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Reviewing the state of HCV and HBV in children
The natural histories of hepatitis B virus (HBV) and hepatitis C virus (HCV) are very different in children, compared with their progress in adults, and depends on age at time of infection, mode of acquisition, ethnicity, and genotype, according to a review in a special pediatric issue of Clinics in Liver Disease.
Most children infected perinatally or vertically continue to be asymptomatic but are at uniquely higher risk of developing chronic viral hepatitis and progressing to liver cirrhosis and hepatocellular carcinoma (HCC), according to Krupa R. Mysore, MD, and Daniel H. Leung, MD, both of the Baylor College of Medicine, Houston. In addition, because the risk of progression to cancer along with such other liver damage is high in children, the reviewers stated that HCV and HBV can be classified as oncoviruses.
Their article assessed overall epidemiology, viral characteristics, and immune responses, as well as prevention, clinical manifestations, and current advances in the treatment of hepatitis B and C in children.
Because of the introduction of universal infant vaccination for HBV in the United States in 1991, the incidence of acute hepatitis B in U.S. children (those aged less than 19 years) has decreased from approximately 13.80/100,000 population (in children aged 10-19 years) in the 1980s to 0.34/100,000 population in 2002, Dr. Mysore and Dr. Leung wrote.
However, they added that those children who have chronic HBV remain at high risk for HCC, with a 100-fold greater incidence, compared with the HBV-negative population.
Similarly, HCV is a significant problem in children, with an estimated prevalence in the United States of 0.2% and 0.4% for children aged 6-11 years and 12-19 years, respectively. Vertical transmission from the mother is responsible for more than 60% of pediatric HCV infection and adds approximately 7,200 new cases in the United States yearly. Older children can acquire the virus through intravenous and intranasal drug use and high-risk sexual activity, they stated.
“Our understanding of the pathobiology and immunology of hepatitis B and C is unprecedented. As new antiviral therapies are being developed for the pediatric population, the differences in management and monitoring between children and adults with HBV and HCV are beginning to narrow but are still important,” the authors wrote.
They pointed out that soon-to-be-available treatments for HCV will be curative in children aged as young as 3 years. “[T]his will change the natural history of HCV and the prevalence of hepatocellular carcinoma over the next several decades for the better,” Dr. Mysore and Dr. Leung concluded.
They reported that they had no conflicts of interest to disclose.
SOURCE: Mysore KR et al. Clin Liver Dis. 2018; 22:703-22.
The natural histories of hepatitis B virus (HBV) and hepatitis C virus (HCV) are very different in children, compared with their progress in adults, and depends on age at time of infection, mode of acquisition, ethnicity, and genotype, according to a review in a special pediatric issue of Clinics in Liver Disease.
Most children infected perinatally or vertically continue to be asymptomatic but are at uniquely higher risk of developing chronic viral hepatitis and progressing to liver cirrhosis and hepatocellular carcinoma (HCC), according to Krupa R. Mysore, MD, and Daniel H. Leung, MD, both of the Baylor College of Medicine, Houston. In addition, because the risk of progression to cancer along with such other liver damage is high in children, the reviewers stated that HCV and HBV can be classified as oncoviruses.
Their article assessed overall epidemiology, viral characteristics, and immune responses, as well as prevention, clinical manifestations, and current advances in the treatment of hepatitis B and C in children.
Because of the introduction of universal infant vaccination for HBV in the United States in 1991, the incidence of acute hepatitis B in U.S. children (those aged less than 19 years) has decreased from approximately 13.80/100,000 population (in children aged 10-19 years) in the 1980s to 0.34/100,000 population in 2002, Dr. Mysore and Dr. Leung wrote.
However, they added that those children who have chronic HBV remain at high risk for HCC, with a 100-fold greater incidence, compared with the HBV-negative population.
Similarly, HCV is a significant problem in children, with an estimated prevalence in the United States of 0.2% and 0.4% for children aged 6-11 years and 12-19 years, respectively. Vertical transmission from the mother is responsible for more than 60% of pediatric HCV infection and adds approximately 7,200 new cases in the United States yearly. Older children can acquire the virus through intravenous and intranasal drug use and high-risk sexual activity, they stated.
“Our understanding of the pathobiology and immunology of hepatitis B and C is unprecedented. As new antiviral therapies are being developed for the pediatric population, the differences in management and monitoring between children and adults with HBV and HCV are beginning to narrow but are still important,” the authors wrote.
They pointed out that soon-to-be-available treatments for HCV will be curative in children aged as young as 3 years. “[T]his will change the natural history of HCV and the prevalence of hepatocellular carcinoma over the next several decades for the better,” Dr. Mysore and Dr. Leung concluded.
They reported that they had no conflicts of interest to disclose.
SOURCE: Mysore KR et al. Clin Liver Dis. 2018; 22:703-22.
The natural histories of hepatitis B virus (HBV) and hepatitis C virus (HCV) are very different in children, compared with their progress in adults, and depends on age at time of infection, mode of acquisition, ethnicity, and genotype, according to a review in a special pediatric issue of Clinics in Liver Disease.
Most children infected perinatally or vertically continue to be asymptomatic but are at uniquely higher risk of developing chronic viral hepatitis and progressing to liver cirrhosis and hepatocellular carcinoma (HCC), according to Krupa R. Mysore, MD, and Daniel H. Leung, MD, both of the Baylor College of Medicine, Houston. In addition, because the risk of progression to cancer along with such other liver damage is high in children, the reviewers stated that HCV and HBV can be classified as oncoviruses.
Their article assessed overall epidemiology, viral characteristics, and immune responses, as well as prevention, clinical manifestations, and current advances in the treatment of hepatitis B and C in children.
Because of the introduction of universal infant vaccination for HBV in the United States in 1991, the incidence of acute hepatitis B in U.S. children (those aged less than 19 years) has decreased from approximately 13.80/100,000 population (in children aged 10-19 years) in the 1980s to 0.34/100,000 population in 2002, Dr. Mysore and Dr. Leung wrote.
However, they added that those children who have chronic HBV remain at high risk for HCC, with a 100-fold greater incidence, compared with the HBV-negative population.
Similarly, HCV is a significant problem in children, with an estimated prevalence in the United States of 0.2% and 0.4% for children aged 6-11 years and 12-19 years, respectively. Vertical transmission from the mother is responsible for more than 60% of pediatric HCV infection and adds approximately 7,200 new cases in the United States yearly. Older children can acquire the virus through intravenous and intranasal drug use and high-risk sexual activity, they stated.
“Our understanding of the pathobiology and immunology of hepatitis B and C is unprecedented. As new antiviral therapies are being developed for the pediatric population, the differences in management and monitoring between children and adults with HBV and HCV are beginning to narrow but are still important,” the authors wrote.
They pointed out that soon-to-be-available treatments for HCV will be curative in children aged as young as 3 years. “[T]his will change the natural history of HCV and the prevalence of hepatocellular carcinoma over the next several decades for the better,” Dr. Mysore and Dr. Leung concluded.
They reported that they had no conflicts of interest to disclose.
SOURCE: Mysore KR et al. Clin Liver Dis. 2018; 22:703-22.
FROM CLINICS IN LIVER DISEASE
HIV superinfection: No boost to broadly neutralizing antibodies
Infection by a second HIV strain after established primary infection (HIV superinfection) has been associated with broader antibody production, and such events are analogous to heterologous prime-boost immunizations, according to a report published in Cell Host & Microbe.
This phenomenon offers an opportunity to assess how the human immune system responds to sequential exposure to two distinct HIV envelope (Env) antigens, according to the authors, Daniel J. Sheward, a PhD student and scientific officer at the University of Cape Town, South Africa, and his colleagues.
Mr. Sheward and his colleagues followed 108 women recruited in acute/early infection and screened for superinfection over approximately 2 years in the Centre for the AIDS Programme of Research in South Africa (CAPRISA 002 cohort). In a previous study, they identified five superinfected participants, all of whom were superinfected between 3 and 10 months following primary infection. Only two of these patients developed antibodies capable of neutralizing heterologous viruses at 2 years, and one individual developed extremely potent broadly neutralizing antibodies (bnAbs). However, the contribution of superinfection itself to the development of antibody breadth in these individuals was not clear, prompting the current study (Cell Host Microbe. 2018 Oct 10;24[4]:593-9).
