Fievre Q: une zoonose souvent méconnue [Q fever, a zoonosis often overlooked].

Q fever is a zoonosis caused by an intracellular Gram-negative bacteria, Coxiella burnetii. Animals are the main reservoir and transmission to men generally is occurring by inhalation of contaminated aerosols. Acute Q fever generally is benign and usually resolves spontaneously. When symptomatic, the clinical presentation typically includes one of the following three syndromes: a flu-like illness, a granulomatous hepatitis or an atypical pneumonia. Individuals presenting risk factors such as patients with valvular heart diseases and vascular prostheses, as well as pregnant women and immuno-suppressed patients represent a population at risk of chronic infection, with endocarditis as the most common clinical form.

Lack of association between beta-herpesvirus infection and bronchiolitis obliterans syndrome in lung transplant recipients in the era of antiviral prophylaxis.

BACKGROUND: Cytomegalovirus (CMV), human herpesvirus-6 and -7 (HHV-6 and -7) are beta-herpesviruses that commonly reactivate and have been proposed to trigger acute rejection and chronic allograft injury. We assessed the contribution of these viruses in the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. METHODS: Quantitative real-time polymerase chain reaction of bronchoalveolar lavage samples were performed for CMV, HHV-6 and -7 in a prospective cohort of lung transplant recipients. A time-dependent Cox regression analysis was used to correlate the risk of BOS and acute rejection in patients with and without beta-herpesviruses infection. RESULTS: Ninety-three patients were included in the study over a period of 3 years. A total of 581 samples from bronchoalveolar lavage were obtained. Sixty-one patients (65.6%) had at least one positive result for one of the beta-herpesviruses: 48 patients (51.6%) for CMV and 19 patients (20.4%) for both HHV-6 and -7. Median peak viral load was 3419 copies/mL for CMV, 258 copies/mL for HHV-6, and 665 copies/mL for HHV-7. Acute rejection (>or=grade 2) occurred in 46.2% and BOS (>or=stage 1) in 19.4% of the patients. In the Cox regression model the relative risk of acute rejection or BOS was not increased in patients with any beta-herpesviruses reactivation. Acute rejection was the only independently associated risk factor for BOS. CONCLUSIONS: In lung transplant recipients receiving prolonged antiviral prophylaxis, reactivation of beta-herpesviruses within the allograft was common. However, despite high viral loads in many patients, virus replication was not associated with the development of rejection or BOS.

Intraarterial nimodipine for the treatment of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage: a preliminary study.

OBJECTIVE: Despite dramatic advances in all medical era, cerebral vasospasm is still the major complication in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to assess the influence of intraarterial (IA) nimodipine in the treatment of symptomatic vasospasm and in preventing neurological disabilities. MATERIALS AND METHODS: We retrospectively reviewed 10 patients of SAH who received IA nimodipine in 15 procedures. The decision to perform angiography and endovascular treatment was based on the neurological examination, brain computed tomography (CT) and CT-angiography. The procedure reports, anesthesia records, neurological examination before and after the procedure, brain imaging and short- and long-term outcome were studied. RESULTS: The average dose of nimodipine was 2 mg. The median change in mean arterial pressure at 10 min was -10 mmHg. No significant change of heart rate was observed at 10 min. There was radiological improvement in 80% of the procedures. Neurological improvement was noted after eight out of 12 procedures when nimodipine was used as the sole treatment and after 10 out of 15, overall. Six patients clinically improved after the treatment and had good outcome. In one patient, an embolus caused fatal anterior and middle cerebral arteries infarction. There was no other neurological deficit or radiological abnormality due to the nimodipine treatment itself. CONCLUSION: Low-dose IA nimodipine is a valid adjunct for the endovascular treatment of cerebral vasospasm. Beneficial effects are achieved in some patients, prompting a prospective control study.

Regulation of neurotrophic factors and energy metabolism by antidepressants in astrocytes.

There is growing evidence that astrocytes are involved in the neuropathology of major depression. In particular, decreases in glial cell density observed in the cerebral cortex of individuals with major depressive disorder are accompanied by a reduction of several astrocytic markers suggesting that astrocyte dysfunction may contribute to the pathophysiology of major depression. In rodents, glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors and antidepressant treatment prevents the stress-induced reduction of astrocyte number in the hippocampus. Collectively, these data support the existence of a link between astrocyte loss or dysfunction, depressive-like behavior and antidepressant treatment. Astrocytes are increasingly recognized to play important roles in neuronal development, neurotransmission, synaptic plasticity and maintenance of brain homeostasis. It is also well established that astrocytes provide trophic, structural, and metabolic support to neurons. In this article, we review evidence that antidepressants regulate energy metabolism and neurotrophic factor expression with particular emphasis on studies in astrocytes. These observations support a role for astrocytes as new targets for antidepressants. The contribution of changes in astrocyte glucose metabolism and neurotrophic factor expression to the therapeutic effects of antidepressants remains to be established.

Vitamin D deficiency and a CYP27B1-1260 promoter polymorphism are associated with chronic hepatitis C and poor response to interferon-alfa based therapy.

BACKGROUND & AIMS: Vitamin D is an important immune modulator and preliminary data indicated an association between vitamin D deficiency and sustained virologic response (SVR) rates in hepatitis C virus (HCV) genotype 1 patients. We, therefore, performed a comprehensive analysis on the impact of vitamin D serum levels and of genetic polymorphisms with functional relevance within the vitamin D cascade on chronic hepatitis C and its treatment. METHODS: Vitamin D serum levels, genetic polymorphisms within the vitamin D receptor and 1α-hydroxylase were determined in a cohort of 468 HCV genotype 1, 2, and 3 infected patients who were treated with interferon-alfa based regimens. RESULTS: Chronic hepatitis C was associated with a high incidence of severe vitamin D deficiency compared to controls (25(OH)D(3)<10 ng/ml in 25% versus 12%, p<0.00001). 25(OH)D(3) deficiency correlated with SVR in HCV genotype 2 and 3 patients (50% and 81% SVR for patients with and without severe vitamin D deficiency, respectively, p<0.0001). In addition, the CYP27B1-1260 promoter polymorphism rs10877012 had substantial impact on 1,25-dihydroxyvitamin D serum levels (72, 61, and 60 pmol/ml for rs10877012 AA, AC, and CC, respectively, p=0.04) and on SVR rates in HCV genotype 1, 2, and 3 infected patients (77% and 65% versus 42% for rs10877012 AA, AC, and CC, respectively, p=0.02). CONCLUSIONS: Chronic hepatitis C virus infection is associated with vitamin D deficiency. Reduced 25-hydroxyvitamin D levels and CYP27B1-1260 promoter polymorphism leading to reduced 1,25-dihydroxyvitamin D levels are associated with failure to achieve SVR in HCV genotype 1, 2, and 3 infected patients.

Idiopathic recurrent neuroretinitis: effects of long-term immunosuppression.

OBJECTIVE: To determine the efficacy of long-term immunosuppressive therapy in patients with recurrent idiopathic neuroretinitis. METHODS: A retrospective review of 30 patients with recurrent idiopathic neuroretinitis identified 7 who received ongoing immunosuppression with prednisone and/or azathioprine for whom adequate follow-up information was available. We calculated the number of attacks per unit of time for each patient before and after treatment to derive mean attack rates for the group. RESULTS: For the entire group, we found a rate of 0.58 attacks per year prior to the initiation of immunosuppressive treatment, which decreased to 0.16 attacks per year following immunosuppression. This represents a reduction in the attack rate of 0.41, or a 72% decrease in attack frequency. CONCLUSIONS: Our study suggests a possible role for long-term immunosuppressive treatment in patients with recurrent idiopathic neuroretinitis. A longer follow-up interval, more standardized treatment regimens, and additional outcome measures might reveal a greater benefit of treatment.

Les biomarqueurs prédictifs dans le cancer colorectal [Predictive biomarkers in colorectal cancer]

While for many years the diagnosis and therapy of colon cancer did not change drastically, recently new drugs (irinotecan and oxaliplatin, used in adjuvant or neo-adjuvant approaches) and even more recently the introduction of therapies targeting the epidermal growth factor receptor (EGFR) through the monoclonal antibodies cetuximab and panitumumab, are revolutionizing the field. The finding that only patients with a tumor with a wild type (non mutated) KRAS gene respond to anti-EGFR therapy has also affected the way pathologists address colorectal cancer. Molecular analysis of the KRAS gene has become almost a routine in a very short period of time. Pathologists will have to be prepared for a new era: from standard morphology based diagnostic procedures to the prediction of response to therapy using molecular tools.

Cell-mediated immunity to predict cytomegalovirus disease in high-risk solid organ transplant recipients.

Late-onset cytomegalovirus (CMV) disease commonly occurs after discontinuation of antiviral prophylaxis. We determined the utility of testing CD8+ T-cell response against CMV as a predictor of late-onset CMV disease after a standard course of antiviral prophylaxis. Transplant patients at high-risk for CMV disease were enrolled. CD8+ T-cell-mediated immunity (CMI) was tested using the QuantiFERON-CMV assay at baseline, 1, 2 and 3 months posttransplant by measurement of interferon-gamma response to whole blood stimulation with a 21-peptide pool. The primary outcome was the ability of CMI testing to predict CMV disease in the first 6 months posttransplant. There were 108 evaluable patients (D+/R+ n = 39; D-/R+ n = 34; D+/R- n = 35) of whom 18 (16.7%) developed symptomatic CMV disease. At the end of prophylaxis, CMI was detectable in 38/108 (35.2%) patients (cutoff 0.1 IU/mL interferon-gamma). CMV disease occurred in 2/38 (5.3%) patients with a detectable interferon-gamma response versus 16/70 (22.9%) patients with a negative response; p = 0.038. In the subgroup of D+/R- patients, CMV disease occurred in 1/10 (10.0%) patients with a detectable interferon-gamma response (cutoff 0.1 IU/mL) versus 10/25 (40.0%) patients with a negative CMI, p = 0.12. Monitoring of CMI may be useful for predicting late-onset CMV disease.

Influence of triamcinolone intravitreal injection on retinochoroidal healing processes.

To analyze the effects of triamcinolone intravitreal injection on the wound healing processes after argon laser retinal photocoagulation, wild type C57BL/6J mice, 8-12 weeks old underwent a standard argon laser photocoagulation protocol. After pentobarbital anesthesia and pupil dilatation, argon laser lesions were induced (50microm, 400mW, 0.05s). Two photocoagulation impacts created two disc diameters from the optic nerve in both eyes. The photocoagulated mice were divided into four groups: Group I (n=12), photocoagulation controls, did not receive any intravitreous injection. Group II (n=12), received an intravitreous injection of 1microl of balanced salt solution (BSS). Group III (n=12), received an intravitreous injection of 1microl containing 15microg of triamcinolone acetonide (TAAC) in BSS. Two mice from each of these three groups were sacrificed at 1, 3, 7, 14 days and 2 and 4 months after photocoagulation. Group IV (n=10) received 1.5, 3, 7.5, 15, or 30microg of TAAC and were all sacrificed on day 14. The enucleated eyes were subjected to systematic analysis of the cellular remodeling processes taking place within the laser lesion and its vicinity. To this purpose, specific antibodies against GFAP, von Willebrand factor, F4/80 and KI67 were used for the detection of astrocytes, activated Müller cells, vascular endothelial cells, infiltrating inflammatory cells and actively proliferating cells. TUNEL reaction was also carried out along with nuclear DAPI staining. Temporal and spatial observations of the created photocoagulation lesions demonstrate that 24h following the argon laser beam, a localized and well-delineated affection of the RPE cells and choroid is observed in mice in Groups I and II. The inner retinal layers in these mice eyes are preserved while TUNEL positive (apoptotic) cells are observed at the retinal outer nuclear layer level. At this stage, intense staining with GFAP is associated with activated retinal astrocytes and Müller cells throughout the laser path. From day 3 after photocoagulation, dilated new choroidal capillaries are detected on the edges of the laser lesion. These processes are accompanied by infiltration of inflammatory cells and the presence of proliferating cells within the lesion site. Mice in Group III treated with 15microg/mul of triamcinolone showed a decreased number of infiltrating inflammatory cells and proliferating cells, which was not statistically significant compared to uninjected laser treated controls. The development of new choroidal capillaries on the edges of the laser lesion was also inhibited during the first 2 months after photocoagulation. However, on month 4 the growth of new vessels was observed in these mice treated with TAAC. Mice of Group IV did not show any development of new capillaries even with small doses. After argon laser photocoagulation of the mouse eye, intravitreal injection of triamcinolone markedly influenced the retina and choroid remodeling and healing processes. Triamcinolone is a powerful inhibitor of the formation of neovessels in this model. However, this inhibition is transient. These observations should provide a practical insight for the mode of TAAC use in patients with wet AMD.

Anisoylated plasminogen streptokinase activator complex versus streptokinase in acute myocardial infarction. Preliminary results of a randomised study.

25 patients with acute myocardial infarction pain lasting more than 20 minutes which was not relieved by nitrates, whose ECGs showed ST segment elevations of 1 mm or more in 2 or more ECG leads, and who presented less than 3 hours after onset of their symptoms were randomly assigned to one of 2 thrombolytic treatment groups: a single intravenous bolus of anisoylated plasminogen streptokinase activator complex (APSAC) 30U in 5 minutes or an intravenous infusion of streptokinase 1,500,000U over 60 minutes. 3 to 4 hours after the administration of the thrombolytic agent, all patients received intravenous heparin at full dosage for 24 hours. The patency of the infarct-related coronary vessels was assessed by angiography 1 to 4 hours after administration of the thrombolytic agent. Clinical signs, ECGs, pulse, blood pressure and temperature were monitored regularly for 24 hours after treatment or as clinically appropriate. APSAC seemed to be at least as effective as streptokinase in terms of patency of the infarct-related vessel (92% vs 63%, respectively). The adverse events were similar and none was life-threatening. APSAC and streptokinase caused similar falls in blood fibrinogen levels. APSAC, given as a bolus injection over 5 minutes, was easier to administer than streptokinase, which was given as an infusion during 60 minutes.

Five years of denosumab exposure in women with postmenopausal osteoporosis: results from the first two years of the FREEDOM extension.

The 3-year FREEDOM trial assessed the efficacy and safety of 60 mg denosumab every 6 months for the treatment of postmenopausal women with osteoporosis. Participants who completed the FREEDOM trial were eligible to enter an extension to continue the evaluation of denosumab efficacy and safety for up to 10 years. For the extension results presented here, women from the FREEDOM denosumab group had 2 more years of denosumab treatment (long-term group) and those from the FREEDOM placebo group had 2 years of denosumab exposure (cross-over group). We report results for bone turnover markers (BTMs), bone mineral density (BMD), fracture rates, and safety. A total of 4550 women enrolled in the extension (2343 long-term; 2207 cross-over). Reductions in BTMs were maintained (long-term group) or occurred rapidly (cross-over group) following denosumab administration. In the long-term group, lumbar spine and total hip BMD increased further, resulting in 5-year gains of 13.7% and 7.0%, respectively. In the cross-over group, BMD increased at the lumbar spine (7.7%) and total hip (4.0%) during the 2-year denosumab treatment. Yearly fracture incidences for both groups were below rates observed in the FREEDOM placebo group and below rates projected for a "virtual untreated twin" cohort. Adverse events did not increase with long-term denosumab administration. Two adverse events in the cross-over group were adjudicated as consistent with osteonecrosis of the jaw. Five-year denosumab treatment of women with postmenopausal osteoporosis maintained BTM reduction and increased BMD, and was associated with low fracture rates and a favorable risk/benefit profile.

Médecine d'urgence [Emergency medicine: updates 2013].

New evidences published this year are susceptible to change the management of several medical emergencies. Combined antiplatelet therapy might be beneficial for the management of TIA or minor stroke and rapid blood pressure lowering might improve the outcome in patients with intracerebral hemorrhage. A restrictive red cell transfusion strategy is indicated in case of upper digestive bleeding and coagulation factors concentrates are superior to fresh frozen plasma for urgent warfarin reversal. Prolonged systemic steroid therapy is not warranted in case of acute exacerbation of BPCO, and iterative physiotherapy is not beneficial after acute whiplash. Finally, family presence during cardiopulmonary resuscitation may reduce post-traumatic stress disorder among relatives.

Lecture d'articles médicaux: quelques pièges à éviter [Reading medical articles--what pitfalls to avoid]

Critical reading and careful interpretation of results of the medical literature is a difficult task for primary care physicians. Being aware of common potential pitfalls that may bias results of a study is helpful. Among common pitfalls, odds ratios are often interpreted as relative risks, which overestimate the impact of a risk factor. Randomized controlled trials assessing the effectiveness of a new drug or a new target disease often use surrogate markers instead of clinical events as outcomes. Results of these trials should be considered with caution before using their results for clinical practice. For screening, observational studies often yield potentially biased or conflicting results. As clinical guidelines and expert opinions are often conflicting, primary care physicians should wait for results of large clinical trials in clinical events before changing their practice for screening or new drugs.

The EuroSIDA study: Regional differences in the HIV-1 epidemic and treatment response to antiretroviral therapy among HIV-infected patients across Europe--a review of published results.

EuroSIDA is a pan-European observational study that follows 14,265 HIV-infected patients from 31 European countries, Israel and Argentina, of which 2,560 are patients from eastern Europe (EE). The study group has performed several analyses addressing regional differences in the HIV-epidemic across Europe, where all countries were divided into five regions: south, west central, north, east central Europe and EE. Significant regional differences in patients' characteristics and pattern of AIDS diagnoses were documented. More patients from EE were diagnosed with tuberculosis compared to other regions. Significantly fewer HIV-infected patients in EE, who fulfilled the criteria for starting combination antiretroviral therapy (cART), actually received cART as compared with other regions of Europe. Those, receiving cART in EE had a lower initial virologic response rate irrespectively of the regimen used, although it has improved within years. Besides, treatment failure was more common in this region. Thus, improvements in the clinical management of HIV patients in EE are urgently needed. Strategies include creating scientific collaborations for HIV clinicians as well as teaching clinicians about the most advanced HIV management at clinically oriented courses held in eastern Europe.