BACKGROUND: Management of recurrent mitral regurgitation (MR) or relevant iatrogenic mitral valve (MV) stenosis after mitral transcatheter edge-to-edge repair (M-TEER) emerges as an increasingly relevant clinical issue. Surgery after M-TEER is associated with higher morbidity and mortality. Electrosurgical leaflet laceration and stabilization of the implant (ELASTA-Clip) followed by transcatheter mitral valve replacement (TMVR) is an innovative, less-invasive treatment option for patients with TEER failure. OBJECTIVES: The authors sought to evaluate the early results of ELASTA-Clip followed by transapical TMVR in patients with symptomatic failed M-TEER (defined as persistent or recurrent MR, or iatrogenic MV stenosis). METHODS: Data from symptomatic patients with failed M-TEER who underwent ELASTA-Clip followed by compassionate use or commercial transapical TMVR using the Abbott Tendyne system were retrospectively collected from 8 tertiary care centers in 4 countries. Safety and efficacy of the procedure were assessed up to 1 year according to Mitral Valve Academic Research Consortium (MVARC) criteria. RESULTS: A total of 22 patients (mean age 77.8 ± 9.2 years, 40.9% [9/22] female) at high surgical risk (EuroSCORE II 8.0 ± 0.4, STS score 7.2% ± 1.1%) with symptomatic residual MR ≥3+ (n = 21) or iatrogenic MV stenosis (n = 1) after failed M-TEER were followed for a median period of 8.5 [Q1-Q3: 2.6-11.6] months. The ELASTA-Clip procedure (90.9% [20/22] transseptal, 9.1% [2/22] transapical) followed by TMVR were successful in all patients (22/22). Technical success according to MVARC was achieved in 21 patients (21/22, 95.4%) without left ventricular outflow tract obstruction or conversion to sternotomy. At 30 days, 3 patients had paravalvular leak progression, ischemic stroke occurred in 3 patients (3/20, 15.0%). Baseline MR (≥3+ in 95.5% [21/22]) was reduced to grade 1+ or less in all patients with durable results in 89.5% (17/19) (P < 0.001). NYHA functional class significantly improved to ≤II in 81.3% (13/16) at discharge (P < 0.001) and 72.2% (13/18) at last follow-up (P < 0.001). At 30 days, all patients (20/20) were alive. Three patients (3/20, 15.0%) were rehospitalized for heart failure (uncontrolled atrial fibrillation in 2 cases) and 1 of them (1/22, 4.5%) underwent a reintervention (valve retensioning). CONCLUSIONS: Transapical TMVR after ELASTA-Clip is a feasible and less invasive option for the management of failed M-TEER that can be performed with acceptable results in a carefully selected patient population. Particular attention is required to avoid paravalvular leakage and measures to minimize the risk of periprocedural cerebrovascular events need to be implemented in future larger-scale prospective studies with longer-term follow-up.

• MeSH
• časové faktory MeSH
• chirurgická náhrada chlopně * přístrojové vybavení   škodlivé účinky   MeSH
• compassionate use trials MeSH
• elektrochirurgie škodlivé účinky   MeSH
• iatrogenní nemoci MeSH
• lidé MeSH
• mitrální chlopeň * chirurgie   diagnostické zobrazování   patofyziologie   MeSH
• mitrální insuficience * chirurgie   diagnostické zobrazování   patofyziologie   etiologie   MeSH
• mitrální stenóza * chirurgie   diagnostické zobrazování   patofyziologie   etiologie   MeSH
• neúspěšná terapie MeSH
• obnova funkce MeSH
• recidiva * MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční chlopně umělé * MeSH
• srdeční katetrizace * přístrojové vybavení   škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

In clinical trials, dabrafenib plus trametinib improved overall survival (OS) compared with single-agent BRAF inhibitors (BRAFi) in patients with BRAF V600-mutant unresectable or metastatic melanoma. We investigated dabrafenib plus trametinib therapy in a compassionate-use setting [Named Patient Program (NPP); DESCRIBE II]. A retrospective chart review of patients with BRAF V600-mutated unresectable stage III/IV melanoma receiving dabrafenib plus trametinib as compassionate use was conducted. Treatment patterns and duration, clinical outcomes, and tolerability were evaluated. Of 271 patients, 92.6% had stage IV melanoma, including 36.5% with brain metastases. Overall, 162 patients (59.8%) were BRAFi naive and 171 (63.1%) received first-line dabrafenib plus trametinib. Among BRAFi-naive patients, the overall response rate (ORR) was 67.3%, median OS (mOS) was 20.0 months, and median progression-free survival (mPFS) was 7.5 months. In BRAFi-naive patients with known brain metastases (n = 62), ORR was 61.3%, mOS was 15.5 months, and mPFS was 6.2 months. Eighty-four patients received BRAFi monotherapy for >30 days and switched to dabrafenib plus trametinib prior to progression. Of these 84 patients, 63 had known disease status at the time of switch, and 22 improved with the combination therapy. No new safety signals were identified, and dabrafenib plus trametinib was well tolerated. Dabrafenib plus trametinib showed substantial clinical activity in NPP patients with BRAF V600-mutated unresectable or metastatic melanoma. Analysis of treatment patterns demonstrated the effectiveness of the combination in patients with brain metastases and across lines of therapy with a well tolerated and manageable safety profile.

