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    <recommendedItem id="20100101_19_330"
                     title="Immune Cells Point to Skin Cancer Risk after Transplants (CME/CE)"
                     score="0.006"
                     href="http://www.medpagetoday.com/Nephrology/KidneyTransplantation/tb/18200?impressionId=1265788049088"
                     
      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="0.004"
                     href="http://www.medpagetoday.com/Gastroenterology/LiverTransplantation/tb/18203?impressionId=1265788049088"
                     
      &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="20100101_19_280"
                     title="Better Overall Diabetes Care Lowers Nephropathy Risk (CME/CE)"
                     score="-0"
                     href="http://www.medpagetoday.com/Nephrology/Diabetes/tb/18136?impressionId=1265788049088"
                     
      &lt;p&gt;Simultaneously achieving tight glucose control and other targets in diabetes reduces the risk of kidney complications, researchers found.&lt;/p&gt;
&lt;p&gt;An aggressive multifactorial intervention appeared to delay diabetic nephropathy better when more targets were achieved (&lt;em&gt;P&lt;/em&gt;=0.002 for trend) in a longitudinal study of Chinese patients led by Ming-Chia Hsieh, MD, PhD, of Kaohsiung Medical University Hospital in Kaohsiung, Taiwan.&lt;/p&gt;
&lt;p&gt;The risk of new-onset microalbuminaria dropped 27.1% for those who met the American Diabetes Association-recommended goal of less than 7% glycosylated hemoglobin (&lt;em&gt;P&lt;/em&gt;=0.03), the researchers reported in the Jan. 25 &lt;em&gt;Archives of Internal Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Reaching the systolic blood pressure goal of less than 130 mm Hg reduced this risk 35.5% (&lt;em&gt;P&lt;/em&gt;=0.002). Achieving the HDL cholesterol goal  --  over 50 mg/dL for women and 40 mg/dL for men  --  reduced the risk by 28.5% (&lt;em&gt;P&lt;/em&gt;=0.02).&lt;/p&gt;
&lt;p&gt;&quot;The control of microalbuminuria may halt progress to overt nephropathy and reduce occurrence of cardiovascular events in these patients,&quot; Hsieh&apos;s group wrote.&lt;/p&gt;
&lt;p&gt;They suggested that this type of intensive intervention &quot;can be used at the very early stages of diabetic renal disease.&quot;&lt;/p&gt;
&lt;p&gt;Prior studies had suggested that intensive therapy could prevent nephropathy in patients who had already started showing signs of progression.&lt;/p&gt;
&lt;p&gt;So to see if starting earlier would be as effective, Hsieh and colleagues initiated a longitudinal cohort study of 1,290 patients with type 2 diabetes and normoalbuminuria in which participants received intensified treatment to meet ADA-recommended goals on glucose, blood pressure, cholesterol, and triglycerides.&lt;/p&gt;
&lt;p&gt;To this end, patients got the combined efforts of a physician, nurse, and dietitian working together on counseling and patient education to modify behavior.&lt;/p&gt;
&lt;p&gt;By the end of the intervention patients were more likely to have switched from single agent glucose-lowering treatment to insulin plus an oral hypoglycemic agent and to have gone on an antihypertensive (74% versus 48% baseline), statin (58.1% versus 28.0% baseline), and fibrate (14.0% versus 3.0% baseline).&lt;/p&gt;
&lt;p&gt;By the end of the study period, the mean glycosylated hemoglobin was 7.3%, while blood pressure averaged 129.3/74.4 mm Hg. Mean LDL cholesterol was 98.6 mg/dL, triglycerides were at 116.0 mg/dL, and mean HDL cholesterol was 53.6 mg/dL.&lt;/p&gt;
&lt;p&gt;Over the 4.5 years of follow-up, 16.4% of patients developed new-onset microalbuminuria.&lt;/p&gt;
&lt;p&gt;Unlike attainment of HDL cholesterol, glycosylated hemoglobin, and systolic blood pressure goals, reaching those for LDL cholesterol, diastolic blood pressure, and triglycerides appeared to have little impact on kidney function.&lt;/p&gt;
&lt;p&gt;But the more targets patients reached, the less likely they were to develop microalbuminuria (&lt;em&gt;P&lt;/em&gt;=0.002).&lt;/p&gt;
&lt;p&gt;The majority of participants in the study reached one or two of the treatment targets (71.4%) and 8.1% achieved three.&lt;/p&gt;
&lt;p&gt;Those who did reach two or three of the goals were at significantly lower risk of new-onset microalbuminuria than the 20.5% who didn&apos;t reach any of the goals (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Those who reached one target tended to be at lower risk as well, but the effect was not significant compared with reaching none of the goals (&lt;em&gt;P&lt;/em&gt;=0.35).&lt;/p&gt;
&lt;p&gt;One of the concerns with the tight glucose control goal has been hypoglycemia. In the study, 217 patients had at least one episode. Four cases involved major hypoglycemia, though without clinical morbidity or mortality.&lt;/p&gt;
&lt;p&gt;Overall, 37 patients died from any cause during the study period.&lt;/p&gt;
&lt;p&gt;A &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/13818&quot; target=&quot;_blank&quot;&gt;review&lt;/a&gt; of recent large trials of aggressive glycemic control  --  U.K. Prospective Diabetes Study (UKPDS) and the U.S.-based ACCORD, ADVANCE, and VA Diabetes trials  --  suggested a two- to threefold increased risk of severe hypoglycemia without macrovascular benefits.&lt;/p&gt;
&lt;p&gt;In the recent &lt;a href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; mce_href=&quot;http://www.medpagetoday.com/Cardiology/Diabetes/9739&quot; target=&quot;_blank&quot;&gt;ACCORD&lt;/a&gt; trial, tight glucose control that brought hemoglobin A1c close to 6%, with a target of less than the standard 7.0%, resulted in 22% excess mortality risk.&lt;/p&gt;
&lt;p&gt;The search for a reason behind this risk has yet to turn up a culprit. &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ADA/14635&quot; target=&quot;_blank&quot;&gt;Analyses&lt;/a&gt; have suggested that hypoglycemia isn&apos;t to blame and that the lower A1c levels themselves aren&apos;t a problem.&lt;/p&gt;
&lt;p&gt;In the wake of the negative findings from ACCORD, ADVANCE, and the VA trials, leading diabetologists had suggested that pushing too hard in people who couldn&apos;t reach the targets might have been at fault.&lt;/p&gt;
&lt;p&gt;Rather than a one-size-fits all approach, the ADA guidelines suggest individualizing treatment targets.&lt;/p&gt;
&lt;p&gt;Hsieh&apos;s group acknowledged that &quot;even with close attention, not all our patients could achieve the ADA-recommended goals,&quot; but re-emphasized that for patients who could achieve targets, there were benefits.&lt;/p&gt;
&lt;p&gt;The researchers cautioned that their study was limited by lack of a comparison group, no data on genetic factors, and use of potentially arbitrary treatment target cutoff points.&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 researchers reported no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20090101_1_812"
                     title="Melanoma Risk Up Almost Fourfold After Kidney Graft"
                     score="-0.005"
                     href="