Research Briefs The Potential Dangers of Treating “Chronic Lyme Disease”
“Chronic Lyme disease” is sometimes a catchall diagnosis for patients with a wide spectrum of musculoskeletal and neuropsychiatric symptoms, fatigue, and generalized pain. And that, in turn, has led to a variety of treatments: courses of antibiotics lasting for months to years, intravenous (IV) infusions of hydrogen peroxide, immunoglobulin therapy, and even stem cell transplants. Those treatments, though, may not lead to substantial long-term improvement—in fact, they can be downright harmful. Clinicians, health departments, and patients have all contacted the Centers for Disease Control and Prevention with reports of life-threatening complications resulting from treatment for chronic Lyme disease, including metastatic bacterial infections, septic shock, Clostridium difficile colitis, and abscesses. Morbidity and Mortality Weekly Report (MMWR) describes five cases that “highlight the severity and scope” of adverse effects caused by the use of unproven treatments for chronic Lyme disease. One patient with fatigue and joint pain, for instance, was diagnosed with chronic Lyme disease, babesiosis, and Bartonella infection. When her symptoms worsened despite multiple courses of oral antibiotics, she was switched to IV ceftriaxone and cefotaxime. However, the pain did not lessen; she became hypotensive and tachycardic, and was placed in intensive care. Her condition continued to worsen, and she died. Her death was attributed to septic shock related to central venous catheter-associated bacteremia. In another case, a woman was first diagnosed with amyotrophic lateral sclerosis (ALS), then, as a second opinion, with chronic Lyme disease. After seven months of intensive anti microbial treatment, the pain improved, but she got weaker. She also developed intractable C. difficile infection that required prolonged treatment. However, she died of complications of ALS—an example, the researchers say, of a missed opportunity for appropriate treatment due to misdiagnosis. Antibiotics and immunoglobulin therapies are effective and necessary treatments for many conditions, MMWR emphasizes—“however, unnecessary antibiotic and immunoglobulin use provides no benefit to patients while putting them at risk for adverse events.” Source: MMWR, June 2017
Calculating the Risk of Parkinson’s-Related Cognitive Deficits Current treatments for Parkinson’s disease are only effective in improving motor deficits, but the loss of cognitive abilities is just as devastating. Approximately 25% of patients also experience cognitive deficits that impair function. One problem in developing treatments, however, is that patients with cognitive effects vary widely. Being able to predict the
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chance that someone with Parkinson’s will develop cognitive deficits could be a useful tool, researchers from Brigham and Women’s Hospital say. And they think they might have created just the thing: a computer-based risk calculator. The researchers combined data from 3,200 patients with Parkinson’s disease, representing more than 25,000 individual clinical assessments. They evaluated seven known clinical and genetic risk factors associated with developing dementia, and then used the information to build the risk calculator. “By allowing clinical researchers to identify and select only patients at high risk for developing dementia, this tool could help in the design of ‘smarter’ trials that require a manageable number of participating patients,” says Clemens Scherzer, MD, the lead investigator. By improving clinical trial design, the risk calculator could help in the discovery of new treatments, the researchers say, and then help determine which patients would most benefit from those treatments. Source: National Institutes of Health, June 2017
Which AML Patients Are Good Candidates for Immunotherapy? Some patients with acute myeloid leukemia (AML) may have trouble with immunotherapy after chemotherapy, researchers say, and they think they’ve found one reason why. The team wanted to perform a “deep assessment” of the state of the adaptive immune system in AML patients in remission after chemotherapy. They used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system. They say their approach was unique in that they established a comprehensive picture of the adaptive “immunome” by simultaneously examining the genetic, phenotypic, and functional consequences of chemotherapy. Their assessment revealed a “dramatic impact” in the B-cell compartment, which appeared slower to recover than the T-cell compartment. Of 10 patients in the study, only two generated protective titers in response to vaccination. Most had abnormal frequencies of transitional and memory B cells. The researchers say the inability of AML patients to produce protective antibody titers in response to influenza vaccination is likely due to multiple B-cell abnormalities. They found similar patterns across all of the patients. When they ranked patients based on time elapsed since chemotherapy, the degree of dysfunction was lesser in patients who were farther away from chemotherapy. The “consistent finding” of a reduction of memory B cells in all the AML patients suggests that humoral immunity reconstitution is “a very long process.” The researchers say that a better understanding of the changes in adaptive immune cell subsets after chemotherapy will be useful in designing immunotherapies that can work with existing immune capacity. Source: Journal of Translational Medicine, July 2017
