Role of size and composition of traffic and agricultural aerosols in the molecular responses triggered in airway epithelial cells

The increased levels of fine particles in the atmosphere are suspected of aggravating cardiopulmonary diseases, but the determinants of particle toxicity are poorly understood. This work aims at studying the role of composition and size in the toxicity of size-segregated particulate matter (PM) collected at different sites on human bronchial epithelial cells. PM were sampled at a traffic urban site (Urb S) and a rural site (Rur S) during the pesticide-spreading period. Ultrafine (UF), fine (F), and coarse (C) PM were characterized by their shape and chemical composition. Whatever the site, the finest PM (UF and F) induced the mRNA expression of CYP1A1, a biomarker of polyaromatic hydrocarbons (PAH) exposure, NQO-1 and heme HO-1, two antioxidant responsive element-driven genes; and two effect biomarkers, GM-CSF, a proinflammatory cytokine and amphiregulin (AR), a growth factor. C PM have a low or no effect. Interestingly, AR is more strongly induced by rural PM at the same mass exposure. These discrepancies suggest involvement of PM chemical composition: rural PM bearing the characteristics of aged aerosols with a high content of water-soluble components, and PM at urban kerbside sites containing mainly water-insoluble components. To conclude, we provide evidence that the finest PM fractions, whatever their origin, are more prone to induce exposure and effect biomarkers. The AR differential expression suggests a source-dependent effect requiring further investigation because of the role of this growth factor in airway remodeling, a characteristic feature of chronic lung respiratory diseases exacerbated by particulate pollution.     

Ciguatera risk management in French Polynesia: The case study of Raivavae Island (Australes Archipelago)

Based on epidemiological data available through long-term monitoring surveys conducted by both the Public Health Directorate and the Louis Malardé Institute, ciguatera is highly endemic in French Polynesia, most notably in Raivavae (Australes) which appears as a hot spot of ciguatera with an average incidence rate of 140 cases/10,000 population for the period 2007-2008. In order to document the ciguatera risk associated with Raivavae lagoon, algal and toxin-based field monitoring programs were conducted in this island from April 2007 to May 2008. Practically, the distribution, abundance and toxicity of Gambierdiscus populations, along with the toxicity levels in 160 fish distributed within 25 distinct species, were assessed in various sampling locations. Herbivores such as Scarids (parrotfish) and Acanthurids (unicornfish) were rated as high-risk species based on receptor-binding assay toxicity data. A map of the risk stratification within the Raivavae lagoon was also produced, which indicates that locations where both natural and man-made disturbances have occurred remained the most susceptible to CFP incidents. Our findings also suggest that, locally, the traditional knowledge about ciguatera may not be scientifically complete but is functionally correct. Community education resulted in self-regulating behaviour towards avoidance of high-risk fish species and fishing locations.     

Emerging viral infectious diseases and pregnancy

Various emerging diseases have been reported in recent years as epidemiologic monitoring improves. These infections can compromise the pregnancy, through adverse maternal outcomes, as well as the outcome for the child following transmission. We report a review of the literature concerning the most quoted emergent virus (H5N1, SARS Coronavirus, Chikungunya, West Nile virus), and relate the perinatal management.     

Renal function and clinical outcome of patients with cancer-associated venous thromboembolism randomized to receive apixaban or dalteparin. Results from the Caravaggio trial

The effect of renal impairment (RI) on risk of bleeding and recurrent thrombosis in cancer patients treated with direct oral anticoagulants for venous thromboembolism (VTE) is undefined. We ran a prespecified analysis of the randomized Caravaggio study to evaluate the role of RI as a risk factor for bleeding or recurrence in patients treated with dalteparin or apixaban for cancer-associated VTE. RI was graded as moderate (creatinine clearance between 30-59 mL/minute; 275 patients) and mild (between 60-89 mL/minute; 444 patients). In the 1142 patients included in this analysis, the incidence of major bleeding was similar in patients with moderate vs. no or mild RI (HR 1.06-95% CI: 0.53-2.11), with no difference in the relative safety of apixaban and dalteparin. Recurrent VTE was not different in moderate vs. no or mild RI (HR=0.67, 95% CI: 0.38-1.20); in moderate RI, apixaban reduced recurrent VTE compared to dalteparin (HR=0.27, 95% CI: 0.08-0.96; P for interaction 0.1085). At multivariate analysis, no association was found between variation of renal function over time and major bleeding or recurrent VTE. Advanced or metastatic cancer was the only independent predictor of major bleeding (HR=2.84, 95% CI: 1.20-6.71), with no effect of treatment with apixaban or dalteparin. In our study, in cancer patients treated with apixaban or dalteparin, moderate RI was not associated with major bleeding or recurrent VTE. In patients with moderate renal failure, the safety profile of apixaban was confirmed with the potential for improved efficacy in comparison to dalteparin. ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT03045406","term_id":"NCT03045406"}}NCT03045406.     

