• MeSH
• cerebrovaskulární poruchy MeSH
• magnetická rezonanční angiografie MeSH
• nádory mozku MeSH
• nemoci mozku MeSH

• Konspekt
• Lékařské vědy. Lékařství
• NLK Obory
• radiologie, nukleární medicína a zobrazovací metody
• neurologie

Sepse je život ohrožující stav vznikající na podkladě dysregulované odpovědi hostitelského organismu na infekci. Pohled na problematiku sepse se v posledních desetiletích dramaticky vyvíjí, což je dáno rychlým nárůstem nových poznatků o její epidemiologii, patofyziologii i léčbě. Z tohoto důvodu byla v roce 2016 představena nová mezinárodní kritéria a definice sepse a septického šoku „The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)“, která vznikla na podkladě konsenzuálního stanoviska mezinárodního panelu expertů (The Society of Critical Care Medicine a The European Society of Intensive Care Medicine). Hlavním cílem zavedení nových kritérií a definice sepse bylo rozšířit povědomí odborné veřejnosti o sepsi jako onemocnění s vysokou mortalitou, a to především v situacích, kdy není včas diagnostikována a léčena. Sepsis-3 má být východiskem pro preklinický i klinický výzkum, ale také pro rozvoj nových diagnostických metod a pro léčbu pacientů se sepsí a septickým šokem.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Over the last decades, the approach to sepsis is evolving dramatically, mainly as a result of a rapid increase in the knowledge of its epidemiology, physiopathology, and management. In this context, the new international criteria and definition for sepsis, The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), were introduced in 2016. The criteria were established consensually by the Task Force which consisted of experts from the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. The main goal is the expansion of awareness of the professional public about this medical condition with a high fatality rate, particularly when not diagnosed and treated early. Sepsis-3 should also serve as a benchmark for future preclinical and clinical research, development of new diagnostic methods, and the terapy of patients with sepsis and septic shock.

• Klíčová slova
• SEPSIS-3,
• MeSH
• lidé MeSH
• multiorgánové selhání komplikace   patofyziologie   MeSH
• sepse * dějiny   diagnóza   klasifikace   MeSH
• septický šok diagnóza   patofyziologie   MeSH
• terminologie jako téma MeSH
• vyhodnocení orgánové dysfunkce MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• souhrny MeSH

The dysregulation of inflammatory response to surgical injury affects outcomes. Alarmins, the earliest bioactive substances from damaged cells, play a crucial role in initiating the inflammation. We analyzed serum levels of alarmins (S100A8, S100A12, high mobility group box, and heat shock protein 70) after major abdominal surgery (MAS) in surgical (S) (n = 82) and nonsurgical (NS) groups (n = 35). The main objective was determining a role of selected alarmins in host response to MAS. The secondary objectives were (i) evaluation of the relationship among alarmins and selected biomarkers (C-reactive protein, interleukin-6), (ii) influence of the place of gastrointestinal resection, and (iii) role of alarmins in MAS for cancer. Except for HMGB1, the levels of all alarmins were higher in the S group compared with the NS group. In the S group, positive correlations were found between S100A8 and both IL-6 and CRP. Additionally, the S100A8 level was higher (p < 0.01) in patients who underwent upper gastrointestinal tract (GIT) surgery compared to middle and lower GIT resections. Alarmins levels did not differ between cancer and noncancer patients. MAS is able to elicit increase in alarmin levels. S100A8 can be considered a potential biomarker of surgical injury, especially in the upper part of the GIT.

• MeSH
• alarminy krev   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein analýza   MeSH
• chirurgie trávicího traktu * MeSH
• dospělí MeSH
• kalgranulin A krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• protein HMGB1 krev   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Background: Major abdominal surgery (MAS) is high-risk intervention usually accompanied by tissue injury leading to a release of signaling danger molecules called alarmins. This study evaluates the surgical injury caused by two fundamental types of gastrointestinal surgical procedures (open surgery and laparoscopy) in relation to the inflammation elicited by alarmins. Patients and methods: Patients undergoing MAS were divided into a mixed laparoscopy group (LPS) and an open surgery group (LPT). Serum levels of alarmins (S100A8, S100A12, HMGB1, and HSP70) and biomarkers (leukocytes, C-reactive protein [CRP], and interleukin-6 [IL-6]) were analyzed between the groups. The secondary objectives were to compare LPT and LPS cancer subgroups and to find the relationship between procedure and outcome (intensive care unit length of stay [ICU-LOS] and hospital length of stay [H-LOS]). Results: A total of 82 patients were analyzed. No significant difference was found in alarmin levels between the mixed LPS and LPT groups. IL-6 was higher in the LPS group on day 2 (p=0.03) and day 3 (p=0.04). Significantly higher S100A8 protein levels on day 1 (p=0.02) and day 2 (p=0.01) and higher S100A12 protein levels on day 2 (p=0.03) were obtained in the LPS cancer subgroup. ICU-LOS and H-LOS were longer in the LPS cancer subgroup. Conclusion: The degree of surgical injury elicited by open MAS as reflected by alarmins is similar to that of laparoscopic procedures. Nevertheless, an early biomarker of inflammation (IL-6) was higher in the laparoscopy group, suggesting a greater inflammatory response. Moreover, the levels of S100A8 and S100A12 were higher with a longer ICU-LOS and H-LOS in the LPS cancer subgroup.