The researchers compared neutralization breadth (defined as the percent of heterologous viruses neutralized) present in plasma sampled 2 years post infection between the previously identified superinfected participants and the remaining CAPRISA 002 cohort participants. Four virus strains accounted for the superinfections. Antibody breadth was compared at 2 years post infection to four of the five of the superinfected participants, as they all had at least 2 years of antiretroviral-naive follow-up.
The researchers compared the peak neutralizing antibody (nAb) titers against all four superinfecting viruses with their matched primary infecting virus, as well as with the nAb titers that increased against early/founder viruses in 22 other participants in the CAPRISA 002 cohort.
They found that titers to the superinfecting virus strains were comparable with those seen in single infections from the rest of the cohort. In contrast, two other superinfecting virus strains developed exceedingly high neutralizing titers against themselves. Also, HIV superinfection did not appear to boost nAb memory responses primed by the initial infection.
Notably, superinfection did not elicit bnAB responses to epitopes conserved in both infecting viruses. The one individual who appeared to have developed a bnAB response, upon analysis, was found to have breadth of response attributable to a single antibody lineage that only affected the superinfecting virus. This indicated that superinfection did not facilitate breadth by directing responses to an Env conserved in both infecting viruses, according to Mr. Sheward and his colleagues.
“HIV superinfection fails to efficiently recruit neutralizing memory B cells and, at best, results in additive nAb responses rather than a synergistic effect leading to cross-neutralization; a distinction that is highly relevant for vaccine design. ... [W]hile sequential immunizations with heterologous Env immunogens may be able to improve the potency of elicited responses, alone, they are unlikely to promote the development of bnAbs,” the researchers concluded.
The study was funded by the Centre for the AIDS Programme of Research in South Africa and the South African Medical Research Council. The authors reported that they had no disclosures.
SOURCE: Sheward DJ et al. Cell Host Microbe. 2018 Oct 10;24[4]:593-9.
Infection by a second HIV strain after established primary infection (HIV superinfection) has been associated with broader antibody production, and such events are analogous to heterologous prime-boost immunizations, according to a report published in Cell Host & Microbe.
This phenomenon offers an opportunity to assess how the human immune system responds to sequential exposure to two distinct HIV envelope (Env) antigens, according to the authors, Daniel J. Sheward, a PhD student and scientific officer at the University of Cape Town, South Africa, and his colleagues.
Mr. Sheward and his colleagues followed 108 women recruited in acute/early infection and screened for superinfection over approximately 2 years in the Centre for the AIDS Programme of Research in South Africa (CAPRISA 002 cohort). In a previous study, they identified five superinfected participants, all of whom were superinfected between 3 and 10 months following primary infection. Only two of these patients developed antibodies capable of neutralizing heterologous viruses at 2 years, and one individual developed extremely potent broadly neutralizing antibodies (bnAbs). However, the contribution of superinfection itself to the development of antibody breadth in these individuals was not clear, prompting the current study (Cell Host Microbe. 2018 Oct 10;24[4]:593-9).
The researchers compared neutralization breadth (defined as the percent of heterologous viruses neutralized) present in plasma sampled 2 years post infection between the previously identified superinfected participants and the remaining CAPRISA 002 cohort participants. Four virus strains accounted for the superinfections. Antibody breadth was compared at 2 years post infection to four of the five of the superinfected participants, as they all had at least 2 years of antiretroviral-naive follow-up.
The researchers compared the peak neutralizing antibody (nAb) titers against all four superinfecting viruses with their matched primary infecting virus, as well as with the nAb titers that increased against early/founder viruses in 22 other participants in the CAPRISA 002 cohort.
They found that titers to the superinfecting virus strains were comparable with those seen in single infections from the rest of the cohort. In contrast, two other superinfecting virus strains developed exceedingly high neutralizing titers against themselves. Also, HIV superinfection did not appear to boost nAb memory responses primed by the initial infection.
Notably, superinfection did not elicit bnAB responses to epitopes conserved in both infecting viruses. The one individual who appeared to have developed a bnAB response, upon analysis, was found to have breadth of response attributable to a single antibody lineage that only affected the superinfecting virus. This indicated that superinfection did not facilitate breadth by directing responses to an Env conserved in both infecting viruses, according to Mr. Sheward and his colleagues.
“HIV superinfection fails to efficiently recruit neutralizing memory B cells and, at best, results in additive nAb responses rather than a synergistic effect leading to cross-neutralization; a distinction that is highly relevant for vaccine design. ... [W]hile sequential immunizations with heterologous Env immunogens may be able to improve the potency of elicited responses, alone, they are unlikely to promote the development of bnAbs,” the researchers concluded.
The study was funded by the Centre for the AIDS Programme of Research in South Africa and the South African Medical Research Council. The authors reported that they had no disclosures.
SOURCE: Sheward DJ et al. Cell Host Microbe. 2018 Oct 10;24[4]:593-9.
Infection by a second HIV strain after established primary infection (HIV superinfection) has been associated with broader antibody production, and such events are analogous to heterologous prime-boost immunizations, according to a report published in Cell Host & Microbe.
This phenomenon offers an opportunity to assess how the human immune system responds to sequential exposure to two distinct HIV envelope (Env) antigens, according to the authors, Daniel J. Sheward, a PhD student and scientific officer at the University of Cape Town, South Africa, and his colleagues.
Mr. Sheward and his colleagues followed 108 women recruited in acute/early infection and screened for superinfection over approximately 2 years in the Centre for the AIDS Programme of Research in South Africa (CAPRISA 002 cohort). In a previous study, they identified five superinfected participants, all of whom were superinfected between 3 and 10 months following primary infection. Only two of these patients developed antibodies capable of neutralizing heterologous viruses at 2 years, and one individual developed extremely potent broadly neutralizing antibodies (bnAbs). However, the contribution of superinfection itself to the development of antibody breadth in these individuals was not clear, prompting the current study (Cell Host Microbe. 2018 Oct 10;24[4]:593-9).
The researchers compared neutralization breadth (defined as the percent of heterologous viruses neutralized) present in plasma sampled 2 years post infection between the previously identified superinfected participants and the remaining CAPRISA 002 cohort participants. Four virus strains accounted for the superinfections. Antibody breadth was compared at 2 years post infection to four of the five of the superinfected participants, as they all had at least 2 years of antiretroviral-naive follow-up.
The researchers compared the peak neutralizing antibody (nAb) titers against all four superinfecting viruses with their matched primary infecting virus, as well as with the nAb titers that increased against early/founder viruses in 22 other participants in the CAPRISA 002 cohort.
They found that titers to the superinfecting virus strains were comparable with those seen in single infections from the rest of the cohort. In contrast, two other superinfecting virus strains developed exceedingly high neutralizing titers against themselves. Also, HIV superinfection did not appear to boost nAb memory responses primed by the initial infection.
Notably, superinfection did not elicit bnAB responses to epitopes conserved in both infecting viruses. The one individual who appeared to have developed a bnAB response, upon analysis, was found to have breadth of response attributable to a single antibody lineage that only affected the superinfecting virus. This indicated that superinfection did not facilitate breadth by directing responses to an Env conserved in both infecting viruses, according to Mr. Sheward and his colleagues.
“HIV superinfection fails to efficiently recruit neutralizing memory B cells and, at best, results in additive nAb responses rather than a synergistic effect leading to cross-neutralization; a distinction that is highly relevant for vaccine design. ... [W]hile sequential immunizations with heterologous Env immunogens may be able to improve the potency of elicited responses, alone, they are unlikely to promote the development of bnAbs,” the researchers concluded.
The study was funded by the Centre for the AIDS Programme of Research in South Africa and the South African Medical Research Council. The authors reported that they had no disclosures.
SOURCE: Sheward DJ et al. Cell Host Microbe. 2018 Oct 10;24[4]:593-9.
FROM CELL HOST & MICROBE
Key clinical point: Sequential immunizations with heterologous HIV Env immunogens are unlikely to promote broadly neutralizing antibodies.
Major finding: HIV superinfection does not efficiently recruit cross-reactive memory B cells.