First imaging results of an intraindividual comparison of 11C-acetate and 18F-fluorocholine PET/CT in patients with prostate cancer at early biochemical first or second relapse after prostatectomy or radiotherapy

Purpose

¹⁸F-Fluorocholine (FCH) and ¹¹C-acetate (ACE) PET are widely used for detection of recurrent prostate cancer (PC). We present the first results of a comparative, prospective PET/CT study of both tracers evaluated in the same patients presenting with recurrence and low PSA to compare the diagnostic information provided by the two tracers.

Methods

The study group comprised 23 patients studied for a rising PSA level after radical prostatectomy (RP, 7 patients, PSA ≤3 ng/ml), curative radiotherapy (RT, 7 patients, PSA ≤5 ng/ml) or RP and salvage RT (9 patients, PSA ≤5 ng/ml). Both FCH and ACE PET/CT scans were performed in a random sequence a median of 4 days (range 0 to 11 days) apart. FCH PET/CT was started at injection (307?±?16 MBq) with a 10-min dynamic acquisition of the prostate bed, followed by a whole-body PET scan and late (45 min) imaging of the pelvis. ACE PET/CT was performed as a double whole-body PET scan starting 5 and 22 min after injection (994?±?72 MBq), and a late view (45 min) of the prostate bed. PET/CT scans were blindly reviewed by two independent pairs of two experienced nuclear medicine physicians, discordant subgroup results being discussed to reach a consensus for positive, negative end equivocal results.

Results

PET results were concordant in 88 out of 92 local, regional and distant findings (Cohen’s kappa 0.929). In particular, results were concordant in all patients concerning local status, bone metastases and distant findings. Lymph-node results were concordant in 19 patients and different in 4 patients. On a per-patient basis results were concordant in 22 of 23 patients (14 positive, 5 negative and 3 equivocal). In only one patient was ACE PET/CT positive for nodal metastases while FCH PET/CT was overall negative; interestingly, the ACE-positive and FCH-negative lymph nodes became positive in a second FCH PET/CT scan performed a few months later.

Conclusion

Overall, ACE and FCH PET/CT showed excellent concordance, on both a per-lesion and a per-patient basis, suggesting that both tracers perform equally for recurrent prostate cancer staging.     

Rationale for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment or prevention of peritoneal carcinomatosis

Up to now, the prognosis of peritoneal carcinomatosis from GI tract cancers remains very poor. Intraperitoneal hyperthermic chemotherapy has been proposed in the prevention or treatment of peritoneal carcinomatosis. The rationale for this locoregional approach comes from a better knowledge of the physiopathology of the disease. Intraperitoneal chemotherapy achieves high local drug concentration with limited systemic toxicity. It should be performed during or immediately after surgery to be effective towards microscopic residual tumor cells. A synergistic cytotoxic effect has been demonstrated when heat is combined with antineoplastic drugs. Intraperitoneal hyperthermic chemotherapy might not be regarded as the panacée but as a promising step in the management of peritoneal carcinomatosis. Some randomized studies of gastric cancer with macroscopic serosal invasion have suggested the efficacy of hyperthermic intraperitoneal chemotherapy for the prevention of peritoneal carcinomatosis. In patients with peritoneal carcinomatosis, some studies suggest, in selected cases, the positive effect of hyperthermic intraperitoneal chemotherapy on survival, when combined with cytoreductive surgery.     

Clinical Situations in Which the Diagnosis of Autism is Debatable: An Analysis and Recommendations

The “autism spectrum disorder” (ASD) construct and its current diagnostic criteria have led to the inclusion of increasingly heterogeneous and decreasingly atypical individuals under its definition. This broad category, based on the polymorphic clinical expression of common genetic variants underpinning the risk of autism, is likely beneficial for certain individuals. However, determining the boundaries between ASD and typical individuals, as well as those with other neurodevelopmental conditions, remains an issue of which the importance is growing with the increase in ASD prevalence. We identified four clinical contexts associated with a questionable, poorly justified, or unhelpful ASD diagnosis: (1) those in which diagnostic instruments raise uncertainties, (2) in the context of a subclinical presentation, (3) when early autistic signs tend to fade away during development, and (4) when comorbidities are prominent. We argue that in certain cases, a diagnosis of ASD may not be the most suitable, timely, or helpful medical act and provide recommendations for clinical practice when facing such situations.