• Publikační typ
• časopisecké články MeSH

Vav3 is a key modulator of GTP-hydrolases of the Rho/Rac family, which are crucially involved in cell proliferation. Vav3 is alternatively spliced in full-length Vav3-alpha and N-terminal truncated Vav3.1 lacking its self-regulatory domains. The aim of our study was to estimate the clinical impact of Vav3 and all other Vav family members in ovarian cancer. Purification of a stem-cell like side-population (SP) from ovarian cancer cell lines was performed by flow cytometry/FACS. Differences in gene expression between SP and NSP were assessed by Gene Array analysis and confirmed by RT-PCR and immunoblot. In addition, Vav mRNA expression was determined in 150 epithelial ovarian cancers. Clinicopathological parameters, platinum-sensitivity and survival were analyzed and associated with Vav expression. SP fractions of ovarian cancer cell lines exhibited marked overexpression of Vav3.1 (p < 0.001). Vav1 and Vav2 did not prove to be of clinicopathologic relevance in ovarian cancer. High Vav3.1 expression correlated with higher FIGO stage and residual disease. Furthermore, Vav3.1 overexpression was associated with poor progression-free (HR = 2.820, p = 0.0001) and overall survival (HR = 2.842, p = 0.0001). Subgroup analyses revealed an impact of Vav3.1 on survival in Type-II but not in Type-I cancers. Notably, platinum-refractory cancers showed marked overexpression of Vav3.1 compared to other subsets of platinum-sensitivity (15.848 vs. 6.653, p = 0.0001). In conclusion, Vav3.1 is over-expressed in stem-cell like SP fractions and is clinically relevant in the pathophysiology of ovarian cancer. The N-terminal truncated Vav3.1 may be decisively involved in mechanisms causing genuine multi-drug resistance.

• MeSH
• fosforylace účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky účinky léků   metabolismus   MeSH
• nádory vaječníků farmakoterapie   genetika   metabolismus   MeSH
• organoplatinové sloučeniny terapeutické užití   MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• protein - isoformy metabolismus   MeSH
• protoonkogenní proteiny c-vav metabolismus   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: Despite increasing interest, prospective data on the use of degradable starch microsphere-transarterial chemoembolization (DSM-TACE) in the management of patients with unresectable HCC are still scarce. The objective of the HepaStar study was to collect prospective safety and effectiveness data in a prospective multicenter observational study. MATERIALS AND METHODS: Between January 2017 and December 2022, consecutive participants with unresectable or recurrent HCC treated with DSM-TACE as standard of care at 6 participating centers in Europe were enrolled. Tumor response was evaluated according to the mRECIST criteria. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were assessed by using Kaplan-Meier analysis and Common Terminology Criteria for Adverse Events, version 5. Liver function deterioration was assessed by monitoring changes in liver blood tests during the follow-up. RESULTS: Seventy-nine participants (median age, 69 years (IQR, 51-87 years); 67 men (85%)) were enrolled and treated. The median follow-up time was 18 months (IQR 9.5-38.0 months). The estimated median OS and PFS for the entire cohort was 32 months (CI, 95% 21-NaN) and 9 months (CI, 95% 7-NaN), respectively. Eleven (13.9%) participants experienced at least one grade 3 or 4 AE. The most frequent grade 3-4 AE was elevated bilirubin (2.2%, 5 of 79). Deterioration of bilirubin, AST, ALT, and albumin were observed in 24.1%, 23.7%, 19%, and 24% of participants, respectively. CONCLUSION: DSM-TACE achieves promising survival in patients with unresectable or recurrent HCC. This technique shows a favorable safety profile both in terms of treatment-related AEs and liver function deterioration. KEY POINTS: Question Although degradable starch microspheres transarterial chemoembolization is widely used in clinical practice across Europe, prospective data on its application in hepatocellular carcinoma patients remains limited. Findings Degradable starch microspheres transarterial chemoembolization results in promising survival rates, good tumor response rates, and low rates of treatment-related adverse events. Clinical relevance In patients with unresectable hepatocellular carcinoma, degradable starch microspheres transarterial chemoembolization represents a safe and effective alternative to more well-established chemoembolization techniques like conventional transarterial chemoembolization and drug-eluting beads transarterial chemoembolization.

• MeSH
• chemoembolizace * metody   MeSH
• hepatocelulární karcinom * terapie   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrosféry MeSH
• nádory jater * terapie   mortalita   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• škrob * aplikace a dávkování   MeSH
• výsledek terapie 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
• multicentrická studie MeSH
• pozorovací studie MeSH

BACKGROUND & AIMS: Prevention of hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is critical for eliminating HCV in Europe. We estimated the impact of current and scaled-up HCV treatment with and without scaling up opioid substitution therapy (OST) and needle and syringe programmes (NSPs) across Europe over the next 10 years. METHODS: We collected data on PWID HCV treatment rates, PWID prevalence, HCV prevalence, OST, and NSP coverage from 11 European settings. We parameterised an HCV transmission model to setting-specific data that project chronic HCV prevalence and incidence among PWID. RESULTS: At baseline, chronic HCV prevalence varied from <25% (Slovenia/Czech Republic) to >55% (Finland/Sweden), and <2% (Amsterdam/Hamburg/Norway/Denmark/Sweden) to 5% (Slovenia/Czech Republic) of chronically infected PWID were treated annually. The current treatment rates using new direct-acting antivirals (DAAs) may achieve observable reductions in chronic prevalence (38-63%) in 10 years in Czech Republic, Slovenia, and Amsterdam. Doubling the HCV treatment rates will reduce prevalence in other sites (12-24%; Belgium/Denmark/Hamburg/Norway/Scotland), but is unlikely to reduce prevalence in Sweden and Finland. Scaling-up OST and NSP to 80% coverage with current treatment rates using DAAs could achieve observable reductions in HCV prevalence (18-79%) in all sites. Using DAAs, Slovenia and Amsterdam are projected to reduce incidence to 2 per 100 person years or less in 10 years. Moderate to substantial increases in the current treatment rates are required to achieve the same impact elsewhere, from 1.4 to 3 times (Czech Republic and France), 5-17 times (France, Scotland, Hamburg, Norway, Denmark, Belgium, and Sweden), to 200 times (Finland). Scaling-up OST and NSP coverage to 80% in all sites reduces treatment scale-up needed by 20-80%. CONCLUSIONS: The scale-up of HCV treatment and other interventions is needed in most settings to minimise HCV transmission among PWID in Europe. LAY SUMMARY: Measuring the amount of HCV in the population of PWID is uncertain. To reduce HCV infection to minimal levels in Europe will require scale-up of both HCV treatment and other interventions that reduce injecting risk (especially OST and provision of sterile injecting equipment).

• MeSH
• antivirové látky terapeutické užití   MeSH
• chronická hepatitida C * farmakoterapie   epidemiologie   prevence a kontrola   MeSH
• incidence MeSH
• intravenózní abúzus drog * komplikace   epidemiologie   prevence a kontrola   MeSH
• lidé MeSH
• odhad potřeb MeSH
• opiátová substituční terapie metody   MeSH
• přenos infekční nemoci prevence a kontrola   statistika a číselné údaje   MeSH
• prevalence MeSH
• programy výměny jehel a stříkaček metody   organizace a řízení   MeSH
• teoretické modely MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Geografické názvy
• Evropa MeSH

Kalendářní přehled významných událostí a výročí souvisejících s péčí o duševně nemocné

• MeSH
• lékaři MeSH
• psychiatrie MeSH
• výročí a významné události MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie

• MeSH
• dějiny 17. století MeSH
• dějiny 18. století MeSH
• dějiny 19. století MeSH
• lékaři dějiny   MeSH
• psychiatrie dějiny   MeSH
• ústavy pro duševně nemocné dějiny   MeSH
• Check Tag
• dějiny 17. století MeSH
• dějiny 18. století MeSH
• dějiny 19. století MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• dějiny lékařství

• MeSH
• dějiny 19. století MeSH
• lékaři dějiny   MeSH
• služby péče o duševní zdraví dějiny   MeSH
• ústavy pro duševně nemocné dějiny   MeSH
• Check Tag
• dějiny 19. století MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Psychiatrie
• NLK Obory
• psychiatrie
• dějiny lékařství