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    <recommendedItem id="20100101_19_391"
                     title="Rare Genetic Deletion Linked to Morbid Obesity (CME/CE)"
                     score="0.009"
                     href="http://www.medpagetoday.com/Genetics/GeneralGenetics/tb/18286?impressionId=1265803240603"
                     
      &lt;p&gt;Missing sections of DNA may have a powerful impact on weight for a small segment of the population, researchers said.&lt;/p&gt;
&lt;p&gt;Nearly all teens and adults found to have a particular deletion of roughly 30-genes on chromosome 16p11.2 were obese  --  most morbidly so  --  with a body mass index of at least 40 kg/m&lt;sup&gt;2&lt;/sup&gt;, Philippe Froguel, MD, PhD, of Imperial College London, and colleagues reported in &lt;em&gt;Nature&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;While the variant appeared to explain only a small proportion of morbid obesity  --  0.7% in the study population  --  it was never present in healthy, normal-weight controls.&lt;/p&gt;
&lt;p&gt;&quot;Although the recent rise in obesity in the developed world is down to an unhealthy environment, with an abundance of unhealthy food and many people taking very little exercise, the difference in the way people respond to this environment is often genetic,&quot; Froguel said in a prepared statement.&lt;/p&gt;
&lt;p&gt;But with further findings like these, it may be possible to identify such individuals through genetic testing, he said.&lt;/p&gt;
&lt;p&gt;If so, &quot;We can then offer them appropriate support and medical interventions, such as the option of weight-loss surgery, to improve their long-term health,&quot; Froguel declared.&lt;/p&gt;
&lt;p&gt;Although researchers speculate that one in 20 cases of obesity may have a genetic cause, the genetic component remains largely elusive.&lt;/p&gt;
&lt;p&gt;Even accounting for such a small fraction of cases, the newly discovered 16p11.2 variant would be the second most frequent known genetic cause of obesity, Froguel&apos;s group said.&lt;/p&gt;
&lt;p&gt;Extensive genome-wide association studies have linked numerous single nucleotide polymorphisms (SNPs) to obesity, but added all together they account for only a small fraction of the known heritable component, the researchers said.&lt;/p&gt;
&lt;p&gt;&quot;The &apos;common disease, common variant&apos; hypothesis is increasingly coming under challenge,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Their team first identified the genetic deletion in teen and adults with learning difficulties or delayed development.&lt;/p&gt;
&lt;p&gt;Because the 31 individuals who had the nearly identical deletions of at least 593 kilobases at chromosome 16p11.2 in one copy of their DNA all had a BMI of over 30 kg/m&lt;sup&gt;2&lt;/sup&gt;, the researchers decided to dig a little deeper.&lt;/p&gt;
&lt;p&gt;&quot;Cohorts with extreme phenotypes that include obesity may be enriched for rare but very potent risk variants,&quot; making them easier to discover, they wrote.&lt;/p&gt;
&lt;p&gt;So they undertook a case-control study among 312 patients at three centers in Britain and France who presented with congenital malformations, developmental delay, or both, in addition to obesity.&lt;/p&gt;
&lt;p&gt;The same deletions were seen in 2.9% of these individuals.&lt;/p&gt;
&lt;p&gt;The function of the missing genes are not well known, but some have previously been associated with delayed development, autism, and schizophrenia.&lt;/p&gt;
&lt;p&gt;Notably, though, the frequency of deletion of these genes in the obese case-control cohort was &quot;appreciably higher&quot; than the less than 1% seen in the autism and other studies that didn&apos;t include obesity as an inclusion criteria, the researchers said.&lt;/p&gt;
&lt;p&gt;A second independent survey of genetic data at eight cytogenetic centers in France, Switzerland, and Estonia turned up a 0.6% rate among 3,947 people with developmental delay, malformations, or both, but who were not selected for obesity (&lt;em&gt;P&lt;/em&gt;=0.00022 versus the cohort selected for obesity).&lt;/p&gt;
&lt;p&gt;Analysis of those with the missing genes revealed an age-dependent link to weight: All four teens and adults were obese. Children were often obese (four of 15) or overweight (two of 15). Children under 2 years all had normal weight.&lt;/p&gt;