Study details: Neutralizing antibody responses were compared between 4 superinfected individuals and 22 singly infected individuals in the CAPRISA 002 cohort.
Disclosures: The study was funded by the Centre for the AIDS Programme of Research in South Africa and the South African Medical Research Council. The authors reported that they had no disclosures.
Source: Sheward DJ et al. Cell Host Microbe. 2018 Oct 10;24[4]:593-9.
Smoking neglected in patients with PAD
Patients with claudication consulting a peripheral arterial disease provider are often active smokers, rarely receive evidence-based cessation interventions, and frequently relapse if they do quit, according to a report published online in the Journal of the American Heart Association.
More than one-third of patients with claudication consulting PAD specialists are active smokers, as seen in a data analysis of an international registry, wrote Krishna K. Patel, MD, of the department of cardiology, University of Missouri–Kansas City, and her colleagues.
The authors assessed 1,272 patients with PAD and new or worsening claudication who were enrolled at 16 vascular specialty clinics from 2011 to 2015 in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry, (Clinicaltrials.gov: NCT01419080).
In-person interviews obtained smoking status from the patients and information on cessation interventions at baseline and at 3, 6, and 12 months. At baseline, 474 (37%) patients were active, 660 (52%) were former, and 138 (11%) were never smokers.
Among active smokers, only 16% were referred to cessation counseling, and only 11% were prescribed pharmacologic treatment.
At 3 months, the probability of quitting smoking was 21%. Those who kept smoking had a probability of quitting during the next 9 months that varied between 11% and 12% (P less than .001). The probability of relapse was high, with more than one-third of initial quitters (36%) resuming smoking, and at 12 months; 72% of all original smokers continued to smoke, according to the authors.
The high level of initial smoking and the failed efforts at attempting cessation are clinically important because cigarette smoking is the most important and modifiable risk factor for PAD, and patients with PAD who smoke have higher rates of disease progression, according to Dr. Patel and her colleagues.
“Few patients receive formal cessation interventions. The dynamic nature of these patients’ smoking practices also underscores the need for ongoing assessment of smoking, even among those who report that they have quit, and consistent offering of evidence-based cessation support. Future research should focus on identifying optimal strategies for implementing consistent cessation support,” the researchers concluded.
The study was funded by grants from the Netherlands Organization for Scientific Research and an unrestricted grant from W. L. Gore & Associates. One of the authors owns the copyright for a Peripheral Artery Questionnaire used in the study and serves as a consultant to United Healthcare, Bayer, and Novartis, with research grants from Abbot Vascular and Novartis. Another author is supported by an unrestricted research grant by Merck and Boston Scientific. The remaining authors reported having no disclosures.
SOURCE: Patel KR et al. J Am Heart Assoc. 2018;7:e010076. doi: 10.1161/JAHA.118.010076.
Patients with claudication consulting a peripheral arterial disease provider are often active smokers, rarely receive evidence-based cessation interventions, and frequently relapse if they do quit, according to a report published online in the Journal of the American Heart Association.
More than one-third of patients with claudication consulting PAD specialists are active smokers, as seen in a data analysis of an international registry, wrote Krishna K. Patel, MD, of the department of cardiology, University of Missouri–Kansas City, and her colleagues.
The authors assessed 1,272 patients with PAD and new or worsening claudication who were enrolled at 16 vascular specialty clinics from 2011 to 2015 in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry, (Clinicaltrials.gov: NCT01419080).
In-person interviews obtained smoking status from the patients and information on cessation interventions at baseline and at 3, 6, and 12 months. At baseline, 474 (37%) patients were active, 660 (52%) were former, and 138 (11%) were never smokers.
Among active smokers, only 16% were referred to cessation counseling, and only 11% were prescribed pharmacologic treatment.
At 3 months, the probability of quitting smoking was 21%. Those who kept smoking had a probability of quitting during the next 9 months that varied between 11% and 12% (P less than .001). The probability of relapse was high, with more than one-third of initial quitters (36%) resuming smoking, and at 12 months; 72% of all original smokers continued to smoke, according to the authors.
The high level of initial smoking and the failed efforts at attempting cessation are clinically important because cigarette smoking is the most important and modifiable risk factor for PAD, and patients with PAD who smoke have higher rates of disease progression, according to Dr. Patel and her colleagues.
“Few patients receive formal cessation interventions. The dynamic nature of these patients’ smoking practices also underscores the need for ongoing assessment of smoking, even among those who report that they have quit, and consistent offering of evidence-based cessation support. Future research should focus on identifying optimal strategies for implementing consistent cessation support,” the researchers concluded.
The study was funded by grants from the Netherlands Organization for Scientific Research and an unrestricted grant from W. L. Gore & Associates. One of the authors owns the copyright for a Peripheral Artery Questionnaire used in the study and serves as a consultant to United Healthcare, Bayer, and Novartis, with research grants from Abbot Vascular and Novartis. Another author is supported by an unrestricted research grant by Merck and Boston Scientific. The remaining authors reported having no disclosures.
SOURCE: Patel KR et al. J Am Heart Assoc. 2018;7:e010076. doi: 10.1161/JAHA.118.010076.
Patients with claudication consulting a peripheral arterial disease provider are often active smokers, rarely receive evidence-based cessation interventions, and frequently relapse if they do quit, according to a report published online in the Journal of the American Heart Association.
More than one-third of patients with claudication consulting PAD specialists are active smokers, as seen in a data analysis of an international registry, wrote Krishna K. Patel, MD, of the department of cardiology, University of Missouri–Kansas City, and her colleagues.
The authors assessed 1,272 patients with PAD and new or worsening claudication who were enrolled at 16 vascular specialty clinics from 2011 to 2015 in the PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry, (Clinicaltrials.gov: NCT01419080).
In-person interviews obtained smoking status from the patients and information on cessation interventions at baseline and at 3, 6, and 12 months. At baseline, 474 (37%) patients were active, 660 (52%) were former, and 138 (11%) were never smokers.
Among active smokers, only 16% were referred to cessation counseling, and only 11% were prescribed pharmacologic treatment.
At 3 months, the probability of quitting smoking was 21%. Those who kept smoking had a probability of quitting during the next 9 months that varied between 11% and 12% (P less than .001). The probability of relapse was high, with more than one-third of initial quitters (36%) resuming smoking, and at 12 months; 72% of all original smokers continued to smoke, according to the authors.
The high level of initial smoking and the failed efforts at attempting cessation are clinically important because cigarette smoking is the most important and modifiable risk factor for PAD, and patients with PAD who smoke have higher rates of disease progression, according to Dr. Patel and her colleagues.
“Few patients receive formal cessation interventions. The dynamic nature of these patients’ smoking practices also underscores the need for ongoing assessment of smoking, even among those who report that they have quit, and consistent offering of evidence-based cessation support. Future research should focus on identifying optimal strategies for implementing consistent cessation support,” the researchers concluded.
The study was funded by grants from the Netherlands Organization for Scientific Research and an unrestricted grant from W. L. Gore & Associates. One of the authors owns the copyright for a Peripheral Artery Questionnaire used in the study and serves as a consultant to United Healthcare, Bayer, and Novartis, with research grants from Abbot Vascular and Novartis. Another author is supported by an unrestricted research grant by Merck and Boston Scientific. The remaining authors reported having no disclosures.
SOURCE: Patel KR et al. J Am Heart Assoc. 2018;7:e010076. doi: 10.1161/JAHA.118.010076.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point: Patients with PAD are often smokers, rarely receive cessation interventions, and frequently relapse if they quit.
Major finding: Only 16% of active smokers received cessation counseling, and at 3 months, the probability of quitting smoking was 21%.
Study details: Interview study of 1,272 patients with PAD and new or worsening claudication who were enrolled in the PORTRAIT registry.
Disclosures: Study funding included an unrestricted grant from W. L. Gore & Associates. One author owns the copyright for the Peripheral Artery Questionnaire used in the study and has ties to several pharmaceutical companies. Another author is supported by an unrestricted corporate research grant. The remaining authors reported having no disclosures.
Source: Patel KR et al. J Am Heart Assoc. 2018;7:e010076. doi: 10.1161/JAHA.118.010076.
