Wild strains of Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were tested in an experimental hyperbaric chamber to determine the possible effect of hyperbaric oxygen on the susceptibility of these strains to the antibiotics ampicillin, ampicillin + sulbactam, cefazolin, cefuroxime, cefoxitin, gentamicin, sulfamethoxazole + trimethoprim, colistin, oxolinic acid, ofloxacin, tetracycline, and aztreonam during their cultivation at 23 °C and 36.5 °C. Ninety-six-well inoculated microplates with tested antibiotics in Mueller-Hinton broth were cultured under standard incubator conditions (normobaric normoxia) for 24 h or in an experimental hyperbaric chamber (HAUX, Germany) for 24 h at 2.8 ATA of 100% oxygen (hyperbaric hyperoxia). The hyperbaric chamber was pressurised with pure oxygen (100%). Both cultures (normoxic and hyperoxic) were carried out at 23 °C and 36.5 °C to study the possible effect of the cultivation temperature. No significant differences were observed between 23 and 36.5 °C cultivation with or without the 2-h lag phase in Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Cultivation in a hyperbaric chamber at 23 °C and 36.5 °C with or without a 2-h lag phase did not produce significant changes in the minimum inhibitory concentration (MIC) of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. For the tested strains of Pseudomonas aeruginosa, the possible effect of hyperbaric oxygen on their antibiotic sensitivity could not be detected because the growth of these bacteria was completely inhibited by 100% hyperbaric oxygen at 2.8 ATA under all hyperbaric conditions tested at 23 °C and 36.5 °C. Subsequent tests with wild strains of pseudomonads, burkholderias, and stenotrophomonads not only confirmed the fact that these bacteria stop growing under hyperbaric conditions at a pressure of 2.8 ATA of 100% oxygen but also indicated that inhibition of growth of these bacteria under hyperbaric conditions is reversible.

• MeSH
• ampicilin farmakologie   MeSH
• anaerobní bakterie MeSH
• antibakteriální látky farmakologie   MeSH
• Bacteria MeSH
• Escherichia coli MeSH
• hyperbarická oxygenace * MeSH
• Klebsiella pneumoniae MeSH
• kombinace léků trimethoprim a sulfamethoxazol farmakologie   MeSH
• kyslík MeSH
• lidé MeSH
• mikrobiální testy citlivosti MeSH
• oxidační stres MeSH
• pseudomonádové infekce * MeSH
• Pseudomonas aeruginosa MeSH
• sulbaktam MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• aktivátory chloridových kanálů terapeutické užití   MeSH
• aminofenoly * terapeutické užití   MeSH
• benzodioxoly * terapeutické užití   MeSH
• chinoliny terapeutické užití   MeSH
• chinolony * terapeutické užití   MeSH
• cystická fibróza * farmakoterapie   genetika   MeSH
• dospělí MeSH
• exokrinní pankreatická insuficience farmakoterapie   etiologie   genetika   MeSH
• fixní kombinace léků MeSH
• genotyp MeSH
• indoly * terapeutické užití   MeSH
• lidé MeSH
• protein CFTR * genetika   MeSH
• pyrazoly * terapeutické užití   MeSH
• pyridiny terapeutické užití   MeSH
• pyrrolidiny terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

• MeSH
• akrylamidy * MeSH
• aniliny terapeutické užití   MeSH
• erbB receptory genetika   MeSH
• indoly * MeSH
• inhibitory proteinkinas terapeutické užití   MeSH
• lidé MeSH
• mutace MeSH
• nádory centrálního nervového systému * diagnostické zobrazování   farmakoterapie   genetika   MeSH
• nádory plic * farmakoterapie   genetika   patologie   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   genetika   patologie   MeSH
• pemetrexed terapeutické užití   MeSH
• platina terapeutické užití   MeSH
• pyrimidiny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

Burns are a major global healthcare concern, often complicated by the presence of bacteria such as Pseudomonas aeruginosa in the wounds. Silver-based dressings are commonly used in the treatment of burns but can cause skin irritation and delay healing time. Medical-grade honey (MGH) provides an interesting alternative. This study investigated the antimicrobial effects and possible cytotoxicity of L-Mesitran Soft (MGH-gel) and its individual components, Medihoney (Manuka), Flammazine (silver sulphadiazine), and silver nitrate (AgNO3) in an ex vivo human burn wound model. Bacterial survival and wound healing parameters, including re-epithelialization and keratinocyte proliferation were assessed. L-Mesitran, Flammazine, and AgNO3 reduced P. aeruginosa numbers below detection levels. L-Mesitran Soft exhibited a significantly stronger antimicrobial effect compared to Medihoney. The individual components of L-Mesitran contributed significantly to its antibacterial efficacy, thus suggesting synergistic activities. Moreover, L-Mesitran, Flammazine, and AgNO3 slightly inhibited re-epithelialization while Medihoney treatment resulted in a complete lack of re-epithelialization and keratinocyte proliferation. Furthermore, clinical cases illustrated the effectiveness of MGH therapy in infected burns. Overall, L-Mesitran Soft had similar effects as silver-based products on bacterial load and epidermal regeneration, but outperformed Medihoney. Therefore, supplemented MGH could be used as an effective alternative to silver-based dressings for P. aeruginosa-infected burns.

