OBJECTIVE

To describe outcomes of prospective trials of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC).

METHODS

Two trials of SBRT for patients with active HCC unsuitable for standard locoregional therapies were conducted from 2004 to 20<em>1</em>0. All patients had Child-Turcotte-Pugh class A disease, with at least 700 <em>mL</em> of non-HCC liver. The SBRT dose range was 24 to 54 Gy in six fractions. Primary end points were toxicity and local control at <em>1</em> year (LC<em>1</em>y), defined as no progressive disease (PD) of irradiated HCC by RECIST (Response Evaluation Criteria in Solid Tumors).

RESULTS

A total of <em>1</em>02 patients were evaluable (Trial <em>1</em>, 2004 to 2007: n = 50; Trial 2, 2007 to 20<em>1</em>0: n = 52). Underlying liver disease was hepatitis B in 38% of patients, hepatitis C in 38%, alcohol related in 25%, other in <em>1</em>4%, and none in 7%. Fifty-two percent received prior therapies (no prior sorafenib). TNM stage was III in 66%, and 6<em>1</em>% had multiple lesions. Median gross tumor volume was <em>1</em><em>1</em>7.0 <em>mL</em> (range, <em>1</em>.3 to <em>1</em>,9<em>1</em>3.4 <em>mL</em>). Tumor vascular thrombosis (TVT) was present in 55%, and extrahepatic disease was present in <em>1</em>2%. LC<em>1</em>y was 87% (95% CI, 78% to 93%). SBRT dose (hazard ratio [HR] = 0.96; P = .02) and being in Trial 2 (HR = 0.38; P = .03) were associated with LC<em>1</em>y on univariate analysis. Toxicity ≥ grade 3 was seen in 30% of patients. In seven patients (two with TVT PD), death was possibly related to treatment (<em>1</em>.<em>1</em> to 7.7 months after SBRT). Median overall survival was <em>1</em>7.0 months (95% CI, <em>1</em>0.4 to 2<em>1</em>.3 months), for which only TVT (HR = 2.47; P = .0<em>1</em>) and being in Trial 2 (HR = 0.49; P = .0<em>1</em>) were significant on multivariate analysis.

CONCLUSIONS

These results provide strong rationale for studying SBRT for HCC in a randomized trial.

BACKGROUND

Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment.

OBJECTIVE

To assess the benefit of HAART in patients with advanced AIDS and anemia.

METHODS

Prospective, multicenter cohort study.

METHODS

The Viral Activation Transfusion Study (VATS), with enrollment from August <em>1</em>995 through July <em>1</em>998 and follow-up through June <em>1</em>999.

METHODS

528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia.

METHODS

In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use.

RESULTS

At baseline, patients had a median CD4(+) lymphocyte count of 0.0<em>1</em>5 x <em>1</em>0(9) cell/L, median plasma HIV RNA level of 4.8 log(<em>1</em>0) copies/<em>mL</em>, and median hemoglobin concentration of 73 g/L. Use of HAART increased from <em>1</em>% of active patients in January <em>1</em>996 to 79% of active patients in January <em>1</em>999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.00<em>1</em> for both comparisons). Rates of non-CMV disease were 0.<em>1</em>5 event/ person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [ P < 0.00<em>1</em>]; adjusted rate ratio, 0.66 [ P < 0.05]). Rates of CMV disease were 0.<em>1</em>0 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [ P < 0.0<em>1</em>]; adjusted rate ratio, <em>1</em>.0<em>1</em> [ P>> 0.2]). Results were similar in patients with baseline CD4(+) lymphocyte counts less than 0.0<em>1</em>0 x <em>1</em>0(9) cells/L.

CONCLUSIONS

The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.

BACKGROUND

Raltegravir (MK-05<em>1</em>8) is an HIV-<em>1</em> integrase inhibitor with potent in-vitro activity against HIV-<em>1</em> strains including those resistant to currently available antiretroviral drugs. The aim of this study was to assess the safety and efficacy of raltegravir when added to optimised background regimens in HIV-infected patients.

METHODS

HIV-infected patients with HIV-<em>1</em> RNA viral load over 5000 copies per mL, CD4 cell counts over 50 cells per muL, and documented genotypic and phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, and one protease inhibitor were randomly assigned to receive raltegravir (200 mg, 400 mg, or 600 mg) or placebo orally twice daily in this multicentre, triple-blind, dose-ranging, randomised study. The primary endpoints were change in viral load from baseline at week 24 and safety. Analyses were done on a modified intention-to-treat basis. This trial is registered with ClinicalTrials.gov, with the number NCT00<em>1</em>05<em>1</em>57.

RESULTS

<em>1</em>79 patients were eligible for randomisation. 44 patients were randomly assigned to receive 200 mg raltegravir, 45 to receive 400 mg raltegravir, and 45 to receive 600 mg raltegravir; 45 patients were randomly assigned to receive placebo. One patient in the 200 mg group did not receive treatment and was therefore excluded from the analyses. For all groups, the median duration of previous antiretroviral therapy was 9.9 years (range 0.4-<em>1</em>7.3 years) and the mean baseline viral load was 4.7 (SD 0.5) log<em>1</em>0 copies per mL. Four patients discontinued due to adverse experiences, three (2%) of the <em>1</em>33 patients across all raltegravir groups and one (2%) of the 45 patients on placebo. 4<em>1</em> patients discontinued due to lack of efficacy: <em>1</em>4 (<em>1</em><em>1</em>%) of the <em>1</em>33 patients across all raltegravir groups and 27 (60%) of the 45 patients on placebo. At week 24, mean change in viral load from baseline was -<em>1</em>.80 (95% CI -2.<em>1</em>0 to -<em>1</em>.50) log<em>1</em>0 copies per mL in the 200 mg group, -<em>1</em>.87 (-2.<em>1</em>6 to -<em>1</em>.58) log<em>1</em>0 copies per mL in the 400 mg group, -<em>1</em>.84 (-2.<em>1</em>0 to -<em>1</em>.58) log<em>1</em>0 copies per mL in the 600 mg group, and -0.35 (-0.6<em>1</em> to -0.09) log(<em>1</em>0) copies per mL for the placebo group. Raltegravir at all doses showed a safety profile much the same as placebo; there were no dose-related toxicities.

CONCLUSIONS

In patients with few remaining treatment options, raltegravir at all doses studied provided better viral suppression than placebo when added to an optimised background regimen. The safety profile of raltegravir is comparable with that of placebo at all doses studied.

Human beta-defensins (HBDs) are antimicrobial peptides that may play a role in mucosal defense. Diminished activity of these peptides has been implicated in the pathogenesis of cystic fibrosis (CF) lung disease. We show that HBD-<em>1</em> and HBD-2 mRNAs are expressed in excised surface and submucosal gland epithelia from non-CF and CF patients. The pro-inflammatory cytokine interleukin-<em>1</em>beta stimulated the expression of HBD-2 but not HBD-<em>1</em> mRNA and peptide in primary cultures of airway epithelia. HBD-<em>1</em> was found in bronchoalveolar lavage (BAL) fluid from normal volunteers, CF patients, and patients with inflammatory lung diseases, whereas HBD-2 was detected in BAL fluid from patients with CF or inflammatory lung diseases, but not in normal volunteers. Both HBD-<em>1</em> and HBD-2 were found in BAL fluid in concentrations of several ng/<em>ml</em>, and both recombinant peptides showed salt-sensitive bactericidal activity. These data suggest that in the lung HBD-2 expression is induced by inflammation, whereas HBD-<em>1</em> may serve as a defense in the absence of inflammation.

During flavivirus infection in vitro, nonstructural protein NS<em>1</em> is released in a host-restricted fashion from infected mammalian cells but not vector-derived insect cells. In order to analyze the biological relevance of NS<em>1</em> secretion in vivo, we developed a sensitive enzyme-linked immunosorbent assay (ELISA) to detect the protein in the sera of dengue virus-infected patients. The assay was based on serotype <em>1</em> NS<em>1</em>-specific mouse and rabbit polyclonal antibody preparations for antigen immunocapture and detection, respectively. With purified dengue virus type <em>1</em> NS<em>1</em> as a protein standard, the sensitivity of our capture ELISA was less than <em>1</em> ng/<em>ml</em>. When a panel of patient sera was analyzed, the NS<em>1</em> antigen was found circulating from the first day after the onset of fever up to day 9, once the clinical phase of the disease is over. The NS<em>1</em> protein could be detected even when viral RNA was negative in reverse transcriptase-PCR or in the presence of immunoglobulin M antibodies. NS<em>1</em> circulation levels varied among individuals during the course of the disease, ranging from several nanograms per milliliter to several micrograms per milliliter, and peaked in one case at 50 microg/<em>ml</em> of serum. Interestingly, NS<em>1</em> concentrations did not differ significantly in serum specimens obtained from patients experiencing primary or secondary dengue virus infections. These findings indicate that NS<em>1</em> protein detection may allow early diagnosis of infection. Furthermore, NS<em>1</em> circulation in the bloodstream of patients during the clinical phase of the disease suggests a contribution of the nonstructural protein to dengue virus pathogenesis.

BACKGROUND

Kidney disease in type 2 diabetes mellitus (DM) is more heterogeneous than in type <em>1</em> DM. Reduced glomerular filtration rate (GFR) among individuals with type 2 DM may not always be due to classic diabetic glomerulosclerosis, which is associated with albuminuria and retinopathy.

OBJECTIVE

To determine the prevalence of chronic renal insufficiency (CRI), defined as a GFR less than 60 mL/min per <em>1</em>.73 m2 body surface area (BSA) in the absence of microalbuminuria or macroalbuminuria and diabetic retinopathy among adults with type 2 DM.

METHODS

Cross-sectional analysis of adults aged 40 years or older with type 2 DM in the Third National Health and Nutrition Examination Survey, a probability sample of the total civilian US noninstitutionalized population conducted from <em>1</em>988-<em>1</em>994.

METHODS

The GFR per <em>1</em>.73 m2 BSA, calculated with serum creatinine, urea nitrogen, and serum albumin levels using the Modification of Diet in Renal Disease Study prediction equation; albuminuria, assessed using spot urine albumin/creatinine ratio; and presence of retinopathy, determined with fundus photography.

RESULTS

Overall, <em>1</em>3% (sampled n = <em>1</em>7<em>1</em>) of adults with type 2 DM (n = <em>1</em><em>1</em>97) had CRI with a population estimate of <em>1</em>.<em>1</em> million. Among these adults with CRI, diabetic retinopathy was noted in 28% (n = 58), while the frequencies of microalbuminuria and macroalbuminuria were 45% (n = 64) and <em>1</em>9% (n = 47), respectively. Retinopathy and albuminuria (microalbuminuria or macroalbuminuria) were both absent in 30% (n = 5<em>1</em>) of adults with type 2 DM and CRI. The population estimate of adults with type 2 DM and CRI in the absence of diabetic retinopathy or albuminuria was approximately 0.3 million.

CONCLUSIONS

A substantial burden of CRI among persons with type 2 DM in the United States is likely due to renal parenchymal disease other than classic diabetic glomerulosclerosis. Approaches to screening renal disease in the type 2 DM population should incorporate assessment of GFR in addition to monitoring urine albumin excretion and funduscopic changes to ensure that individuals with type 2 DM and CRI not due to diabetic glomerulosclerosis will receive appropriate intervention.

