BACKGROUND: Human metapneumovirus (hMPV) epidemiology, clinical characteristics and risk factors for poor outcome after allogeneic stem cell transplantation (allo-HCT) remain a poorly investigated area. METHODS: This retrospective multicenter cohort study examined the epidemiology, clinical characteristics, and risk factors for poor outcomes associated with human metapneumovirus (hMPV) infections in recipients of allo-HCT. RESULTS: We included 428 allo-HCT recipients who developed 438 hMPV infection episodes between January 2012 and January 2019. Most recipients were adults (93%). hMPV infections were diagnosed at a median of 373 days after allo-HCT. The infections were categorized as upper respiratory tract disease (URTD) or lower respiratory tract disease (LRTD), with 60% and 40% of cases, respectively. Patients with hMPV LRTD experienced the infection earlier in the transplant course and had higher rates of lymphopenia, neutropenia, corticosteroid use, and ribavirin therapy. Multivariate analysis identified lymphopenia and corticosteroid use (>30 mg/d) as independent risk factors for LRTD occurrence. The overall mortality at day 30 after hMPV detection was 2% for URTD, 12% for possible LRTD, and 21% for proven LRTD. Lymphopenia was the only independent risk factor associated with day 30 mortality in LRTD cases. CONCLUSIONS: These findings highlight the significance of lymphopenia and corticosteroid use in the development and severity of hMPV infections after allo-HCT, with lymphopenia being a predictor of higher mortality in LRTD cases.

• Klíčová slova
• SARS-CoV-2, allogeneic hematopoietic stem cell transplantation, community-acquired respiratory virus, human coronavirus, human metapneumovirus, immunocompromised, immunodeficiency score index, multiplex PCR assay, paramyxovirus, upper and lower respiratory tract disease,
• MeSH
• dospělí MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• infekce dýchací soustavy * epidemiologie   etiologie   farmakoterapie   MeSH
• infekce viry z čeledi Paramyxoviridae * epidemiologie   MeSH
• kohortové studie MeSH
• lidé MeSH
• lymfopenie * MeSH
• Metapneumovirus * MeSH
• retrospektivní studie MeSH
• transplantace hematopoetických kmenových buněk * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• hormony kůry nadledvin MeSH

BACKGROUND: Several treatment approaches in cystic fibrosis (CF) aim to correct CF transmembrane conductance regulator (CFTR) function; the efficacy of each approach is dependent on the mutation(s) present. A need remains for more effective treatments to correct functional deficits caused by the F508del mutation. METHODS: Two placebo-controlled, phase 2a studies evaluated GLPG2222, given orally once daily for 29 days, in subjects homozygous for F508del (FLAMINGO) or heterozygous for F508del and a gating mutation, receiving ivacaftor (ALBATROSS). The primary objective of both studies was to assess safety and tolerability. Secondary objectives included assessment of pharmacokinetics, and of the effect of GLPG2222 on sweat chloride concentrations, pulmonary function and respiratory symptoms. RESULTS: Fifty-nine and 37 subjects were enrolled into FLAMINGO and ALBATROSS, respectively. Treatment-related treatment-emergent adverse events (TEAEs) were reported by 29.2% (14/48) of subjects in FLAMINGO and 40.0% (12/30) in ALBATROSS; most were mild to moderate in severity and comprised primarily respiratory, gastrointestinal, and infection events. There were no deaths or discontinuations due to TEAEs. Dose-dependent decreases in sweat chloride concentrations were seen in GLPG2222-treated subjects (maximum decrease in FLAMINGO: -17.6 mmol/L [GLPG2222 200 mg], p < 0.0001; ALBATROSS: -7.4 mmol/L [GLPG2222 300 mg], p < 0.05). No significant effects on pulmonary function or respiratory symptoms were reported. Plasma GLPG2222 concentrations in CF subjects were consistent with previous studies in healthy volunteers and CF subjects. CONCLUSIONS: GLPG2222 was well tolerated. Sweat chloride reductions support on-target enhancement of CFTR activity in subjects with F508del mutation(s). Significant improvements in clinical endpoints were not demonstrated. Observed safety results support further evaluation of GLPG2222, including in combination with other CFTR modulators. FUNDING: Galapagos NV. Clinical trial registration numbers FLAMINGO, NCT03119649; ALBATROSS, NCT03045523.

