The frequency and outcome of recurrent lupus nephritis (RLN) among recipients of a kidney allograft vary among single-center reports. From the United Network for Organ Sharing files, we estimated the period prevalence and predictors of RLN in recipients who received a transplant between 1987 and 2006 and assessed the effects of RLN on allograft failure and recipients' survival. Among 6850 recipients of a kidney allograft with systemic lupus erythematosus, 167 recipients had RLN, 1770 experienced rejection, and 4913 control subjects did not experience rejection. The period prevalence of RLN was 2.44%. Non-Hispanic black race, female gender, and age Ͻ33 years each independently increased the odds of RLN. Graft failure occurred in 156 (93%) of those with RLN, 1517 (86%) of those with rejection, and 923 (19%) of control subjects without rejection. Although recipients with RLN had a fourfold greater risk for graft failure compared with control subjects without rejection, only 7% of graft failure episodes were attributable to RLN compared and 43% to rejection. During follow-up, 867 (13%) recipients died: 27 (16%) in the RLN group, 313 (18%) in the rejection group, and 527 (11%) in the control group. In summary, severe RLN is uncommon in recipients of a kidney allograft, but black recipients, female recipient, and younger recipients are at increased risk. Although RLN significantly increases the risk for graft failure, it contributes far less than rejection to its overall incidence; therefore, these findings should not keep patients with lupus from seeking a kidney transplant.

BackgroundInfections related to injection drug use are common. Harm reduction strategies such as syringe exchange programs and skin care clinics aim to prevent these infections in injection drug users (IDUs). Syringe exchange programs are currently prohibited by law in Florida. The goal of this study was to estimate the mortality and cost of injection drug use-related bacterial infections over a 12-month period to the county safety-net hospital in Miami, Florida. Additionally, the prevalence of HIV and hepatitis C virus among this cohort of hospitalized IDUs was estimated.Methods and FindingsIDUs discharged from Jackson Memorial Hospital were identified using the International Classification of Diseases, Ninth Revision, codes for illicit drug abuse and endocarditis, bacteremia or sepsis, osteomyelitis and skin and soft tissue infections (SSTIs). 349 IDUs were identified for chart abstraction and 92% were either uninsured or had publicly funded insurance. SSTIs, the most common infection, were reported in 64% of IDUs. HIV seroprevalence was 17%. Seventeen patients (4.9%) died during their hospitalization. The total cost for treatment for injection drug use-related infections to Jackson Memorial Hospital over the 12-month period was $11.4 million.ConclusionsInjection drug use-related bacterial infections represent a significant morbidity for IDUs in Miami-Dade County and a substantial financial cost to the county hospital. Strategies aimed at reducing risk of infections associated with injection drug use could decrease morbidity and the cost associated with these common, yet preventable infections.

ObjectivesThe goal of this work was to explore the dynamic concentration profiles of 42 amino acids and the significance of these profiles in relation to sepsis, with the aim of providing guidance for clinical therapies.MethodsThirty-five critically ill patients with sepsis were included. These patients were further divided into sepsis (12 cases) and severe sepsis (23 cases) groups or survivor (20 cases) and non-survivor (15 cases) groups. Serum samples from the patients were collected on days 1, 3, 5, 7, 10, and 14 following intensive care unit (ICU) admission, and the serum concentrations of 42 amino acids were measured.ResultsThe metabolic spectrum of the amino acids changed dramatically in patients with sepsis. As the disease progressed further or with poor prognosis, the levels of the different amino acids gradually increased, decreased, or fluctuated over time. The concentrations of sulfur-containing amino acids (SAAs), especially taurine, decreased significantly as the severity of sepsis worsened or with poor prognosis of the patient. The serum concentrations of SAAs, especially taurine, exhibited weak negative correlations with the Sequential Organ Failure Assessment (SOFA) (r=-0.319) and Acute Physiology and Chronic Health Evaluation (APACHE) II (r=-0.325) scores. The areas under the receiver operating characteristic curves of cystine, taurine, and SAA levels and the SOFA and APACHE II scores, which denoted disease prognosis, were 0.623, 0.674, 0.678, 0.86, and 0.857, respectively.ConclusionsCritically ill patients with disorders of amino acid metabolism, especially of SAAs such as cystine and taurine, may provide an indicator of the need for the nutritional support of sepsis in the clinic.Trial RegistrationClinicalTrial.gov identifier NCT01818830.