&lt;p&gt;So to see whether the deletion was independent of neurodevelopmental problems, Froguel&apos;s group examined genome-wide association study data from general population cohorts totaling 11,856 individuals along with 2,772 from childhood obesity and adult morbid obesity case-control studies, 931 in an extreme early-onset obesity study, and 141 who had bariatric weight-loss surgery.&lt;/p&gt;
&lt;p&gt;All adult carriers of the deletion were obese with the exception of one who was apparently diabetic. Each of the seven children and adolescents who carried the variant had a BMI in the top 0.1% for their age and gender.&lt;/p&gt;
&lt;p&gt;None had any reported developmental or cognitive problems. Four had reported hyperphagia with excessive hunger and food intake.&lt;/p&gt;
&lt;p&gt;Altogether, the 16p11.2 deletions predicted 29.8-fold elevated risk of obesity (&lt;em&gt;P&lt;/em&gt;=0.00000058) and 43.0-fold elevated risk of morbid obesity (&lt;em&gt;P&lt;/em&gt;=0.000000064) compared with lean or normal weight.&lt;/p&gt;
&lt;p&gt;By extrapolation, the researchers extrapolated that about 0.4% of all morbidly obese cases are attributable to an inherited 16p11.2 deletion, with 0.3% arising from a de novo deletion in the same genetic region.&lt;/p&gt;
&lt;p&gt;&quot;Although they may be heterogeneous in nature, these deletions are highly likely to be the causal variants,&quot; they wrote.&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 supported by &quot;Le Conseil Regional Nord Pas de Calais/FEDER&quot; along with various governmental and industry supporters for the various component studies.&lt;/p&gt;&lt;p&gt;The researchers reported no financial conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.008"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265803240603"
                     
      Monitoring two types of immune cells in kidney transplant recipients might identify patients with an increased risk of skin cancer, British investigators reported.&lt;br&gt;
&lt;br&gt;Increased levels of T-regulatory cells (Tregs) more than doubled the risk of squamous cell cancer of the skin. Decreased levels of natural killer (NK) cells were associated with more than a five-fold increased risk of skin cancer.&lt;br&gt;
&lt;br&gt;Both immune parameters had substantially greater predictive power than a history of squamous-cell skin cancer, according to an online report in the &lt;em&gt;Journal of the American Society of Nephrology&lt;/em&gt; by a team of Oxford University investigators.&lt;/p&gt;
&lt;p&gt;&quot;Squamous cell cancer of the skin affects about 30% of kidney transplant patients after 10 years of immunosuppression,&quot; Robert Carroll, MD, currently of Queen Elizabeth Hospital in Woodville, Australia, observed in a statement.&lt;/p&gt;
&lt;p&gt;&quot;A small number of patients develop multiple skin cancers per year, but there is no laboratory test to determine which transplant recipients will develop multiple skin cancers in the future.&quot;&lt;/p&gt;
&lt;p&gt;&quot;If a test can confirm high risk of skin cancer development, this may help clinicians to tailor immunosuppressive regimens for individual patients,&quot; he added.&lt;/p&gt;
&lt;p&gt;Long-term immunosuppression, such as that required for transplant recipients, confers an increased risk of squamous-cell skin cancer.&lt;/p&gt;
&lt;p&gt;Estimates of the magnitude have ranged as high as 200 times greater than the general population, the authors wrote. Additionally, 3% of organ transplant recipients require extensive plastic surgery each year as a result of skin cancer lesions.&lt;/p&gt;
&lt;p&gt;Age at transplantation and the immunosuppression dosage are the principal determinants of skin-cancer risk, and the dosage of immunosuppression also influences the risk of metastasis from squamous-cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;In the general population, cancer has been associated with increased levels of Tregs, including CDR&lt;sup&gt;+&lt;/sup&gt;CD25&lt;sup&gt;high&lt;/sup&gt;FOXP3&lt;sup&gt;+&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD28&lt;sup&gt;-&lt;/sup&gt; cells. The same types of cells could play a role in the risk of skin cancer among organ transplant recipients, the authors wrote.&lt;/p&gt;
&lt;p&gt;Within the tumor microenvironment, Tregs may impair the antitumor activity of CD8&lt;sup&gt;+&lt;/sup&gt; and NK cell. However, in organ transplant recipients, Tregs help control or prevent rejections and may help improve long-term outcomes.&lt;/p&gt;
&lt;p&gt;Different immunosuppressive drugs affect Tregs differently, the authors continued. Sirolimus (Rapamune), for example, increases the number of FOXP3&lt;sup&gt;+&lt;/sup&gt; cells, whereas cyclosporine decreases Treg numbers.&lt;/p&gt;
&lt;p&gt;&quot;Tregs have not been assessed in relation to cancer after transplantation,&quot; the authors wrote. &quot;We therefore investigated the hypothesis that squamous-cell cancer in kidney transplant recipients would be associated with an increased number of Tregs.&quot;&lt;/p&gt;
&lt;p&gt;To examine the hypothesis, investigators phenotyped peripheral blood from 65 kidney transplant recipients with squamous skin cancer and 51 recipients without skin cancer, matched for age, sex, and duration of immunosuppression.&lt;/p&gt;
&lt;p&gt;They also quantified lymphocyte populations in skin cancer lesions from a subset of 25 patients and matched them with 25 other nontransplant patients with squamous cell cancer of the skin.&lt;/p&gt;
&lt;p&gt;The kidney transplant recipients had a median follow-up of 340 days. The investigators found that a concentration of &amp;gt;35 peripheral FOXP3&lt;sup&gt;+&lt;/sup&gt;CD4&lt;sup&gt;+&lt;/sup&gt;CD127&lt;sup&gt;low&lt;/sup&gt; regulatory T cells/&amp;#181;L was associated with a hazard ratio for squamous cell skin cancer of 2.48 (95% CI 1.04 to 5.98).&lt;/p&gt;
&lt;p&gt;An NK cell count &amp;lt;100 cells/&amp;#181;L was associated with a skin cancer hazard ratio of 5.6 (95% CI 1.31 to 24). A history of squamous cell cancer of the skin increased the risk of skin cancer recurrence by a third (HR 1.33, 95% CI 1.15 to 1.53).&lt;/p&gt;
&lt;p&gt;&quot;If similar immune phenotypes are predictive in other kidney transplant recipient populations, then immune phenotype method has the potential to inform immunosuppressive regimen manipulation in kidney transplant recipients at high risk for developing multiple squamous cell cancers,&quot; the authors concluded.&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 authors had no relevant disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_331"
                     title="Physicians Must Treat Transplant Tourists"
                     score="0.005"
                     href="http://www.medpagetoday.com/Gastroenterology/LiverTransplantation/tb/18203?impressionId=1265803240603"
                     
      &lt;p&gt;Patients who travel to foreign countries for organ transplants may return with more problems than they left with  --  and physicians here have a moral responsibility to treat them, researchers asserted in a transplant journal.&lt;/p&gt;
&lt;p&gt;&quot;Medical tourism&quot; has been on the rise as demand for organs outpaces supply and U.S. healthcare costs skyrocket, Thomas D. Schiano, MD, and Rosamond Rhodes, PhD, of Mount Sinai School of Medicine, reported in &lt;em&gt;Liver Transplantation&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Researchers have estimated that 300 medical tourism transplants occurred between 2004 and 2006, with more than 40% of transplant tourists residing in New York or California, which have only 18% of the total U.S. population. (See &lt;a href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/12564&quot; mce_href=&quot;http://www.medpagetoday.com/PublicHealthPolicy/HealthPolicy/12564&quot; target=&quot;_blank&quot;&gt;International Medical Trade Turns Big Business&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;Yet physicians have had little guidance on delivering care to these patients, and some transplant centers may turn them away, based on their actions, Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;Their questions about treatment arose with a 46-year-old Chinese patient who had been put on a waiting list for a liver transplant here because of end-stage liver disease.&lt;/p&gt;
&lt;p&gt;The patient waited on the list for a year as his disease progressed from 18 points to 21 points on a 40-point severity scale.&lt;/p&gt;
&lt;p&gt;Rather than wait any longer, the patient flew to China and had a liver transplant there.&lt;/p&gt;
&lt;p&gt;Many transplanted organs in China come from executed prisoners, raising concerns about disease. Also, foreign transplants may be compromised by poor organ matching, unhealthy donors, and post-transplant infections, while some transplant centers abroad may use substandard surgical techniques, the researchers said.&lt;/p&gt;
&lt;p&gt;Foreign centers are also less likely to send patients home with adequate records and education than centers here, they asserted.&lt;/p&gt;
&lt;p&gt;Three months after his transplant in China, the patient came back to the clinic at Mount Sinai for follow-up care because he was about to run out of imunosuppressive medication.&lt;/p&gt;
&lt;p&gt;Two months after that, the patient developed sepsis due to diffuse intrahepatic biliary stricturing related to hepatic artery thrombosis.&lt;/p&gt;
&lt;p&gt;He required three additional hospitalizations for biliary sepsis, and at that point, retransplantation was the only viable option, Schiano said.&lt;/p&gt;
&lt;p&gt;However, members of the medical team had conflicting views about giving the patient another new liver.&lt;/p&gt;
&lt;p&gt;&quot;He was a medically suitable candidate,&quot; Schiano and Rhodes wrote, &quot;but there was disagreement about whether it was morally right to provide him with a transplant.&quot;&lt;/p&gt;
&lt;p&gt;The clinicians had few ethical guidelines to refer to in making their decision because many deal solely with moral issues related to donors and foreign medical standards.&lt;/p&gt;
&lt;p&gt;For example, the International Society for Heart and Lung Transplantation issued a statement against accepting organs from prisoners in April 2007, and the American Association for the Study of Liver Diseases and the International Liver Transplant Society endorsed similar policies.&lt;/p&gt;
&lt;p&gt;The American Medical Association&apos;s guidelines on medical tourism focus on best practices  --  for example, the procedure must be voluntary, it can&apos;t limit the alternatives offered to patients, and patients should only be referred to accredited institutions.&lt;/p&gt;
&lt;p&gt;While the United Network for Organ Sharing (UNOS)&apos;s statement on medical tourism does maintain that the medical community has an obligation to provide care for these patients, it stops short of offering further direction to transplant programs.&lt;/p&gt;
&lt;p&gt;&quot;Little guidance is provided for dealing with the specific problems of patients who choose to become transplant tourists,&quot; Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;Instead, they created some ethical guidance for the &quot;moral quandary.&quot;&lt;/p&gt;
&lt;p&gt;Physicians have a &quot;professional obligation to promote the good of patients&quot; as well as a &quot;professional responsibility to adhere to medicine&apos;s commitment to nonjudgmental regard,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;&quot;Taken together, the moral principles of beneficence and nonjudgmental regard direct us to treat potential or returning transplant tourists as we would treat other patients under our care by focusing on providing the medical treatment and support they need,&quot; they continued.&lt;/p&gt;
&lt;p&gt;Physicians shouldn&apos;t deny patients post-transplantation care, and they ought to provide emergent care at the very least. They may refer the patient to another transplant center for long-term follow-up if they regard it as unethical to continue treatment.&lt;/p&gt;
&lt;p&gt;Patients should also be informed about the possibility of transplant tourism when they are not eligible for a transplant in the U.S. or when they are likely to die before reaching the top of the transplant list, Schiano and Rhodes wrote.&lt;/p&gt;
&lt;p&gt;&quot;Patients should not be threatened with abandonment by a center&apos;s refusal to provide care upon their return,&quot; they added.&lt;/p&gt;
&lt;p&gt;As for the 46-year-old patient who was transplanted in China, the Mount Sinai team decided a transplant program must treat all patients on the basis of their need &quot;regardless of what they might have done or how they secured their transplant organ.&quot;&lt;/p&gt;
&lt;p&gt;&quot;Although [the patient] had a long, complicated transplantation course,&quot; they wrote, &quot;he is currently doing well.&quot;&lt;/p&gt;
&lt;p&gt;Mount Sinai has seen a total of nine patients who pursued transplants in China. Three of those had post-transplant problems but had been turned away elsewhere &quot;because several transplant centers in our region do not render care to transplant tourists,&quot; the authors wrote.&lt;/p&gt;
&lt;p&gt;Seven of those nine patients have hepatitis B. Another three had had a renal transplant in India, and subsequently developed liver failure, the authors reported.&lt;/p&gt;

    </recommendedItem>
    <recommendedItem id="20090101_1_125"
                     title="Donor Age No Barrier to Cadaver Kidney Success"
                     score="-0.005"
                     href="