Publikace se zaměřuje na různé aspekty pneumonie a na její management v klinické praxi. Určeno odborné veřejnosti.

• MeSH
• klinické lékařství MeSH
• pneumonie MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• pneumologie a ftizeologie

• Publikační typ
• abstrakt z konference MeSH

Background: Programmed cell death 1/programmed death ligand 1 (PD-1/PD-L1) immune-checkpoint blockade is a promising new therapeutic strategy in cancer. However, expression patterns and prognostic significance of PD-L1 and PD-1 are still controversial in human malignant pleural mesothelioma (MPM). Methods: Formalin-fixed paraffin-embedded (FFPE) tumor samples from 203 MPM patients receiving standard treatment without immunotherapy were collected from 5 European centers. PD-L1 and PD-1 expression of tumor cells (TCs) and tumor-infiltrating lymphocytes (TILs) were measured by immunohistochemistry and correlated with clinical parameters and long-term outcome. Results: High (>10%) PD-L1 TC and PD-1 TILs expressions were found in 18 (8%) and 39 (24%) patients, respectively. PD-L1 was rarely expressed by TILs [≥1%, n=13 (8%); >10%, n=1]. No significant associations were found between the PD-L1 or PD-1 expression of TCs or TILs and clinicopathological parameters such as stage or histological subtype. Notably, patients with high (>10%) TC-specific PD-L1 expression exhibited significantly worse median overall survival (OS) (6.3 vs. 15.1 months of those with low TC PD-L1 expression; HR: 2.51, P<0.001). In multivariate cox regression analysis adjusted for clinical parameters, high TC PD-L1 expression (>10%) proved to be an independent negative prognostic factor for OS (HR: 2.486, P=0.005). There was no significant correlation between PD-L1 or PD-1 expression of TILs and OS. Conclusions: In this multicenter cohort study, we demonstrate that high (>10%) PD-L1 expression of TCs independently predicts worse OS in MPM. Further studies are warranted to investigate the value of PD-L1/PD-1 expression as a marker for treatment response in MPM patients receiving immunotherapy.

• Publikační typ
• časopisecké články MeSH

Sarkoidóza je multisystémové granulomatózní onemocnění neznámé etiologie, které obvykle postihuje jedince středního a staršího věku, nejčastěji ženy starší 40 let. Příznaky, se kterými se může setkat lékař prvního kontaktu, mohou být velmi nespecifické. Nejtypičtější potíže se objevují u akutní formy nemoci, tzv. Löfgrenova syndromu s typickou bilaterální hilovou lymfadenopatií zjišťovanou na skiagramu hrudníku, s negativním tuberkulinovým testem, s výsevem nodózního erytému na bércích, často provázeném oboustrannou artritidou talokrurálního skloubení. Löfgrenův syndrom má obvykle dobrou prognózu, ve většině případů nastává spontánní remise onemocnění. Při podezření na toto onemocnění je indikováno doplnění skiagramu hrudníku a při patologickém nálezu je vhodné odeslat nemocného k pneumologovi.

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that typically affects middle-aged and elderly individuals, most commonly women over 40 years of age. The symptoms that a primary care physician may encounter can be very non-specific. The most characteristic complaints occur in the acute form of the disease, Löfgren syndrome, presenting with a typical bilateral hilar lymphadenopathy detected on chest skiagram, a negative tuberculin test, and an eruption of erythema nodosum in the crural region, often accompanied by bilateral arthritis of the talocrural joint. Löfgren syndrome is usually associated with a good prognosis, with most cases developing spontaneous remission of the disease. When this disease is suspected, an additional chest skiagram is indicated and, in the case of a pathological finding, it is advisable to refer the patient to a pulmonologist.

• MeSH
• biopsie metody   MeSH
• bronchoalveolární laváž MeSH
• bronchoalveolární lavážní tekutina cytologie   MeSH
• diagnostické techniky dýchacího ústrojí MeSH
• glukokortikoidy aplikace a dávkování   MeSH
• klinické laboratorní techniky MeSH
• krevní obraz MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• sarkoidóza * diagnostické zobrazování   farmakoterapie   klasifikace   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

AIM: To compare survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with modern-era drugs (antifolates, antiangiogenics, tyrosine kinase and anaplastic lymphoma kinase inhibitors, immunotherapy) with treatment initiation in 2011-12 and 2015-16, respectively. PATIENTS AND METHODS: Prospective data from Czech TULUNG Registry (960 patients from 2011-12 and 512 patients from 2015-16) were analyzed. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression-free survival (PFS); Cox proportional hazards model to assess factors associated with 2-year survival. RESULTS: Survival at 2 years was more frequent in cohort 2015-16 compared to cohort 2011-12 (43.2% vs. 24% for adenocarcinoma; p<0.001 and 28.7% vs. 11.8% for squamous-cell lung carcinoma; p=0.002). Assignment to cohort 2015-16 and treatment multilinearity (two or more lines in sequence) were associated with higher probability of 2-year survival (hazard ratio=0.666 and hazard ratio=0.597; p<0.001). Comparison of 2-year survivors from both cohorts showed no differences. CONCLUSION: Survival at 2 years probability in stage IIIB-IV NSCLC doubled between 2011-12 and 2015-16; advanced-stage NSCLC may be considered a chronic disease in a large proportion of patients.

• MeSH
• adenokarcinom plic epidemiologie   mortalita   patologie   terapie   MeSH
• chronická nemoc MeSH
• dospělí MeSH
• kohortové studie MeSH
• kombinovaná terapie MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• nádory plic epidemiologie   mortalita   patologie   terapie   MeSH
• následné studie MeSH
• nemalobuněčný karcinom plic epidemiologie   mortalita   patologie   terapie   MeSH
• prognóza MeSH
• registrace statistika a číselné údaje   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom epidemiologie   mortalita   patologie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Background: Cardiopulmonary exercise testing (CPET) is a standard part of preoperative evaluation in patients before lung surgical resection. According to current guidelines the risk of such a procedure is estimated according to maximum oxygen consumption (VO2max). Chronotropic incompetence (CI) is a prevalent condition which could possibly influence cardiopulmonary fitness. The aim of this study was to assess the prevalence of CI in patients before surgical lung resections and its influence on CPET results. Methods: This study enrolled 154 patients (97 men) of average age 66.4±8.3 with newly diagnosed lung cancer indicated for surgical lung resections. All patients underwent CPET (cycle ergometry). Age predicted maximal HR was calculated using the traditional equation (220 - age). Three levels of CI were defined as, 85% HRpred, 80% HRpred and 70% HRpred. The influence of CI on CPET results was evaluated. Results: CI was present in the following ratios: 85% HRpred-48.7%; 80% HRpred-39.6% and 70% HRpred-16.9%. A significant negative correlation was also found between VO2max, maximal heart rate (HR) and maximal work load among all CI groups (P<0.0001). The presence of CI significantly correlated with beta-blocker treatment (P<0.0001). Conclusions: CI significantly decreases VO2max in patients before lung cancer surgery. It is strongly associated with beta-blocker treatment which could negatively influence risk assessment. It is thus a matter for future discussion, as to whether the evaluation of CI should be part of preoperative care guidelines.

• Publikační typ
• časopisecké články MeSH

• MeSH
• adjuvantní chemoterapie MeSH
• analýza přežití MeSH
• doba přežití bez progrese choroby MeSH
• docetaxel terapeutické užití   MeSH
• lidé MeSH
• nemalobuněčný karcinom plic * farmakoterapie   patologie   MeSH
• nivolumab terapeutické užití   MeSH
• protinádorové látky imunologicky aktivní terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie MeSH
• Check Tag
• lidé MeSH

Sarkoidóza je multisystémové granulomatózní onemocnění neznámé etiologie, které obvykle postihuje jedince středního a staršího věku, nejčastěji ženy starší 40 let. Příznaky, se kterými se může setkat lékař prvního kontaktu, mohou být velmi nespecifické. Nejtypičtější potíže se objevují u akutní formy nemoci, tzv. Löfgrenova syndromu s typickou bilaterální hilovou lymfadenopatií zjišťovanou na skiagramu hrudníku, s negativním tuberkulinovým testem, s výsevem nodózního erytému na bércích, často provázeném oboustrannou artritidou talokrurálního skloubení. Löfgrenův syndrom má obvykle dobrou prognózu, ve většině případů nastává spontánní remise onemocnění. Při podezření na toto onemocnění je indikováno doplnění skiagramu hrudníku a při patologickém nálezu je vhodné odeslat nemocného k pneumologovi.

Sarcoidosis is a multisystem granulomatous disease of unknown aetiology that typically affects middle-aged and elderly individuals, most commonly women over 40 years of age. The symptoms that a primary care physician may encounter can be very non-specific. The most characteristic complaints occur in the acute form of the disease, Löfgren syndrome, presenting with a typical bilateral hilar lymphadenopathy detected on chest skiagram, a negative tuberculin test, and an eruption of erythema nodosum in the crural region, often accompanied by bilateral arthritis of the talocrural joint. Löfgren syndrome is usually associated with a good prognosis, with most cases developing spontaneous remission of the disease. When this disease is suspected, an additional chest skiagram is indicated and, in the case of a pathological finding, it is advisable to refer the patient to a pulmonologist.

