BACKGROUND: ExteNET showed that neratinib, an irreversible pan-HER tyrosine kinase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET. METHODS: In this international, randomised, double-blind, placebo-controlled, phase 3 trial, women aged 18 years or older with stage 1-3c (amended to stage 2-3c) HER2-positive breast cancer who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab were eligible. Patients were randomly assigned to oral neratinib 240 mg/day or placebo for 1 year. Randomisation was stratified according to hormone receptor (HR) status (HR-positive vs. HR-negative), nodal status (0, 1-3 or 4+), and trastuzumab regimen (sequentially vs. concurrently with chemotherapy). Overall survival was analysed by intention to treat. ExteNET is registered (Clinicaltrials.gov: NCT00878709) and is complete. RESULTS: Between July 9, 2009, and October 24, 2011, 2840 women received neratinib (n = 1420) or placebo (n = 1420). After a median follow-up of 8.1 (IQR, 7.0-8.8) years, 127 patients (8.9%) in the neratinib group and 137 patients (9.6%) in the placebo group in the intention-to-treat population had died. Eight-year overall survival rates were 90.1% (95% CI 88.3-91.6) with neratinib and 90.2% (95% CI 88.4-91.7) with placebo (stratified hazard ratio 0.95; 95% CI 0.75-1.21; p = 0.6914). CONCLUSIONS: Overall survival in the extended adjuvant setting was comparable for neratinib and placebo after a median follow-up of 8.1 years in women with early-stage HER2-positive breast cancer.

• MeSH
• dvojitá slepá metoda MeSH
• lidé MeSH
• nádory prsu * MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   MeSH
• receptor erbB-2 MeSH
• trastuzumab škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

• Klíčová slova
• neratinib,
• MeSH
• analýza přežití MeSH
• inhibitory tyrosinkinasy * aplikace a dávkování   MeSH
• lidé MeSH
• nádory prsu * farmakoterapie   MeSH
• trastuzumab terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Neratinib, an irreversible tyrosine-kinase inhibitor of HER1, HER2, and HER4, has clinical activity in patients with HER2-positive metastatic breast cancer. We aimed to investigate the efficacy and safety of 12 months of neratinib after trastuzumab-based adjuvant therapy in patients with early-stage HER2-positive breast cancer. METHODS: We did this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial at 495 centres in Europe, Asia, Australia, New Zealand, and North and South America. Eligible women (aged ≥18 years, or ≥20 years in Japan) had stage 1-3 HER2-positive breast cancer and had completed neoadjuvant and adjuvant trastuzumab therapy up to 2 years before randomisation. Inclusion criteria were amended on Feb 25, 2010, to include patients with stage 2-3 HER2-positive breast cancer who had completed trastuzumab therapy up to 1 year previously. Patients were randomly assigned (1:1) to receive oral neratinib 240 mg per day or matching placebo. The randomisation sequence was generated with permuted blocks stratified by hormone receptor status (hormone receptor-positive [oestrogen or progesterone receptor-positive or both] vs hormone receptor-negative [oestrogen and progesterone receptor-negative]), nodal status (0, 1-3, or ≥4), and trastuzumab adjuvant regimen (sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system. Patients, investigators, and trial sponsors were masked to treatment allocation. The primary outcome was invasive disease-free survival, as defined in the original protocol, at 2 years after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00878709. FINDINGS: Between July 9, 2009, and Oct 24, 2011, we randomly assigned 2840 women to receive neratinib (n=1420) or placebo (n=1420). Median follow-up time was 24 months (IQR 20-25) in the neratinib group and 24 months (22-25) in the placebo group. At 2 year follow-up, 70 invasive disease-free survival events had occurred in patients in the neratinib group versus 109 events in those in the placebo group (stratified hazard ratio 0·67, 95% CI 0·50-0·91; p=0·0091). The 2-year invasive disease-free survival rate was 93·9% (95% CI 92·4-95·2) in the neratinib group and 91·6% (90·0-93·0) in the placebo group. The most common grade 3-4 adverse events in patients in the neratinib group were diarrhoea (grade 3, n=561 [40%] and grade 4, n=1 [<1%] vs grade 3, n=23 [2%] in the placebo group), vomiting (grade 3, n=47 [3%] vs n=5 [<1%]), and nausea (grade 3, n=26 [2%] vs n=2 [<1%]). QT prolongation occurred in 49 (3%) patients given neratinib and 93 (7%) patients given placebo, and decreases in left ventricular ejection fraction (≥grade 2) in 19 (1%) and 15 (1%) patients, respectively. We recorded serious adverse events in 103 (7%) patients in the neratinib group and 85 (6%) patients in the placebo group. Seven (<1%) deaths (four patients in the neratinib group and three patients in the placebo group) unrelated to disease progression occurred after study drug discontinuation. The causes of death in the neratinib group were unknown (n=2), a second primary brain tumour (n=1), and acute myeloid leukaemia (n=1), and in the placebo group were a brain haemorrhage (n=1), myocardial infarction (n=1), and gastric cancer (n=1). None of the deaths were attributed to study treatment in either group. INTERPRETATION: Neratinib for 12 months significantly improved 2-year invasive disease-free survival when given after chemotherapy and trastuzumab-based adjuvant therapy to women with HER2-positive breast cancer. Longer follow-up is needed to ensure that the improvement in breast cancer outcome is maintained. FUNDING: Wyeth, Pfizer, Puma Biotechnology.