OBJECTIVE

To determine the prevalence of 25-hydroxyvitamin D (25[OH]D) deficiency and associations between 25(OH)D deficiency and cardiovascular risk factors in children and adolescents.

METHODS

With a nationally representative sample of children aged <em>1</em> to 2<em>1</em> years in the National Health and Nutrition Examination Survey 200<em>1</em>-2004 (n = 6275), we measured serum 25(OH)D deficiency and insufficiency (25[OH]D (<em>1</em>5 ng/<em>mL</em> and <em>1</em>5-29 ng/<em>mL</em>, respectively) and cardiovascular risk factors.

RESULTS

Overall, 9% of the pediatric population, representing 7.6 million US children and adolescents, were 25(OH)D deficient and 6<em>1</em>%, representing 50.8 million US children and adolescents, were 25(OH)D insufficient. Only 4% had taken 400 IU of vitamin D per day for the past 30 days. After multivariable adjustment, those who were older (odds ratio [OR]: <em>1</em>.<em>1</em>6 [95% confidence interval (CI): <em>1</em>.<em>1</em>2 to <em>1</em>.20] per year of age), girls (OR: <em>1</em>.9 [<em>1</em>.6 to 2.4]), non-Hispanic black (OR: 2<em>1</em>.9 [<em>1</em>3.4 to 35.7]) or Mexican-American (OR: 3.5 [<em>1</em>.9 to 6.4]) compared with non-Hispanic white, obese (OR: <em>1</em>.9 [<em>1</em>.5 to 2.5]), and those who drank milk less than once a week (OR: 2.9 [2.<em>1</em> to 3.9]) or used >4 hours of television, video, or computers per day (OR: <em>1</em>.6 [<em>1</em>.<em>1</em> to 2.3]) were more likely to be 25(OH)D deficient. Those who used vitamin D supplementation were less likely (OR: 0.4 [0.2 to 0.8]) to be 25(OH)D deficient. Also, after multivariable adjustment, 25(OH)D deficiency was associated with elevated parathyroid hormone levels (OR: 3.6; [<em>1</em>.8 to 7.<em>1</em>]), higher systolic blood pressure (OR: 2.24 mmHg [0.98 to 3.50 mmHg]), and lower serum calcium (OR: -0.<em>1</em>0 mg/dL [-0.<em>1</em>5 to -0.04 mg/dL]) and high-density lipoprotein cholesterol (OR: -3.03 mg/dL [-5.02 to -<em>1</em>.04]) levels compared with those with 25(OH)D levels>> or =30 ng/<em>mL</em>.

CONCLUSIONS

25(OH)D deficiency is common in the general US pediatric population and is associated with adverse cardiovascular risks.

BACKGROUND

Whether local exposure to major roadways adversely affects lung-function growth during the period of rapid lung development that takes place between <em>1</em>0 and <em>1</em>8 years of age is unknown. This study investigated the association between residential exposure to traffic and 8-year lung-function growth.

METHODS

In this prospective study, 3677 children (mean age <em>1</em>0 years [SD 0.44]) participated from <em>1</em>2 southern California communities that represent a wide range in regional air quality. Children were followed up for 8 years, with yearly lung-function measurements recorded. For each child, we identified several indicators of residential exposure to traffic from large roads. Regression analysis was used to establish whether 8-year growth in lung function was associated with local traffic exposure, and whether local traffic effects were independent of regional air quality.

RESULTS

Children who lived within 500 m of a freeway (motorway) had substantial deficits in 8-year growth of forced expiratory volume in <em>1</em> s (FEV(<em>1</em>), -8<em>1</em> <em>mL</em>, p=0.0<em>1</em> [95% CI -<em>1</em>43 to -<em>1</em>8]) and maximum midexpiratory flow rate (MMEF, -<em>1</em>27 <em>mL</em>/s, p=0.03 [-243 to -<em>1</em><em>1</em>), compared with children who lived at least <em>1</em>500 m from a freeway. Joint models showed that both local exposure to freeways and regional air pollution had detrimental, and independent, effects on lung-function growth. Pronounced deficits in attained lung function at age <em>1</em>8 years were recorded for those living within 500 m of a freeway, with mean percent-predicted 97.0% for FEV<em>1</em> (p=0.0<em>1</em>3, relative to>><em>1</em>500 m [95% CI 94.6-99.4]) and 93.4% for MMEF (p=0.006 [95% CI 89.<em>1</em>-97.7]).

CONCLUSIONS

Local exposure to traffic on a freeway has adverse effects on children's lung development, which are independent of regional air quality, and which could result in important deficits in attained lung function in later life.

BACKGROUND

Donepezil hydrochloride (Aricept) is a selective acetylcholinesterase inhibitor developed for the treatment of Alzheimer disease. This phase 3 study was <em>1</em> of 2 pivotal trials undertaken to establish the efficacy and safety of using donepezil in patients with mild to moderately severe Alzheimer disease.

OBJECTIVE

To further examine the efficacy and safety of using donepezil in the treatment of patients with mild to moderately severe Alzheimer disease. To examine the relationships between plasma donepezil concentrations, inhibition of red blood cell acetylcholinesterase activity, and clinical response.

METHODS

This was a <em>1</em>2-week, double-blind, placebo-controlled, parallel-group trial with a 3-week single-blind washout. Outpatients at 23 centers in the United States were randomized to receive placebo, 5 mg of donepezil hydrochloride, or <em>1</em>0 mg of donepezil hydrochloride (5 mg/d during week <em>1</em> then <em>1</em>0 mg/d thereafter) administered once daily at bedtime. Primary efficacy was measured using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Clinician's Interview-Based Impression of Change including caregiver information (CIBIC plus).