• Klíčová slova
• skiagram hrudníku,
• MeSH
• biopsie metody   MeSH
• bronchoalveolární laváž MeSH
• bronchoalveolární lavážní tekutina cytologie   MeSH
• diagnostické techniky dýchacího ústrojí MeSH
• glukokortikoidy aplikace a dávkování   MeSH
• klinické laboratorní techniky MeSH
• krevní obraz MeSH
• lidé MeSH
• počítačová rentgenová tomografie MeSH
• sarkoidóza * diagnostické zobrazování   farmakoterapie   klasifikace   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Spitzoid melanocytic lesions represent a heterogeneous group of proliferations with ambiguous and overlapping terminology. The exact distinction of a Spitz nevus from a Spitzoid melanoma can be very difficult or, in some cases, impossible. Among the Spitzoid lesions, there is a lesion termed an atypical Spitz tumour (AST) that has intermediate histopathologic features between those of a Spitz nevus and a Spitzoid melanoma and thus uncertain malignant potential. There are several rare cases of patients with a Spitzoid melanoma initially misdiagnosed as a Spitz nevus or an AST with fatal consequences. It is, therefore, advised to perform a molecular characterization in cases where uncertain skin lesions are presented, as it may provide extended set of information with a possible impact on the treatment options. Furthermore, preventive measures, such as regular physical and skin examinations, as well as thorough scheduling of individual follow-up visits, are essential in patients with potentially malignant skin nevi. CASE REPORT: We report a case of a young adult female with a history of AST excision with a negative sentinel lymph node biopsy (SLNB) and insufficient follow-up. Four years after the primary dermatological diagnosis, she presented with a giant tumour in the right hemithorax. Radical en bloc resection of the tumour with right pneumonectomy and resection of the pericardium with reconstruction of the pericardium using mesh was performed. A definitive histopathological examination revealed a metastatic melanoma. The association of the previously diagnosed AST and subsequent appearance of melanoma metastases led to a retrospective re-evaluation of the initial lesion. The suspected diagnosis of Spitzoid melanoma, however, was not confirmed. Moreover, the molecular examination revealed a major discordance between the initial lesion and the lung tumour, which most likely excluded the possible association of the lung metastasis with the initial skin lesion. The initial skin lesion was a BRAF-mutant melanoma with Spitzoid features and termed as AST, while the giant lung metastasis was NRAS-mutant melanoma. The subsequent postoperative course was complicated by the appearance of brain metastases that were stereotactically irradiated. Nevertheless, despite complex specialised medical care, the patient's clinical condition rapidly deteriorated. By this time, no active oncological treatment was possible. The patient was delegated to local hospice for palliative care six months after the surgery and died three weeks later. CONCLUSIONS: Our patient was surgically treated at the age of 20 for AST and died four years later of metastatic NRAS-mutant melanoma most likely of different occult origin. Molecular characterization, as well as the close clinical follow-up should be always precisely performed in patients with uncertain skin lesions, such as AST.

• MeSH
• epiteloidní a vřetenobuněčný névus genetika   patologie   MeSH
• GTP-fosfohydrolasy genetika   MeSH
• lidé MeSH
• melanom genetika   sekundární   MeSH
• membránové proteiny genetika   MeSH
• mladý dospělý MeSH
• mnohočetné primární nádory genetika   patologie   MeSH
• mutace MeSH
• nádory kůže genetika   patologie   sekundární   MeSH
• nádory plic sekundární   MeSH
• protoonkogenní proteiny B-raf genetika   MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

INTRODUCTION: We assessed the Aurora A kinase inhibitor, alisertib, plus paclitaxel (henceforth referred to as alisertib/paclitaxel) as second-line treatment for SCLC. METHODS: In this double-blind study, patients with relapsed or refractory SCLC were stratified by relapse type (sensitive versus resistant or refractory) and brain metastases and randomized 1:1 to alisertib/paclitaxel or placebo plus paclitaxel (henceforth referred to as placebo/paclitaxel) in 28-day cycles. The primary end point was progression-free survival (PFS). Associations of c-Myc expression in tumor tissue (prespecified) and genetic alterations in circulating tumor DNA (retrospective) with clinical outcome were evaluated. RESULTS: A total of 178 patients were enrolled (89 in each arm). The median PFS was 3.32 months with alisertib/paclitaxel versus 2.17 months with placebo/paclitaxel (hazard ratio [HR] = 0.77, 95% confidence limit [CI]: 0.557-1.067, p = 0.113 in the intent-to-treat population versus HR = 0.71, 95% CI: 0.509-0.985, p = 0.038 with corrected analysis applied). Among 140 patients with genetic alternations, patients with cell cycle regulator mutations (cyclin-dependent kinase 6 gene [CDK6], retinoblastoma-like 1 gene [RBL1], retinoblastoma-like 2 gene [RBL2], and retinoblastoma 1 gene [RB1]) had significantly improved PFS with alisertib/paclitaxel versus with placebo/paclitaxel (3.68 versus 1.80 months, respectively [HR = 0.395, 95% CI: 0.239-0.654, p = 0.0003]), and overall survival (7.20 versus 4.47 months, respectively [HR = 0.427, 95% CI: 0.259-0.704, p = 0.00085]). A subset of patients with c-Myc expression showed significantly improved PFS with alisertib/paclitaxel. The incidence of grade 3 or higher drug-related adverse events was 67% (58 patients) with alisertib/paclitaxel versus 22% (25 patients) with placebo/paclitaxel. Twelve patients (14%) versus 11 (12%) died on study, including four versus zero treatment-related deaths. CONCLUSIONS: Efficacy signals were seen with alisertib/paclitaxel in relapsed or refractory SCLC. c-Myc expression and mutations in cell cycle regulators may be potential predictive biomarkers of alisertib efficacy; further prospective validations are warranted.

• MeSH
• azepiny MeSH
• biologické markery MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nádory plic * farmakoterapie   MeSH
• paclitaxel * MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• pyrimidiny MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH