<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_277"
                     title="Liver Cell Culture System Might Test New HCV Drugs (CME/CE)"
                     score="0.002"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/18133?impressionId=1265809246951"
                     
      &lt;p&gt;Researchers say they can now grow liver cells that maintain their functions long enough to test potential treatments for hepatitis C.&lt;/p&gt;
&lt;p&gt;The method uses so-called &quot;micropatterned co-cultures&quot; of primary human hepatocytes and supportive stroma, according to Sangeeta N. Bhatia, MD, PhD, of MIT, and colleagues.&lt;/p&gt;
&lt;p&gt;The co-cultures were able to support the entire life cycle of hepatitis C, including infection and replication, Bhatia and colleagues reported online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Coupled with reporter systems, the co-cultures have &quot;potential as a high-throughput platform for simultaneous assessment of in vitro efficacy and toxicity&quot; of antiviral drugs, the researchers said.&lt;/p&gt;
&lt;p&gt;The lack of such a system has been a roadblock to testing potential treatments for the virus, which affects 130 million people around the world, the researchers noted in the journal.&lt;/p&gt;
&lt;p&gt;Recently, they added, researchers have been able to propagate the virus in human hepatoma cells, but those cells, among other issues, proliferate abnormally and have disturbed gene expression.&lt;/p&gt;
&lt;p&gt;To overcome those obstacles, the researchers turned to primary hepatocytes, which would make a better test system, except that they are notoriously hard to maintain in culture.&lt;/p&gt;
&lt;p&gt;To form the co-cultures, Bhatia and colleagues seeded multi-well plates with human hepatocytes, followed several hours later by murine fibroblasts.&lt;/p&gt;
&lt;p&gt;&quot;If you just put cells on a surface in an unorganized way, they lose their function very quickly,&quot; Bhatia said in a statement. &quot;If you specify which cells sit next to each other, you can extend the lifetime of the cells and help them maintain their function.&quot;&lt;/p&gt;
&lt;p&gt;In a series of experiments, Bhatia and colleagues found:&lt;ul&gt; &lt;li&gt;Pseudoparticles bearing the hepatitis C glycoproteins E1 and E2 were able to infect between 1% and 3% of the hepatocytes, but did not infect the fibroblasts.&lt;/li&gt; &lt;li&gt;A hepatitis C virus modified to express a fluorescent protein persistently replicated over a two-week period.&lt;/li&gt; &lt;li&gt;Infectious virus was found in the co-culture supernatant from four through 12 days after initial infection.&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;The researchers also tested some possible therapeutics, including antibodies against viral entry factors and viral protease inhibitors, and were able to show effects on replication of hepatitis C.&lt;/p&gt;
&lt;p&gt;They were also able to test two or more drugs simultaneously to show the feasibility of combination drug studies using the system.&lt;/p&gt;
&lt;p&gt;Although the system is &quot;an important step forward,&quot; Bhatia and colleagues said, the co-cultures have some limitations, including the relatively inefficient uptake of virus.&lt;/p&gt;
&lt;p&gt;But they concluded that the co-cultures have the potential to be a &quot;highly valuable system for studies of (hepatitis C) biology.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;This study had support from the Greenberg Medical Research Institute, the Ellison Medical Foundation, the Starr Foundation, the Ronald A. Shellow Memorial Fund, the Richard Salomon Family Foundation, and the NIH. The researchers said they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_1752"
                     title="DDW: Risk of IBD Increased with GI Bacterial Infection"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/DDW/tb/14521?impressionId=1265809246951"
                     
      CHICAGO, June 3 -- Gastroenteritis caused by &lt;em&gt;Salmonella&lt;/em&gt; or &lt;em&gt;Campylobacter&lt;/em&gt; infection may predispose patients to inflammatory bowel disease (IBD), a large, population-based study showed.
              &lt;p&gt; 
              &lt;p&gt;Although the overall risk for developing IBD was low, it was three times greater in patients who had a laboratory-confirmed infection with one of the two bacteria (HR 2.9, 95% CI 2.2 to 3.9), according to Henrik Nielsen, M.D., of Aalborg Hospital in Denmark.
              &lt;p&gt; 
              &lt;p&gt;After excluding IBD cases diagnosed within one year of bacterial infection, the risk of developing the condition was still doubled (1.9, 95% CI 1.4 to 2.6), he reported at Digestive Disease Week here and online in &lt;em&gt;Gastroenterology&lt;/em&gt;.
