms are similarly affected.

Punch biopsy reveals classic signs of lupus: vacuolar alteration of the basal cell layer, perivascular infiltrate around appendicial structures, and modest epidermal atrophy. Bloodwork yields no evidence of systemic lupus erythematosus (SLE).

What is the diagnosis?

DISCUSSION
Lupus, as a general topic, can be utterly confusing. Here are some facts that might help you make sense of the subject:

Purely cutaneous forms of lupus are commonly seen in dermatology; they manifest in sun-exposed skin as scaly annular lesions with clearing centers. Somewhat confusingly, however, cases of systemic lupus erythematosus (SLE) can present with similar cutaneous signs—and furthermore, patients with purely cutaneous lupus (subacute cutaneous lupus) may exhibit some systemic symptoms (just not enough to meet the strict criteria for SLE). Lupus in general is far more common in women than in men.

The “butterfly rash” seen in this case is uncommon but can occur in either cutaneous or systemic lupus. In most cases, though, this particular rash is a manifestation of seborrhea, psoriasis, rosacea or eczema—not lupus at all.

There are, of course, many other types of lupus. Another common form is discoid lupus (DLE), which manifests with round, scaly lesions on the head, neck, or ears; these are often misidentified as actinic keratosis, eczema, or psoriasis. DLE can be localized or generalized, purely cutaneous or a manifestation of SLE.

The key to diagnosis lies in first considering lupus in the differential and then biopsying the lesion (or sending the patient to someone who will). Once the clinical diagnosis is histologically confirmed (typical results include vacuolar interface dermatitis with sparse lymphocytic perivascular infiltrate), an immunologic workup is warranted. Also, depending on the predominant organ systems involved, the patient should be thoroughly evaluated by a dermatology or rheumatology specialist (or both).

Lupus is an autoimmune process, but in some ways it’s more useful to think of it as a form of vasculitis—which is why it can affect almost any organ system. The very first lupus patient I ever saw was in the psych ward having a psychotic break, which turned out to be secondary to a lupus-induced cerebritis. Since then, I’ve seen it affect the pericardium, kidneys, lungs, and joints. Lupus is even a major item in the differential of alopecia! SLE in particular is associated with an increase in thrombotic events and accounts for most early deaths from lupus (ie, within the first five years of diagnosis, when the cause of death is usually renal or pulmonary).

The patient in this case proved to have only cutaneous disease. She’ll respond nicely to a combination of sun protection and oral antimalarials (hydroxychloroquine) but will probably have recurrences every spring. Although unlikely to ever develop SLE, she is statistically more likely to develop other autoimmune diseases.

TAKE-HOME LEARNING POINTS
• Cutaneous lupus is more common than you might imagine. Lesions and eruptions in sun-exposed skin should prompt consideration of that item in the differential.

• Many forms of lupus have been identified, including neonatal lupus and overlapping syndromes involving lupus and lichen planus or even pemphigus.

• Though UV exposure is not always the cause, almost every type of lupus is worsened by UV light exposure.

• The differential for lupus is vast but includes psoriasis, sarcoidosis, dermatomyositis, and drug eruptions.

A month ago, a 33-year-old woman noticed skin changes on her arms and face. The affected areas have recently begun to itch and burn—particularly, the patient notes, since she spent an extended period in the sun over the weekend. She has used an antifungal cream (nystatin) on the rash, to no avail.

The patient denies joint pain, fever, and malaise. She has a sister with multiple sclerosis, but her family history is otherwise unremarkable. The patient’s only medication is oral contraceptives, which she has taken since the birth of her first and only child last year.

EXAMINATION
The patient is afebrile and in no particular distress. A florid red rash covers both cheeks, sparing the nose entirely. The margins are somewhat indurated and redder than the clearing centers. The follicular orifices are somewhat patulous, and a fine scale covers the affected areas of the face. The lateral brachial and triceps (sun-exposed) areas of both arms are similarly affected.

Punch biopsy reveals classic signs of lupus: vacuolar alteration of the basal cell layer, perivascular infiltrate around appendicial structures, and modest epidermal atrophy. Bloodwork yields no evidence of systemic lupus erythematosus (SLE).

What is the diagnosis?

DISCUSSION
Lupus, as a general topic, can be utterly confusing. Here are some facts that might help you make sense of the subject:

Purely cutaneous forms of lupus are commonly seen in dermatology; they manifest in sun-exposed skin as scaly annular lesions with clearing centers. Somewhat confusingly, however, cases of systemic lupus erythematosus (SLE) can present with similar cutaneous signs—and furthermore, patients with purely cutaneous lupus (subacute cutaneous lupus) may exhibit some systemic symptoms (just not enough to meet the strict criteria for SLE). Lupus in general is far more common in women than in men.