Frailty tied to higher mortality after major vascular surgery
Frailty defined as functional dependence is a predictor of mortality risk in elderly patients having major vascular surgery, a meta-analysis of studies has found
“Functional dependency may be recommended for use in rapid screening for frailty in major vascular surgery because of the high quality of associated evidence. Additionally, information on central muscle mass also adds incremental predictive value to long-term survival of elderly patients after major vascular surgery,” the study investigaters stated. However, they pointed out that “other newly developed frailty tools require further validation in more studies” before they should be adopted.
The report, published in the European Journal of Vascular and Endovascular Surgery, evaluated the effect of frailty in major vascular surgery from a search of MEDLINE, Embase, Cochrane Database, and Scopus through May 2018. Data were extracted from the articles related to surgery for abdominal aortic aneurysms (AAA) and lower extremity artery disease (LEAD), and a modified Newcastle-Ottawa scale was used to assess the quality of the included studies, according to Jiarong Wang, MD, of the department of vascular surgery, Sichuan University, Sichuan Province, China, and colleagues. A total of 22 cohort studies and one randomized controlled trial was used in the final analysis. The reviewers expressed the impact of frailty on outcomes as odds ratios (OR) or hazard ratios (HR) using a random effects model.
The researchers found that frailty, in terms of functional dependence, was associated with a significantly increased 30-day mortality risk in patients with AAA without heterogeneity (OR 5.15) and also in LEAD patients (OR 3.29). Functionally dependent patients also had a significantly increased 30-day mortality risk, compared with independent patients (OR 4.49), and similar results were observed after stratifying those who underwent AAA repair (OR 5.14) or lower extremity revascularization (OR 4.18). Even for patients who underwent endovascular procedures rather than open surgery, functional dependency was also associated with a significantly increased 30-day mortality risk (OR 4.90). In addition, with regard to 30-day morbidity, frailty was associated with a significantly increased risk in both AAA (OR 2.79) and LEAD (OR 1.40) patients.
As far as long-term outcomes were concerned, frailty was associated with a significantly increased risk of long-term all-cause mortality in the overall studied population (HR 2.22), as well as in patients with AAA repair (HR 2.10) and LEAD revascularization (HR 2.46). Dr. Wang and colleagues found that central muscle mass was the only tool with moderate quality of evidence predicting long-term survival after major vascular surgery (HR .48), with other single-domain tools such as nutrition or cognition scoring being of low quality. The modified Frailty Index was the only multi-domain tool with moderate quality in predicting mortality for AAA, while others were scored as low or very low, the authors added.
“Future research is warranted to establish consensus on how to select the optimal frailty tool for certain clinical settings,” they concluded.
The authors reported that they had no conflicts of interest and no funding sources for the study.
SOURCE: Wang, J et al. Eur J Vasc Endovasc Surg. 2018;56:591-602.
Frailty defined as functional dependence is a predictor of mortality risk in elderly patients having major vascular surgery, a meta-analysis of studies has found
“Functional dependency may be recommended for use in rapid screening for frailty in major vascular surgery because of the high quality of associated evidence. Additionally, information on central muscle mass also adds incremental predictive value to long-term survival of elderly patients after major vascular surgery,” the study investigaters stated. However, they pointed out that “other newly developed frailty tools require further validation in more studies” before they should be adopted.
The report, published in the European Journal of Vascular and Endovascular Surgery, evaluated the effect of frailty in major vascular surgery from a search of MEDLINE, Embase, Cochrane Database, and Scopus through May 2018. Data were extracted from the articles related to surgery for abdominal aortic aneurysms (AAA) and lower extremity artery disease (LEAD), and a modified Newcastle-Ottawa scale was used to assess the quality of the included studies, according to Jiarong Wang, MD, of the department of vascular surgery, Sichuan University, Sichuan Province, China, and colleagues. A total of 22 cohort studies and one randomized controlled trial was used in the final analysis. The reviewers expressed the impact of frailty on outcomes as odds ratios (OR) or hazard ratios (HR) using a random effects model.
The researchers found that frailty, in terms of functional dependence, was associated with a significantly increased 30-day mortality risk in patients with AAA without heterogeneity (OR 5.15) and also in LEAD patients (OR 3.29). Functionally dependent patients also had a significantly increased 30-day mortality risk, compared with independent patients (OR 4.49), and similar results were observed after stratifying those who underwent AAA repair (OR 5.14) or lower extremity revascularization (OR 4.18). Even for patients who underwent endovascular procedures rather than open surgery, functional dependency was also associated with a significantly increased 30-day mortality risk (OR 4.90). In addition, with regard to 30-day morbidity, frailty was associated with a significantly increased risk in both AAA (OR 2.79) and LEAD (OR 1.40) patients.
As far as long-term outcomes were concerned, frailty was associated with a significantly increased risk of long-term all-cause mortality in the overall studied population (HR 2.22), as well as in patients with AAA repair (HR 2.10) and LEAD revascularization (HR 2.46). Dr. Wang and colleagues found that central muscle mass was the only tool with moderate quality of evidence predicting long-term survival after major vascular surgery (HR .48), with other single-domain tools such as nutrition or cognition scoring being of low quality. The modified Frailty Index was the only multi-domain tool with moderate quality in predicting mortality for AAA, while others were scored as low or very low, the authors added.
“Future research is warranted to establish consensus on how to select the optimal frailty tool for certain clinical settings,” they concluded.
The authors reported that they had no conflicts of interest and no funding sources for the study.
SOURCE: Wang, J et al. Eur J Vasc Endovasc Surg. 2018;56:591-602.
Frailty defined as functional dependence is a predictor of mortality risk in elderly patients having major vascular surgery, a meta-analysis of studies has found
“Functional dependency may be recommended for use in rapid screening for frailty in major vascular surgery because of the high quality of associated evidence. Additionally, information on central muscle mass also adds incremental predictive value to long-term survival of elderly patients after major vascular surgery,” the study investigaters stated. However, they pointed out that “other newly developed frailty tools require further validation in more studies” before they should be adopted.
The report, published in the European Journal of Vascular and Endovascular Surgery, evaluated the effect of frailty in major vascular surgery from a search of MEDLINE, Embase, Cochrane Database, and Scopus through May 2018. Data were extracted from the articles related to surgery for abdominal aortic aneurysms (AAA) and lower extremity artery disease (LEAD), and a modified Newcastle-Ottawa scale was used to assess the quality of the included studies, according to Jiarong Wang, MD, of the department of vascular surgery, Sichuan University, Sichuan Province, China, and colleagues. A total of 22 cohort studies and one randomized controlled trial was used in the final analysis. The reviewers expressed the impact of frailty on outcomes as odds ratios (OR) or hazard ratios (HR) using a random effects model.
The researchers found that frailty, in terms of functional dependence, was associated with a significantly increased 30-day mortality risk in patients with AAA without heterogeneity (OR 5.15) and also in LEAD patients (OR 3.29). Functionally dependent patients also had a significantly increased 30-day mortality risk, compared with independent patients (OR 4.49), and similar results were observed after stratifying those who underwent AAA repair (OR 5.14) or lower extremity revascularization (OR 4.18). Even for patients who underwent endovascular procedures rather than open surgery, functional dependency was also associated with a significantly increased 30-day mortality risk (OR 4.90). In addition, with regard to 30-day morbidity, frailty was associated with a significantly increased risk in both AAA (OR 2.79) and LEAD (OR 1.40) patients.
As far as long-term outcomes were concerned, frailty was associated with a significantly increased risk of long-term all-cause mortality in the overall studied population (HR 2.22), as well as in patients with AAA repair (HR 2.10) and LEAD revascularization (HR 2.46). Dr. Wang and colleagues found that central muscle mass was the only tool with moderate quality of evidence predicting long-term survival after major vascular surgery (HR .48), with other single-domain tools such as nutrition or cognition scoring being of low quality. The modified Frailty Index was the only multi-domain tool with moderate quality in predicting mortality for AAA, while others were scored as low or very low, the authors added.
“Future research is warranted to establish consensus on how to select the optimal frailty tool for certain clinical settings,” they concluded.
The authors reported that they had no conflicts of interest and no funding sources for the study.
SOURCE: Wang, J et al. Eur J Vasc Endovasc Surg. 2018;56:591-602.
FROM EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY
Key clinical point: Frailty was associated with increased short- and long-term mortality in major vascular surgery.