• MeSH
• compassionate use trials MeSH
• dospělí MeSH
• imidazoly aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom farmakoterapie   genetika   MeSH
• nádory kůže farmakoterapie   genetika   MeSH
• oximy aplikace a dávkování   MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• pyridony aplikace a dávkování   MeSH
• pyrimidinony aplikace a dávkování   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• remdesivir,
• MeSH
• antivirové látky terapeutické užití   MeSH
• compassionate use trials MeSH
• COVID-19 * MeSH
• farmakoterapie COVID-19 MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• vyvíjení léků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH
• zprávy MeSH

According to data from recent studies from Europe, a large percentage of patients have restricted access to innovative medicines for metastatic melanoma. Melanoma World Society and European Association of Dermato-oncology conducted a Web-based survey on access to first-line recommended treatments for metastatic melanoma by current guidelines (National Comprehensive Center Network, European Society for Medical Oncology [ESMO] and European Organization for Research and Treatment of Cancer/European Association of Dermato-oncology/European dermatology Forum) among melanoma experts from 27 European countries, USA, China, Australia, Argentina, Brazil, Chile and Mexico from September 1st, 2017 to July 1st, 2018. Data on licencing and reimbursement of medicines and the number of patient treated were correlated with the data on health expenditure per capita (HEPC), Mackenbach score of health policy performance, health technology assessment (HTA), ASCO and ESMO Magnitude of clinical benefit scale (ESMO MCBS) scores of clinical benefit and market price of medicines. Regression analysis for evaluation of correlation between the parameters was carried out using SPSS software. The estimated number of patients without access in surveyed countries was 13768. The recommended BRAFi + MEKi combination and anti-PD1 immunotherapy were fully reimbursed/covered in 19 of 34 (55.8%) and 17 of 34 (50%) countries, and combination anti-CTLA4+anti-PD1 in was fully covered in 6 of 34 (17.6%) countries. Median delay in reimbursement was 991 days, and it was in significant correlation with ESMO MCBS (p = 0.02), median market price (p = 0.001), HEPC and Mackenbach scores (p < 0.01). Price negotiations or managed entry agreements (MEAs) with national authorities were necessary for reimbursement. In conclusion, great discrepancy exists in metastatic melanoma treatment globally. Access to innovative medicines is in correlation with economic parameters as well as with healthcare system performance parameters. Patient-oriented drug development, market access and reimbursement pathways must be urgently found.

• MeSH
• compassionate use trials MeSH
• dávkové mechanismy MeSH
• dodržování směrnic MeSH
• hrubý domácí produkt MeSH
• klinické zkoušky jako téma statistika a číselné údaje   MeSH
• koupě zacílená na zvýšení kvality a hodnoty péče MeSH
• lidé MeSH
• melanom farmakoterapie   ekonomika   epidemiologie   sekundární   MeSH
• náklady na léky MeSH
• předpisy - poplatky MeSH
• průzkumy a dotazníky MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• socioekonomické faktory MeSH
• testované léky ekonomika   zásobování a distribuce   terapeutické užití   MeSH
• vývoj člověka MeSH
• zdravotní priority MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH
• Latinská Amerika MeSH
• Rusko MeSH

In rare disorders, there are often no standard therapy recommendations. Patients with refractory disease may require novel experimental approaches. Applied as second- up to fourth-line treatment, lenalidomide (10-25 mg perorally on days 1-21 in a 28-day cycle) was used in our cohort of four adult patients with aggressive, multisystem and relapsing diseases. Complete and long-lasting remissions (more than 1 year, no maintenance therapy) were achieved in patients with Langerhans cell histiocytosis (11 cycles, combination with dexamethasone and etoposide, consolidated by allogeneic blood stem cell transplant) and plasma-cell Castleman disease (15 cycles, monotherapy). Mixed response with complete disappearance of brain infiltrates was reached in Erdheim-Chester disease (6 cycles, monotherapy) and gastrointestinal bleeding was well controlled in multiple angiomatosis (9 cycles, combination with thalidomide). For disease activity evaluation each patient underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography scan imaging, which was complemented by clinical and laboratory investigations.

• MeSH
• autologní transplantace MeSH
• compassionate use trials * MeSH
• dospělí MeSH
• Erdheimova-Chesterova nemoc farmakoterapie   MeSH
• histiocytóza z Langerhansových buněk * farmakoterapie   patologie   MeSH
• homologní transplantace MeSH
• hyperplazie velkých lymfatických uzlin * farmakoterapie   patologie   MeSH
• inhibitory angiogeneze * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• počítačová rentgenová tomografie MeSH
• pozitronová emisní tomografie MeSH
• přežití bez známek nemoci MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• retrospektivní studie MeSH
• thalidomid MeSH
• transplantace hematopoetických kmenových buněk MeSH
• výsledek terapie MeSH
• vzácné nemoci MeSH
• záchranná terapie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH