Defective angiogenesis in hypoplastic human fetal lungs correlates with nitric oxide synthase deficiency that occurs despite enhanced angiopoietin-2 and VEGF.

Lung hypoplasia (LH) is a life-threatening congenital abnormality with various causes. It involves vascular bed underdevelopment with abnormal arterial muscularization leading to pulmonary hypertension. Because underlying molecular changes are imperfectly known and sometimes controversial, we determined key factors of angiogenesis along intrauterine development, focusing at the angiopoietin (ANG)/Tie-2 system. Lung specimens from medical terminations of pregnancy (9-37 wk) were used, including LH due to congenital diaphragmatic hernia (CDH) or other causes, and nonpulmonary disease samples were used as controls. ELISA determination indicated little ANG-1 change during pregnancy and no effect of LH, whereas Tie-2 declined similarly between 9 and 37 wk in LH and controls. By contrast, ANG-2 markedly increased in LH from 24 wk, whereas it remained stable in controls. Because VEGF increased also, this was interpreted as an attempt to overcome vascular underdevelopment. Hypothesizing that its inefficiency might be due to impaired downstream mechanism, endothelial nitric oxide synthase (eNOS) was determined by semiquantitative Western blot and found to be reduced by approximately 75%, mostly in the instance of CDH. In conclusion, angiogenesis remains defective in hypoplastic lungs despite reactive enhancement of VEGF and ANG-2 production, which could be due, at least in part, to insufficient eNOS expression.

[Extension of beta-lactamases producing bacteria is a worldwide concern]. / Diffusion communautaire des entérobactéries sécrétrices de bêta-lactamase à spectre élargi (EBLSE).

Since 2000's, community extended-spectrum beta-lactamases (ESBL) producing bacteria have spread worldwide, i.e. mostly Escherichia coli that produce ESBL such as CTX-M enzymes. Previous cephalosporins and fluoroquinolones usage are the two most frequent risk factors identified in patients that harbor ESBL-producing bacteria. In addition surveys have shown an alarming trend of associated resistance to others classes of antimicrobial agents among isolates. The emergence of ESBL-producing isolates limits the therapeutic options considerably. For serious systemic infections caused by ESBL-producing bacteria, carbapenems should be regarded as drugs of choice. Preventing the spread and appropriately managing these infections caused by community acquired ESBL producing bacteria have become mandatory.

Prevalence of monoclonal gammopathy in HIV patients in 2014.

INTRODUCTION: In non-HIV patients, Monoclonal Gammopathy of Undetermined Significance (MGUS) is associated with an increased risk of subsequent development of haematologic malignancies, especially multiple myeloma (MM) and it has been recently demonstrated that MM is always preceded by a MGUS phase. A higher prevalence of MGUS and MM has been observed in HIV patients compared to the general population. Nevertheless, it has been shown that MGUS in the context of HIV can disappear with antiretroviral therapy (ART). So, measuring MGUS prevalence in HIV patients in the recent period appears of special interest. MATERIALS AND METHODS: From January to June 2014, in each out-patient seen in our unit, a serum protein electrophoresis was performed. RESULTS: A total of 393 patients were screened. Eight patients with HIV2 and one patient with HIV1+HIV2 infection were excluded. Finally, 383 patients (173 female, 210 male) with HIV1 infection were analyzed. Characteristics of patients were as follows: median age 42.2 years (19.1-79.1), hepatitis B virus (HBV) and/or hepatitis C virus (HCV) co-infection 47 (18.8%), median CD4 610 (2-1758), CD8 793 (113-4010), presence of a past AIDS event for 88 patients (23%). Median time with HIV infection was 11 years (0-30). Three hundred fifty-nine patients (93.7%) were on ART for a median duration of 105 months (0-287). For 320 patients (83.6%), viral load was below 50 viral copies/ml. Twelve cases of MGUS (3.1%) were observed: IgG Kappa (five cases), IgG Lambda (five cases), biclonal with two IgG Kappa (one case) and in one case, three monoclonal immunoglobulins were observed (IgG Kappa×2+IgG Lambda). The monoclonal immunoglobulin's level was low and below 1 g/l in all cases except two (2.1 and 11.6 g/l). No factor was found to be predictive of the presence of MGUS in particular age, CD4, HBV/HCV co-infection, viral load or ART. CONCLUSIONS: In the context of modern ART, the prevalence of MGUS remains above those observed in the general population. Even if the level of monoclonal spike observed in our cohort is generally low, an excess risk of subsequent development of MM could be present. Nevertheless, a prospective follow-up of HIV patients with MGUS is necessary to determine this risk.

Anaplastic Large Cell Lymphoma Occurring in an HIV-Positive Patient.

Cases of anaplastic large-cell lymphoma (ALCL) of T phenotype are sparse in the setting of HIV patients. We report herein a case of T-ALCL, with an advanced stage, pulmonary involvement, high HIV viral load, and low CD4 level. Anaplastic lymphoma kinase (ALK) protein expression was negative. Anthracyclin-based chemotherapy was unsuccessful. The literature review was performed focusing on incidence, clinical characteristics, prognosis, and physiopathology of ALCL in HIV patients. More data are needed to improve the knowledge of such cases and to define a better treatment approach.