Major finding: Frailty was associated with a fourfold increased risk of 30-day mortality and a doubled increased risk of long-term mortality after major vascular surgery.
Study details: A meta-analysis of 22 cohort studies and one randomized controlled trial.
Disclosures: The authors reported that they had no conflicts of interest and no funding sources for the study.
Source: Wang, J et al., 2018. Eur J Vasc Endovasc Surg. 56:591-602.
Claudication, CLI differ significantly in hospital readmission, costs, mortality
Patients treated for claudication vs. critical limb ischemia (CLI) differed significantly in their initial cost of admission, readmission costs, length of stay (LOS), days to readmission, and mortality (during initial admission, as well as any admission), according to the results of a database analysis of more than 90,000 patients in the Nationwide Readmission Database.
Readmissions were influenced not only by the admission diagnosis and intervention performed “but more importantly and significantly by the patient’s characteristics such as age, sex, CCI [Charlson Comorbidity Index], and various other demographic factors,” wrote Rennier A. Martinez, MD, of JFK Medical Center, Atlantis, Fla., and his colleagues. The report was published in the October issue of Annals of Vascular Surgery.
The study used the International Classification of Diseases, Ninth Revision (ICD-9) codes and queried the Nationwide Readmission Database for 2013 and 2014 for all 92,769 adult patients admitted with the principal diagnosis of claudication (ICD-9 code 440.21; n = 33,055 patients) or CLI (ICD-9 code 440.22e440.24; n = 59,714 patients) who underwent percutaneous angioplasty (ICD-9 code 39.50, 39.90), peripheral bypass (ICD-9 code 39.29), or aortofemoral bypass (ICD-9 code 39.25).
The 30-day readmission rates were 9.0% for claudication and 19.3% for CLI. Similarly, the any readmission rates were 21.5% and 40.4% for claudication vs. CLI.
Significant differences were found for claudication and CLI, respectively, on initial cost of admission ($18,548 vs. $29,148), readmission costs ($14,726 vs. $17,681), LOS (4 days vs. 9 days), days to readmission (73 days vs. 59 days), mortality during initial admission (256 vs. 1,363), and mortality during any admission (538 vs. 3,838), all P less than .001.
Univariate and multivariate logistic regression analysis found that claudication, CLI, angioplasty, peripheral bypass, aortofemoral bypass, female sex, age younger than 65, Charlson Comorbidity Index, LOS, and primary expected payer status were all significant predictors of 30-day and overall readmissions at varying degrees.
The researchers also found that the five most common disease readmission groups were other vascular procedures (12.6%), amputation of lower limb except toes (6.3%), sepsis (5.4%), heart failure (4.9%), and postoperative or other device infections (4.8%) (Ann Vasc Surg. 2018;52:96-107).
The increased costs and higher levels of morbidity and mortality seen with CLI vs. claudication are not surprising given previous research showing that there are higher rates of complications in patients with CLI. A previous review showed there was a threefold higher risk of myocardial infarction, stroke, and vascular death in patients with CLI compared with patients with claudication, according Dr. Martinez and his colleagues.
“Readmissions after lower extremity procedures for patients admitted for claudication or CLI are influenced not only by the admission diagnosis and intervention performed but more importantly and significantly by the patient’s characteristics such as age, sex, CCI, and various other demographic factors,” the researchers wrote. “It is paramount to continue to perform this kind of study to better identify patients at risk for readmission and work toward prevention,” they concluded.
Dr. Martinez and his colleagues did not report disclosures, but indicated that the study did not receive any outside funding.
SOURCE: Martinez RA et al. Ann Vasc Surg. 2018;52:96-107.
Patients treated for claudication vs. critical limb ischemia (CLI) differed significantly in their initial cost of admission, readmission costs, length of stay (LOS), days to readmission, and mortality (during initial admission, as well as any admission), according to the results of a database analysis of more than 90,000 patients in the Nationwide Readmission Database.
Readmissions were influenced not only by the admission diagnosis and intervention performed “but more importantly and significantly by the patient’s characteristics such as age, sex, CCI [Charlson Comorbidity Index], and various other demographic factors,” wrote Rennier A. Martinez, MD, of JFK Medical Center, Atlantis, Fla., and his colleagues. The report was published in the October issue of Annals of Vascular Surgery.
The study used the International Classification of Diseases, Ninth Revision (ICD-9) codes and queried the Nationwide Readmission Database for 2013 and 2014 for all 92,769 adult patients admitted with the principal diagnosis of claudication (ICD-9 code 440.21; n = 33,055 patients) or CLI (ICD-9 code 440.22e440.24; n = 59,714 patients) who underwent percutaneous angioplasty (ICD-9 code 39.50, 39.90), peripheral bypass (ICD-9 code 39.29), or aortofemoral bypass (ICD-9 code 39.25).
The 30-day readmission rates were 9.0% for claudication and 19.3% for CLI. Similarly, the any readmission rates were 21.5% and 40.4% for claudication vs. CLI.
Significant differences were found for claudication and CLI, respectively, on initial cost of admission ($18,548 vs. $29,148), readmission costs ($14,726 vs. $17,681), LOS (4 days vs. 9 days), days to readmission (73 days vs. 59 days), mortality during initial admission (256 vs. 1,363), and mortality during any admission (538 vs. 3,838), all P less than .001.
Univariate and multivariate logistic regression analysis found that claudication, CLI, angioplasty, peripheral bypass, aortofemoral bypass, female sex, age younger than 65, Charlson Comorbidity Index, LOS, and primary expected payer status were all significant predictors of 30-day and overall readmissions at varying degrees.
The researchers also found that the five most common disease readmission groups were other vascular procedures (12.6%), amputation of lower limb except toes (6.3%), sepsis (5.4%), heart failure (4.9%), and postoperative or other device infections (4.8%) (Ann Vasc Surg. 2018;52:96-107).
The increased costs and higher levels of morbidity and mortality seen with CLI vs. claudication are not surprising given previous research showing that there are higher rates of complications in patients with CLI. A previous review showed there was a threefold higher risk of myocardial infarction, stroke, and vascular death in patients with CLI compared with patients with claudication, according Dr. Martinez and his colleagues.
“Readmissions after lower extremity procedures for patients admitted for claudication or CLI are influenced not only by the admission diagnosis and intervention performed but more importantly and significantly by the patient’s characteristics such as age, sex, CCI, and various other demographic factors,” the researchers wrote. “It is paramount to continue to perform this kind of study to better identify patients at risk for readmission and work toward prevention,” they concluded.
Dr. Martinez and his colleagues did not report disclosures, but indicated that the study did not receive any outside funding.
SOURCE: Martinez RA et al. Ann Vasc Surg. 2018;52:96-107.
Patients treated for claudication vs. critical limb ischemia (CLI) differed significantly in their initial cost of admission, readmission costs, length of stay (LOS), days to readmission, and mortality (during initial admission, as well as any admission), according to the results of a database analysis of more than 90,000 patients in the Nationwide Readmission Database.
Readmissions were influenced not only by the admission diagnosis and intervention performed “but more importantly and significantly by the patient’s characteristics such as age, sex, CCI [Charlson Comorbidity Index], and various other demographic factors,” wrote Rennier A. Martinez, MD, of JFK Medical Center, Atlantis, Fla., and his colleagues. The report was published in the October issue of Annals of Vascular Surgery.
The study used the International Classification of Diseases, Ninth Revision (ICD-9) codes and queried the Nationwide Readmission Database for 2013 and 2014 for all 92,769 adult patients admitted with the principal diagnosis of claudication (ICD-9 code 440.21; n = 33,055 patients) or CLI (ICD-9 code 440.22e440.24; n = 59,714 patients) who underwent percutaneous angioplasty (ICD-9 code 39.50, 39.90), peripheral bypass (ICD-9 code 39.29), or aortofemoral bypass (ICD-9 code 39.25).
The 30-day readmission rates were 9.0% for claudication and 19.3% for CLI. Similarly, the any readmission rates were 21.5% and 40.4% for claudication vs. CLI.