The “butterfly rash” seen in this case is uncommon but can occur in either cutaneous or systemic lupus. In most cases, though, this particular rash is a manifestation of seborrhea, psoriasis, rosacea or eczema—not lupus at all.

There are, of course, many other types of lupus. Another common form is discoid lupus (DLE), which manifests with round, scaly lesions on the head, neck, or ears; these are often misidentified as actinic keratosis, eczema, or psoriasis. DLE can be localized or generalized, purely cutaneous or a manifestation of SLE.

The key to diagnosis lies in first considering lupus in the differential and then biopsying the lesion (or sending the patient to someone who will). Once the clinical diagnosis is histologically confirmed (typical results include vacuolar interface dermatitis with sparse lymphocytic perivascular infiltrate), an immunologic workup is warranted. Also, depending on the predominant organ systems involved, the patient should be thoroughly evaluated by a dermatology or rheumatology specialist (or both).

Lupus is an autoimmune process, but in some ways it’s more useful to think of it as a form of vasculitis—which is why it can affect almost any organ system. The very first lupus patient I ever saw was in the psych ward having a psychotic break, which turned out to be secondary to a lupus-induced cerebritis. Since then, I’ve seen it affect the pericardium, kidneys, lungs, and joints. Lupus is even a major item in the differential of alopecia! SLE in particular is associated with an increase in thrombotic events and accounts for most early deaths from lupus (ie, within the first five years of diagnosis, when the cause of death is usually renal or pulmonary).

The patient in this case proved to have only cutaneous disease. She’ll respond nicely to a combination of sun protection and oral antimalarials (hydroxychloroquine) but will probably have recurrences every spring. Although unlikely to ever develop SLE, she is statistically more likely to develop other autoimmune diseases.

TAKE-HOME LEARNING POINTS
• Cutaneous lupus is more common than you might imagine. Lesions and eruptions in sun-exposed skin should prompt consideration of that item in the differential.

• Many forms of lupus have been identified, including neonatal lupus and overlapping syndromes involving lupus and lichen planus or even pemphigus.

• Though UV exposure is not always the cause, almost every type of lupus is worsened by UV light exposure.

• The differential for lupus is vast but includes psoriasis, sarcoidosis, dermatomyositis, and drug eruptions.

A month ago, a 33-year-old woman noticed skin changes on her arms and face. The affected areas have recently begun to itch and burn—particularly, the patient notes, since she spent an extended period in the sun over the weekend. She has used an antifungal cream (nystatin) on the rash, to no avail.

The patient denies joint pain, fever, and malaise. She has a sister with multiple sclerosis, but her family history is otherwise unremarkable. The patient’s only medication is oral contraceptives, which she has taken since the birth of her first and only child last year.

EXAMINATION
The patient is afebrile and in no particular distress. A florid red rash covers both cheeks, sparing the nose entirely. The margins are somewhat indurated and redder than the clearing centers. The follicular orifices are somewhat patulous, and a fine scale covers the affected areas of the face. The lateral brachial and triceps (sun-exposed) areas of both arms are similarly affected.

Punch biopsy reveals classic signs of lupus: vacuolar alteration of the basal cell layer, perivascular infiltrate around appendicial structures, and modest epidermal atrophy. Bloodwork yields no evidence of systemic lupus erythematosus (SLE).

What is the diagnosis?

DISCUSSION
Lupus, as a general topic, can be utterly confusing. Here are some facts that might help you make sense of the subject:

Purely cutaneous forms of lupus are commonly seen in dermatology; they manifest in sun-exposed skin as scaly annular lesions with clearing centers. Somewhat confusingly, however, cases of systemic lupus erythematosus (SLE) can present with similar cutaneous signs—and furthermore, patients with purely cutaneous lupus (subacute cutaneous lupus) may exhibit some systemic symptoms (just not enough to meet the strict criteria for SLE). Lupus in general is far more common in women than in men.

The “butterfly rash” seen in this case is uncommon but can occur in either cutaneous or systemic lupus. In most cases, though, this particular rash is a manifestation of seborrhea, psoriasis, rosacea or eczema—not lupus at all.

