PURPOSE: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) have a poor prognosis. The phase I/II NP30179 study (ClinicalTrials.gov identifier: NCT03075696) evaluated glofitamab monotherapy in patients with R/R B-cell lymphomas, with obinutuzumab pretreatment (Gpt) to mitigate the risk of cytokine release syndrome (CRS) with glofitamab. We present data for patients with R/R MCL. METHODS: Eligible patients with R/R MCL (at least one previous therapy) received Gpt (1,000 or 2,000 mg) 7 days before the first glofitamab dose (single dose or split over 2 days if required). Glofitamab step-up dosing was administered once a day on days 8 (2.5 mg) and 15 (10 mg) of cycle 1, with a target dose of 16 or 30 mg once every 3 weeks from cycle 2 day 1 onward, for 12 cycles. Efficacy end points included investigator-assessed complete response (CR) rate, overall response rate (ORR), and duration of CR. RESULTS: Of 61 enrolled patients, 60 were evaluable for safety and efficacy. Patients had received a median of two previous therapies (range, 1-5). CR rate and ORR were 78.3% (95% CI, 65.8 to 87.9) and 85.0% (95% CI, 73.4 to 92.9), respectively. In patients who had received previous treatment with a Bruton tyrosine kinase inhibitor (n = 31), CR rate was 71.0% (95% CI, 52.0 to 85.8) and ORR was 74.2% (95% CI, 55.4 to 88.1). CRS after glofitamab administration occurred in 70.0% of patients, with a lower incidence in the 2,000 mg (63.6% [grade ≥2, 22.7%]) versus 1,000 mg (87.5%; grade ≥2, 62.5%) Gpt cohort. Four adverse events led to glofitamab withdrawal (all infections). CONCLUSION: Fixed-duration glofitamab induced high CR rates in heavily pretreated patients with R/R MCL; the safety profile was manageable with appropriate support.

• MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized administration & dosage   therapeutic use   adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   MeSH
• Lymphoma, Mantle-Cell * drug therapy   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase I MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH

BACKGROUND: The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting. METHODS: Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests. RESULTS: A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS. CONCLUSIONS: In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.

• MeSH
• Anilides * therapeutic use   pharmacology   administration & dosage   MeSH
• Axitinib * therapeutic use   pharmacology   administration & dosage   MeSH
• Adult MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   pharmacology   administration & dosage   MeSH
• Carcinoma, Renal Cell * drug therapy   mortality   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Kidney Neoplasms * drug therapy   pathology   mortality   MeSH
• Nivolumab * therapeutic use   pharmacology   administration & dosage   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   MeSH
• Pyridines therapeutic use   MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Comparative Study MeSH

OBJECTIVES: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short-,intermediate-, and long-term post-discharge complications among these patients. METHODS: A retrospective multicenter cohort study assessing outcomes of elderly individuals (≥60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-month post-discharge IBD-related complication rates defined as steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6 month and mortality at 12 month among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. RESULTS: In a cohort of 654 patients hospitalized for IBD {age 68.9 (interquartile range [IQR]): 63.9-75.2 years, 60.9% ulcerative colitis (UC)}, 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6 months, and 12 months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs 33.1%, p = 0.8; 40.5% vs 42.5%, p = 0.66; and 4.6% vs 8%, p = 0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3 months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An UC diagnosis was the sole risk factor for complication at 6 months (aOR 1.5). Clostridioides difficile infection did not significantly impact outcomes or interact with IBD type. CONCLUSIONS: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1 year.

• MeSH
• Clostridioides difficile MeSH
• Hospitalization statistics & numerical data   MeSH
• Inflammatory Bowel Diseases * complications   MeSH
• Clostridium Infections * complications   epidemiology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Patient Discharge MeSH
• Retrospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Symptom Flare Up MeSH
• Patient Readmission statistics & numerical data   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

