Signal Integration of IFN-I and IFN-II With TLR4 Involves Sequential Recruitment of STAT1-Complexes and NFkB to Enhance Pro-inflammatory Transcription

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Specific enhancer selection by IRF3, IRF5 and IRF9 is determined by ISRE half-sites, 5' and 3' flanking bases, collaborating transcription factors and the chromatin environment in a combinatorial fashion

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Screening and monitoring of the BTK C481S mutation in a real-world cohort of patients with relapsed/refractory chronic lymphocytic leukaemia during ibrutinib therapy

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL). Acquired mutations emerging at position C481 in the BTK tyrosine kinase domain are the predominant genetic alterations associated with secondary ibrutinib resistance. To assess the correlation between disease progression, and the emergence and temporal dynamics of the most common resistance mutation BTKC481S , sensitive (10-4 ) time-resolved screening was performed in 83 relapsed/refractory CLL patients during single-agent ibrutinib treatment. With a median follow-up time of 40 months, BTKC481S was detected in 48·2% (40/83) of the patients, with 80·0% (32/40) of them showing disease progression during the examined period. In these 32 cases, representing 72·7% (32/44) of all patients experiencing relapse, emergence of the BTKC481S mutation preceded the symptoms of clinical relapse with a median of nine months. Subsequent Bcl-2 inhibition therapy applied in 28/32 patients harbouring BTKC481S and progressing on ibrutinib conferred clinical and molecular remission across the patients. Our study demonstrates the clinical value of sensitive BTKC481S monitoring with the largest longitudinally analysed real-world patient cohort reported to date and validates the feasibility of an early prediction of relapse in the majority of ibrutinib-treated relapsed/refractory CLL patients experiencing disease progression

Az endoszkópos vizsgálatok pulzoximetriás monitorozásának jelentősége | Az MTA VEAB Gasztroenterológiai Munkabizottságának prospektív multicentrikus vizsgálata

Introduction: Recent guidelines recommend routine pulse oximetric monitoring during endoscopy, however, this has not been the common practice yet in the majority of the local endoscopic units. Aims: To draw attention to the importance of the routine use of pulse oximetric recording during endoscopy. Method: A prospective multicenter study was performed with the participation of 11 gastrointestinal endoscopic units. Data of pulse oximetric monitoring of 1249 endoscopic investigations were evaluated, of which 1183 were carried out with and 66 without sedation. Results: Oxygen saturation less than 90% was observed in 239 cases corresponding to 19.1% of all cases. It occurred most often during endoscopic retrograde cholangiopancreatography (31.2%) and proximal enteroscopy (20%). Procedure-related risk factors proved to be the long duration of the investigation, premedication with pethidine (31.3%), and combined sedoanalgesia with pethidine and midazolam (34.38%). The age over 60 years, obesity, consumption of hypnotics or sedatives, severe cardiopulmonary state, and risk factor scores III and IV of the American Society of Anestwere found as patient-related risk factors. Conclusion: To increase the safety of patients undergoing endoscopic investigation, pulse oximeter and oxygen supplementation should be the standard requirement in all of the endoscopic investigation rooms. Pulse oximetric monitoring is advised routinely during endoscopy with special regard to the risk factors of hypoxemia. Orv. Hetil., 2013, 154, 825–833. </jats:p