              &lt;p&gt; 
              &lt;p&gt;&quot;Our results have implications for the understanding of the pathogenesis of IBD and for clinicians who should be aware of the higher risk of IBD in &lt;em&gt;Salmonella&lt;/em&gt; and &lt;em&gt;Campylobacter&lt;/em&gt; gastroenteritis patients, both in the short and long term,&quot; Dr. Nielsen and his colleagues wrote.
              &lt;p&gt; 
              &lt;p&gt;In recent years, there has been an increase in the incidence of IBD coinciding with a rise in the number of food-borne intestinal infections, according to Dr. Nielsen.
              &lt;p&gt; 
              &lt;p&gt;Both genetic and environmental factors, including bacterial infections, are believed to contribute to the development of IBD, he said, although the mechanisms remain unclear.
              &lt;p&gt; 
              &lt;p&gt;Previous studies exploring the relationship between gastroenteritis and IBD have been mostly subject to various limitations, including small size and cross-sectional design, Dr. Nielsen said.
              &lt;p&gt; 
              &lt;p&gt;So he and his colleagues turned to the Danish Civil Registration System, which contains information on every resident of Denmark, to address the issue.
              &lt;p&gt; 
              &lt;p&gt;They identified 13,148 individuals who had a laboratory-confirmed case of gastroenteritis caused by infection with either &lt;em&gt;Salmonella&lt;/em&gt; or &lt;em&gt;Campylobacter&lt;/em&gt; from 1991 to 2003.
              &lt;p&gt; 
              &lt;p&gt;These patients were matched by age and gender to 26,216 controls who had not been exposed to the bacteria.
              &lt;p&gt; 
              &lt;p&gt;All patients were followed for up to 15 years (mean 7.5).
              &lt;p&gt; 
              &lt;p&gt;Through follow-up, 1.2% of individuals with a laboratory-confirmed case of gastroenteritis caused by one of the two bacteria and 0.5% of the controls developed IBD.
              &lt;p&gt; 
              &lt;p&gt;The risk of developing IBD among exposed individuals was greatest in the year after infection but persisted throughout follow-up.
              &lt;p&gt; 
              &lt;p&gt;The hazard rate ratio for IBD was 2.9 (95% CI 2.1 to 3.9) for the whole period and 1.9 (1.3 to 2.6) if the first year after &lt;em&gt;Salmonella&lt;/em&gt;/&lt;em&gt;Campylobacter&lt;/em&gt; infection was excluded.
              &lt;p&gt; 
              &lt;p&gt;The increased risk in exposed subjects was observed throughout the observation period of 15 years and was independent of age and gender of the patient.
              &lt;p&gt; 
              &lt;p&gt;The magnitude of the association was similar for both &lt;em&gt;Salmonella&lt;/em&gt; and &lt;em&gt;Campylobacter&lt;/em&gt; and for both Crohn&apos;s disease and ulcerative colitis.
              &lt;p&gt; 
              &lt;p&gt;Dr. Nielsen acknowledged that the study could not prove a causal relationship and that laboratory-confirmed cases of these infections represent a minor fraction of actual infections in the community.
              &lt;p&gt; 
              &lt;p&gt;Considering these limitations, the findings should not change the way clinicians manage patients with gastroenteritis caused by one of these two bacteria, he said.
              &lt;p&gt; 
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt;Dr. Nielsen reported no conflicts of interest.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
         
    </recommendedItem>
    <recommendedItem id="20090101_19_1760"
                     title="DDW: Novel Biologics Thwart Recurrent &lt;em&gt;C. Diff&lt;/em&gt;"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/DDW/tb/14533?impressionId=1265809246951"
                     
       CHICAGO, June 3 -- Two investigational monoclonal antibody drugs, added to standard antibiotics, prevented recurrent &lt;em&gt;Clostridium difficile&lt;/em&gt; infections in a randomized trial, researchers reported.
              &lt;p&gt; 
              &lt;p&gt;The two biologics reduced recurrent &lt;em&gt;C. difficile&lt;/em&gt; diarrhea by 70%, according to Donna Ambrosino, M.D., of the University of Massachusetts Medical School, at a press briefing here at Digestive Disease Week.
              &lt;p&gt; 
              &lt;p&gt;In the 200-patient, multicenter study, patients receiving antibiotic treatment for an initial &lt;em&gt;C. difficile&lt;/em&gt; episode who received a single infusion of the antibodies had recurrent diarrhea within 12 weeks at a rate of 6.9%, compared with 25.3% of patients infused with saline (&lt;em&gt;P&lt;/em&gt;=0.0004).
