BACKGROUND: Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA. OBJECTIVES: This study sought to evaluate the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia. METHODS: REALIZE-K (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA-induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/day); those with hyperkalemia started SZC. Participants with normokalemia (potassium: 3.5-5.0 mEq/L) on SZC and spironolactone ≥25 mg/day were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/day without rescue therapy for hyperkalemia [months 1-6]). The 5 secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening heart failure (HF) events (hospitalizations and urgent visits). RESULTS: Overall, 203 participants were randomized (SZC: 102; placebo: 101). Higher percentage of SZC- vs placebo-treated participants had optimal response (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; P < 0.001). SZC (vs placebo) improved the first 4 secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR: 4.58; 95% CI: 2.78-7.55; P < 0.001); receiving spironolactone ≥25 mg/day (81% vs 50%; OR: 4.33; 95% CI: 2.50-7.52; P < 0.001); time to hyperkalemia (HR: 0.51; 95% CI: 0.37-0.71; P < 0.001); and time to decrease/discontinuation of spironolactone due to hyperkalemia (HR: 0.37; 95% CI: 0.17-0.73; P = 0.006). There was no between-group difference in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at 6 months (-1.01 points; 95% CI: -6.64 to 4.63; P = 0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of cardiovascular (CV) death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal P = 0.034). CONCLUSIONS: In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalemia and down-titration/discontinuation of spironolactone. Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients With Symptomatic HFrEF Receiving Spironolactone; NCT04676646).
- MeSH
- antagonisté mineralokortikoidních receptorů * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- hyperkalemie * farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- silikáty * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- spironolakton * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- srdeční selhání * farmakoterapie MeSH
- tepový objem účinky léků fyziologie 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
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF). However, MRAs are often underused because of hyperkalemia concerns. OBJECTIVES: The purpose of this study was to assess whether sodium zirconium cyclosilicate (SZC), a nonabsorbed crystal that traps and rapidly lowers potassium, enables MRA use in patients with HFrEF and prevalent hyperkalemia (or at high risk). METHODS: REALIZE-K is a prospective, double-blind, placebo-controlled trial in patients with HFrEF (NYHA functional class II-IV; left ventricular ejection fraction ≤40%), optimal therapy (except MRA), and prevalent hyperkalemia (or at high risk). During the open-label run-in, all participants underwent protocol-mandated spironolactone titration (target: 50 mg daily); those with prevalent (cohort 1) or incident (cohort 2) hyperkalemia during titration started SZC. Participants achieving normokalemia while on spironolactone ≥25 mg daily were randomized to continuing SZC or matching placebo for 6 months. The primary composite endpoint was proportion of participants with optimal response (normokalemia, on spironolactone ≥25 mg daily, no rescue for hyperkalemia [months 1-6]). RESULTS: Of 365 patients (run-in), 202 were randomized. Baseline characteristics included mean age 70 years, prevalent comorbidities (78% estimated glomerular filtration rate <60 mL/min/1.73 m2, 38% atrial fibrillation/flutter), high N-terminal pro B-type natriuretic peptide (median 1,136 pg/mL), and high HFrEF therapy use (64% sacubitril/valsartan, 96% beta-blocker, 42% sodium glucose co-transporter 2 inhibitor). At randomization, 78% were receiving spironolactone 50 mg daily. CONCLUSIONS: REALIZE-K is the first trial to evaluate whether SZC can enable rapid and safe MRA optimization and long-term continuation in patients with HFrEF and prevalent/high risk of hyperkalemia. (Study to Assess Efficacy and Safety of SZC for the Management of High Potassium in Patients with Symptomatic HFrEF Receiving Spironolactone [REALIZE-K]; NCT04676646).
- MeSH
- antagonisté mineralokortikoidních receptorů * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- dvojitá slepá metoda MeSH
- hyperkalemie * farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- silikáty * terapeutické užití aplikace a dávkování MeSH
- spironolakton * aplikace a dávkování terapeutické užití škodlivé účinky MeSH
- srdeční selhání * farmakoterapie patofyziologie MeSH
- tepový objem * fyziologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
BACKGROUND: While much research has been done to identify individual workplace lung carcinogens, little is known about joint effects on risk when workers are exposed to multiple agents. OBJECTIVES: We investigated the pairwise joint effects of occupational exposures to asbestos, respirable crystalline silica, metals (i.e., nickel, chromium-VI), and polycyclic aromatic hydrocarbons (PAH) on lung cancer risk, overall and by major histologic subtype, while accounting for cigarette smoking. METHODS: In the international 14-center SYNERGY project, occupational exposures were assigned to 16,901 lung cancer cases and 20,965 control subjects using a quantitative job-exposure matrix (SYN-JEM). Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for ever vs. never exposure using logistic regression models stratified by sex and adjusted for study center, age, and smoking habits. Joint effects among pairs of agents were assessed on multiplicative and additive scales, the latter by calculating the relative excess risk due to interaction (RERI). RESULTS: All pairwise joint effects of lung carcinogens in men were associated with an increased risk of lung cancer. However, asbestos/metals and metals/PAH resulted in less than additive effects; while the chromium-VI/silica pair showed marginally synergistic effect in relation to adenocarcinoma (RERI: 0.24; CI: 0.02, 0.46; p = 0.05). In women, several pairwise joint effects were observed for small cell lung cancer including exposure to PAH/silica (OR = 5.12; CI: 1.77, 8.48), and to asbestos/silica (OR = 4.32; CI: 1.35, 7.29), where exposure to PAH/silica resulted in a synergistic effect (RERI: 3.45; CI: 0.10, 6.8). DISCUSSION: Small or no deviation from additive or multiplicative effects was observed, but co-exposure to the selected lung carcinogens resulted generally in higher risk than exposure to individual agents, highlighting the importance to reduce and control exposure to carcinogens in workplaces and the general environment. https://doi.org/10.1289/EHP13380.