BACKGROUND: The combination of ibrutinib and venetoclax leverages complementary mechanisms of action and has shown promising clinical activity in mantle cell lymphoma (MCL). This study evaluated the efficacy and safety of ibrutinib-venetoclax compared with ibrutinib-placebo in patients with relapsed or refractory MCL. METHODS: SYMPATICO is a multicentre, randomised, double-blind, placebo-controlled, phase 3 study performed at 84 hospitals in Europe, North America, and Asia-Pacific. Eligible patients were adults (aged ≥18 years) with pathologically confirmed relapsed or refractory MCL after one to five previous lines of therapy and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Patients were randomly assigned (1:1) to receive oral ibrutinib 560 mg once daily concurrently with oral venetoclax (5-week ramp-up to 400 mg once daily) or placebo for 2 years, then single-agent ibrutinib 560 mg once daily until disease progression or unacceptable toxicity. Randomisation and treatment assignment occurred via interactive response technology using a stratified permuted block scheme (block sizes of 2 and 4) with stratification by ECOG performance status, previous lines of therapy, and tumour lysis syndrome risk category. Patients and investigators were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03112174, and is closed to enrolment. FINDINGS: Between April 26, 2018, and Aug 28, 2019, 267 patients were enrolled and randomly assigned; 134 to the ibrutinib-venetoclax group and 133 to the ibrutinib-placebo group. 211 (79%) of 267 patients were male and 56 (21%) were female. With a median follow-up of 51·2 months (IQR 48·2-55·3), median progression-free survival was 31·9 months (95% CI 22·8-47·0) in the ibrutinib-venetoclax group and 22·1 months (16·5-29·5) in the ibrutinib-placebo group (hazard ratio 0·65 [95% CI 0·47-0·88]; p=0·0052). The most common grade 3-4 adverse events were neutropenia (42 [31%] of 134 patients in the ibrutinib-venetoclax group vs 14 [11%] of 132 patients in the ibrutinib-placebo group), thrombocytopenia (17 [13%] vs ten [8%]), and pneumonia (16 [12%] vs 14 [11%]). Serious adverse events occurred in 81 (60%) of 134 patients in the ibrutinib-venetoclax group and in 79 (60%) of 132 patients in the ibrutinib-placebo group. Treatment-related deaths occurred in three (2%) of 134 patients in the ibrutinib-venetoclax group (n=1 COVID-19 infection, n=1 cardiac arrest, and n=1 respiratory failure) and in two (2%) of 132 patients in the ibrutinib-placebo group (n=1 cardiac failure and n=1 COVID-19-related pneumonia). INTERPRETATION: The combination of ibrutinib-venetoclax significantly improved progression-free survival compared with ibrutinib-placebo in patients with relapsed or refractory MCL. The safety profile was consistent with known safety profiles of the individual drugs. These findings suggest a positive benefit-risk profile for ibrutinib-venetoclax treatment. FUNDING: Pharmacyclics (an AbbVie Company) and Janssen Research and Development.

• MeSH
• Adenine * analogs & derivatives   MeSH
• Bridged Bicyclo Compounds, Heterocyclic * administration & dosage   therapeutic use   adverse effects   MeSH
• Progression-Free Survival MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local drug therapy   pathology   MeSH
• Lymphoma, Mantle-Cell * drug therapy   pathology   mortality   MeSH
• Piperidines * administration & dosage   MeSH
• Antineoplastic Combined Chemotherapy Protocols * therapeutic use   adverse effects   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sulfonamides * administration & dosage   therapeutic use   adverse effects   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: In our previous study on erythropoiesis-stimulating agent (ESA) treatment in lower risk myelodysplastic syndromes from the European MDS (EUMDS) Registry, we showed that patients treated with ESAs had longer survival compared with patients who receive red blood cell transfusion (RBCT). In this study, with a longer follow up time and more patients included, we aimed to assess long-term effects on survival and health-related quality of life (HRQoL) of exposure to ESAs with or without RBCT in patients with lower risk myelodysplastic syndromes. METHODS: The EUMDS Registry is a non-interventional, longitudinal, real-world registry prospectively enrolling newly diagnosed patients older than 18 years with lower risk (International Prognostic Scoring System low or intermediate-1) myelodysplastic syndromes from 16 European countries and Israel. The analysis was restricted to patients with haemoglobin concentrations less than 100 g/L enrolled between Jan 1, 2008, and July 1, 2019, with last censoring of data on Dec 31, 2021. Patient management was recorded every 6 months, including treatment, transfusions, and HRQoL. ESA treatment followed local guidelines. The patients were separated into four groups at each study visit: no ESA or RBCT, ESA only, ESA plus RBCT, and RBCT only. The data were analysed longitudinally over time according to ESA and RBCT status during each 6-month interval, using propensity score matching. The main outcomes were median overall survival and leukaemia-free survival, and HRQoL. This study is registered with ClinicalTrials.gov, NCT00600860, as is ongoing. FINDINGS: 2448 patients (the ESA-unexposed group [n=1265] and ESA-exposed group [n=1183]) were diagnosed before July 1, 2019; 1520 (62·1%) were male and 928 (37·9%) were female. Median follow-up time was 3·9 years (IQR 1·6-6·5). After applying eligibility criteria and propensity matching, there were 426 patients in the ESA-unexposed group and 744 patients in the ESA-exposed group. Median overall survival in the ESA exposed group was 44·9 months (95% CI 40·2-50·5) compared with 34·8 months (28·6-39·2) in the ESA unexposed group; the absolute difference was 10·1 months (95% CI 2·2-18·0; hazard ratio [HR] 0·70 [95% CI 0·59-0·83]; p<0·0001). Patients without RBCT in the presence or absence of ESA exposure maintained significantly better HRQoL than those with RBCT, irrespective of ESA exposure (linear mixed effect model of EQ-5d-3L index score, RBCT coefficient -0·04 [95% CI -0·06 to 0·03], p<0·0001; linear mixed effect model of VAS, -4·57 [-6·02 to -3·13], p<0·0001). INTERPRETATION: ESA treatment in patients with lower risk myelodysplastic syndromes significantly improves overall survival when started before or early after the onset of regular transfusion therapy. Avoiding RBCT is associated with significantly better HRQoL. FUNDING: H2020 European Research Council, Novartis Pharmacy B V Oncology Europe, Amgen, BMS/Celgene International, Janssen Pharmaceutica, Takeda Pharmaceuticals International, and Gilead Sciences.