              &lt;p&gt; 
              &lt;p&gt;Dr. Ambrosino called this &quot;a dramatic result&quot; and predicted the therapy would be approved within a few years.
              &lt;p&gt; 
              &lt;p&gt;The two antibodies target the &lt;em&gt;C. difficile&lt;/em&gt; A and B toxins thought to be responsible for infection symptoms, principally diarrhea, hypotension, and dehydration.
              &lt;p&gt; 
              &lt;p&gt;Patients with confirmed, symptomatic &lt;em&gt;C. difficile&lt;/em&gt; infections were enrolled while under treatment with metronidazole or vancomycin, with 101 assigned to the antibody treatment and 99 to placebo.
              &lt;p&gt; 
              &lt;p&gt;About 30% of patients were infected with the epidemic BI/NAP/027 strain and a similar fraction had histories of prior &lt;em&gt;C. difficile&lt;/em&gt; infection. Half were hospitalized at the time of enrollment.
              &lt;p&gt; 
              &lt;p&gt;The two antibody drugs, called CDA1 and CDB1, were each given at 10 mg/kg. Antibiotic therapy for the initial episode was administered for the normal duration.
              &lt;p&gt; 
              &lt;p&gt;Efficacy of the antibody drugs in preventing recurrent diarrhea was undiminished in patients with the BI/NAP/027 strain or with prior &lt;em&gt;C. difficile&lt;/em&gt; infection history.
              &lt;p&gt; 
              &lt;p&gt;In those patients, the recurrence rate with antibody treatment was 6.9% to 8.0%, compared with 31.6% to 37.5% for the placebo group (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for both subgroups).
              &lt;p&gt; 
              &lt;p&gt;Dr. Ambrosino said there was also a strong trend toward reduced severity of the initial episode in the antibody-treated patients.
              &lt;p&gt; 
              &lt;p&gt;Just under 30% of patients receiving the two biologics had more than five unformed stools per day for two days, compared with 43.4% of the placebo group (&lt;em&gt;P&lt;/em&gt;=0.056).
              &lt;p&gt; 
              &lt;p&gt;Duration of hospitalization in the initial episode was virtually identical between groups. But subsequent hospitalizations were much less frequent with antibody therapy: 8.9% versus 20.2% (&lt;em&gt;P&lt;/em&gt;=0.028).
              &lt;p&gt; 
              &lt;p&gt;Adverse effects were more common in the placebo group, and mainly reflected the effects of &lt;em&gt;C. difficile&lt;/em&gt; infection, such as hypotension and dehydration.
              &lt;p&gt; 
              &lt;p&gt;Dr. Ambrosino said the researchers had not calculated number-needed-to-treat values for the antibody therapy to prevent recurrences.
              &lt;p&gt; 
              &lt;p&gt;Nicholas J. Shaheen, M.D., M.P.H., of the University of North Carolina in Chapel Hill, N.C., who moderated the press briefing, said &lt;em&gt;C. difficile&lt;/em&gt; infection has recently become a significant clinical problem beyond the hospital setting.
              &lt;p&gt; 
              &lt;p&gt;&quot;It&apos;s an increasingly virulent infection that&apos;s now infecting walking, talking, normal people in the community. It makes appropriate therapy [for &lt;em&gt;C. difficile&lt;/em&gt;] even more important,&quot; he said.
              &lt;p&gt; 
              &lt;p&gt;He questioned whether patients might be put off by antibody therapy as &quot;scary&quot; as well as expensive.
              &lt;p&gt; 
              &lt;p&gt;Dr. Ambrosino responded that other monoclonals have an excellent safety record. &quot;It&apos;s one of the great advantages of this drug, it&apos;s a completely human antibody,&quot; she said.
              &lt;p&gt; 
              &lt;p&gt;She acknowledged that cost would be a factor. &quot;We assume it would be targeted to patients who need it the most,&quot; she said, but argued that it could ultimately result in a cost savings by reducing recurrent infection.
              &lt;p&gt; 
              &lt;p&gt;&lt;table cellspacing=&quot;0&quot; hspace=&quot;1&quot; style=&quot;border-style:solid; border-width:1px; border-color:#8dabbc; font-family:arial; font-size:12px; background-color:#DBE9F2; padding:5px 5px 5px 5px;&quot;&gt;
&lt;tr&gt;&lt;td&gt; Dr. Ambrosino is director of MassBiologics, a part of the University of Massachusetts Medical School.