RESULTS

A total of 468 patients entered the study, more than 97% of whom were included in the intention-to-treat (end point) analyses. The use of donepezil produced statistically significant improvements in ADAS-cog, CIBIC plus, and Mini-Mental State Examination scores, relative to placebo. The mean drug-placebo differences, at end point, for the groups receiving 5 mg/d and <em>1</em>0 mg/d of donepezil hydrochloride were, respectively, 2.5 and 3.<em>1</em> units for ADAS-cog (P<.00<em>1</em>); 0.3 and 0.4 units for CIBIC plus (P< or =.008); and <em>1</em>.0 and <em>1</em>.3 units for Mini-Mental State Examination (P< or =.004). On the CIBIC plus scale, 32% and 38% of patients, respectively, treated with 5 mg/d and <em>1</em>0 mg/d of donepezil hydrochloride demonstrated clinical improvement (a score of <em>1</em>, 2, or 3) compared with placebo (<em>1</em>8%). The mean (+/-SEM) donepezil plasma concentrations at study end point were 25.9 +/- 0.7 ng/mL and 50.6 +/- <em>1</em>.9 ng/mL in the groups receiving dosages of 5 mg/d and <em>1</em>0 mg/d, respectively. Corresponding mean (+/-SEM) percentages of inhibition of red blood cell acetylcholinesterase activity were 63.9% +/- 0.9% and 74.7% +/- <em>1</em>.2% for these 2 dosages, respectively. There was a statistically significant positive correlation between plasma concentrations of donepezil and acetylcholinesterase inhibition; the EC50 (50% effect) was obtained at a concentration of <em>1</em>5.6 ng/mL. A plateau of inhibition (80%-90%) was reached at plasma donepezil concentrations higher than 50 ng/mL. The correlations between plasma drug concentrations and both ADAS-cog (P<.00<em>1</em>) and CIBIC plus (P = .006) were also statistically significant, as were the correlations between red blood cell acetylcholinesterase inhibition and change in ADAS-cog (P<.00<em>1</em>) and CIBIC plus (P = .005). The incidence of treatment-emergent adverse events with both dosages of donepezil (68%-78%) was comparable with that observed with placebo (69%). The use of <em>1</em>0 mg/d of donepezil hydrochloride was associated with transient mild nausea, insomnia, and diarrhea. There were no treatment-emergent clinically significant changes in vital signs or clinical laboratory test results. More important, the use of donepezil was not associated with the hepatotoxic effects observed with acridine-based cholinesterase inhibitors.

CONCLUSIONS

Donepezil hydrochloride (5 and <em>1</em>0 mg) administered once daily is a well-tolerated and efficacious agent for treating the symptoms of mild to moderately severe Alzheimer disease.

Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after <em>1</em> h even at low concentrations (<em>1</em>0 microg/<em>ml</em>). At concentrations below <em>1</em> mg/<em>ml</em> CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/<em>ml</em> dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at <em>1</em> h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic <em>1</em>25I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately <em>1</em>0 microg/<em>ml</em>) were cleared rapidly from the circulation (<2% recovered dose in blood at <em>1</em> h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation times ( approximately 20-40% recovered dose in blood at <em>1</em> h) with generation-dependent clearance rates; lower generations circulated longer. For both anionic and cationic species blood levels at <em>1</em> h correlated with the extent of liver capture observed (30-90% recovered dose at <em>1</em> h). <em>1</em>25I-Labelled PAMAM dendrimers injected intraperitoneally were transferred to the bloodstream within an hour and their subsequent biodistribution mirrored that seen following i.v. injection. Inherent toxicity would suggest it unlikely that higher generation cationic dendrimers will be suitable for parenteral administration, especially if they are to be used at a high dose. In addition it is clear that dendrimer structure must also be carefully tailored to avoid rapid hepatic uptake if targeting elsewhere (e.g. tumour targeting) is a primary objective.

Gastric infection with Helicobacter pylori is a cosmopolitan problem, and is especially common in developing regions where there is also a high prevalence of gastric cancer. These infections are known to cause gastritis and peptic ulcers, and dramatically enhance the risk of gastric cancer. Eradication of this organism is an important medical goal that is complicated by the development of resistance to conventional antimicrobial agents and by the persistence of a low level reservoir of H. pylori within gastric epithelial cells. Moreover, economic and practical problems preclude widespread and intensive use of antibiotics in most developing regions. We have found that sulforaphane [(-)-<em>1</em>-isothiocyanato-(4R)-(methylsulfinyl)butane], an isothiocyanate abundant as its glucosinolate precursor in certain varieties of broccoli and broccoli sprouts, is a potent bacteriostatic agent against 3 reference strains and 45 clinical isolates of H. pylori [minimal inhibitory concentration (MIC) for 90% of the strains is <or=4 microg/<em>ml</em>], irrespective of their resistance to conventional antibiotics. Further, brief exposure to sulforaphane was bactericidal, and eliminated intracellular H. pylori from a human epithelial cell line (HEp-2). In complementary experiments, sulforaphane blocked benzo[a]pyrene-evoked forestomach tumors in ICR mice. This protection resulted from induction of phase 2 detoxication and antioxidant enzymes, and was abrogated in mice lacking the nrf2 gene, which regulates phase 2 enzymes. Thus, the dual actions of sulforaphane in inhibiting Helicobacter infections and blocking gastric tumor formation offer hope that these mechanisms might function synergistically to provide diet-based protection against gastric cancer in humans.

OBJECTIVE

To measure the short-term effects of an electronic nicotine delivery device ("e cigarette", ENDD) on desire to smoke, withdrawal symptoms, acceptability, pharmacokinetic properties and adverse effects.

METHODS

Single blind randomised repeated measures cross-over trial of the Ruyan V8 ENDD.

METHODS

University research centre in Auckland, New Zealand.

METHODS

40 adult dependent smokers of <em>1</em>0 or more cigarettes per day.

METHODS

Participants were randomised to use ENDDs containing <em>1</em>6 mg nicotine or 0 mg capsules, Nicorette nicotine inhalator or their usual cigarette on each of four study days 3 days apart, with overnight smoking abstinence before use of each product.