- MeSH
- azbest * toxicita MeSH
- chrom toxicita MeSH
- karcinogeny toxicita MeSH
- lidé MeSH
- nádory plic * chemicky indukované epidemiologie MeSH
- oxid křemičitý toxicita MeSH
- plíce MeSH
- polycyklické aromatické uhlovodíky * toxicita MeSH
- pracovní expozice * MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- MeSH
- azbest škodlivé účinky MeSH
- látky znečišťující vzduch v pracovním prostředí * MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci dýchací soustavy etiologie MeSH
- nemoci z povolání * etiologie MeSH
- oxid křemičitý škodlivé účinky MeSH
- prach MeSH
- pracovní podmínky MeSH
- silikóza etiologie MeSH
- znečištění ovzduší MeSH
- znečištění vzduchu ve vnitřním prostředí MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
OBJECTIVES: Malignant pleural mesothelioma (MPM) is an aggressive disease with grim prognosis due to lack of effective treatment options. Disease prediction in association with early diagnosis may both contribute to improved MPM survival. Inflammation and autophagy are two processes associated with asbestos-induced transformation. We evaluated the level of two autophagic factors ATG5 and HMGB1, microRNAs (miRNAs) such as miR-126 and miR-222, and the specific biomarker of MPM, soluble mesothelin related proteins (Mesothelin) in asbestos-exposed individuals, MPM patients, and healthy subjects. The performance of these markers in detecting MPM was investigated in pre-diagnostic samples of asbestos-subjects who developed MPM during the follow-up and compared for the three groups. RESULTS: The ATG5 best distinguished the asbestos-exposed subjects with and without MPM, while miR-126 and Mesothelin were found as a significant prognostic biomarker for MPM. ATG5 has been identified as an asbestos-related biomarker that can help to detect MPM with high sensitivity and specificity in pre-diagnostic samples for up to two years before diagnosis. To utilize this approach practically, higher number of cases has to be tested in order to give the combination of the two markers sufficient statistical power. Performance of the biomarkers should be confirmed by testing their combination in an independent cohort with pre-diagnostic samples.
- MeSH
- Atg5 MeSH
- azbest * škodlivé účinky MeSH
- časná diagnóza MeSH
- GPI-vázané proteiny škodlivé účinky MeSH
- lidé MeSH
- maligní mezoteliom * MeSH
- mezotelin MeSH
- mezoteliom * diagnóza MeSH
- mikro RNA * MeSH
- nádorové biomarkery metabolismus MeSH
- nádory pleury * diagnóza MeSH
- nádory plic * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The association of mesothelioma, a lethal lung disease, with asbestos has led to an absolute ban on asbestos in at least 55 countries worldwide. The purpose of this paper is to review residual exposure to asbestos as well as other emerging causes of mesothelioma outside asbestos. The review provides detailed description of asbestos minerals, their geographical locations, mesothelioma in these areas, as well as contemporary possible sources of asbestos exposure. Second, we examine other emerging causes of mesothelioma including: ionizing radiation as the second most important risk factor after asbestos, particularly relevant to patients undergoing radiotherapy, third, carbon nanotubes which are under investigation and fourth, Simian virus 40. In the case of asbestos per se, the greatest risk is from occupational exposure during mining and subsequent processing. Of the non-occupational exposures, environmental exposure is most serious, followed by exposure from indoor asbestos minerals and secondary familial exposure. Overall, asbestos is still a major risk factor, but alternative causes should not be neglected, especially in young people, in women and those with a history of radiotherapy or living in high-risk locations.