Research Briefs Legionnaires’ Disease in Health Care Settings
Investigation by the Centers for Disease Control and Prevention (CDC) of 27 outbreaks of Legionnaires’ disease between 2000 and 2014 found health-care–associated Legionnaires’ disease accounted for 33% of the outbreaks, 57% of outbreak-associated cases, and 85% of outbreakassociated deaths. Nearly all were attributed to water system exposures that could have been prevented by effective water management programs. CDC researchers analyzed 2015 surveillance data from 20 states and the New York City metropolitan area that reported more than 90% of confirmed legionellosis cases to the Supplemental Legionnaires’ Disease Surveillance System. Of 2,809 cases, 553 were health-care–associated. Definite cases accounted for 3%, and possible cases accounted for 17% of all of the cases reported. Although only a small percentage was definitely related to health care settings, the fatality rate was high at 12%. Of the 85 definite health-care–associated Legionnaires’ disease cases, 80% were associated with long-term-care facilities. Of the 468 possible cases, 13% were “possibly” associated with long-term-care facilities, 49% with hospitals, and 26% with clinics. The CDC says the number of definite cases and facilities reported is “likely an underestimate,” in part because of a lack of Legionella-specific testing. Another explanation is that hospital stays are typically shorter than the 10-day period used in the analysis. One-fourth of patients with definite health-care–associated Legionnaires’ disease die. Health care providers play a critical role in prevention and response, the CDC says, by rapidly identifying and reporting cases. Legionnaires’ disease is “clinically indistinguishable” from other causes of pneumonia, the researchers note. The preferred diagnostic method is to concurrently obtain a lower respiratory sputum sample for culture on selective media and a Legionella urinary antigen test. In health care facilities, the researchers say, “prevention of the first case of Legionnaires’ disease is the ultimate goal.” The best way to do that, they advise, is to have an effective water management program. Source: Morbidity and Mortality Weekly Report, June 2017
How Well Does Metabolic Syndrome Predict Prognosis in STEMI? Metabolic syndrome (MetS) is common among patients with coronary artery disease (CAD) and highly prevalent in those with acute ST-elevation myocardial infarction (STEMI). But are all elements of MetS equally good predictors of clinical severity and prognosis? To find out, researchers from Sestre Milosrdnice University Hospital Center in Zagreb, Croatia, prospectively analyzed data from 250 patients with acute STEMI treated with primary percutaneous coronary intervention. MetS was defined according
to the revised National Cholesterol Education Program–Adult Treatment Panel III (NCEP–ATP III) and International Diabetes Federation (IDF) criteria. Of the 250 patients, 231 survived for inclusion in the 12-month follow-up. Patients with and without MetS were analyzed according to obesity indices: body mass index (BMI), central-body adiposity index (BAI), conicity index (Cindex), visceral adiposity index (VAI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Patients with acute STEMI had high rates of central obesity, increased VAI, WHtR, and very high BAI, dyslipidemia, and hypertension. However, they had lower rates of overall obesity and hyperglycemia. The NCEP–ATP III and several other obesity indices were superior to overall obesity (BMI) in predicting acute STEMI severity—clinical presentation, in-hospital complications, and severity of CAD. WC and MetS as defined by IDF criteria had no influence on it. Moreover, MetS as defined by NCEP-ATP III or IDF and obesity indices had no influence on prognosis of major adverse cardiovascular events (MACE). Cindex greater than 1.25/1.18, very high BAI, and WHtR of 63/58 or greater increased the risk of total in-hospital complications, dyspnea, and heart failure, respectively. The number of significantly stenosed coronary arteries increased the risk of total MACE. WHR independently increased the risk of significant stenosis of coronary segment 1 and proximal/middle coronary artery segments. Source: Archives of Medical Science, June 2017
Getting a Better Picture of Skin Cancer
A handheld detector that offers noninvasive real-time imaging can help dermatologic surgeons get a better idea of skin cancer dimensions before committing to surgery, according to a recent study. Current imaging technologies can lead to excessive or incomplete removal of the cancer, the researchers say. However, multispectral optoacoustic tomography (MSOT) allows the user to differentiate tissue chromophores—the part of the molecule responsible for its color—and exogenous contrast agents based on their spectral signatures. The researchers performed MSOT imaging with handheld scanners on 21 patients with nonmelanoma skin cancers. All of the lesions had recognizable images on the MSOT devices, visualizing the shape and thickness of the lesions and providing images with well-resolved tissue chromophores. Aggressive types of skin cancers can involve deeper structures, the researchers note—another reason the MSOT detector could be useful. In one case, the depth of the basal cell carcinoma, which included its underlying vasculature, reached beyond 3 mm, which might have gone undetected by other imaging modalities, they say. Source: Photoacoustics, June 2017 n
Vol. 42 No. 9 • September 2017 • P&T 591 ®
“Chronic Lyme disease” is sometimes a catchall diagnosis for patients with a wide spectrum of musculoskeletal and neuropsychiatric symptoms, fatigue, and generalized pain. And that, in turn, has led to a variety of treatments: courses of antibiotics lasting for months to years, intravenous (IV) infusions of hydrogen peroxide, immunoglobulin therapy, and even stem cell transplants. Those treatments, though, may not lead to substantial long-term improvement—in fact, they can be downright harmful. Clinicians, health departments, and patients have all contacted the Centers for Disease Control and Prevention with reports of life-threatening complications resulting from treatment for chronic Lyme disease, including metastatic bacterial infections, septic shock, Clostridium difficile colitis, and abscesses. Morbidity and Mortality Weekly Report (MMWR) describes five cases that “highlight the severity and scope” of adverse effects caused by the use of unproven treatments for chronic Lyme disease. One patient with fatigue and joint pain, for instance, was diagnosed with chronic Lyme disease, babesiosis, and Bartonella infection. When her symptoms worsened despite multiple courses of oral antibiotics, she was switched to IV ceftriaxone and cefotaxime. However, the pain did not lessen; she became hypotensive and tachycardic, and was placed in intensive care. Her condition continued to worsen, and she died. Her death was attributed to septic shock related to central venous catheter-associated bacteremia. In another case, a woman was first diagnosed with amyotrophic lateral sclerosis (ALS), then, as a second opinion, with chronic Lyme disease. After seven months of intensive anti microbial treatment, the pain improved, but she got weaker. She also developed intractable C. difficile infection that required prolonged treatment. However, she died of complications of ALS—an example, the researchers say, of a missed opportunity for appropriate treatment due to misdiagnosis. Antibiotics and immunoglobulin therapies are effective and necessary treatments for many conditions, MMWR emphasizes—“however, unnecessary antibiotic and immunoglobulin use provides no benefit to patients while putting them at risk for adverse events.” Source: MMWR, June 2017
Calculating the Risk of Parkinson’s-Related Cognitive Deficits Current treatments for Parkinson’s disease are only effective in improving motor deficits, but the loss of cognitive abilities is just as devastating. Approximately 25% of patients also experience cognitive deficits that impair function. One problem in developing treatments, however, is that patients with cognitive effects vary widely. Being able to predict the
590 P&T • ®
September 2017 • Vol. 42 No. 9
chance that someone with Parkinson’s will develop cognitive deficits could be a useful tool, researchers from Brigham and Women’s Hospital say. And they think they might have created just the thing: a computer-based risk calculator. The researchers combined data from 3,200 patients with Parkinson’s disease, representing more than 25,000 individual clinical assessments. They evaluated seven known clinical and genetic risk factors associated with developing dementia, and then used the information to build the risk calculator. “By allowing clinical researchers to identify and select only patients at high risk for developing dementia, this tool could help in the design of ‘smarter’ trials that require a manageable number of participating patients,” says Clemens Scherzer, MD, the lead investigator. By improving clinical trial design, the risk calculator could help in the discovery of new treatments, the researchers say, and then help determine which patients would most benefit from those treatments. Source: National Institutes of Health, June 2017
Which AML Patients Are Good Candidates for Immunotherapy? Some patients with acute myeloid leukemia (AML) may have trouble with immunotherapy after chemotherapy, researchers say, and they think they’ve found one reason why. The team wanted to perform a “deep assessment” of the state of the adaptive immune system in AML patients in remission after chemotherapy. They used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system. They say their approach was unique in that they established a comprehensive picture of the adaptive “immunome” by simultaneously examining the genetic, phenotypic, and functional consequences of chemotherapy. Their assessment revealed a “dramatic impact” in the B-cell compartment, which appeared slower to recover than the T-cell compartment. Of 10 patients in the study, only two generated protective titers in response to vaccination. Most had abnormal frequencies of transitional and memory B cells. The researchers say the inability of AML patients to produce protective antibody titers in response to influenza vaccination is likely due to multiple B-cell abnormalities. They found similar patterns across all of the patients. When they ranked patients based on time elapsed since chemotherapy, the degree of dysfunction was lesser in patients who were farther away from chemotherapy. The “consistent finding” of a reduction of memory B cells in all the AML patients suggests that humoral immunity reconstitution is “a very long process.” The researchers say that a better understanding of the changes in adaptive immune cell subsets after chemotherapy will be useful in designing immunotherapies that can work with existing immune capacity. Source: Journal of Translational Medicine, July 2017