              &lt;p&gt; 
              &lt;p&gt;The agents were co-developed by MassBiologics and Medarex of Princeton, N.J., with  commercial rights recently licensed to Merck.
              &lt;p&gt; 
              &lt;p&gt;The study was funded by MassBiologics and Medarex.
              &lt;p&gt; 
              &lt;p&gt;Dr. Ambrosino reported no conflicts of interest other than her employment with MassBiologics.
              &lt;p&gt; 
              &lt;p&gt;Dr. Shaheen reported relationships with AstraZeneca, Barrx Medical, CSA Medical, Procter &amp;amp; Gamble, Takeda, and TAP.&lt;/td&gt;&lt;/tr&gt;&lt;/table&gt;
    </recommendedItem>
    <recommendedItem id="20090101_19_2885"
                     title="ICAAC: MRSA Heart Infections Growing in Inner Cities (CME/CE)"
                     score="-0.005"
                     href="http://www.medpagetoday.com/MeetingCoverage/ICAAC/tb/15955?impressionId=1265809246951"
                     
      &lt;p&gt;SAN FRANCISCO -- Methicillin-resistant &lt;em&gt;Staphylococcus aureus&lt;/em&gt; (MRSA) is becoming the leading cause of staph-associated infective endocarditis in some areas, a researcher said here.&lt;/p&gt;
&lt;p&gt;Over an eight-year period starting in 2000, the proportion of such cases caused by MRSA went from 25% to 85% in an inner city hospital, according to Graeme Forrest, MBBS, of Oregon Health and Science University.&lt;/p&gt;
&lt;p&gt;The rise of MRSA cases at the University of Maryland in Baltimore -- where Forrest and colleagues carried out the study -- was paralleled by a drop in cases caused by drug-susceptible &lt;em&gt;S. aureus&lt;/em&gt;, he said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy.&lt;/p&gt;
&lt;p&gt;The lack of proven antimicrobial treatments suggests an &quot;urgent need&quot; for new therapies, Forrest said, as well as a need to evaluate early surgery in such patients.&lt;/p&gt;
&lt;p&gt;Forrest said the study only has data from a single institution, but he suspects that situation is the same in other inner city hospitals, where social conditions -- including issues such as injection drug use and over-crowding -- have increased rates of community-acquired MRSA.&lt;/p&gt;
&lt;p&gt;For the study, the researchers looked at 1,356 episodes of proven or probable infective endocarditis from 740 patients from 2000 through 2007.&lt;/p&gt;
&lt;p&gt;Of those, 425 patients met criteria for &lt;em&gt;S. aureus&lt;/em&gt; endocarditis, with MRSA accounting for 286 (or 67%) of all such cases and susceptible &lt;em&gt;S. aureus&lt;/em&gt; for 139 (or 33%).&lt;/p&gt;
&lt;p&gt;The increase in MRSA cases -- which went from from 25% of &lt;em&gt;S. aureus&lt;/em&gt; cases to 85% over the time period -- was significant at &lt;em&gt;P&lt;/em&gt;=0.005, Forrest said.&lt;/p&gt;
&lt;p&gt;In 2000, he and colleagues found, the incidence of MRSA infective endocarditis was 22%, but it climbed to 58% in 2007. At the same time, susceptible &lt;em&gt;S. aureus&lt;/em&gt; fell from 55% in 2000 to under 10% in 2007. The changes were significant at &lt;em&gt;P&lt;/em&gt;=0.03.&lt;/p&gt;
&lt;p&gt;The turning point, Forrest said, came in 2002 for reasons that are not clear, but probably have to do with the prevalence of MRSA in the community.&lt;/p&gt;
&lt;p&gt;The change had a significant effect on mortality, he said: Survival was 90% for those with drug-susceptible infections, compared with 79% for those with MRSA (&lt;em&gt;P&lt;/em&gt;=0.004).&lt;/p&gt;
&lt;p&gt;The finding &quot;makes sense ... as there have been reports that infective endocarditis caused by MRSA is increasing among IV drug users,&quot; said Lindsay Grayson, MD, of the Austin Hospital in Melbourne, Australia. Grayson, one of the meeting&apos;s program co-chairs, was not part of the research.&lt;/p&gt;
&lt;p&gt;But, he added, the issue is likely limited to the inner cities. &quot;Outside of that setting I am not aware of any reports&quot; that MRSA-associated endocarditis is increasing.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was not funded. Forrest did not report any potential conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_643"
                     title="ACS: Nationwide Deaths From C. Difficile Colitis Climb"
                     score="-0.006"
                     href="