Incidence of non-AIDS-defining cancers before and during the highly active antiretroviral therapy era in a cohort of human immunodeficiency virus-infected patients.

PURPOSE: To determine incidence of non-AIDS-defining cancers (NADC) in HIV-infected patients before (P1) and during (P2) the use of highly active antiretroviral therapy (HAART) relative to that observed in the French general population (FGP) of the same age and sex. PATIENTS AND METHODS: Sex- and age-adjusted NADC standardized incidence ratios (SIR), with FGP as reference, were estimated in 1992 to 1995 (P1) and in 1996 to 1999 (P2) in a French Hospital Database on HIV prospective hospital cohort study. RESULTS: NADCs were diagnosed in 260 patients during P1 and 391 patients during P2 among the 77,025 patients included in the database between January 1, 1992, and December 31, 1999. Estimated incidence of all cancers was higher in HIV-infected men than in FGP during both periods (P1 SIR = 2.36 and P2 SIR = 1.91). No excess of cancers was observed among HIV-infected women in either period. Incidence of all cancers did not change from P1 to P2 in either sex (SIR = 0.96 for men and 1.00 for women). In contrast, incidence of Hodgkin's disease (HD) was higher than in FGP in both sexes and both periods and increased in P2 as compared with P1; incidence of lung cancer was higher in both sexes during P2. CONCLUSION: Relative to FGP, the overall incidence of NADCs was increased in HIV-infected men but not in women and did not differ between P1 and P2. Only HD was much more common in HIV infection, and the potential role of HAART on HD cannot be excluded.     

Safety profile of different low-molecular weight heparins used at therapeutic dose.

Low-molecular weight heparins (LMWHs) have been shown to be as safe and effective as unfractionated heparin (UFH) for the treatment of acute venous thrombosis and non-life-threatening pulmonary embolism. Different reports have shown that LMWHs may also be used to treat patients with unstable angina or non-Q-wave infarction. The safety of LMWHs used at therapeutic dose has been widely studied in pivotal clinical trials and analysed in several meta-analyses. However, despite the wide development and use of LMWHs, several issues regarding the safety and optimal use of LMWHs remain unanswered. The main adverse effect of LMWHs is bleeding and it is uncertain whether a weight-adjusted dosage regimen without laboratory monitoring can be used in patients with a high risk of bleeding, such as patients with renal failure, elderly patients, obese patients or pregnant women. These patients are usually excluded from clinical trials and only a few studies, not sufficiently powered to estimate efficacy and safety, have been carried out in these special populations. Most of the available data comes from pharmacokinetic or population pharmacodynamic studies or clinical reports. Results in patients with renal impairment who are not undergoing haemodialysis suggest that a reduction in calculated creatinine clearance levels is associated with an increased risk of accumulation of anti-Xa activity, the extent of which differs depending on the individual LMWH and the extent to which the compound is cleared by the kidney. The limited data available regarding the use of therapeutic doses of LMWHs in obese patients suggest that there is no need to cap the dose at a maximal allowable dose. Long-term (3-month) treatment with LMWHs appears to be as effective and safe as oral anticoagulant therapy for the treatment of venous thromboembolism. It appears that each LMWH is a distinct compound with unique pharmacokinetic and pharmacodynamic profiles. Until more data are available regarding these special populations, periodic monitoring of anti-Xa activity levels may be recommended to detect accumulation and/or an overdose and minimise the bleeding risk. The non-haemorrhagic adverse effects of the LMWHs include heparin-induced thrombocytopenia (HIT) and osteoporosis. The incidence of HIT appears to be lower with LMWHs than with UFH; there is currently not enough data to compare the frequency of HIT between the various LMWHs. LMWHs also appear to carry a lower risk of causing osteoporosis than UFH. In conclusion, studies that include special population patients are required to make conclusive recommendations concerning the safety and monitoring of the different LMWHs.     

An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association.

The association of pleuropulmonary blastoma and cystic nephroma is an uncommon entity, with only 4 cases of such an association in the same patient described in English literature. We report a 5th histologically documented case in a 32-month-old boy. The boy underwent a pulmonary biopsy that showed a pleuropulmonary blastoma and a nephrectomy that showed a cystic nephroma. The pleuropulmonary mass showed an important regression with postbiopsy chemotherapy, allowing subsequent tumorectomy. To date very little is known about this rare entity, and a genetic link between these 2 tumors is hypothesized.     

Early variations of circulating interleukin-6 and interleukin-10 levels during thoracic radiotherapy are predictive for radiation pneumonitis.

PURPOSE: To investigate variations of circulating serum levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), and interleukin-10 (IL-10) during three-dimensional conformal radiation therapy (3D-CRT) in patients with non-small-cell lung cancer and correlate these variations with the occurrence of radiation pneumonitis. PATIENTS AND METHODS: Ninety-six patients receiving 3D-CRT for stage I to III disease were evaluated prospectively. Circulating cytokine levels were determined before, every 2 weeks during, and at the end of treatment. Radiation pneumonitis was evaluated prospectively between 6 and 8 weeks after 3D-CRT. The predictive value of clinical, dosimetric, and biologic (cytokine levels) factors was evaluated both in univariate and multivariate analyses. RESULTS: Forty patients (44%) experienced score 1 or more radiation pneumonitis. No association was found between baseline cytokine levels and the risk of radiation pneumonitis. In the whole population, mean levels of TNFalpha, IL-6, and IL-10 remained stable during radiotherapy. IL-6 levels were significantly higher (P = .047) during 3D-CRT in patients with radiation pneumonitis. In the multivariate analysis, covariations of IL-6 and IL-10 levels during the first 2 weeks of 3D-CRT were evidenced as independently predictive of radiation pneumonitis in this series (P = .011). CONCLUSION: Early variations of circulating IL-6 and IL-10 levels during 3D-CRT are significantly associated with the risk of radiation pneumonitis. Variations of circulating IL-6 and IL-10 levels during 3D-CRT may serve as independent predictive factors for this complication.     

Effects of Air Pollution on Adults with Chronic Obstructive Pulmonary Disease

Few studies have been conducted on the effects of air pollution on patients with chronic obstructive pulmonary disease (COPD). During a 14-mo period, 39 Parisian adults with severe COPD were monitored by their physicians. Daily levels of 4 air pollutants were provided by an urban air-quality network. Exacerbation of COPD was associated only with ozone (O₃) (odds ratio [OR] = 1.44 for a 10-μg/m³ increase in O₃; 95% confidence interval [Cl] = 1.14, 1.82), with a lag of 2-3 days. The effect of O₃ was greater in patients whose carbon dioxide pressure (PaCO₂) was higher than 43 mm Hg (OR = 1.83; 95% Cl = 1.36, 2.47) vs. those with a lower PaCO₂ (OR = 1.26; 95% Cl = 0.90, 1.77). The effect of O₃ was unchanged, regardless of the maintenance medications used. The only air pollutant to which patients with severe COPD were particularly sensitive was O₃.     

Surveillance of γδ T Cells Predicts Cytomegalovirus Infection Resolution in Kidney Transplants

Cytomegalovirus (CMV) infection in solid-organ transplantation is associated with increased morbidity and mortality, particularly if a CMV mutant strain with antiviral resistance emerges. Monitoring CMV–specific T cell response could provide relevant information for patient care. We and others have shown the involvement of Vδ2^neg γδ T cells in controlling CMV infection. Here, we assessed if Vδ2^neg γδ T cell kinetics in peripheral blood predict CMV infection resolution and emergence of a mutant strain in high–risk recipients of kidney transplants, including 168 seronegative recipients receiving organs from seropositive donors (D+R−) and 104 seropositive recipients receiving antithymocyte globulins (R+/ATG). Vδ2^neg γδ T cell percentages were serially determined in patients grafted between 2003 and 2011. The growing phase of Vδ2^neg γδ T cells was monitored in each infected patient, and the expansion rate during this phase was estimated individually by a linear mixed model. A Vδ2^neg γδ T cell expansion rate of ˃0.06% per day predicted the growing phase. The time after infection at which an expansion rate of 0.06% per day occurred was correlated with the resolution of CMV DNAemia (r=0.91; P<0.001). At 49 days of antiviral treatment, Vδ2^neg γδ T cell expansion onset was associated with recovery, whereas absence of expansion was associated with recurrent disease and DNAemia. The appearance of antiviral–resistant mutant CMV strains was associated with delayed Vδ2^neg γδ T cell expansion (P<0.001). In conclusion, longitudinal surveillance of Vδ2^neg γδ T cells in recipients of kidney transplants may predict CMV infection resolution and antiviral drug resistance.     

Mycoplasma genitalium,an agent of reemerging sexually transmitted infections

M. genitalium is a reemerging microorganism, responsible for sexually transmissible infections (STIs), with prevalence which varies depending on the country and population group studied. We report here M. genitalium prevalence among the specimens received for STI diagnosis in our routine microbiological laboratory in the university hospital in Marseille, France. We tested 4 624 samples from 3 793 patients using qPCR for M. genitalium, C. trachomatis, N. gonorrheae, T. pallidum. Of these samples, 528 (13.6%) patients were tested positive for at least one pathogen and 126 (3.3%) were positive for M. genitalium. M. genitalium is the second most prevalent micro‐organism detected in women after C. trachomatis (10.4%) and the third most prevalent in men after C. trachomatis (5.1%) and N. gonorrhoeae (4.4%). We observed no significant differences between the prevalence of M. genitalium in vaginal, urethral and urine specimens (p = 0.9). Prevalence of M. genitalium is significantly higher in patients aged between 10–30 years (4.1%) compared to those aged between 30 and 50 years (2.7%) (p = 0.02, RR = 1.54 [1.06–2.24]) and patients over 50 years of age (1.1%) (p = 0.003, RR= 3.98 [1.47–10.8]). M. genitalium is a common agent of STI, therefore we suggest that this micro‐organism should be systematically tested during chronic, recurrent, or antibiotic resistant genital infections and in populations at high‐risk of STIs.