There are, of course, many other types of lupus. Another common form is discoid lupus (DLE), which manifests with round, scaly lesions on the head, neck, or ears; these are often misidentified as actinic keratosis, eczema, or psoriasis. DLE can be localized or generalized, purely cutaneous or a manifestation of SLE.

The key to diagnosis lies in first considering lupus in the differential and then biopsying the lesion (or sending the patient to someone who will). Once the clinical diagnosis is histologically confirmed (typical results include vacuolar interface dermatitis with sparse lymphocytic perivascular infiltrate), an immunologic workup is warranted. Also, depending on the predominant organ systems involved, the patient should be thoroughly evaluated by a dermatology or rheumatology specialist (or both).

Lupus is an autoimmune process, but in some ways it’s more useful to think of it as a form of vasculitis—which is why it can affect almost any organ system. The very first lupus patient I ever saw was in the psych ward having a psychotic break, which turned out to be secondary to a lupus-induced cerebritis. Since then, I’ve seen it affect the pericardium, kidneys, lungs, and joints. Lupus is even a major item in the differential of alopecia! SLE in particular is associated with an increase in thrombotic events and accounts for most early deaths from lupus (ie, within the first five years of diagnosis, when the cause of death is usually renal or pulmonary).

The patient in this case proved to have only cutaneous disease. She’ll respond nicely to a combination of sun protection and oral antimalarials (hydroxychloroquine) but will probably have recurrences every spring. Although unlikely to ever develop SLE, she is statistically more likely to develop other autoimmune diseases.

TAKE-HOME LEARNING POINTS
• Cutaneous lupus is more common than you might imagine. Lesions and eruptions in sun-exposed skin should prompt consideration of that item in the differential.

• Many forms of lupus have been identified, including neonatal lupus and overlapping syndromes involving lupus and lichen planus or even pemphigus.

• Though UV exposure is not always the cause, almost every type of lupus is worsened by UV light exposure.

• The differential for lupus is vast but includes psoriasis, sarcoidosis, dermatomyositis, and drug eruptions.

NASHVILLE, TENN. – By 2010, U.S. octogenarians with acute ischemic stroke received intravenous thrombolytic treatment about as often as younger patients, showing that a sharp, age-related disparity in thrombolytic use a decade before had disappeared, based on comprehensive national data.

The 2010 data from the Nationwide Inpatient Sample further showed that the sex-based disparity in treatment with intravenous tissue plasminogen activator (TPA) seen in 2000 resolved as well from 2000 to 2010, but other disparities worsened with declines during the period in use of TPA at rural hospitals relative to urban hospitals and at nonteaching hospitals, compared with teaching hospitals, Dr. Michelle P. Lin said at the International Stroke Conference.

Perhaps most importantly, the statistics showed a “dramatic” increase in TPA use among all age groups during the decade ending in 2010, when thrombolytic therapy was administered to 3.5%-3.9% of adult patients regardless of their age, said Dr. Lin of the department of neurology at the University of Southern California in Los Angeles. In 2000, U.S. patients received TPA at less than a third of that rate.

Low TPA use in 2000 among patients aged 80 or older in part reflected the low number of octogenarians enrolled in the trials that documented the safety and efficacy of TPA for acute ischemicstroke patients, Dr. Lin said at the International Stroke Conference, sponsored by the American Heart Association.

Data from the National Inpatient Sample included information on the treatment received by 5,932,175 patients with acute ischemic stroke at more than 1,000 U.S. hospitals during 2000-2010. The age breakdown of the nearly 6 millionpatients showed 28% were aged 18-64 years, 37% were65-79, and 35% were 80 years or older.

In 2000, medical staffs administered intravenous treatment with TPA to 1.02% of these patients aged 18-64 years, 0.92% of patients aged 65-79 years, and 0.47% of patients aged 80 or older. By 2010, the annual rates of TPA use ran 3.61% in those 18-64 years, 3.87% among those 65-79 years, and 3.55% in patients 80 years or older. In an adjusted analysis, this translated into a greater than threefold increase in TPA use among the 18- to 64-year-olds, a nearly fourfold rise in patients 65-79 years, and a nearly sevenfold jump among those 80 or older, a 24% average annual increased rate among the oldest patients, who averaged 86 years old, Dr. Lin reported.

The data also showed that among the octogenarians during 2000-2005, TPA use in women lagged behind use in men by a relative 15%, but this completely disappeared during 2006-2010, when usage rates in men and women evened out. TPA use among African Americans, Hispanics, and Asians, compared with whites, remained significantly below the rate in whites throughout the decade, although the extent of the disparity narrowed for African Americans and Asians during the second half of the decade, compared with the first half.