METHODS

The primary outcome was change in desire to smoke, measured as "area under the curve" on an <em>1</em><em>1</em>-point visual analogue scale before and at intervals over <em>1</em> h of use. Secondary outcomes included withdrawal symptoms, acceptability and adverse events. In nine participants, serum nicotine levels were also measured.

RESULTS

Over 60 min, participants using <em>1</em>6 mg ENDD recorded 0.82 units less desire to smoke than the placebo ENDD (p=0.006). No difference in desire to smoke was found between <em>1</em>6 mg ENDD and inhalator. ENDDs were more pleasant to use than inhalator (p=0.0<em>1</em>6) and produced less irritation of mouth and throat (p<0.00<em>1</em>). On average, the ENDD increased serum nicotine to a peak of <em>1</em>.3 mg/ml in <em>1</em>9.6 min, the inhalator to 2.<em>1</em> ng/ml in 32 min and cigarettes to <em>1</em>3.4 ng/ml in <em>1</em>4.3 min.

CONCLUSIONS

The <em>1</em>6 mg Ruyan V8 ENDD alleviated desire to smoke after overnight abstinence, was well tolerated and had a pharmacokinetic profile more like the Nicorette inhalator than a tobacco cigarette. Evaluation of the ENDD for longer-term safety, potential for long-term use and efficacy as a cessation aid is needed. Trial registration No.<em>1</em>2607000587404, Australia and New Zealand Clinical Trials Register.

Six major hepatitis C virus (HCV) genotypes and numerous subtypes have been described, and recently a seventh major genotype was discovered. Genotypes show significant molecular and clinical differences, such as differential response to combination therapy with interferon-alpha and ribavirin. Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH<em>1</em> (genotype 2a). By development of JFH<em>1</em>-based intergenotypic recombinants containing Core, envelope protein <em>1</em> and 2 (E<em>1</em>, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a strains, as well as subtype <em>1</em>b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a/JFH<em>1</em> (6a/2a, in E<em>1</em> and E2) and J4/JFH<em>1</em> (<em>1</em>b/2a, in NS2 and NS3); viability of J8/JFH<em>1</em> (2b/2a) and QC69/JFH<em>1</em> (7a/2a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype <em>1</em>-7 recombinants with infectivity titers of <em>1</em>0(3.7) to <em>1</em>0(5.2) 50% tissue culture infectious dose/<em>mL</em> and HCV RNA titers of <em>1</em>0(7.0) to <em>1</em>0(7.9) IU/<em>mL</em>. Huh7.5 cultures infected with genotype <em>1</em>-6 viruses had similar spread kinetics, intracellular Core, NS5A, and lipid amounts, and colocalization of Core and NS5A with lipids. Treatment with interferon-alpha2b but not ribavirin or amantadine showed a significant antiviral effect. Infection with all genotypes could be blocked by specific antibodies against the putative coreceptors CD8<em>1</em> and scavenger receptor class B type I in a dose-dependent manner. Finally, neutralizing antibodies in selected chronic phase HCV sera had differential effects against genotype <em>1</em>-7 viruses.

CONCLUSIONS

We completed and characterized a panel of JFH<em>1</em>-based cell culture systems of all seven major HCV genotypes and important subtypes and used these viruses in comparative studies of antivirals, HCV receptor interaction, and neutralizing antibodies.

BACKGROUND

Artemisinin-resistant Plasmodium falciparum has been reported in Pailin, western Cambodia, detected as a slow parasite clearance rate in vivo. Emergence of this phenotype in western Thailand and possibly elsewhere threatens to compromise the effectiveness of all artemisinin-based combination therapies. Parasite genetics is associated with parasite clearance rate but does not account for all variation. We investigated contributions of both parasite genetics and host factors to the artemisinin-resistance phenotype in Pursat, western Cambodia.

METHODS

Between June 19 and Nov 28, 2009, and June 26 and Dec 6, 2010, we enrolled patients aged 10 years or older with uncomplicated falciparum malaria, a density of asexual parasites of at least 10,000 per μL of whole blood, no symptoms or signs of severe malaria, no other cause of febrile illness, and no chronic illness. We gave participants 4 mg/kg artesunate at 0, 24, and 48 h, 15 mg/kg mefloquine at 72 h, and 10 mg/kg mefloquine at 96 h. We assessed parasite density on thick blood films every 6 h until undetectable. The parasite clearance half-life was calculated from the parasite clearance curve. We genotyped parasites with 18 microsatellite markers and patients for haemoglobin E, α-thalassaemia, and a mutation of G6PD, which encodes glucose-6-phosphate dehydrogenase. To account for the possible effects of acquired immunity on half-life, we used three surrogates for increased likelihood of exposure to P falciparum: age, sex, and place of residence. This study is registered with ClinicalTrials.gov, number NCT00341003.

RESULTS

We assessed 3504 individuals from all six districts of Pursat province seeking treatment for malaria symptoms. We enrolled 168 patients with falciparum malaria who met inclusion criteria. The geometric mean half-life was 5·85 h (95% CI 5·54-6·18) in Pursat, similar to that reported in Pailin (p=0·109). We identified two genetically different parasite clone groups: parasite group 1 (PG1) and parasite group 2 (PG2). Non-significant increases in parasite clearance half-life were seen in patients with haemoglobin E (0·55 h; p=0·078), those of male sex (0·96 h; p=0·064), and in 2010 (0·68 h; p=0·068); PG1 was associated with a significant increase (0·79 h; p=0·033). The mean parasite heritability of half-life was 0·40 (SD 0·17).

CONCLUSIONS

Heritable artemisinin resistance is established in a second Cambodian province. To accurately identify parasites that are intrinsically susceptible or resistant to artemisinins, future studies should explore the effect of erythrocyte polymorphisms and specific immune responses on half-life variation.

BACKGROUND

Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health.

OBJECTIVE

Different definitions have been proposed to define the ischemic penumbra from perfusion-CT (PCT) data, based on parameters and thresholds tested only in small pilot studies. The purpose of this study was to perform a systematic evaluation of all PCT parameters (cerebral blood flow, volume [CBV], mean transit time [MTT], time-to-peak) in a large series of acute stroke patients, to determine which (combination of) parameters most accurately predicts infarct and penumbra.

METHODS

One hundred and thirty patients with symptoms suggesting hemispheric stroke < or =<em>1</em>2 hours from onset were enrolled in a prospective multicenter trial. They all underwent admission PCT and follow-up diffusion-weighted imaging/fluid-attenuated inversion recovery (DWI/FLAIR); 25 patients also underwent admission DWI/FLAIR. PCT maps were assessed for absolute and relative reduced CBV, reduced cerebral blood flow, increased MTT, and increased time-to-peak. Receiver-operating characteristic curve analysis was performed to determine the most accurate PCT parameter, and the optimal threshold for each parameter, using DWI/FLAIR as the gold standard.

RESULTS

The PCT parameter that most accurately describes the tissue at risk of infarction in case of persistent arterial occlusion is the relative MTT (area under the curve=0.962), with an optimal threshold of <em>1</em>45%. The PCT parameter that most accurately describes the infarct core on admission is the absolute CBV (area under the curve=0.927), with an optimal threshold at 2.0 <em>ml</em> x <em>1</em>00 g(-<em>1</em>).

CONCLUSIONS

In a large series of <em>1</em>30 patients, the optimal approach to define the infarct and the penumbra is a combined approach using 2 PCT parameters: relative MTT and absolute CBV, with dedicated thresholds.

Forty critically ill surgical patients with documented infections were studied during their stay in an intensive care unit. Among these patients, <em>1</em>9 developed septic shock and <em>1</em>6 died, 9 of them from septic shock. Interleukin <em>1</em> beta (IL-<em>1</em> beta), tumor necrosis factor (TNF alpha), and interleukin 6 (IL-6) were measured each day and every <em>1</em> or 2 hours when septic shock occurred. Although IL-<em>1</em> beta was never found, TNF alpha was most often observed in the serum at a level under <em>1</em>00 pg/<em>mL</em> except during septic shock. During these acute episodes TNF alpha level reached several hundred pg/<em>mL</em>, but only for a few hours. In contrast, IL-6 was always increased in the serum of acutely ill patients (peak to 500,000 pg/<em>mL</em>). There was a direct correlation between IL-6 peak serum level and TNF alpha peak serum level during septic shock and between IL-6 serum level and temperature or C-reactive protein serum level. Moreover, IL-6 correlated well with APACHE II score, and the mortality rate increased significantly in the group of patients who presented with IL-6 serum level above <em>1</em>000 pg/<em>mL</em>. Thus, IL-6 appears to be a good marker of severity during bacterial infection.

OBJECTIVE

We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines.

METHODS

We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (<em>1</em>8 mixed-, <em>1</em>7 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (<em>1</em> ng/<em>mL</em>) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-<em>1</em>beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale.

RESULTS

IBS patients showed significantly (P < .0<em>1</em>7) higher baseline TNF-alpha, IL-<em>1</em>beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-<em>1</em>beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .00<em>1</em>) with anxiety in patients with IBS.

CONCLUSIONS

Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.

We analyzed Lung Health Study (LHS) data to assess the effect of self-reported lower respiratory illnesses resulting in physician visits (LRI) on lung function. Participants were 5,887 smokers aged 35-60 yr, FEV(<em>1</em>)/FVC < 0.70 and FEV(<em>1</em>) of 55-90% predicted. Two-thirds were randomized into an intensive smoking cessation program (SI); one-third were advised only to stop smoking (UC). For 5 yr participants had annual spirometry and questioning regarding LRI. SI had greater rates of smoking cessation than usual care (UC) with fewer LRI (p = 0.0008). Sustained quitters had fewer LRI than continuing smokers (p = 0.0003). In the year LRI occurred, FEV(<em>1</em>) did not change in sustained quitters, but decreased significantly in smokers (p = 0.000<em>1</em>) with some recovery the following year if no LRI occurred. Over 5 yr, LRI had a significant effect on rate of decline of FEV(<em>1</em>) only in smokers. In smokers averaging one LRI/yr over 5 yr there were additional declines in FEV(<em>1</em>) of 7 <em>ml</em> /yr (p = 0.00<em>1</em>). Smokers with more than one LRI/yr had greater declines. Chronic bronchitis was associated with increased frequencies of LRI, but did not affect their influence on lung function. Smoking and LRI had an interactive effect on FEV(<em>1</em>) in people with mild COPD, and in smokers frequent LRI may influence the long-term course of the disease.

Current antiretroviral therapy is effective in suppressing but not eliminating HIV-<em>1</em> infection. Understanding the source of viral persistence is essential for developing strategies to eradicate HIV-<em>1</em> infection. We therefore investigated the level of plasma HIV-<em>1</em> RNA in patients with viremia suppressed to less than 50-75 copies/<em>ml</em> on standard protease inhibitor- or non-nucleoside reverse transcriptase inhibitor-containing antiretroviral therapy using a new, real-time PCR-based assay for HIV-<em>1</em> RNA with a limit of detection of one copy of HIV-<em>1</em> RNA. Single copy assay results revealed that >80% of patients on initial antiretroviral therapy for 60 wk had persistent viremia of one copy/<em>ml</em> or more with an overall median of 3.<em>1</em> copies/<em>ml</em>. The level of viremia correlated with pretherapy plasma HIV-<em>1</em> RNA but not with the specific treatment regimen. Longitudinal studies revealed no significant decline in the level of viremia between 60 and <em>1</em><em>1</em>0 wk of suppressive antiretroviral therapy. These data suggest that the persistent viremia on current antiretroviral therapy is derived, at least in part, from long-lived cells that are infected prior to initiation of therapy.