• MeSH
• adjuvantní chemoterapie MeSH
• analýza přežití MeSH
• chinoliny aplikace a dávkování   škodlivé účinky   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• internacionalita MeSH
• invazivní růst nádoru patologie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mastektomie metody   MeSH
• nádory prsu farmakoterapie   mortalita   patologie   chirurgie   MeSH
• následné studie MeSH
• přežití po terapii bez příznaků nemoci MeSH
• proporcionální rizikové modely MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   MeSH
• receptor erbB-2 metabolismus   MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• staging nádorů MeSH
• trastuzumab aplikace a dávkování   škodlivé účinky   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Karcinom prsu je heterogenní skupina nádorového onemocnění, která v incidenci u žen dlouhodobě stojí na prvním místě. Karcinomy prsu s pozitivitou receptoru 2 pro lidský epidermální růstový faktor (human epidermal qrowth factor receptor 2, HER2) tvoří zhruba 15-20 % všech karcinomů a jsou spojeny s agresivnějšími projevy, vyšším procentem rekurence a nižším přežitím, zůstanou-li neléčeny1 Výrazného posunu ve zlepšení prognózy pacientů bylo dosaženo s příchodem nových molekul, konkrétně molekulárních protilátek cílících na HER2 (trastuzumab, pertuzumab), a zároveň nových tyrosinkinázových inhibitorů, mezi něž patří lapatinib, tucatinib a neratinib. Neratinib je malá molekula inhibitoru tyrosinkinázy, která interaguje s HER2. Na základě výsledků registrační studie byl schválen do prodloužené adjuvance po podání trastuzumabu u pacientek s HER2 pozitivním karcinomem prsu a s pozitivitou hormonálních receptorů (hormone receptor, HR).

Breast cancer is a heterogeneous group of cancers, which has long been ranked first in incidence in women. HER2 (human epidermal growth factor 2) positive breast cancers account for approximately 15-20% of all cancers and are associated with more aggressive manifestations, higher recurrence rates and lower survival if left untreated.1 A significant shift in improved prognosis has been achieved with the advent of new molecules, specifically molecular antibodies targeting HER2 (specifically trastuzumab, pertuzumab), as well as new tyrosine kinase inhibitors (TKIs), including lapatinib, tucatinib and neratinib. Neratinib is a small molecule TKI that interacts with HER2. Based on the results of a registrational study, it has been approved for extended adjuvant treatment after trastuzumab in patients with HER2-positive HR (hormone receptor status) positive breast cancer.

• Klíčová slova
• neratinib, Transtuzumab emtansin, pertuzumab, studie ExteNET,
• MeSH
• adjuvantní chemoterapie MeSH
• erbB receptory účinky léků   MeSH
• geny erbB-2 * MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• inhibitory tyrosinkinasy farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádory prsu * diagnóza   farmakoterapie   genetika   MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH

The following protocol has been designed to investigate the extent of infection, as determined by seropositivity in the general population, in any country in which COVID-19 virus infection has been reported. Each country may need to tailor some aspects of this protocol to align with public health, laboratory and clinical systems, according to capacity, availability of resources and cultural appropriateness. However, using a standardized protocol such as this one below, epidemiological exposure data and biological samples can be systematically collected and shared rapidly in a format that can be easily aggregated, tabulated and analyzed across many different settings globally for timely estimates of COVID-19 virus infection severity and attack rates, as well as to inform public health responses and policy decisions. This is particularly important in the context of a novel respiratory pathogen, such as COVID-19 virus.

• MeSH
• COVID-19 epidemiologie   prevence a kontrola   MeSH
• epidemický výskyt choroby prevence a kontrola   MeSH
• epidemiologická měření MeSH
• koronavirové infekce epidemiologie   prevence a kontrola   MeSH
• sběr dat metody   MeSH
• séroepidemiologické studie MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• epidemiologie
• veřejné zdravotnictví
• NLK Publikační typ
• publikace WHO

PURPOSE OF THE STUDY: Diabetics may have an increased fracture risk, depending on disease duration, quality of metabolic adjustment and extent of comorbidities, and on an increased tendency to fall. The aim of this retrospective one-centre study consisted in detecting differences in fracture healing between patients with and without diabetes mellitus. Data of patients with the most common fracture among older patients were analyzed. MATERIAL AND METHODS: Classification of distal radius fractures was established according to the AO classification. Inital assessment and follow-up were made by conventional X-rays with radiological default settings. To evaluate fracture healing, formation of callus and sclerotic border, assessment of the fracture gap, and evidence of consolidation signs were used. RESULTS: The authors demonstrated that fracture morphology does not influence fracture healing regarding time span, neither concerning consolidation signs nor in fracture gap behaviour. However, tendency for bone remodeling is around 70% lower in investigated diabetics than in non-diabetics, while probability for a successful fracture consolidation is 60% lower. CONCLUSIONS: To corroborate the authors hypothesis of delayed fracture healing in patients with diabetes mellitus, prospective studies incorporating influencing factors like duration of metabolic disease, quality of diabetes control, medical diabetes treatment, comorbidities and secondary diseases, like chronic nephropathy and osteoporosis, have to be carried out.

• MeSH
• diabetes mellitus metabolismus   patofyziologie   MeSH
• fraktury vřetenní kosti patofyziologie   chirurgie   MeSH
• glukosa metabolismus   MeSH
• hojení fraktur fyziologie   MeSH
• komplikace diabetu metabolismus   MeSH
• kostní svalek růst a vývoj   patologie   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• nezhojené fraktury chirurgie   MeSH
• osteoblasty patologie   fyziologie   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• vnitřní fixace fraktury metody   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * MeSH
• nádory štítné žlázy * chirurgie   patologie   MeSH
• následné studie MeSH
• papilární karcinom štítné žlázy MeSH
• papilární karcinom * chirurgie   patologie   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• retrospektivní studie MeSH
• tyreoidektomie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• komentáře MeSH
• souhrny MeSH