Dr. Lin and her associates also analyzed TPA use relative to the demographic setting of the hospital and its teaching status. During 2000-2010, the relative usage of TPA at rural hospitals, compared with urban hospitals, fell from 65% of the comparator level to 36%. Among nonteaching hospitals, the rate of TPA use dropped from 52% of the teaching hospitals’ level to 49%.

Dr. Lin said she had no relevant financial disclosures.

[email protected]
On Twitter @mitchelzoler

NASHVILLE, TENN. – By 2010, U.S. octogenarians with acute ischemic stroke received intravenous thrombolytic treatment about as often as younger patients, showing that a sharp, age-related disparity in thrombolytic use a decade before had disappeared, based on comprehensive national data.

The 2010 data from the Nationwide Inpatient Sample further showed that the sex-based disparity in treatment with intravenous tissue plasminogen activator (TPA) seen in 2000 resolved as well from 2000 to 2010, but other disparities worsened with declines during the period in use of TPA at rural hospitals relative to urban hospitals and at nonteaching hospitals, compared with teaching hospitals, Dr. Michelle P. Lin said at the International Stroke Conference.

Perhaps most importantly, the statistics showed a “dramatic” increase in TPA use among all age groups during the decade ending in 2010, when thrombolytic therapy was administered to 3.5%-3.9% of adult patients regardless of their age, said Dr. Lin of the department of neurology at the University of Southern California in Los Angeles. In 2000, U.S. patients received TPA at less than a third of that rate.

Low TPA use in 2000 among patients aged 80 or older in part reflected the low number of octogenarians enrolled in the trials that documented the safety and efficacy of TPA for acute ischemicstroke patients, Dr. Lin said at the International Stroke Conference, sponsored by the American Heart Association.

Data from the National Inpatient Sample included information on the treatment received by 5,932,175 patients with acute ischemic stroke at more than 1,000 U.S. hospitals during 2000-2010. The age breakdown of the nearly 6 millionpatients showed 28% were aged 18-64 years, 37% were65-79, and 35% were 80 years or older.

In 2000, medical staffs administered intravenous treatment with TPA to 1.02% of these patients aged 18-64 years, 0.92% of patients aged 65-79 years, and 0.47% of patients aged 80 or older. By 2010, the annual rates of TPA use ran 3.61% in those 18-64 years, 3.87% among those 65-79 years, and 3.55% in patients 80 years or older. In an adjusted analysis, this translated into a greater than threefold increase in TPA use among the 18- to 64-year-olds, a nearly fourfold rise in patients 65-79 years, and a nearly sevenfold jump among those 80 or older, a 24% average annual increased rate among the oldest patients, who averaged 86 years old, Dr. Lin reported.

The data also showed that among the octogenarians during 2000-2005, TPA use in women lagged behind use in men by a relative 15%, but this completely disappeared during 2006-2010, when usage rates in men and women evened out. TPA use among African Americans, Hispanics, and Asians, compared with whites, remained significantly below the rate in whites throughout the decade, although the extent of the disparity narrowed for African Americans and Asians during the second half of the decade, compared with the first half.

Dr. Lin and her associates also analyzed TPA use relative to the demographic setting of the hospital and its teaching status. During 2000-2010, the relative usage of TPA at rural hospitals, compared with urban hospitals, fell from 65% of the comparator level to 36%. Among nonteaching hospitals, the rate of TPA use dropped from 52% of the teaching hospitals’ level to 49%.

Dr. Lin said she had no relevant financial disclosures.

[email protected]
On Twitter @mitchelzoler

NASHVILLE, TENN. – By 2010, U.S. octogenarians with acute ischemic stroke received intravenous thrombolytic treatment about as often as younger patients, showing that a sharp, age-related disparity in thrombolytic use a decade before had disappeared, based on comprehensive national data.

The 2010 data from the Nationwide Inpatient Sample further showed that the sex-based disparity in treatment with intravenous tissue plasminogen activator (TPA) seen in 2000 resolved as well from 2000 to 2010, but other disparities worsened with declines during the period in use of TPA at rural hospitals relative to urban hospitals and at nonteaching hospitals, compared with teaching hospitals, Dr. Michelle P. Lin said at the International Stroke Conference.

Perhaps most importantly, the statistics showed a “dramatic” increase in TPA use among all age groups during the decade ending in 2010, when thrombolytic therapy was administered to 3.5%-3.9% of adult patients regardless of their age, said Dr. Lin of the department of neurology at the University of Southern California in Los Angeles. In 2000, U.S. patients received TPA at less than a third of that rate.

Low TPA use in 2000 among patients aged 80 or older in part reflected the low number of octogenarians enrolled in the trials that documented the safety and efficacy of TPA for acute ischemicstroke patients, Dr. Lin said at the International Stroke Conference, sponsored by the American Heart Association.

Data from the National Inpatient Sample included information on the treatment received by 5,932,175 patients with acute ischemic stroke at more than 1,000 U.S. hospitals during 2000-2010. The age breakdown of the nearly 6 millionpatients showed 28% were aged 18-64 years, 37% were65-79, and 35% were 80 years or older.

In 2000, medical staffs administered intravenous treatment with TPA to 1.02% of these patients aged 18-64 years, 0.92% of patients aged 65-79 years, and 0.47% of patients aged 80 or older. By 2010, the annual rates of TPA use ran 3.61% in those 18-64 years, 3.87% among those 65-79 years, and 3.55% in patients 80 years or older. In an adjusted analysis, this translated into a greater than threefold increase in TPA use among the 18- to 64-year-olds, a nearly fourfold rise in patients 65-79 years, and a nearly sevenfold jump among those 80 or older, a 24% average annual increased rate among the oldest patients, who averaged 86 years old, Dr. Lin reported.

The data also showed that among the octogenarians during 2000-2005, TPA use in women lagged behind use in men by a relative 15%, but this completely disappeared during 2006-2010, when usage rates in men and women evened out. TPA use among African Americans, Hispanics, and Asians, compared with whites, remained significantly below the rate in whites throughout the decade, although the extent of the disparity narrowed for African Americans and Asians during the second half of the decade, compared with the first half.

Dr. Lin and her associates also analyzed TPA use relative to the demographic setting of the hospital and its teaching status. During 2000-2010, the relative usage of TPA at rural hospitals, compared with urban hospitals, fell from 65% of the comparator level to 36%. Among nonteaching hospitals, the rate of TPA use dropped from 52% of the teaching hospitals’ level to 49%.

Dr. Lin said she had no relevant financial disclosures.

[email protected]
On Twitter @mitchelzoler

For patients with secondary acute myeloid leukemia, induction therapy with cytarabine in combination with amonafide L-malate did not improve complete remission rates over the standard treatment of cytarabine and daunorubicin, investigators reported online March 2 in the Journal of Clinical Oncology.

Between January 2008 and August 2010, 433 patients with previously untreated secondary AML were randomly assigned to receive an intravenous infusion of cytarabine once per day for 7 days, plus either amonafide or daunorubicin for 4 days. The complete remission rate was 46% in the amonafide-plus-cytarabine group and 45% in the daunorubicin-plus-cytarabine group (P = .81), reported Dr. Richard M. Stone of Dana-Farber Cancer Institute, Boston, and associates.

“Although amonafide does not seem to provide benefit over standard induction therapy with daunorubicin, analyses of the data from this clinical trial may provide critical background information for tests of subsequent drugs that may have promise in this important disease subgroup, such as the liposomal-encapsulated daunorubicin/cytarabine CPX-351, the nuclear export inhibitor KPT-330, or the BCL-2 antagonist ABT-199,” they concluded.

Read the complete article here: (doi:10.1200/JCO.2014.57.0952).

For patients with secondary acute myeloid leukemia, induction therapy with cytarabine in combination with amonafide L-malate did not improve complete remission rates over the standard treatment of cytarabine and daunorubicin, investigators reported online March 2 in the Journal of Clinical Oncology.

Between January 2008 and August 2010, 433 patients with previously untreated secondary AML were randomly assigned to receive an intravenous infusion of cytarabine once per day for 7 days, plus either amonafide or daunorubicin for 4 days. The complete remission rate was 46% in the amonafide-plus-cytarabine group and 45% in the daunorubicin-plus-cytarabine group (P = .81), reported Dr. Richard M. Stone of Dana-Farber Cancer Institute, Boston, and associates.

“Although amonafide does not seem to provide benefit over standard induction therapy with daunorubicin, analyses of the data from this clinical trial may provide critical background information for tests of subsequent drugs that may have promise in this important disease subgroup, such as the liposomal-encapsulated daunorubicin/cytarabine CPX-351, the nuclear export inhibitor KPT-330, or the BCL-2 antagonist ABT-199,” they concluded.

Read the complete article here: (doi:10.1200/JCO.2014.57.0952).

For patients with secondary acute myeloid leukemia, induction therapy with cytarabine in combination with amonafide L-malate did not improve complete remission rates over the standard treatment of cytarabine and daunorubicin, investigators reported online March 2 in the Journal of Clinical Oncology.

Between January 2008 and August 2010, 433 patients with previously untreated secondary AML were randomly assigned to receive an intravenous infusion of cytarabine once per day for 7 days, plus either amonafide or daunorubicin for 4 days. The complete remission rate was 46% in the amonafide-plus-cytarabine group and 45% in the daunorubicin-plus-cytarabine group (P = .81), reported Dr. Richard M. Stone of Dana-Farber Cancer Institute, Boston, and associates.

“Although amonafide does not seem to provide benefit over standard induction therapy with daunorubicin, analyses of the data from this clinical trial may provide critical background information for tests of subsequent drugs that may have promise in this important disease subgroup, such as the liposomal-encapsulated daunorubicin/cytarabine CPX-351, the nuclear export inhibitor KPT-330, or the BCL-2 antagonist ABT-199,” they concluded.

Read the complete article here: (doi:10.1200/JCO.2014.57.0952).

NASHVILLE, TENN. – When acute ischemic stroke patients undergo an emergency endovascular procedure is it best done with general anesthesia or nongeneral anesthesia?

A post hoc analysis of data collected by a Dutch randomized, controlled trial of intra-arterial therapy suggested that nongeneral anesthesia was associated with substantially better patient outcomes, and the findings convinced the Dutch investigators who ran the study to stick with nongeneral anesthesia as their default approach.

In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) (N. Engl. J. Med. 2015;372:11-20), 216 acute ischemic stroke patients underwent intra-arterial treatment following randomization. Among these patients, 79 were treated with general anesthesia and 137 with nongeneral anesthesia. The anesthesia choice was made on a case-by-case basis by each participating interventionalist.

The study’s primary endpoint – 90-day status rated as a good function based on a modified Rankin sale score of 0-2 – occurred in 38% of the intra-arterial patients treated with nongeneral anesthesia, 23% of the intra-arterial patients treated with general anesthesia, and 19% among the control patients who received standard treatment without intra-arterial intervention.

Mitchel L. Zoler/Frontline Medical News

“The effect on outcome that we found with intra-arterial treatment in MR CLEAN was not observed in the subgroup of patients treated with general anesthesia,” said Dr. Olvert A. Berkhemer at the International Stroke Conference. The analysis also showed that patients in the general and nongeneral anesthesia subgroups had similar stroke severity as measured by their National Institutes of Health Stroke Scale score, said Dr. Berkhemer, a researcher at the Academic Medical Center in Amsterdam.

But U.S. stroke specialists who heard the report cautioned that unidentified confounders might explain the results, and they also expressed skepticism that the Dutch observations would deter U.S. interventionalists from continuing to use general anesthesia when they perform endovascular procedures.

“The big concern [about this analysis] is that there may have been some things about the general anesthesia patients that they did not account for. I suspect there is a huge bias, that general anesthesia patients were sicker,” said Dr. Bruce Ovbiagele, professor and chief of neurology at the Medical University of South Carolina in Charleston. “At my institution they have used nongeneral anesthesia, but I have been at other places where they usually use general anesthesia; it is variable,” Dr. Ovbiagele added.

Mitchel L. Zoler/Frontline Medical News

Dr. Berkhemer’s analysis also showed that general anesthesia linked with a delayed start to treatment, but without resulting in a significant difference in time to reperfusion. He noted that “sometimes you cannot do the procedure without general anesthesia,” and in MR CLEAN 6 of the 137 intra-arterial patients who started with nongeneral anesthesia eventually received general anesthesia because of discomfort and pain, Dr. Berkhemer said at the conference, sponsored by the American Heart Association.

He speculated that patients who did not receive general anesthesia did better because they did not undergo acute episodes of reduced blood pressure caused by the hypotensive effect of general anesthesia.

Mitchel L. Zoler/Frontline Medical News

The findings reinforced the approach already used in most of the Dutch centers that participated in MR CLEAN, where nongeneral anesthesia is preferred when possible. “In our center we always use nongeneral anesthesia, we are happy with that and we are not going to change,” said Dr. Diederik W.J. Dippel, lead investigator of MR CLEAN and professor of neurology at Erasmus University Medical Center in Rotterdam, The Netherlands. This prejudice against general anesthesia would make it hard to run a trial in The Netherlands that matched the two anesthesia approaches against each other, Dr. Dippel added.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – When acute ischemic stroke patients undergo an emergency endovascular procedure is it best done with general anesthesia or nongeneral anesthesia?

A post hoc analysis of data collected by a Dutch randomized, controlled trial of intra-arterial therapy suggested that nongeneral anesthesia was associated with substantially better patient outcomes, and the findings convinced the Dutch investigators who ran the study to stick with nongeneral anesthesia as their default approach.

In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) (N. Engl. J. Med. 2015;372:11-20), 216 acute ischemic stroke patients underwent intra-arterial treatment following randomization. Among these patients, 79 were treated with general anesthesia and 137 with nongeneral anesthesia. The anesthesia choice was made on a case-by-case basis by each participating interventionalist.

The study’s primary endpoint – 90-day status rated as a good function based on a modified Rankin sale score of 0-2 – occurred in 38% of the intra-arterial patients treated with nongeneral anesthesia, 23% of the intra-arterial patients treated with general anesthesia, and 19% among the control patients who received standard treatment without intra-arterial intervention.

Mitchel L. Zoler/Frontline Medical News

“The effect on outcome that we found with intra-arterial treatment in MR CLEAN was not observed in the subgroup of patients treated with general anesthesia,” said Dr. Olvert A. Berkhemer at the International Stroke Conference. The analysis also showed that patients in the general and nongeneral anesthesia subgroups had similar stroke severity as measured by their National Institutes of Health Stroke Scale score, said Dr. Berkhemer, a researcher at the Academic Medical Center in Amsterdam.

But U.S. stroke specialists who heard the report cautioned that unidentified confounders might explain the results, and they also expressed skepticism that the Dutch observations would deter U.S. interventionalists from continuing to use general anesthesia when they perform endovascular procedures.

“The big concern [about this analysis] is that there may have been some things about the general anesthesia patients that they did not account for. I suspect there is a huge bias, that general anesthesia patients were sicker,” said Dr. Bruce Ovbiagele, professor and chief of neurology at the Medical University of South Carolina in Charleston. “At my institution they have used nongeneral anesthesia, but I have been at other places where they usually use general anesthesia; it is variable,” Dr. Ovbiagele added.

Mitchel L. Zoler/Frontline Medical News

Dr. Berkhemer’s analysis also showed that general anesthesia linked with a delayed start to treatment, but without resulting in a significant difference in time to reperfusion. He noted that “sometimes you cannot do the procedure without general anesthesia,” and in MR CLEAN 6 of the 137 intra-arterial patients who started with nongeneral anesthesia eventually received general anesthesia because of discomfort and pain, Dr. Berkhemer said at the conference, sponsored by the American Heart Association.

He speculated that patients who did not receive general anesthesia did better because they did not undergo acute episodes of reduced blood pressure caused by the hypotensive effect of general anesthesia.

Mitchel L. Zoler/Frontline Medical News

The findings reinforced the approach already used in most of the Dutch centers that participated in MR CLEAN, where nongeneral anesthesia is preferred when possible. “In our center we always use nongeneral anesthesia, we are happy with that and we are not going to change,” said Dr. Diederik W.J. Dippel, lead investigator of MR CLEAN and professor of neurology at Erasmus University Medical Center in Rotterdam, The Netherlands. This prejudice against general anesthesia would make it hard to run a trial in The Netherlands that matched the two anesthesia approaches against each other, Dr. Dippel added.

[email protected]

On Twitter @mitchelzoler

NASHVILLE, TENN. – When acute ischemic stroke patients undergo an emergency endovascular procedure is it best done with general anesthesia or nongeneral anesthesia?

A post hoc analysis of data collected by a Dutch randomized, controlled trial of intra-arterial therapy suggested that nongeneral anesthesia was associated with substantially better patient outcomes, and the findings convinced the Dutch investigators who ran the study to stick with nongeneral anesthesia as their default approach.

In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) (N. Engl. J. Med. 2015;372:11-20), 216 acute ischemic stroke patients underwent intra-arterial treatment following randomization. Among these patients, 79 were treated with general anesthesia and 137 with nongeneral anesthesia. The anesthesia choice was made on a case-by-case basis by each participating interventionalist.

The study’s primary endpoint – 90-day status rated as a good function based on a modified Rankin sale score of 0-2 – occurred in 38% of the intra-arterial patients treated with nongeneral anesthesia, 23% of the intra-arterial patients treated with general anesthesia, and 19% among the control patients who received standard treatment without intra-arterial intervention.