• MeSH
• Hematinics * therapeutic use   MeSH
• Cohort Studies MeSH
• Quality of Life * MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Myelodysplastic Syndromes * drug therapy   mortality   therapy   complications   MeSH
• Registries MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Erythrocyte Transfusion adverse effects   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH

Článek má za cíl seznámit čtenáře s problematikou farmakogenetického (PGx) vyšetření v oboru psychiatrie, které dnes představuje dostupný a významný nástroj personalizované medicíny. PGx testování umožňuje upravit farmakoterapii na základě genetických predispozic pacientů. V rámci oboru psychiatrie se zaměřuje zejména na polymorfismy v genech odpovědných za metabolismus léčiv, především enzymy cytochromu P450, jako jsou CYP2C19 a CYP2D6. Toto vyšetření může v praxi pomoci predikovat účinnost nebo toxicitu léčiv, a tím zlepšit bezpečnost a efektivitu farmakoterapie. Ve studii realizované v Psychiatrické nemocnici Bohnice byli testováni pacienti, kteří vykazovali známky farmakorezistence, odlišnost ve výsledcích vyšetření monitorování plazmatických hladin (TDM) nebo např. výrazné nežádoucí účinky při terapii běžnými dávkami. Až 75 % testovaných pacientů mělo změněnou funkci jednoho nebo obou testovaných izoenzymů CYP, tedy fenotyp pomalého, ultrarychlého, rychlého nebo intermediárního metabolizéra. Interpretace výsledků PGx vyšetření je klíčová a měla by být prováděna odborníkem, který má zkušenosti v této oblasti, hluboké znalosti farmakokinetiky a také veškeré potřebné informace o konkrétním pacientovi. Pouze v takovém případě může PGx vyšetření významně ovlivnit správný výběr a dávkování psychofarmak, jejichž účinnost závisí na fenotypu pacientů (zejm. risperidon, haloperidol, venlafaxin, tricyklická antidepresiva, es-/citalopram aj.). Správná interpretace výsledků také umožňuje optimalizaci medikace. To přispívá k minimalizaci rizika vzniku vedlejších účinků a zajištění lepších výstupů léčby. Na závěr je uvedena jedna kazuistika reflektující reálnou situaci, kdy PGx vyšetření sehrálo důležitou roli při rozhodování o výběru farmakoterapie.