Low bone mineral density and high incidences of fractures and vitamin D deficiency in 52 pediatric cancer survivors.

OBJECTIVE: To evaluate bone mineral density (BMD), fractures, and vitamin D deficiency in pediatric patients in complete remission of solid tumor; and to identify risk factors for these three abnormalities. STUDY DESIGN: Data were collected prospectively after completion of cancer treatment. Hormonal and vitamin D deficiencies were treated. The patients were evaluated again 1 year later. PATIENTS: 52 consecutive patients, 30 boys and 22 girls. Among them, 21 completed the second evaluation. MEASUREMENTS: A clinical examination, nutritional assessment, and laboratory workup were performed. BMD was measured by absorptiometry. RESULTS: Calcium intake was inadequate in 75% of patients and vitamin D reserves were low in 61.5%. BMD was low at the spine in 32.7%, and at the femur in 24% of patients. Spinal and femoral BMD Z-scores correlated significantly with each other. Femoral BMD Z-score showed significant positive correlations with changes in body mass index, urinary calcium/creatinine ratio, and time since treatment completion, and a significant negative correlation with treatment duration. Fractures were noted in 10 patients but were not correlated with BMD. In the 21 re-evaluated patients, no significant improvements were found in calcium intake, vitamin D status, or BMD Z-score. CONCLUSIONS: Survivors of childhood solid cancer have high rates of insufficient calcium intake, vitamin D deficiency, low bone mass and fractures.

Intermittent treatment for the prevention of malaria during pregnancy in Benin: a randomized, open-label equivalence trial comparing sulfadoxine-pyrimethamine with mefloquine.

BACKGROUND: In the context of the increasing resistance to sulfadoxine-pyrimethamine (SP), we evaluated the efficacy of mefloquine (MQ) for intermittent preventive treatment during pregnancy (IPTp). METHODS: A multicenter, open-label equivalence trial was conducted in Benin from July 2005 through April 2008. Women of all gravidities were randomized to receive SP (1500 mg of sulfadoxine and 75 mg of pyrimethamine) or 15 mg/kg MQ in a single intake twice during pregnancy. The primary end point was the proportion of low-birth-weight (LBW) infants (body weight, <2500 g; equivalence margin, 5%). RESULTS: A total of 1601 women were randomized to receive MQ (n=802)or SP (n=799).In the modified intention-to-treat analysis, which assessed only live singleton births, 59 (8%) of 735 women who were given MQ and 72 (9.8%) of 730 women who were given SP gave birth to LBW infants (difference between low birth weights in treatment groups, -1.8%; 95% confidence interval [CI], -4.8% to 1.1%]), establishing equivalence between the drugs. The per-protocol analysis showed consistent results. MQ was more efficacious than SP in preventing placental malaria (prevalence, 1.7% vs 4.4% of women; P = .005),clinical malaria (incidence rate, 26 cases/10,000 person-months vs. 68 cases/10,000 person-months; P = .007) and maternal anemia at delivery (as defined by a hemoglobin level <10 g/dL) (prevalence, 16% vs 20%; marginally significant at P = .09). Adverse events (mainly vomiting, dizziness, tiredness, and nausea) were more commonly associated with the use of MQ (prevalence, 78% vs 32%; P < 10(-3)) One woman in the MQ group had severe neuropsychiatric symptoms. CONCLUSIONS: MQ proved to be highly efficacious--both clinically and parasitologically--for use as IPTp. However, its low tolerability might impair its effectiveness and requires further investigations.

Rituximab in severe lupus nephritis: early B-cell depletion affects long-term renal outcome.

BACKGROUND AND OBJECTIVES: Standard treatment for lupus nephritis, including corticosteroids and cyclophosphamide, is efficient but is still associated with refractory or relapsing disease, or severe deleterious effects. Rituximab, a monoclonal chimeric anti-B cell antibody, is increasingly used in patients with lupus nephritis, but reported series were small and had a short follow-up. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The authors analyzed clinical and histologic data of 20 patients who were treated with rituximab for lupus nephritis and followed up for at least 12 mo. RESULTS: Nineteen women and one man received rituximab as induction treatment for an active class IV (15 cases) or class V (5 cases) lupus nephritis. Rituximab was given for lupus nephritis refractory to standard treatment (12 cases), for relapsing disease (6 cases), or as first-line treatment (2 cases). Three patients received cyclophosphamide concomitantly with rituximab. Ten received new injections of rituximab as maintenance therapy. Side effects included mainly five infections and four moderate neutropenias. After a median follow-up of 22 mo, complete or partial renal remission was obtained in 12 patients (60%). Lupus nephritis relapsed in one patient, who responded to a new course of rituximab. The achievement of B cell depletion 1 mo after rituximab, which negatively correlated with black ethnicity and hypoalbuminemia, was strongly associated with renal response. Rapidly progressive glomerulonephritis did not respond to rituximab. CONCLUSION: Rituximab is an interesting therapeutic option in relapsing or refractory lupus nephritis when early B cell depletion is obtained.