Mitchel L. Zoler/Frontline Medical News

“The effect on outcome that we found with intra-arterial treatment in MR CLEAN was not observed in the subgroup of patients treated with general anesthesia,” said Dr. Olvert A. Berkhemer at the International Stroke Conference. The analysis also showed that patients in the general and nongeneral anesthesia subgroups had similar stroke severity as measured by their National Institutes of Health Stroke Scale score, said Dr. Berkhemer, a researcher at the Academic Medical Center in Amsterdam.

But U.S. stroke specialists who heard the report cautioned that unidentified confounders might explain the results, and they also expressed skepticism that the Dutch observations would deter U.S. interventionalists from continuing to use general anesthesia when they perform endovascular procedures.

“The big concern [about this analysis] is that there may have been some things about the general anesthesia patients that they did not account for. I suspect there is a huge bias, that general anesthesia patients were sicker,” said Dr. Bruce Ovbiagele, professor and chief of neurology at the Medical University of South Carolina in Charleston. “At my institution they have used nongeneral anesthesia, but I have been at other places where they usually use general anesthesia; it is variable,” Dr. Ovbiagele added.

Mitchel L. Zoler/Frontline Medical News

Dr. Berkhemer’s analysis also showed that general anesthesia linked with a delayed start to treatment, but without resulting in a significant difference in time to reperfusion. He noted that “sometimes you cannot do the procedure without general anesthesia,” and in MR CLEAN 6 of the 137 intra-arterial patients who started with nongeneral anesthesia eventually received general anesthesia because of discomfort and pain, Dr. Berkhemer said at the conference, sponsored by the American Heart Association.

He speculated that patients who did not receive general anesthesia did better because they did not undergo acute episodes of reduced blood pressure caused by the hypotensive effect of general anesthesia.

Mitchel L. Zoler/Frontline Medical News

The findings reinforced the approach already used in most of the Dutch centers that participated in MR CLEAN, where nongeneral anesthesia is preferred when possible. “In our center we always use nongeneral anesthesia, we are happy with that and we are not going to change,” said Dr. Diederik W.J. Dippel, lead investigator of MR CLEAN and professor of neurology at Erasmus University Medical Center in Rotterdam, The Netherlands. This prejudice against general anesthesia would make it hard to run a trial in The Netherlands that matched the two anesthesia approaches against each other, Dr. Dippel added.

[email protected]

On Twitter @mitchelzoler

DAVID PRESSEL, MD, PHD, FHM, medical director of inpatient services at Nemours Children’s Health System, talks about the nature of violence in hospitals and a training program he has helped put into place at his center.

DAVID PRESSEL, MD, PHD, FHM, medical director of inpatient services at Nemours Children’s Health System, talks about the nature of violence in hospitals and a training program he has helped put into place at his center.

DAVID PRESSEL, MD, PHD, FHM, medical director of inpatient services at Nemours Children’s Health System, talks about the nature of violence in hospitals and a training program he has helped put into place at his center.

DAVID LICHTMAN, PA, a hospitalist and director of the Johns Hopkins Central Procedure Service, explains the complicated set of factors used by

individual hospitals to determine which procedures fall under the scope of their HM practitioners.

DAVID LICHTMAN, PA, a hospitalist and director of the Johns Hopkins Central Procedure Service, explains the complicated set of factors used by

individual hospitals to determine which procedures fall under the scope of their HM practitioners.

DAVID LICHTMAN, PA, a hospitalist and director of the Johns Hopkins Central Procedure Service, explains the complicated set of factors used by

individual hospitals to determine which procedures fall under the scope of their HM practitioners.

Although patients with blood clots are oftentimes not admitted to the hospital, there are some exceptions. Monal Shah, MD, physician advisor for Parkland Hospital in Dallas, Texas, and the former section head of hospital medicine at the University of Texas Southwestern Medical Center, discusses some exceptions.

Although patients with blood clots are oftentimes not admitted to the hospital, there are some exceptions. Monal Shah, MD, physician advisor for Parkland Hospital in Dallas, Texas, and the former section head of hospital medicine at the University of Texas Southwestern Medical Center, discusses some exceptions.

Although patients with blood clots are oftentimes not admitted to the hospital, there are some exceptions. Monal Shah, MD, physician advisor for Parkland Hospital in Dallas, Texas, and the former section head of hospital medicine at the University of Texas Southwestern Medical Center, discusses some exceptions.