- MeSH
- azbest * škodlivé účinky MeSH
- lidé MeSH
- maligní mezoteliom * chemicky indukované komplikace MeSH
- mezoteliom * chemicky indukované komplikace MeSH
- minerály MeSH
- mladiství MeSH
- nádory pleury * chemicky indukované komplikace MeSH
- nádory plic * chemicky indukované MeSH
- nanotrubičky uhlíkové * MeSH
- vystavení vlivu životního prostředí škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- azbest škodlivé účinky MeSH
- azbestóza * epidemiologie MeSH
- lidé MeSH
- nemoci z povolání epidemiologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- zprávy MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: In the Czech Republic, asbestos has been classified as a known human carcinogen since 1984. The use of asbestos-containing products was limited to scenarios where the use of other materials was not possible. Since 1997, the manufacture of asbestos materials has been forbidden, and in 1999, the import, manufacture and distribution of all types of asbestos fibres was legally banned by Act No. 157/1998 Coll. Although the use of asbestos is forbidden, the risk of exposure still exists given the ongoing demolition and reconstruction of buildings in which asbestos has been used. In addition, a novel risk has arisen through the quarrying of asbestos-containing aggregates and their subsequent use. The aim of this paper was to describe and evaluate asbestos in terms of history, legislation, current risk of occupational exposure and its health consequences in the Czech Republic over the last three decades. METHODS: This retrospective descriptive study used the collected data on occupational exposure and occupational diseases. The counts of workers occupationally exposed to asbestos were obtained from the Registry of Work Categorization; the numbers and structure of occupational diseases caused by asbestos were taken from the Czech National Registry of Occupational Diseases. Data on the total number of mesothelioma cases recorded in the Czech National Cancer Registry was provided by the Institute of Health Information and Statistics of the Czech Republic. RESULTS: A total of 13,112 subjects were registered as occupationally exposed to asbestos during the period 2001-2020. A total of 687 cases of asbestos-related occupational diseases were reported in the period 1991-2020 in the Czech Republic, comprising 178 cases of asbestosis, 250 cases of pleural hyalinosis, 168 cases of pleural or peritoneal mesothelioma, 90 cases of lung cancer, and one case of laryngeal cancer. The data from the Czech National Cancer Registry, available for a shorter period (1991-2018), reveal 1,389 cases of mesothelioma, of which only ~11% were recognised as occupational, despite the fact that the occupational causality of mesotheliomas is estimated to be up to 90% of mesotheliomas. Moreover, the latency of mesotheliomas since the last occupational exposure reached up to 50 years and this trend is still slightly increasing, unlike asbestosis, where a high cumulative dose of inhaled asbestos is needed. The real proportion of occupational lung cancers may obviously be even higher, especially in smokers, where occupational causes including asbestos are not suspected by most physicians. CONCLUSION: Czech data on asbestos-related occupational diseases, especially cancers, are grossly underestimated, which is most apparent through the low proportion of mesotheliomas diagnosed as occupational. Asbestos materials in older buildings remained in situ and may represent a danger during reconstruction works. The current source of exposure appears to be quarrying of asbestos-containing aggregate and its subsequent use. Awareness of the professional community is therefore crucial, not only for the possibility of compensating those affected, but also for the early detection of the diseases through the dispensary of exposed persons.
- MeSH
- azbest * toxicita MeSH
- azbestóza epidemiologie MeSH
- lidé MeSH
- mezoteliom epidemiologie MeSH
- nádory plic epidemiologie MeSH
- nemoci z povolání * epidemiologie MeSH
- pracovní expozice * škodlivé účinky MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Tvorba seromu po abdominoplastice je jednou z nejčastějších komplikací, se kterou se setkávají plastičtí chirurgové. U 59letého muže, který podstoupil lipoabdominoplastiku, se vytvořil velký podkožní serom, který přetrvával 7 měsíců. Byla provedena perkutánní sklerotizace mastkem. Předkládáme první zprávu o chronickém seromu po lipoabdominoplastice úspěšně léčeném pomocí sklerotizace mastkem.
The formation of a seroma after abdominoplasty is one of the most common complications faced by plastic surgeons. A 59-year-old man underwent lipoabdominoplasty and developed a large subcutaneous seroma that persisted for 7 months. Percutaneous sclerosis with talc was performed. We present the first report of chronic seroma after lipoabdominoplasty successfully treated with talc sclerosis.
- MeSH
- abdominoplastika * metody škodlivé účinky MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lipoabdominoplastika metody škodlivé účinky MeSH
- mastek * terapeutické užití MeSH
- serom etiologie terapie MeSH
- skleroterapie metody škodlivé účinky MeSH
- ultrasonografie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Maligní pleurální výpotek u pacientů s onkologickým onemocněním je známkou nepříznivé prognózy. U symptomatických pacientů máme několik paliativních možností řešení výpotku vedoucích ke zlepšení kvality života. Podle současného konsensu a doporučení není žádná metoda striktně preferována. Rozhodnutí o managementu u každého pacienta závisí na preferenci pacienta, rychlosti tvorby výpotku, expandibilitě plíce a na předpokládané době přežití.
Malignant pleural effusion in patients with oncological disease is a sign of an unfavorable prognosis. In symptomatic patients, we have several palliative options for dealing with the effusion leading to an improvement in quality of life. According to current consensus and guidelines, no method is strictly preferred. Management decisions for each patient depend on patient preference, rate of effusion formation, lung expandability, and expected survival time.