Significant differences were found for claudication and CLI, respectively, on initial cost of admission ($18,548 vs. $29,148), readmission costs ($14,726 vs. $17,681), LOS (4 days vs. 9 days), days to readmission (73 days vs. 59 days), mortality during initial admission (256 vs. 1,363), and mortality during any admission (538 vs. 3,838), all P less than .001.
Univariate and multivariate logistic regression analysis found that claudication, CLI, angioplasty, peripheral bypass, aortofemoral bypass, female sex, age younger than 65, Charlson Comorbidity Index, LOS, and primary expected payer status were all significant predictors of 30-day and overall readmissions at varying degrees.
The researchers also found that the five most common disease readmission groups were other vascular procedures (12.6%), amputation of lower limb except toes (6.3%), sepsis (5.4%), heart failure (4.9%), and postoperative or other device infections (4.8%) (Ann Vasc Surg. 2018;52:96-107).
The increased costs and higher levels of morbidity and mortality seen with CLI vs. claudication are not surprising given previous research showing that there are higher rates of complications in patients with CLI. A previous review showed there was a threefold higher risk of myocardial infarction, stroke, and vascular death in patients with CLI compared with patients with claudication, according Dr. Martinez and his colleagues.
“Readmissions after lower extremity procedures for patients admitted for claudication or CLI are influenced not only by the admission diagnosis and intervention performed but more importantly and significantly by the patient’s characteristics such as age, sex, CCI, and various other demographic factors,” the researchers wrote. “It is paramount to continue to perform this kind of study to better identify patients at risk for readmission and work toward prevention,” they concluded.
Dr. Martinez and his colleagues did not report disclosures, but indicated that the study did not receive any outside funding.
SOURCE: Martinez RA et al. Ann Vasc Surg. 2018;52:96-107.
FROM ANNALS OF VASCULAR SURGERY
Key clinical point: CLI was significantly more expensive and showed higher mortality rates compared with claudication.
Major finding: The 30-day readmission/any readmission rate was 9.0%/21.5% and 19.3%/40.4%, for claudication and CLI, respectively.
Study details: An analysis of more than 90,000 patients in the Nationwide Readmission Database in 2013 and 2014.
Disclosures: The authors did not report disclosures but indicated that the study did not receive any outside funding.
Source: Martinez RA et al. Ann Vasc Surg. 2018;52:96-107.
HCV, HBV, and HIV associated with autoimmune kidney diseases
Chronic viral infection can be associated with a variety of autoimmune kidney diseases, according to a review published in Rheumatic Disease Clinics.
In particular, hepatitis C virus (HCV) infection can cause several kidney disorders. These include cryoglobulinemic glomerulonephritis, membranous nephropathy, fibrillary glomerulopathy, immunotactoid glomerulopathy, and IgA nephropathy, wrote Joshua D. Long and his colleagues at Massachusetts General Hospital, Boston.
Similarly, hepatitis B virus (HBV) infection was found to be associated with both membranous nephropathy and polyarteritis nodosa, and human immunodeficiency virus (HIV) infection can cause HIV-associated nephropathy and HIV-associated immune complex diseases, which affect the kidneys.
In their detailed review, the authors discussed the various causal mechanisms and clinical presentations of each of these various autoimmune kidney diseases caused by HCV, HBV, and HIV, along with current treatment modalities.
“Control of the kidney disease relies primarily on treatment of viremia with antiviral agents; however, immunosuppression also may be needed in severe cases,” said the reviewers. However, “more clinical trials are needed to determine first-line therapies for patients who develop autoimmune kidney diseases in the context of chronic viral infections and to define when adjunctive immunosuppressive therapy is warranted,” they concluded.
One of the authors reported grant support and acting as a consultant for various pharmaceutical companies.
mlesney@mdedge.com
SOURCE: Long JD et al. Rheum Dis Clin N Am 2018;44:675-98.
Chronic viral infection can be associated with a variety of autoimmune kidney diseases, according to a review published in Rheumatic Disease Clinics.
In particular, hepatitis C virus (HCV) infection can cause several kidney disorders. These include cryoglobulinemic glomerulonephritis, membranous nephropathy, fibrillary glomerulopathy, immunotactoid glomerulopathy, and IgA nephropathy, wrote Joshua D. Long and his colleagues at Massachusetts General Hospital, Boston.
Similarly, hepatitis B virus (HBV) infection was found to be associated with both membranous nephropathy and polyarteritis nodosa, and human immunodeficiency virus (HIV) infection can cause HIV-associated nephropathy and HIV-associated immune complex diseases, which affect the kidneys.
In their detailed review, the authors discussed the various causal mechanisms and clinical presentations of each of these various autoimmune kidney diseases caused by HCV, HBV, and HIV, along with current treatment modalities.
“Control of the kidney disease relies primarily on treatment of viremia with antiviral agents; however, immunosuppression also may be needed in severe cases,” said the reviewers. However, “more clinical trials are needed to determine first-line therapies for patients who develop autoimmune kidney diseases in the context of chronic viral infections and to define when adjunctive immunosuppressive therapy is warranted,” they concluded.
One of the authors reported grant support and acting as a consultant for various pharmaceutical companies.
mlesney@mdedge.com
SOURCE: Long JD et al. Rheum Dis Clin N Am 2018;44:675-98.
Chronic viral infection can be associated with a variety of autoimmune kidney diseases, according to a review published in Rheumatic Disease Clinics.
In particular, hepatitis C virus (HCV) infection can cause several kidney disorders. These include cryoglobulinemic glomerulonephritis, membranous nephropathy, fibrillary glomerulopathy, immunotactoid glomerulopathy, and IgA nephropathy, wrote Joshua D. Long and his colleagues at Massachusetts General Hospital, Boston.
Similarly, hepatitis B virus (HBV) infection was found to be associated with both membranous nephropathy and polyarteritis nodosa, and human immunodeficiency virus (HIV) infection can cause HIV-associated nephropathy and HIV-associated immune complex diseases, which affect the kidneys.
In their detailed review, the authors discussed the various causal mechanisms and clinical presentations of each of these various autoimmune kidney diseases caused by HCV, HBV, and HIV, along with current treatment modalities.
“Control of the kidney disease relies primarily on treatment of viremia with antiviral agents; however, immunosuppression also may be needed in severe cases,” said the reviewers. However, “more clinical trials are needed to determine first-line therapies for patients who develop autoimmune kidney diseases in the context of chronic viral infections and to define when adjunctive immunosuppressive therapy is warranted,” they concluded.
One of the authors reported grant support and acting as a consultant for various pharmaceutical companies.
mlesney@mdedge.com
SOURCE: Long JD et al. Rheum Dis Clin N Am 2018;44:675-98.
FROM RHEUMATIC DISEASE CLINICS
Synthetic HCV glycoproteins elicit narrow, but not widely effective antibodies
Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.
Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.
Immunization with two synthetic consensus constructs of hepatitis C virus (HCV) glycoproteins was found to elicit narrow, but not widely effective, virus-neutralizing antibodies in guinea pigs, according to the results of a model study published in the journal Antiviral Research.
Researchers created two novel synthetic E2 glycoprotein immunogens (NotC1 and NotC2) using consensus nucleotide sequences deduced from samples of circulating genotype 1 HCV strains, according to Alexander W. Tarr, PhD, of the Nottingham (England) University Hospitals NHS Trust, and his colleagues.
Expression of these constructs in Drosophila melanogaster cells resulted in high yields of correctly folded, monomeric E2 proteins, which were used to immunize guinea pigs. Both proteins generated antibodies capable of neutralizing the H77 strain of HCV, although NotC1 elicited antibodies that were more potent at neutralizing virus entry. The two sets of glycoprotein-induced antibodies neutralized some HCV strains representing genotype 1, but not those strains representing genotype 2 or genotype 3.
“The broader objective of eliciting antibodies that neutralize patient strains representing multiple genotypes will require further refinement of immunization protocols. A vaccine construct comprising the consensus of a minimal CD81 binding domain might be able to focus the antibody response to conserved epitopes on E2. Additionally, boosting immunized animals with glycoproteins representing different strains might be required to focus the antibody response on to conserved conformational epitopes,” the researchers concluded.
The research was funded by the Medical Research Council, the NIHR Nottingham Biomedical Research Centre, and the European Union. Disclosures were not reported.
SOURCE: Tarr AW et al. Antiviral Research 2018;160:25-37.
FROM ANTIVIRAL RESEARCH
HCV adapts to HIV coinfection
HCV strains evolve differently in HIV-coinfected individuals, according to the results of a database analysis of HCV genetic sequences from patients monoinfected with HCV and those who were coinfected with HIV. The study compared results from 112 coinfected persons (CIPs) and 176 monoinfected persons (MIPs), according to the report published in the journal Infection, Genetics, and Evolution.
Genetic differences between intrahost variants of the HCV hypervariable region 1 (HVR1) were sampled from CIPs and MIPs, and the nucleotide sequences of intrahost HCV HVR1 variants (n = 28,622) obtained were represented using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers. Changes of the intrahost HCV population were detected by measuring coevolution among the HVR1 site using new PhyChem properties extracted from the next-generation sequencing of HVR1 data. Small but statistically significant variances in seven of the PhyChem indexes, measured using these intrahost HVR1 variants, was shown to be strongly associated with CIPs and MIPs (P less than .0001).
“The computational models built using these new markers provide novel opportunities for development of cybermolecular diagnostics,” wrote James Lara, PhD, and his colleagues at the Centers for Disease Control and Prevention.
All HVR1 sequences used (n = 28,622) shared only 6,782 profiles of the selected calculated dinucleotide-based auto covariances of the seven PhyChem indexes. The vast majority (98%-99%) of these profiles were found to be specific to CIPs or MIPs, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals, according to the authors.
Because of the common occurrence of HIV-coinfection in high-risk groups, “HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” Dr. Lara and his colleagues concluded.
The authors reported having no conflicts of interest.
SOURCE: Lara J et al. Infection, Genetics and Evolution. 2018. 65:216-25.
HCV strains evolve differently in HIV-coinfected individuals, according to the results of a database analysis of HCV genetic sequences from patients monoinfected with HCV and those who were coinfected with HIV. The study compared results from 112 coinfected persons (CIPs) and 176 monoinfected persons (MIPs), according to the report published in the journal Infection, Genetics, and Evolution.
Genetic differences between intrahost variants of the HCV hypervariable region 1 (HVR1) were sampled from CIPs and MIPs, and the nucleotide sequences of intrahost HCV HVR1 variants (n = 28,622) obtained were represented using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers. Changes of the intrahost HCV population were detected by measuring coevolution among the HVR1 site using new PhyChem properties extracted from the next-generation sequencing of HVR1 data. Small but statistically significant variances in seven of the PhyChem indexes, measured using these intrahost HVR1 variants, was shown to be strongly associated with CIPs and MIPs (P less than .0001).
“The computational models built using these new markers provide novel opportunities for development of cybermolecular diagnostics,” wrote James Lara, PhD, and his colleagues at the Centers for Disease Control and Prevention.
All HVR1 sequences used (n = 28,622) shared only 6,782 profiles of the selected calculated dinucleotide-based auto covariances of the seven PhyChem indexes. The vast majority (98%-99%) of these profiles were found to be specific to CIPs or MIPs, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals, according to the authors.
Because of the common occurrence of HIV-coinfection in high-risk groups, “HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” Dr. Lara and his colleagues concluded.
The authors reported having no conflicts of interest.
SOURCE: Lara J et al. Infection, Genetics and Evolution. 2018. 65:216-25.
HCV strains evolve differently in HIV-coinfected individuals, according to the results of a database analysis of HCV genetic sequences from patients monoinfected with HCV and those who were coinfected with HIV. The study compared results from 112 coinfected persons (CIPs) and 176 monoinfected persons (MIPs), according to the report published in the journal Infection, Genetics, and Evolution.
Genetic differences between intrahost variants of the HCV hypervariable region 1 (HVR1) were sampled from CIPs and MIPs, and the nucleotide sequences of intrahost HCV HVR1 variants (n = 28,622) obtained were represented using 148 physical-chemical (PhyChem) indexes of DNA nucleotide dimers. Changes of the intrahost HCV population were detected by measuring coevolution among the HVR1 site using new PhyChem properties extracted from the next-generation sequencing of HVR1 data. Small but statistically significant variances in seven of the PhyChem indexes, measured using these intrahost HVR1 variants, was shown to be strongly associated with CIPs and MIPs (P less than .0001).
“The computational models built using these new markers provide novel opportunities for development of cybermolecular diagnostics,” wrote James Lara, PhD, and his colleagues at the Centers for Disease Control and Prevention.
All HVR1 sequences used (n = 28,622) shared only 6,782 profiles of the selected calculated dinucleotide-based auto covariances of the seven PhyChem indexes. The vast majority (98%-99%) of these profiles were found to be specific to CIPs or MIPs, indicating that coevolution among HVR1 sites reflects HCV adaptation to HIV among coinfected individuals, according to the authors.
Because of the common occurrence of HIV-coinfection in high-risk groups, “HCV strains circulating in high-risk groups need to be carefully monitored for the identification of potentially new traits of clinical and public health relevance,” Dr. Lara and his colleagues concluded.
The authors reported having no conflicts of interest.
SOURCE: Lara J et al. Infection, Genetics and Evolution. 2018. 65:216-25.
FROM INFECTION, GENETICS, AND EVOLUTION
Pay attention to kidney disease risk in people living with HIV
The prevalence of chronic kidney disease (CKD) in people living with HIV varied widely, depending on population and criteria, according to a systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.
The review included all studies that involved adults older than 21 years of age, investigated people living with HIV with CKD, reported prevalence of CKD, and were published in a peer-reviewed journal, according to Jungmin Park, PhD, RN, of CHA University, Pocheon-Si, South Korea, and her colleague.
Out of an initial search yielding 1,960 citations in PubMed and 5,356 citations in PsycInfo, the results were pared down to 21 articles, which met all of the inclusion/exclusion criteria and were used for the final analysis.
The risk factors for CKD in people living with HIV cited most often in the studies consisted of medications, hypertension, older age, diabetes mellitus, hepatitis coinfection (with hepatitis C virus more prominent than hepatitis B virus), low CD4+ T-cell count, and race, Dr. Park and her colleague reported.
Of the various risk factors, the only ones unique to HIV were viral load and CD4+ T-cell count. One study reporting on 5,538 treatment-naive patients in mainland China suggested that HIV viral replication in renal cells may be the cause of renal damage in patients with high viral loads, meaning that viral suppression would improve renal function. However, all of these risk factors are intrinsically linked, according to Dr. Park and her colleague. They added that managing viral load alone would be ineffective in preventing CKD: “Therefore [people living with HIV] will need to effectively manage every aspect of their health, including metabolic and cardiovascular systems.”
Of the 43,114 people living with HIV across the 21 studies, 3,218 (7.3%) had CKD. The reported prevalence of CKD ranged from 2.3% to 53.3%, with the African population having the highest prevalence. Some of the wide variation was possibly attributable to differences in the definitions of CKD used across the various studies.
“The risk of under-diagnosis of CKD can lead to long-term health complications. Health care providers must monitor kidney function and treatment for renal damage carefully, especially for people living with HIV with additional diagnoses of diabetes and/or hypertension, and for those who are aging,” Dr. Park and her colleague concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Park, J et al. J Assoc Nurses AIDS Care. 2018;29:655-66.
The prevalence of chronic kidney disease (CKD) in people living with HIV varied widely, depending on population and criteria, according to a systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.
The review included all studies that involved adults older than 21 years of age, investigated people living with HIV with CKD, reported prevalence of CKD, and were published in a peer-reviewed journal, according to Jungmin Park, PhD, RN, of CHA University, Pocheon-Si, South Korea, and her colleague.
Out of an initial search yielding 1,960 citations in PubMed and 5,356 citations in PsycInfo, the results were pared down to 21 articles, which met all of the inclusion/exclusion criteria and were used for the final analysis.
The risk factors for CKD in people living with HIV cited most often in the studies consisted of medications, hypertension, older age, diabetes mellitus, hepatitis coinfection (with hepatitis C virus more prominent than hepatitis B virus), low CD4+ T-cell count, and race, Dr. Park and her colleague reported.
Of the various risk factors, the only ones unique to HIV were viral load and CD4+ T-cell count. One study reporting on 5,538 treatment-naive patients in mainland China suggested that HIV viral replication in renal cells may be the cause of renal damage in patients with high viral loads, meaning that viral suppression would improve renal function. However, all of these risk factors are intrinsically linked, according to Dr. Park and her colleague. They added that managing viral load alone would be ineffective in preventing CKD: “Therefore [people living with HIV] will need to effectively manage every aspect of their health, including metabolic and cardiovascular systems.”
Of the 43,114 people living with HIV across the 21 studies, 3,218 (7.3%) had CKD. The reported prevalence of CKD ranged from 2.3% to 53.3%, with the African population having the highest prevalence. Some of the wide variation was possibly attributable to differences in the definitions of CKD used across the various studies.
“The risk of under-diagnosis of CKD can lead to long-term health complications. Health care providers must monitor kidney function and treatment for renal damage carefully, especially for people living with HIV with additional diagnoses of diabetes and/or hypertension, and for those who are aging,” Dr. Park and her colleague concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Park, J et al. J Assoc Nurses AIDS Care. 2018;29:655-66.
The prevalence of chronic kidney disease (CKD) in people living with HIV varied widely, depending on population and criteria, according to a systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.
The review included all studies that involved adults older than 21 years of age, investigated people living with HIV with CKD, reported prevalence of CKD, and were published in a peer-reviewed journal, according to Jungmin Park, PhD, RN, of CHA University, Pocheon-Si, South Korea, and her colleague.
Out of an initial search yielding 1,960 citations in PubMed and 5,356 citations in PsycInfo, the results were pared down to 21 articles, which met all of the inclusion/exclusion criteria and were used for the final analysis.
The risk factors for CKD in people living with HIV cited most often in the studies consisted of medications, hypertension, older age, diabetes mellitus, hepatitis coinfection (with hepatitis C virus more prominent than hepatitis B virus), low CD4+ T-cell count, and race, Dr. Park and her colleague reported.
Of the various risk factors, the only ones unique to HIV were viral load and CD4+ T-cell count. One study reporting on 5,538 treatment-naive patients in mainland China suggested that HIV viral replication in renal cells may be the cause of renal damage in patients with high viral loads, meaning that viral suppression would improve renal function. However, all of these risk factors are intrinsically linked, according to Dr. Park and her colleague. They added that managing viral load alone would be ineffective in preventing CKD: “Therefore [people living with HIV] will need to effectively manage every aspect of their health, including metabolic and cardiovascular systems.”
Of the 43,114 people living with HIV across the 21 studies, 3,218 (7.3%) had CKD. The reported prevalence of CKD ranged from 2.3% to 53.3%, with the African population having the highest prevalence. Some of the wide variation was possibly attributable to differences in the definitions of CKD used across the various studies.
“The risk of under-diagnosis of CKD can lead to long-term health complications. Health care providers must monitor kidney function and treatment for renal damage carefully, especially for people living with HIV with additional diagnoses of diabetes and/or hypertension, and for those who are aging,” Dr. Park and her colleague concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Park, J et al. J Assoc Nurses AIDS Care. 2018;29:655-66.
FROM THE JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE
Key clinical point: Chronic kidney disease in people living with HIV varies widely across geographic regions.
Major finding: The reported prevalence of CKD in PLWH ranged from 2.3% to 53.3%, with the African population having the highest prevalence.
Study details: Systematic literature review of the PubMed and PsycInfo databases for articles published from January 2000 through August 2016.
Disclosures: The authors reported that they had no conflicts of interest.
Source: J Assoc Nurses AIDS Care. 2018;29:655-66).
HIV testing low in U.S. women engaged in risky behavior
HIV testing rates were low among women whose sexual behaviors increased their risk of HIV infection, and they were especially low among women who reported having anal sex, according to a report published in the American Journal of Obstetrics & Gynecology.
Data from the 2011-2015 National Survey of Family Growth were analyzed to estimate the proportion of sexually active, nonpregnant U.S. women aged 15-44 years who had had an HIV test within the past year. The data was stratified by those who reported anal sex and other risk factors, including having more than two sexual partners, condomless sex with a new partner or multiple partners, gonorrhea in the past year, or any history of syphilis, according to Mary Evans, MD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention and her colleagues.
Among the 42.4 million sexually active women assessed, 9.0 million (20%) reported they had had anal sex in the past year. Of these, 19% reported that their providers asked about their types of intercourse, and 20% reported an HIV test within the past year. Overall, HIV testing was higher among women who reported anal sex and whose providers asked about types of sex engaged in than it was among those women whose provider did not ask (38% vs. 16%, respectively; P less than .001). However, HIV testing in the past year was higher for women with other forms of risky behaviors as compared with anal sex, ranging from 35.8% to 47.2%.
“Women who report sexual behaviors such as anal sex would benefit from an HIV test and an assessment for [prevention with preexposure prophylaxis] eligibility. Women’s health care providers are uniquely poised to provide HIV prevention for women who tend to have frequent encounters with the health care system,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.
HIV testing rates were low among women whose sexual behaviors increased their risk of HIV infection, and they were especially low among women who reported having anal sex, according to a report published in the American Journal of Obstetrics & Gynecology.
Data from the 2011-2015 National Survey of Family Growth were analyzed to estimate the proportion of sexually active, nonpregnant U.S. women aged 15-44 years who had had an HIV test within the past year. The data was stratified by those who reported anal sex and other risk factors, including having more than two sexual partners, condomless sex with a new partner or multiple partners, gonorrhea in the past year, or any history of syphilis, according to Mary Evans, MD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention and her colleagues.
Among the 42.4 million sexually active women assessed, 9.0 million (20%) reported they had had anal sex in the past year. Of these, 19% reported that their providers asked about their types of intercourse, and 20% reported an HIV test within the past year. Overall, HIV testing was higher among women who reported anal sex and whose providers asked about types of sex engaged in than it was among those women whose provider did not ask (38% vs. 16%, respectively; P less than .001). However, HIV testing in the past year was higher for women with other forms of risky behaviors as compared with anal sex, ranging from 35.8% to 47.2%.
“Women who report sexual behaviors such as anal sex would benefit from an HIV test and an assessment for [prevention with preexposure prophylaxis] eligibility. Women’s health care providers are uniquely poised to provide HIV prevention for women who tend to have frequent encounters with the health care system,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.
HIV testing rates were low among women whose sexual behaviors increased their risk of HIV infection, and they were especially low among women who reported having anal sex, according to a report published in the American Journal of Obstetrics & Gynecology.
Data from the 2011-2015 National Survey of Family Growth were analyzed to estimate the proportion of sexually active, nonpregnant U.S. women aged 15-44 years who had had an HIV test within the past year. The data was stratified by those who reported anal sex and other risk factors, including having more than two sexual partners, condomless sex with a new partner or multiple partners, gonorrhea in the past year, or any history of syphilis, according to Mary Evans, MD, of the National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention at the Centers for Disease Control and Prevention and her colleagues.
Among the 42.4 million sexually active women assessed, 9.0 million (20%) reported they had had anal sex in the past year. Of these, 19% reported that their providers asked about their types of intercourse, and 20% reported an HIV test within the past year. Overall, HIV testing was higher among women who reported anal sex and whose providers asked about types of sex engaged in than it was among those women whose provider did not ask (38% vs. 16%, respectively; P less than .001). However, HIV testing in the past year was higher for women with other forms of risky behaviors as compared with anal sex, ranging from 35.8% to 47.2%.
“Women who report sexual behaviors such as anal sex would benefit from an HIV test and an assessment for [prevention with preexposure prophylaxis] eligibility. Women’s health care providers are uniquely poised to provide HIV prevention for women who tend to have frequent encounters with the health care system,” the researchers concluded.
The authors reported that they had no conflicts of interest.
SOURCE: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.
FROM THE AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY
Key clinical point: Health care providers don’t ask sexually active women about risky behavior that would raise their risk of HIV infection.
Major finding: Of women who reported having anal sex, 19% reported that their providers asked about their types of intercourse.
Study details: Data from the 2011-2015 National Survey of Family Growth.
Disclosures: The authors reported that they had no conflicts of interest.
Source: Evans ME et al. Am J Obstet Gynecol. 2018 Oct;219(4):383.e1-7.