BACKGROUND

Standard treatment of critically ill patients undergoing mechanical ventilation is continuous sedation. Daily interruption of sedation has a beneficial effect, and in the general intesive care unit of Odense University Hospital, Denmark, standard practice is a protocol of no sedation. We aimed to establish whether duration of mechanical ventilation could be reduced with a protocol of no sedation versus daily interruption of sedation.

METHODS

Of 428 patients assessed for eligibility, we enrolled <em>1</em>40 critically ill adult patients who were undergoing mechanical ventilation and were expected to need ventilation for more than 24 h. Patients were randomly assigned in a <em>1</em>:<em>1</em> ratio (unblinded) to receive: no sedation (n=70 patients); or sedation (20 mg/<em>mL</em> propofol for 48 h, <em>1</em> mg/<em>mL</em> midazolam thereafter) with daily interruption until awake (n=70, control group). Both groups were treated with bolus doses of morphine (2.5 or 5 mg). The primary outcome was the number of days without mechanical ventilation in a 28-day period, and we also recorded the length of stay in the intensive care unit (from admission to 28 days) and in hospital (from admission to 90 days). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00466492.

RESULTS

27 patients died or were successfully extubated within 48 h, and, as per our study design, were excluded from the study and statistical analysis. Patients receiving no sedation had significantly more days without ventilation (n=55; mean <em>1</em>3.8 days, SD <em>1</em><em>1</em>.0) than did those receiving interrupted sedation (n=58; mean 9.6 days, SD <em>1</em>0.0; mean difference 4.2 days, 95% CI 0.3-8.<em>1</em>; p=0.0<em>1</em>9<em>1</em>). No sedation was also associated with a shorter stay in the intensive care unit (HR <em>1</em>.86, 95% CI <em>1</em>.05-3.23; p=0.03<em>1</em>6), and, for the first 30 days studied, in hospital (3.57, <em>1</em>.52-9.09; p=0.0039), than was interrupted sedation. No difference was recorded in the occurrences of accidental extubations, the need for CT or MRI brain scans, or ventilator-associated pneumonia. Agitated delirium was more frequent in the intervention group than in the control group (n=<em>1</em><em>1</em>, 20%vs n=4, 7%; p=0.0400).

CONCLUSIONS

No sedation of critically ill patients receiving mechanical ventilation is associated with an increase in days without ventilation. A multicentre study is needed to establish whether this effect can be reproduced in other facilities.

BACKGROUND

Danish Society of Anesthesiology and Intensive Care Medicine, the Fund of Danielsen, the Fund of Kirsten Jensa la Cour, and the Fund of Holger og Ruth Hess.

Tumor necrosis factor-alpha (TNF) is a macrophage-derived peptide that is known to be an important mediator in various physiologic and immunologic events. Although the effector function of TNF has received recent attention, there is relatively little information regarding factors that regulate TNF expression. Highly Ia-positive murine peritoneal macrophages obtained via complete Freund's adjuvant elicitation were challenged with lipopolysaccharide (LPS) and assessed for the production and regulation of TNF at the cellular and molecular levels. In response to <em>1</em> microgram/<em>ml</em> LPS, the kinetics of functionally active TNF reached a maximum at approximately 3-4 h. The plateau in TNF levels was concomitant with an accelerated increase in prostaglandin E2 production. The addition of exogenous PGE2 demonstrated a dose-dependent reduction in LPS-induced TNF activity at the cellular level, as well as a significant reduction in TNF mRNA accumulation as assessed by Northern blot and in situ hybridization analysis. The reduction in LPS-stimulated mRNA accumulation by PGE2 was shown to occur at least at the level of transcription, since nuclear run-off analysis showed a specific reduction in TNF transcripts. These studies demonstrate that PGE2 can regulate macrophage-derived TNF gene expression.

The Diabetes Control and Complications Trial (DCCT) has demonstrated that intensive diabetes treatment delays the onset and slows the progression of retinopathy, nephropathy, and neuropathy in patients with IDDM. A detailed description of the effects of this treatment on diabetic nephropathy is presented here. In the primary prevention cohort, intensive treatment reduced the mean adjusted risk of the cumulative incidence of microalbuminuria >> or = 28 micrograms/min) by 34% (95% CI 2, 56%; P = 0.04). Furthermore, intensive treatment decreased the albumin excretion rate (AER) by <em>1</em>5% after the first year of therapy (6.5 vs. 7.7 micrograms/min, P < 0.00<em>1</em>). Thereafter the rates of change for AER within each treatment group were no different from zero, retaining a constant difference in AER between groups in the trial. In the secondary intervention cohort with baseline AER < 28 micrograms/min, intensive therapy reduced the mean adjusted risk of microalbuminuria >> or = 28 micrograms/min) by 43% (95% CI 2<em>1</em>, 58%; P < 0.000<em>1</em>); the risk of a more advanced level of microalbuminuria >> or = 70 micrograms/min) by 56% (95% CI 26, 74%; P = 0.002); and the risk of clinical albuminuria >> or = 208 micrograms/min) by 56% (95% CI <em>1</em>8, 76%; P < 0.0<em>1</em>). In the secondary intervention cohort, values for AER at year <em>1</em> were identical at 9 micrograms/min, but the 6.5% change per year in the conventional group greatly exceeded the rate of change of -0.3% in the intensive group (P < 0.00<em>1</em>). Among the 73 secondary cohort subjects with AER levels>> or = 28 micrograms/min but < or = <em>1</em>39 micrograms/min at baseline, the reduction of progression to clinical albuminuria with intensive therapy was not statistically significant. The longitudinal treatment effect of conventional versus intensive therapy (<em>1</em><em>1</em>.0% vs. 2.5% per year, respectively, P = 0.087) was similar in magnitude to that among patients with AER < 28 micrograms/min at baseline. For the primary, secondary and combined cohorts, there were no significant differences in the rates of change in creatinine clearance (CCr) between treatment groups during the study. Only seven subjects in the entire study (2 intensive, 5 conventional) developed urinary AER>> or = 208 micrograms/min coupled with a CCr < 70 <em>ml</em>/min/<em>1</em>.73 m2. Neither the rate of change of blood pressure nor the appearance of hypertension (BP>> <em>1</em>40/90 mm Hg) differed significantly between treatment groups in the primary, secondary or combined cohorts.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal sympathetic hyperactivity is seminal in the maintenance and progression of hypertension. Catheter-based renal sympathetic denervation has been shown to significantly reduce blood pressure (BP) in patients with hypertension. Durability of effect beyond <em>1</em> year using this novel technique has never been reported. A cohort of 45 patients with resistant hypertension (systolic BP ≥<em>1</em>60 mm Hg on ≥3 antihypertension drugs, including a diuretic) has been originally published. Herein, we report longer-term follow-up data on these and a larger group of similar patients subsequently treated with catheter-based renal denervation in a nonrandomized manner. We treated <em>1</em>53 patients with catheter-based renal sympathetic denervation at <em>1</em>9 centers in Australia, Europe, and the United States. Mean age was 57±<em>1</em><em>1</em> years, 39% were women, 3<em>1</em>% were diabetic, and 22% had coronary artery disease. Baseline values included mean office BP of <em>1</em>76/98±<em>1</em>7/<em>1</em>5 mm Hg, mean of 5 antihypertension medications, and an estimated glomerular filtration rate of 83±20 <em>mL</em>/min per <em>1</em>.73 m(2). The median time from first to last radiofrequency energy ablation was 38 minutes. The procedure was without complication in 97% of patients (<em>1</em>49 of <em>1</em>53). The 4 acute procedural complications included 3 groin pseudoaneurysms and <em>1</em> renal artery dissection, all managed without further sequelae. Postprocedure office BPs were reduced by 20/<em>1</em>0, 24/<em>1</em><em>1</em>, 25/<em>1</em><em>1</em>, 23/<em>1</em><em>1</em>, 26/<em>1</em>4, and 32/<em>1</em>4 mm Hg at <em>1</em>, 3, 6, <em>1</em>2, <em>1</em>8, and 24 months, respectively. In conclusion, in patients with resistant hypertension, catheter-based renal sympathetic denervation results in a substantial reduction in BP sustained out to ≥2 years of follow-up, without significant adverse events.

BACKGROUND

Antibody-based induction therapy plus calcineurin inhibitors (CNIs) reduce acute rejection rates in kidney recipients; however, opportunistic infections and toxic CNI effects remain challenging. Reportedly, mesenchymal stem cells (MSCs) have successfully treated graft-vs-host disease.

OBJECTIVE

To assess autologous MSCs as replacement of antibody induction for patients with end-stage renal disease who undergo ABO-compatible, cross-match-negative kidney transplants from a living-related donor.

METHODS

One hundred fifty-nine patients were enrolled in this single-site, prospective, open-label, randomized study from February 2008-May 2009, when recruitment was completed.

METHODS

Patients were inoculated with marrow-derived autologous MSC (<em>1</em>-2 x <em>1</em>0(6)/kg) at kidney reperfusion and two weeks later. Fifty-three patients received standard-dose and 52 patients received low-dose CNIs (80% of standard); 5<em>1</em> patients in the control group received anti-IL-2 receptor antibody plus standard-dose CNIs.

METHODS

The primary measure was <em>1</em>-year incidence of acute rejection and renal function (estimated glomerular filtration rate [eGFR]); the secondary measure was patient and graft survival and incidence of adverse events.

RESULTS

Patient and graft survival at <em>1</em>3 to 30 months was similar in all groups. After 6 months, 4 of 53 patients (7.5%) in the autologous MSC plus standard-dose CNI group (95% CI, 0.4%-<em>1</em>4.7%; P = .04) and 4 of 52 patients (7.7%) in the low-dose group (95% CI, 0.5%-<em>1</em>4.9%; P = .046) compared with <em>1</em><em>1</em> of 5<em>1</em> controls (2<em>1</em>.6%; 95% CI, <em>1</em>0.5%-32.6%) had biopsy-confirmed acute rejection. None of the patients in either autologous MSC group had glucorticoid-resistant rejection, whereas 4 patients (7.8%) in the control group did (95% CI, 0.6%-<em>1</em>5.<em>1</em>%; overall P = .02). Renal function recovered faster among both MSC groups showing increased eGFR levels during the first month after surgery than the control group. Patients receiving standard-dose CNI had a mean difference of 6.2 mL/min per <em>1</em>.73 m(2) (95% CI, 0.4-<em>1</em><em>1</em>.9; P=.04) and those in the low-dose CNI of <em>1</em>0.0 mL/min per <em>1</em>.73 m(2) (95% CI, 3.8-<em>1</em>6.2; P=.002). Also, during the <em>1</em>-year follow-up, combined analysis of MSC-treated groups revealed significantly decreased risk of opportunistic infections than the control group (hazard ratio, 0.42; 95% CI, 0.20-0.85, P=.02)

CONCLUSIONS

Among patients undergoing renal transplant, the use of autologous MSCs compared with anti-IL-2 receptor antibody induction therapy resulted in lower incidence of acute rejection, decreased risk of opportunistic infection, and better estimated renal function at <em>1</em> year.

BACKGROUND

clinicaltrials.gov Identifier: NCT00658073.