• MeSH
• antibakteriální látky farmakologie   terapeutické užití   MeSH
• Bacteria MeSH
• hojení ran MeSH
• lidé MeSH
• med * MeSH
• popálení * farmakoterapie   komplikace   MeSH
• stříbrná sůl sulfadiazinu farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antidota klasifikace   terapeutické užití   MeSH
• benzodiazepiny otrava   MeSH
• otrava alkoholem diagnóza   farmakoterapie   klasifikace   MeSH
• otrava houbami diagnóza   farmakoterapie   klasifikace   MeSH
• otrava * diagnóza   etiologie   farmakoterapie   klasifikace   ošetřování   MeSH
• paracetamol otrava   MeSH
• uštknutí hadem farmakoterapie   klasifikace   MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Evobrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown preliminary efficacy in people with relapsing multiple sclerosis in a phase 2 trial. Here, we aimed to compare the safety and efficacy of evobrutinib with the active comparator teriflunomide in people with relapsing multiple sclerosis. METHODS: EvolutionRMS1 and evolutionRMS2 were two multicentre, randomised, double-blind, double-dummy, active-controlled, phase 3 trials conducted at 701 multiple sclerosis centres and neurology clinics in 52 countries. Adults aged 18-55 years with relapsing multiple sclerosis (Expanded Disability Status Scale [EDSS] score of 0·0-5·5) were included. Participants were randomly assigned (1:1) using a central interactive web response system to receive either evobrutinib (45 mg twice per day with placebo once per day) or teriflunomide (14 mg once per day with placebo twice per day), all taken orally and in an unfasted state, with randomisation stratified by geographical region and baseline EDSS. All study staff and participants were masked to the study interventions. The primary endpoint for each study was annualised relapse rate based on adjudicated qualified relapses up to 156 weeks, assessed in the full analysis set (defined as all randomly assigned participants) with a negative binomial model. These studies are registered with ClinicalTrials.gov (NCT04338022 for evolutionRMS1 and NCT04338061 for evolutionRMS2, both are terminated). FINDINGS: The primary analysis was done using data for 2290 randomly assigned participants collected from June 12, 2020, to Oct 2, 2023. 1124 participants were included in the full analysis set in evolutionRMS1 (560 in the evobrutinib group and 564 in the teriflunomide group) and 1166 in evolutionRMS2 (583 in each group). 751 (66·8%) participants were female and 373 (33·1%) were male in evolutionRMS1, whereas 783 (67·2%) were female and 383 (32·8%) were male in evolutionRMS2. Annualised relapse rate was 0·15 (95% CI 0·12-0·18 with evobrutinib vs 0·14 [0·11-0·18] with teriflunomide (adjusted RR 1·02 [0·75-1·39]; p=0·55) in evolutionRMS1 and 0·11 (0·09-0·13 vs 0·11 [0·09-0·13]; adjusted RR 1·00 [0·74-1·35]; p=0·51) in evolutionRMS2. The pooled proportion of participants with any treatment-emergent adverse event (TEAE) was similar between treatment groups (976 [85·6%] of 1140 with evobrutinib vs 999 [87·2%] of 1146 with teriflunomide). The most frequently reported TEAEs were COVID-19 (223 [19·6%] with evobrutinib vs 223 [19·5%] with teriflunomide), alanine aminotransferase increased (173 [15·2%] vs 204 [17·8%]), aspartate aminotransferase increased (110 [9·6%] vs 131 [11·4%]), and headache (175 [15·4%] vs 176 [15·4%]). Serious TEAE incidence rates were higher with evobrutinib than teriflunomide (86 [7·5%] vs 64 [5·6%]). Liver enzyme elevations at least 5 × upper limit of normal were more common with evobrutinib than with teriflunomide, particularly in the first 12 weeks (55 [5·0%] vs nine [<1%]). Three people who received evobrutinib and one who received teriflunomide met the biochemical definition of Hy's law; all cases resolved after discontinuation of treatment. There were two deaths (one in each group), neither related to study treatment. INTERPRETATION: The efficacy of evobrutinib was not superior to that of teriflunomide. Together, efficacy and liver-related safety findings do not support the use of evobrutinib in people with relapsing multiple sclerosis. FUNDING: Merck.

• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• hydroxybutyráty * MeSH
• inhibitory proteinkinas terapeutické užití   škodlivé účinky   MeSH
• krotonáty * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nitrily * terapeutické užití   MeSH
• piperidiny MeSH
• proteinkinasa BTK antagonisté a inhibitory   MeSH
• pyrimidiny * terapeutické užití   MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• toluidiny * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• Klíčová slova
• levamizol,
• MeSH
• adjuvancia imunologická * farmakologie   klasifikace   terapeutické užití   MeSH
• imunizace klasifikace   metody   MeSH
• inosin pranobex farmakologie   terapeutické užití   MeSH
• nežádoucí účinky léčiv imunologie   klasifikace   MeSH
• T-lymfocyty imunologie   účinky léků   MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• analgetika MeSH
• anestetika lokální aplikace a dávkování   terapeutické užití   MeSH
• gabapentin aplikace a dávkování   terapeutické užití   MeSH
• kvalita života MeSH
• lidé MeSH
• lidokain aplikace a dávkování   terapeutické užití   MeSH
• postherpetická neuralgie * diagnóza   farmakoterapie   prevence a kontrola   MeSH
• senioři MeSH
• transdermální náplast MeSH
• vakcína proti pásovému oparu MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

Na pracovišti ambulance bolesti v Českých Budějovicích se v posledních dvou letech věnujeme ošetřování akutní progrese chronických bolestí hlavy intranazální aplikací lidokainu. Jedná se o ambulantní, minimálně invazivní a pacienty dobře snášenou metodu. V poloze vleže podáváme malé množství 4% lidokainového gelu opakovaně po 3–5 minutách celkem 3–5krát nosní dírkou na postižené bolestivé polovině hlavy. Aplikátor zavádíme po znecitlivění vstupu do nosu šetrně až do kontaktu se zadní stěnou nosohltanu, pod jehož sliznicí se nachází trigeminální ganglion. Cílem ošetření je ovlivnit lokálním anestetikem ganglion sphenopalatinum a snížit vedení bolesti v povodí trigeminálního nervu z postižené poloviny hlavy a obličeje. Zákrok provádíme opakovaně třikrát týdně. Výkon často kombinujeme s podáním antineuropatické infuze. Metodu jsme vyzkoušeli u pacientů s postherpetickými bolestmi obličeje, při atakách bolestí hlavy u pacientů s roztroušenou sklerózou, u pacientů čekajících na intervenční zákrok při neuralgiích trigeminu na podkladě neurovaskulárního konfliktu. Dobrý efekt byl pozorován i u akutních postpunkčních bolestí hlavy a u migrény. Úlevu od bolesti lze pozorovat po 1–2 hodinách a trvání efektu léčby je velmi individuální: 2 dny až 4 týdny. Opakování zákroku obden a současná aplikace antineuropatické infuze nebo myorelaxační infuze potencují analgetický účinek. Ošetření bývá pacienty dobře snášeno. Při zavádění aplikátoru může dojít k poranění nosní sliznice, během aplikace je patrné slzení, necitlivost a pocit chladu pod okem a v okolí jařmového oblouku ošetřované strany. Občas se vyskytne pálení v oblasti nosohltanu ze zatékajícího lidokainového gelu, což se dá ovlivnit množstvím aplikované látky. Ze zájmu pacientů o opakování aplikace lze usuzovat na pozitivní efekt metody.

At the pain clinic in Budweis, we have been treating the acute progression of chronic headaches using intranasal lidocaine for the past two years. It is an outpatient, minimally invasive method that is well tolerated by patients. In the supine position, we administer a small amount of 4 % lidocaine gel repeatedly after 3-5 minutes a total of 3-5 times through the nostril on the affected painful half of the head. After anesthetizing the entrance to the nose, the applicator is gently inserted until it comes into contact with the back wall of the nasopharynx, under the mucosa of which the trigeminal ganglion is located. The aim of the treatment is to affect the sphenopalatine ganglion with a local anesthetic and to reduce the conduction of pain in the basin of the trigeminal nerve from the affected half of the head and face. We perform the procedure repeatedly 3 times a week. We often combine the procedure with the administration of an antineuropathic infusion. We tried the method in patients with post-herpetic facial pain, in headache attacks in patients with multiple sclerosis, in patients waiting for intervention for trigeminal neuralgia based on neurovascular conflict. A good effect was also observed in acute postpuncture headaches and migraines. The effect can be observed after 1-2 hours and the duration is very individual from 2 days to 4 weeks. Repeating the procedure every other day and simultaneous application of antineuropathic infusion or myorelaxant infusion potentiate the analgesic effect. Treatment is usually well tolerated by patients. When inserting the applicator, the nasal mucosa may be injured, during the application there is steamy lacrimation, numbness and a feeling of coldness under the eye and around the zygomatic arch of the treated side. Sometimes there is a burning sensation in the nasopharynx area from leaking lidocaine gel, which can be influenced by the amount of applied substance. The positive effect of the method can be inferred from the patients‘ interest in repeating the application.

• MeSH
• aplikace intranazální * metody   škodlivé účinky   MeSH
• bolesti hlavy * etiologie   farmakoterapie   klasifikace   MeSH
• dospělí MeSH
• extrakce zubů škodlivé účinky   MeSH
• ganglia parasympatická účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lidokain * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• nervus trigeminus fyziologie   MeSH
• neuralgie trigeminu etiologie   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH
• přehledy MeSH

• Klíčová slova
• kabozantinib,
• MeSH
• anilidy terapeutické užití   MeSH
• antitumorózní látky terapeutické užití   MeSH
• inhibitory tyrosinkinasy terapeutické užití   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• neuroendokrinní nádory * diagnóza   farmakoterapie   MeSH
• pyridiny terapeutické užití   MeSH
• Check Tag
• lidé MeSH