Objective:To investigate the efficacy and safety of levomilnacipran sustained release (SR), an antidepressant candidate in late-stage development, in major depressive disorder (MDD).Method: Between December 2006 and October 2007, a 10-week, randomized, double-blind, placebocontrolled, parallel-group, multicenter, flexible-dose trial assessed once-daily levomilnacipran SR (75 mg or 100 mg) in outpatients (18-70 years) meeting DSM-IV criteria for a major depressive episode (duration ≥ 1 month) with a 17-item Hamilton Depression Rating Scale (HDRS 17 ) score > 22 and Sheehan Disability Scale (SDS) score ≥ 10. Levomilnacipran SR dose was increased to 100 mg/d over 12 days. The primary efficacy measure was Montgomery Asberg Depression Rating Scale (MADRS) score change from baseline to week 10; secondary efficacy measures were the HDRS 17 , SDS, Clinical Global Impressions-Improvement scale, and MADRS response (≥ 50% decrease from baseline) and remission (score ≤ 10). Safety was evaluated according to adverse events, laboratory investigations, and vital signs/physical findings. Results: Efficacy analyses included 276 levomilnacipran SR-treated patients and 277 placebo-treated patients. Levomilnacipran SR was significantly superior to placebo on MADRS total score change from baseline to week 10 (least squares mean difference [LSMD] = −4.2 [95% CI, −5.7 to −2.6]; P < .0001). Statistical significance in favor of levomilnacipran SR was demonstrated on change from baseline to week 10 in HDRS 17 total score (LSMD = −3.4 [95% CI, −4.7 to −2.2]; P < .0001) and SDS total score (LSMD = −3.4 [95% CI, −4.6 to −2.2]; P < .0001) and subscales. Significantly more levomilnacipran SR patients versus placebo patients achieved MADRS response (59.1% vs 42.2%; P < .0001) and remission (46.4% vs 26.0%; P < .0001). Levomilnacipran SR was generally safe and well tolerated; more levomilnacipran SR patients (9.4%) versus placebo patients (6.5%) discontinued due to adverse events, but more placebo patients versus levomilnacipran SR patients discontinued overall (24.9% vs 20.2% Submitted: August 29, 2012; accepted February 1, 2013 (doi:10.4088/JCP.12m08141 Major depressive disorder (MDD) is a common, potentially dangerous, and disabling disorder. It has a chronic recurrent course and is recognized as the most common cause of disability during the course of a working life.1 Effective treatment of MDD is a public health priority.Levomilnacipran (1S, 2R-milnacipran), a potent and selective serotonin-norepinephrine reuptake inhibitor (SNRI) with greater potency for inhibition of norepinephrine (NE) relative to serotonin (5-HT) reuptake, is in clinical development for the treatment of adult MDD. In animal models of depression, it shows a potent antidepressantlike effect 2 suggesting that it may offer therapeutic effects similar to older tricyclic antidepressants without the accompanying safety and tolerability issues. The sustained release (SR) formulation was developed to allow for once-daily dosing.Potency for inhibition of 5-HT reuptake...

Allorejection and recurrence of autoimmunity are the major barriers to transplantation of islets of Langerhans for the cure of type 1 diabetes in humans. CD40-CD154 (CD40 ligand) interaction blockade by the use of anti-CD154 monoclonal antibody (mAb) has shown efficacy in preventing allorejection in several models of organ and cell transplantation. Here we report the beneficial effect of the chronic administration of a hamster anti-murine CD154 mAb, MR1, in prolonging islet graft survival in NOD mice. We explored the transplantation of C57BL/6 islets into spontaneously diabetic NOD mice, a combination in which both allogeneic and autoimmune components are implicated in graft loss. Recipients were treated either with an irrelevant control antibody or with MR1. MR1 administration was effective in prolonging allograft survival, but did not provide permanent protection from diabetes recurrence. The autoimmune component of graft loss was studied in spontaneously diabetic NOD mice that received syngeneic islets from young male NOD mice. In this combination, a less dramatic yet substantial delay in diabetes recurrence was observed in the MR1-treated recipients when compared with the control group. Finally, the allogeneic component was explored by transplanting C57BL/6 islets into chemically induced diabetic male NOD mice. In this setting, long-term graft survival (>100 days) was achieved in MR1-treated mice, whereas control recipients rejected their grafts within 25 days. In conclusion, chronic blockade of CD154 results in permanent protection from allorejection and significantly delays recurrence of diabetes in NOD mice.

IMPORTANCE Community health worker (CHW) intervention is a promising approach to address type 2 diabetes among Latinos. However, evidence from randomized clinical studies is limited.OBJECTIVE To compare a CHW intervention with enhanced usual care. DESIGN, SETTING, AND PARTICIPANTSThis 52-week, single-blind, randomized clinical trial included 300 Latino adults aged 18 to 65 years who were treated in 2 public hospital outpatient clinics in Miami-

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