Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic. Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission. Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5•0 years (IQR 0•5-12•0) and a sex ratio of 1•15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5•06, 95% CI 1•72-14•87; p=0•0035), male sex (2•12, 1•06-4•21; p=0•033), pre-existing medical conditions (3•27, 1•67-6•42; p=0•0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10•46, 5•16-21•23; p<0•0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0•69%, 95% CI 0•20-1•82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support. Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs...

Background In recent years, there has been a revolution in the genomic profiling and molecular typing of lung cancer. A key oncogene is the epidermal growth factor receptor (EGFR). The gold standard for determining EGFR mutation status is tissue biopsy, where a histological specimen is taken by a bronchoscopic or surgical method (transbronchial biopsy, forceps biopsy, etc.). However, in clinical practice the tissue sample is often insufficient for morphological and molecular analysis. Bronchoalveolar lavage is a validated diagnostic method for pathogenic infections in the lower respiratory tract, yet its diagnostic value for oncogenic mutation testing in lung cancer has not been extensively investigated. This study aims to compare the prevalence of EGFR mutation status in bronchoalveolar lavage and peripheral blood referring to the gold standard - tissue biopsy in patients with primary lung adenocarcinoma. Methods Twenty-six patients with adenocarcinoma were examined for EGFR mutation from tissue biopsy, peripheral blood sample and bronchoalveolar lavage. Results Thirteen patients had wild type EGFR and the other 13 had EGFR mutation. EGFR mutation from a peripheral blood sample was identified in 38.5% (5/13) of patients, whereas EGFR mutation obtained from bronchoalveolar lavage (BAL) was identified in 92.3% (12/13). This study demonstrates that a liquid biopsy sample for EGFR status from BAL has a higher sensitivity compared to a venous blood sample.

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Mechanisms of baclofen action on masticitvMilanov IG. Mechanisms of baclofen action on spasticity. Acta Neurol Scand 1993: S5: 305-310. This investigation estimated the mechanisms of baclofen action on spasticity using a batter? of electromyographic methods. Thirty patients with old post-stroke spastic hemiparesis took part in the investigation. They were treated with baclofen-mean daily dose 54.3~11.6 mg for a mean of 26.3~4.9 days. A questionaire for assessment of subjective improvement after treatment used a 5-point scale. For standardization of the neurological examination 5-point scales were used to assess muscle tone, muscle force and tendon reflexes. A battery of electromyographic methods was used to analyse different mechanisms of spasticity: for alpha motoneurone activitythe F wave parameters; for gamma motoneurone activitythe T/H reflex amplitude ratio; for presynaptic inhibitionthe ratio of H reflex amplitudes before and after vibration on the achilles tendon (Hvibr./Hmax); for common interneurone activitythe flexor reflex parameters. Our results revealed that baclofen reduces spastically increased muscle tone and Babinski sign. It has no influence on muscle force, tendon reflexes and ankle clonus. Baclofen acts by normalizing the altered interneurone activity and decreasing of alpha motoneurone activity. When spasticity has altered interneurone activity and increased motoneurone activity, it is better to treat

Isoniazid (H; INH) is an important first-line drug for the treatment of active tuberculosis (TB) and latent TB infection because of its potent early bactericidal activity against Мycobacterium tuberculosis. Currently, TB resistant to INH, alone or in combination with other drugs, is the most common type of drug-resistant TB. Epidemiology of INH-resistant TB, the molecular mechanisms of drug resistance, current methods for diagnosis and therapeutic regimens of this TB form are presented. Studies in the last years have shown that resistance to INH reduces the probability of treatment success and increases the risk of acquiring resistance to other impor­tant first-line drugs. Based on the most recent meta-analyses, the last WHO recommendations for treatment of INH-resistant TB are to include rifampicin (RIF), ethambutol, pyrazinamide and levofloxacin for 6 months, and not to add streptomycin or other injectable agents to the drug regimen. The guideline emphasizes the importance of excluding resistance to RIF before starting the regimen for INH-resistant TB because of the risk for development of multidrug-resistant TB during the treatment course. The WHO recommendations are based on observational studies, not randomized controlled trials, and are thus conditional and based on low certainty in the estimates of effect. There­fore, further work is needed to optimize the treatment and control of INH-resistant TB.