Research Briefs Legionnaires’ Disease in Health Care Settings
Investigation by the Centers for Disease Control and Prevention (CDC) of 27 outbreaks of Legionnaires’ disease between 2000 and 2014 found health-care–associated Legionnaires’ disease accounted for 33% of the outbreaks, 57% of outbreak-associated cases, and 85% of outbreakassociated deaths. Nearly all were attributed to water system exposures that could have been prevented by effective water management programs. CDC researchers analyzed 2015 surveillance data from 20 states and the New York City metropolitan area that reported more than 90% of confirmed legionellosis cases to the Supplemental Legionnaires’ Disease Surveillance System. Of 2,809 cases, 553 were health-care–associated. Definite cases accounted for 3%, and possible cases accounted for 17% of all of the cases reported. Although only a small percentage was definitely related to health care settings, the fatality rate was high at 12%. Of the 85 definite health-care–associated Legionnaires’ disease cases, 80% were associated with long-term-care facilities. Of the 468 possible cases, 13% were “possibly” associated with long-term-care facilities, 49% with hospitals, and 26% with clinics. The CDC says the number of definite cases and facilities reported is “likely an underestimate,” in part because of a lack of Legionella-specific testing. Another explanation is that hospital stays are typically shorter than the 10-day period used in the analysis. One-fourth of patients with definite health-care–associated Legionnaires’ disease die. Health care providers play a critical role in prevention and response, the CDC says, by rapidly identifying and reporting cases. Legionnaires’ disease is “clinically indistinguishable” from other causes of pneumonia, the researchers note. The preferred diagnostic method is to concurrently obtain a lower respiratory sputum sample for culture on selective media and a Legionella urinary antigen test. In health care facilities, the researchers say, “prevention of the first case of Legionnaires’ disease is the ultimate goal.” The best way to do that, they advise, is to have an effective water management program. Source: Morbidity and Mortality Weekly Report, June 2017
How Well Does Metabolic Syndrome Predict Prognosis in STEMI? Metabolic syndrome (MetS) is common among patients with coronary artery disease (CAD) and highly prevalent in those with acute ST-elevation myocardial infarction (STEMI). But are all elements of MetS equally good predictors of clinical severity and prognosis? To find out, researchers from Sestre Milosrdnice University Hospital Center in Zagreb, Croatia, prospectively analyzed data from 250 patients with acute STEMI treated with primary percutaneous coronary intervention. MetS was defined according
to the revised National Cholesterol Education Program–Adult Treatment Panel III (NCEP–ATP III) and International Diabetes Federation (IDF) criteria. Of the 250 patients, 231 survived for inclusion in the 12-month follow-up. Patients with and without MetS were analyzed according to obesity indices: body mass index (BMI), central-body adiposity index (BAI), conicity index (Cindex), visceral adiposity index (VAI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Patients with acute STEMI had high rates of central obesity, increased VAI, WHtR, and very high BAI, dyslipidemia, and hypertension. However, they had lower rates of overall obesity and hyperglycemia. The NCEP–ATP III and several other obesity indices were superior to overall obesity (BMI) in predicting acute STEMI severity—clinical presentation, in-hospital complications, and severity of CAD. WC and MetS as defined by IDF criteria had no influence on it. Moreover, MetS as defined by NCEP-ATP III or IDF and obesity indices had no influence on prognosis of major adverse cardiovascular events (MACE). Cindex greater than 1.25/1.18, very high BAI, and WHtR of 63/58 or greater increased the risk of total in-hospital complications, dyspnea, and heart failure, respectively. The number of significantly stenosed coronary arteries increased the risk of total MACE. WHR independently increased the risk of significant stenosis of coronary segment 1 and proximal/middle coronary artery segments. Source: Archives of Medical Science, June 2017
Getting a Better Picture of Skin Cancer
A handheld detector that offers noninvasive real-time imaging can help dermatologic surgeons get a better idea of skin cancer dimensions before committing to surgery, according to a recent study. Current imaging technologies can lead to excessive or incomplete removal of the cancer, the researchers say. However, multispectral optoacoustic tomography (MSOT) allows the user to differentiate tissue chromophores—the part of the molecule responsible for its color—and exogenous contrast agents based on their spectral signatures. The researchers performed MSOT imaging with handheld scanners on 21 patients with nonmelanoma skin cancers. All of the lesions had recognizable images on the MSOT devices, visualizing the shape and thickness of the lesions and providing images with well-resolved tissue chromophores. Aggressive types of skin cancers can involve deeper structures, the researchers note—another reason the MSOT detector could be useful. In one case, the depth of the basal cell carcinoma, which included its underlying vasculature, reached beyond 3 mm, which might have gone undetected by other imaging modalities, they say. Source: Photoacoustics, June 2017 n
Vol. 42 No. 9 • September 2017 • P&T 591 ®