• Klíčová slova
• CFTR modulator, Cystic fibrosis, F508del, GLPG2222, Gating mutation, Ivacaftor,
• MeSH
• aktivátory chloridových kanálů aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• aminofenoly * aplikace a dávkování   škodlivé účinky   MeSH
• aplikace orální MeSH
• benzoáty * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• benzopyrany * aplikace a dávkování   škodlivé účinky   farmakokinetika   MeSH
• biologická dostupnost MeSH
• chinolony * aplikace a dávkování   škodlivé účinky   MeSH
• cystická fibróza * diagnóza   farmakoterapie   genetika   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• kombinovaná farmakoterapie metody   MeSH
• lidé MeSH
• monitorování léčiv MeSH
• mutace MeSH
• pot * chemie   účinky léků   MeSH
• protein CFTR genetika   MeSH
• respirační funkční testy metody   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• aktivátory chloridových kanálů MeSH
• aminofenoly * MeSH
• benzoáty * MeSH
• benzopyrany * MeSH
• chinolony * MeSH
• GLPG2222 MeSH Prohlížeč
• ivacaftor MeSH Prohlížeč
• protein CFTR MeSH

Research has exposed cancer to be a heterogeneous disease with a high degree of inter-tumoral and intra-tumoral variability. Individual tumors have unique profiles, and these molecular signatures make the use of traditional histology-based treatments problematic. The conventional diagnostic categories, while necessary for care, thwart the use of molecular information for treatment as molecular characteristics cross tissue types.This is compounded by the struggle to keep abreast the scientific advances made in all fields of science, and by the enormous challenge to organize, cross-reference, and apply molecular data for patient benefit. In order to supplement the site-specific, histology-driven diagnosis with genomic, proteomic and metabolomics information, a paradigm shift in diagnosis and treatment of patients is required.While most physicians are open and keen to use the emerging data for therapy, even those versed in molecular therapeutics are overwhelmed with the amount of available data. It is not surprising that even though The Human Genome Project was completed thirteen years ago, our patients have not benefited from the information. Physicians cannot, and should not be asked to process the gigabytes of genomic and proteomic information on their own in order to provide patients with safe therapies. The following consensus summary identifies the needed for practice changes, proposes potential solutions to the present crisis of informational overload, suggests ways of providing physicians with the tools necessary for interpreting patient specific molecular profiles, and facilitates the implementation of quantitative precision medicine. It also provides two case studies where this approach has been used.

• Klíčová slova
• genomics, metronomic chemotherapy, precision medicine, targeted therapy,
• MeSH
• dítě MeSH
• individualizovaná medicína * MeSH
• klinické zkoušky jako téma MeSH
• lékařská onkologie * MeSH
• lidé MeSH
• nádory farmakoterapie   genetika   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• výzkumný projekt MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH

OBJECTIVE: The mechanism of angioplasty is disruption of atherosclerotic plaque, which often results in dissections. Dissection after percutaneous transluminal angioplasty (PTA) remains a significant clinical problem and untreated may cause acute occlusion or later restenosis. Stents are used to manage dissections, which is often followed by in-stent restenosis and occasionally stent fracture. Tack (Intact Vascular, Wayne, Pa) implants have minimal metal and low radial force and are specifically designed for dissection repair. This study evaluated Tack implants for treatment of dissections resulting from standard balloon PTA for femoral-popliteal arterial disease. Twelve-month outcomes after Tack treatment of post-PTA dissections are described. METHODS: This prospective, single-arm study evaluated patients with ischemia (Rutherford clinical category 2-4) caused by lesions of the superficial femoral and popliteal arteries. Patients were treated with standard balloon angioplasty, and post-PTA dissections were treated with Tacks. The primary end points were core laboratory-adjudicated device technical success, defined as the ability of the Tack implants to resolve post-PTA dissection, and device safety, defined as the absence of new-onset major adverse events. Patients were followed up to 12 months after implantation. RESULTS: Tacks were used in 130 patients with post-PTA dissections (74.0% ≥ grade C). Technical success was achieved in 128 (98.5%) patients with no major adverse events at 30 days. The 12-month patency was 76.4%, and freedom from target lesion revascularization was 89.5%. Significant improvement from baseline was observed in Rutherford clinical category (82.8% with grade ≤1) and ankle-brachial index (0.68 ± 0.18 to 0.94 ± 0.15; P < .0001). CONCLUSIONS: Tack implant treatment of post-PTA dissection was safe, produced reasonable patency, and resulted in low rates of target lesion revascularization. Tack treatment represents a new, minimal metal paradigm for dissection repair that can safely improve the clinical results associated with PTA.

• MeSH
• arteria femoralis diagnostické zobrazování   zranění   patofyziologie   MeSH
• arteria poplitea diagnostické zobrazování   zranění   patofyziologie   MeSH
• balónková angioplastika škodlivé účinky   MeSH
• časové faktory MeSH
• cévní protézy * MeSH
• cévy - implantace protéz škodlivé účinky   přístrojové vybavení   MeSH
• dolní končetina krevní zásobení   MeSH
• endovaskulární výkony škodlivé účinky   přístrojové vybavení   MeSH
• kovy * MeSH
• lidé středního věku MeSH
• lidé MeSH
• onemocnění periferních arterií diagnostické zobrazování   patofyziologie   terapie   MeSH
• opakovaná terapie MeSH
• poranění cév diagnostické zobrazování   etiologie   terapie   MeSH
• prospektivní studie MeSH
• protézy - design MeSH
• průchodnost cév MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Názvy látek
• kovy * MeSH