Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

Objective: Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease. // Methods: As development of novel radiotracers and on‐site setup of existing radiotracers is highly time‐consuming and expensive, we used dual‐centre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18F‐flumazenil (18F‐FMZ; GABAA receptor), 18F‐FPEB (metabotropic glutamate receptor 5; mGluR5), 18F‐flutriciclamide (translocator protein; TSPO, microglia activation) and 18F‐deprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpine‐induced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12‐14 weeks after SE) were normalized to a calibration curve, co‐registered to an MRI‐based 2D region‐of‐interest atlas, and activity concentration (Bq/mm2) was calculated. // Results: In epileptogenesis‐associated brain regions, 18F‐FMZ and 18F‐FPEB showed an early decrease after SE. 18F‐FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18F‐FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18F‐flutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5‐15 days and decreasing during the chronic phase. On the other hand, 18F‐deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase. // Significance: Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter‐related targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments

Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

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Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers

Objective: Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease. // Methods: As development of novel radiotracers and on‐site setup of existing radiotracers is highly time‐consuming and expensive, we used dual‐centre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18F‐flumazenil (18F‐FMZ; GABAA receptor), 18F‐FPEB (metabotropic glutamate receptor 5; mGluR5), 18F‐flutriciclamide (translocator protein; TSPO, microglia activation) and 18F‐deprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpine‐induced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12‐14 weeks after SE) were normalized to a calibration curve, co‐registered to an MRI‐based 2D region‐of‐interest atlas, and activity concentration (Bq/mm2) was calculated. // Results: In epileptogenesis‐associated brain regions, 18F‐FMZ and 18F‐FPEB showed an early decrease after SE. 18F‐FMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18F‐FPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18F‐flutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5‐15 days and decreasing during the chronic phase. On the other hand, 18F‐deprenyl autoradiography showed late astrogliosis, peaking in the chronic phase. // Significance: Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of inter‐related targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments

Identification of low-risk patients with acute symptomatic pulmonary embolism for outpatient therapy

Rationale: Patients with acute symptomatic pulmonary embolism (PE) deemed to be at low risk for early complications might be candidates for partial or complete outpatient treatment. Objectives: To develop and validate a clinical prediction rule that accurately identifies patients with PE and low risk of short-term complications and to compare its prognostic ability with two previously validated models (i.e., the Pulmonary Embolism Severity Index [PESI] and the Simplified PESI [sPESI]) Methods: Multivariable logistic regression of a large international cohort of patients with PE prospectively enrolled in the RIETE (Registro Informatizado de la Enfermedad TromboEmbólica) registry. Measurements and Main Results: All-cause mortality, recurrent PE, and major bleeding up to 10 days after PE diagnosis were determined. Of 18,707 eligible patients with acute symptomatic PE, 46 (0.25%) developed recurrent PE, 203 (1.09%) bled, and 471 (2.51%) died. Predictors included in the final model were chronic heart failure, recent immobilization, recent major bleeding, cancer, hypotension, tachycardia, hypoxemia, renal insufficiency, and abnormal platelet count. The area under receiver-operating characteristic curve was 0.77 (95% confidence interval [CI], 0.75-0.78) for the RIETE score, 0.72 (95% CI, 0.70-0.73) for PESI (P<0.05), and 0.71 (95% CI, 0.69-0.73) for sPESI (P<0.05). Our RIETE score outperformed the prognostic value of PESI in terms of net reclassification improvement (P<0.001), integrated discrimination improvement (P<0.001), and sPESI (net reclassification improvement, P<0.001; integrated discrimination improvement, P<0.001). Conclusions: We built a new score, based on widely available variables, that can be used to identify patients with PE at low risk of short-term complications, assisting in triage and potentially shortening duration of hospital stay

Contagious Caprine Pleuropneumonia

Contagious caprine pleuropneumonia (CCPP), caused by Mycoplasma capricolum subsp. capripneumoniae, is an OIE-listed disease affecting goats and wild ungulate species. CCPP is present in Africa, the Middle East, and Central Asia, but its exact distribution is unknown, particularly in Asia. It is enzootic in the Middle East and East Africa, while it has only been sporadically reported in North and Central Africa and, though suspected, has never been identified in West Africa. In addition, there are very few studies reporting the prevalence and losses induced by CCPP, which are greatly underestimated. This uncertainty over the distribution and impact of CCPP is partly due to the fastidious nature of its etiologic agent, which is difficult to identify, particularly when it circulates in an insidious, mild, or asymptomatic form, favored by the use of antibiotic treatments. However, specific molecular and serological tests are now available for the diagnosis of CCPP, even in the absence of isolation. The main limitation of CCPP surveillance remains the lack of awareness by veterinary services. Vaccines based on inactivated antigens in saponin can induce good protection and their variable quality may now be assessed using a specific ELISA. However, they are very expensive, and there is a paucity of vaccine producers to satisfy their demand. Efforts must urgently be directed to the development of cheaper, quality-controlled vaccines to be extensively used in the field. The global campaign to eradicate “peste des petits ruminants” by 2030 may be a great opportunity to target other goat diseases such as CCPP

Characteristics, treatment patterns and outcomes of patients presenting with venous thromboembolic events after knee arthroscopy in the RIETE Registry

Knee arthroscopy is the most common orthopedic procedure worldwide. While incidence of post-arthroscopy venous thromboembolic events (VTE) is low, treatment patterns and patient outcomes have not been described. Patients from the "Registro Informatizado Enfermedad TromboEmbolica" who had confirmed post-arthroscopy VTE were compared to patients with provoked, post bone-fracture, and to patients with unprovoked VTE. Baseline characteristics, presenting signs and symptoms, treatment and outcomes including recurrent VTE, bleeds or death were compared. A total of 101 patients with post-arthroscopy VTE and 19,218 patients with unprovoked VTE were identified. Post-arthroscopy patients were younger (49.5 vs. 66 years, P\u2009&lt;\u20090.0001) and had less history of VTE [5.9% vs. 20%, OR 0.26 (0.11-0.59)]. Among patients with isolated DVT, there were fewer proximal DVT in the post-arthroscopy group [40% vs. 86%, OR 0.11 (0.06-0.19)]. Treatment duration was shorter in the post-arthroscopy group (174\u2009\ub1\u2009140 vs. 311\u2009\ub1\u2009340&nbsp;days, P\u2009&lt;\u20090.0001) and more often with DOAC [OR 3.67 (1.95-6.89)]. Recurrent VTE occurred in 6.18 (1.96-14.9) and 11.9 (11.0-12.8) per 100 patient years [HR 0.52 (0.16-1.26)] after treatment in the post-arthroscopy and unprovoked groups, respectively. Recurrent VTE occurred in 5.17 (1.31-14.1) per 100 patient years in a separate post bone-fracture group (n\u2009=\u2009147), also not statistically different than the post-arthroscopy recurrence rate. After anticoagulation cessation, some patients post-knee arthroscopy develop VTE. While our small sample size precludes drawing firm conclusions, this signal should warrant further research into the optimal treatment duration for these patients, as some patients may be at increased risk for long-term recurrence