PURPOSE OF THE STUDY: Intramedullary nailing is a minimally invasive technique that respects humeral head. However, limited surgical approach does not permit an anatomical reduction. The significance of the reduction on the functional outcome has not been sufficiently investigated. The aim of the study was to examine the functional and radiological postoperative outcome in patients with proximal humeral fractures treated with intramedullary nailing and the significance of reduction. MATERIALS AND METHODS: The study population consisted of 43 patients with proximal humeral fractures that were treated with the Proximal Humerus Nail System (Targon, Aesculap). Mean follow-up period was 23.2 months (SD: 8.9). Shoulder function was assessed with the Constant-Murley Score. Reduction was examined radiographically anteroposterior and true lateral plane. Radiographs of 50 healthy shoulders served as controls. Malreduction was analyzed for 10°, 15° and 20° in both planes. RESULTS: The overall functional results were satisfying; mean CS of all patients at the last follow-up visit was 74.8 (SD: 19.3). Mean normalized CS for age and gender was 78.15 (SD 17.8). Fracture severity seemed to affect clinical outcome to a certain extent; 4-part fractures exhibited inferior results. Mean NSA was 126.5 (SD: 16.9) in anteroposterio and 137.4 (SD: 15.4) in true lateral view. The respective values in the control group were 134.1° (SD 7.1°) in anteroposterior and 133.7° (SD 12.8°) in true lateral view. A malreduction of >20° in the anteroposterior plane and >15° in both anteroposterior and true lateral planes resulted in significantly inferior clinical outcome. Thirteen complications were recorded, four of them being major. DISCUSSION The quality of reduction affected the postoperative outcome to a certain extent. Especially the anteroposterior reduction seemed to play a more important role in the postoperative function than reduction in the true lateral plane. However, this difference was statistically significant only after > 20° malreduction. The worst results in Constant Score were shown, as expected, in the group with malreduction in both planes; even a 15°malreduction resulted in statistically significant difference. The importance of anteroposterior reduction could be due to achievement of better ROM in the frontal plane, most probably because of better levers on the tuberosities. However an absolute anatomical reduction does not have to be achieved at all costs. The overall good results of the fractures in this study despite absence of anatomical reduction could partly result from the limited surgical approach. CONCLUSIONS: The majority of the patients treated with closed reduction and internal fixation with PHN show good postoperative functional results. However, fracture malreduction reduction cannot be always avoided with the use of PHN. Nevertheless, the evaluation of the Constant-Murley score shows an absolute anatomical reduction in not necessary for satisfying functional outcome. The reduction in anteroposterior plane seems to play a more important role in the postsurgical functional outcome. A malreduction that exceeds 15° in both planes or a malreduction of more than 20° in either plane should be avoided.

• MeSH
• dospělí MeSH
• fraktury humeru radiografie   chirurgie   MeSH
• hlavice humeru zranění   chirurgie   MeSH
• intramedulární fixace fraktury škodlivé účinky   metody   MeSH
• kostní hřeby MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• následné studie MeSH
• nezhojené fraktury diagnóza   etiologie   chirurgie   MeSH
• reoperace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ukazatel závažnosti úrazu MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky kontrolované MeSH

• Publikační typ
• komentáře MeSH

Postural stability is one of latent factors affecting game performance of an individual to a certain extent. The presented study deals with monitoring changes of postural stability in ice hockey players after eight week's balance training. The screened sample consisted of junior category ice hockey players divided into experimental (n = 8) and reference groups (n = 8). Postural stability was measured using a stabilographic method on the AMTI AccuSwayPLUS force platform. The level of postural stability was assessed in three tests, namely bipedal stance with and without sight control and bipedal stance with reduced proprioception using the parameters of 95% confidence ellipse, path of CoP and mean velocity of CoP. The level of monitored stability parameters did not indicate any significant differences between the groups in any of the tests at the level of significance α = 0.05. Comparing postural stability of the experimental group between pre-test and post-test showed significant differences in the test without sight control and the test with reduced proprioception in lCoP and vCoP parameters (Z = 2.1004; α ˂ 0.05). Regarding the reference group, no significant changes of the level of postural stability between the pre-test and post-test were found in any of the parameters (Z = 0.3652 to 1.8257; α ˃ 0.05).

• MeSH
• hokej * výchova   MeSH
• lidé MeSH
• mladiství MeSH
• posturální rovnováha * MeSH
• statistika jako téma MeSH
• tělesná výchova MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• hodnotící studie MeSH