Our article aims to introduce the reader to pharmacogenetic (PGx) testing in psychiatry, where it currently represents an available and significant tool in personalized medicine. PGx testing enables the adjustment of pharmacotherapy based on patients' genetic predispositions. In psychiatry, PGx testing focuses on polymorphisms in genes responsible for drug metabolism, primarily cytochrome P450 enzymes such as CYP2C19 and CYP2D6. In clinical practice, these tests can help predict drug efficacy or toxicity, thereby improving the safety and effectiveness of pharmacotherapy. PGx testing, which was conducted at the Bohnice Psychiatric Hospital, was done on patients who exhibited signs of drug resistance, discrepancies in therapeutic drug monitoring (TDM), or significant adverse effects during therapy with standard doses. Results showed that up to 75% of the tested patients had altered function of one or both CYP isoenzymes (i. e., slow, ultra-rapid, rapid, or intermediate metabolizer phenotypes). The interpretation of PGx test results is crucial and should be performed by professionals with expertise in this field. Additionally, a thorough understanding of pharmacokinetics, as well as comprehensive patient-specific information, is required. Only under these conditions can PGx testing significantly influence the correct selection and optimal dosing of psychotropic drugs, especially those whose effectiveness depends on the patient's phenotype (e.g., risperidone, haloperidol, venlafaxine, tricyclic antidepressants, es-/citalopram, etc.). Correct interpretation of PGx results also enables medication optimization, contributing to individualized therapy. This minimizes the risk of side effects and ensures better treatment outcomes. Our article concludes with a case report illustrating a real-life situation in which PGx testing played a key role in guiding pharmacotherapy decisions.

• MeSH
• Cytochrome P-450 CYP2D6 genetics   metabolism   MeSH
• Cytochrome P-450 CYP2C19 genetics   metabolism   MeSH
• Pharmacogenetics * MeSH
• Middle Aged MeSH
• Humans MeSH
• Schizophrenia, Paranoid drug therapy   pathology   MeSH
• Pilot Projects MeSH
• Polymorphism, Genetic MeSH
• Amphetamine-Related Disorders drug therapy   MeSH
• Psychotropic Drugs * administration & dosage   metabolism   therapeutic use   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

Gemtuzumab ozogamicin je zažitou součástí moderní terapie akutní myeloidní leukemie zásadně zlepšující léčebné výsledky. Jeho využití je nicméně omezeno na pacienty v nízkém a středním cytogenetickém riziku. Další omezení pak přichází s možnou toxicitou tohoto léčivého přípravku, zejména s rizikem rozvoje sinusoidálního obstrukčního syndromu a závažných krvácení. Při jeho používání je třeba pečlivě zvážit poměr risk/benefit.

Gemtuzumab ozogamicin is a standard part of acute myeloid leukemia therapy bringing significant improvement of treatment outcome. However, its use is limited to patients in favorable and intermediate cytogenetic risk groups. Another limitation is brought by possible toxicity especially the risk of sinusoidal obstruction syndrome development or severe bleeding complications. It should only be used after a careful assessment of risk/benefit ratio.

• MeSH
• Leukemia, Monocytic, Acute drug therapy   MeSH
• Gemtuzumab * adverse effects   toxicity   MeSH
• Middle Aged MeSH
• Humans MeSH
• Drug-Related Side Effects and Adverse Reactions MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Case Reports MeSH

OBJECTIVES: In an effort to maintain the technical aspects of traditional prosthetic surgical aortic valve replacement (AVR) while reducing invasiveness and facilitate options for concomitant operations, transaxillary lateral mini-thoracotomy endoscopic robotic-assisted aortic valve replacement (RAVR) has been introduced. The present data highlight the contemporary international collaborative experience. METHODS: All consecutive patients undergoing standardized RAVR across 10 international sites (1/2020-7/2024) were evaluated using a central database with 1 year follow-up. RESULTS: A total of 300 patients were analysed with a median predicted risk of 1.6% with aortic stenosis in 85.7%, nearly half with bicuspid valves. Biological prostheses were implanted in 220 (73.3%) with a median valve size 23 mm, 10% receiving aortic root enlargement, with 17% of all patients undergoing concomitant procedures. Median cross-clamp 120 min with no conversions to sternotomy. Median length of stay was 5 days, 4.3% with prolonged ventilation, 1.7% renal failure, 1.0% stroke and 8.3% required re-thoracotomy for evacuation of haemothorax. There were two 30-day operative mortalities (0.7%). The new permanent pacemaker rate for the full cohort was 2.6%. Of 163 patients with complete 1-year clinical and echocardiographic follow-up, mean aortic valve gradient was 10 mmHg and all but 2 patients (1.2%) had trace to no prosthetic or paravalvular insufficiency. CONCLUSIONS: RAVR is safe and effective, providing the reproducible benefits of surgical AVR while affording a less invasive approach that permits the opportunity for concomitant procedures. For low and intermediate risk patients with aortic valve disease, RAVR is a potential reproducible alternative for patients and heart teams.

• MeSH
• Aortic Valve * surgery   MeSH
• Aortic Valve Stenosis * surgery   MeSH
• Heart Valve Prosthesis Implantation * methods   adverse effects   mortality   MeSH
• Middle Aged MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Follow-Up Studies MeSH
• Robotic Surgical Procedures * methods   adverse effects   mortality   statistics & numerical data   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Heart Valve Prosthesis MeSH
• Thoracotomy methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Autoři jsou uváděni v abecedním pořadí, podíl jednotlivých autorů je uveden na konci práce. Souhrn doporučení Preventivní opatření a postupy Doporučujeme, aby v průběhu porodu u žen s rizikovými faktory pro PPH byla sledována krevní ztráta s využitím kalibrovaných kolektorů krve nebo jejich ekvivalentů. (Dobrá klinická praxe) Doporučujeme, aby ženy se závažnými rizikovými faktory pro PŽOK (např. placenta acrreta spectrum nebo hematologické poruchy vyžadující konziliární hematologickou péči) rodily v perinatologickém centru intenzivní péče nebo v perinatologickém centru intermediární péče. (Dobrá klinická praxe) Doporučujeme u pacientek s vysokým rizikem PŽOK v přiměřeném časovém předstihu před porodem formulování plánu péče za účasti multidisciplinárního týmu. (Dobrá klinická praxe) Doporučujeme léčbu anemie antepartálně. Těhotným ženám by měly být podávány preparáty železa, pokud hladina hemoglobinu klesne v I. trimestru < 110 g/l nebo < 105 g/l ve 28. týdnu těhotenství. (Dobrá klinická praxe) Navrhujeme zvážit parenterální podání železa u žen se sideropenickou anemií, nereagující na suplementaci železa perorální cestou. Příčina anemie by měla být zjištěna co nejdříve po ukončení těhotenství. (Slabé doporučení) Pokud se dítě dobře adaptuje, nedoporučujeme dřívější podvaz pupečníku než za 1 min. (Silné doporučení) Doporučujeme pro snížení rizika rozvoje PPH a PŽOK u všech vaginálních porodů profylaktické podání uterotonik ve III. době porodní po porodu dítěte a po podvazu pupečníku. Lékem první volby je oxytocin. (Silné doporučení) Pokud nebyla aktivně vedena III. doba porodní, navrhujeme pro zkrácení trvání III. doby porodní a pro snížení krevní ztráty u vaginálního porodu zvážit provedení masáže dělohy a řízenou trakci za pupečník, provádí-li ji kvalifikovaná osoba. (Slabé doporučení) Doporučujeme podání uterotonik k prevenci rozvoje PPH u žen po vybavení dítěte císařským řezem a po podvazu pupečníku. (Silné doporučení) Navrhujeme zvážit u žen se zvýšeným rizikem PŽOK podání carbetocinu. (Slabé doporučení) Doporučujeme u žen se zvýšeným rizikem PŽOK podstupujících císařský řez jednorázové podání kyseliny tranexamové (TXA). Klinická poznámka: Použití TXA před provedením císařského řezu není explicitně uvedeno v SPC přípravku. Recentní metaanalýza uvádí nejčastější dávkování 1 g i.v. (Silné doporučení) Organizace poskytování péče Doporučujeme, aby každé zdravotnické zařízení, kde je gynekologicko-porodnické pracoviště, mělo pro situace PŽOK vypracováno řízený dokument definující organizační a odborný postup. (Dobrá klinická praxe) Doporučujeme, aby řízený dokument (tj. krizový plán) jednoznačně vymezoval organizační a odborné role jednotlivých členů krizového týmu při vzniku PŽOK (nelékařský personál, porodník, anesteziolog, hematolog apod.) a definoval minimální rozsah vybavení pracoviště pro zajištění péče o pacientky s PŽOK. (Dobrá klinická praxe) Doporučujeme pravidelný simulační trénink krizové situace PŽOK celým krizovým týmem s následným debrífinkem nebo jeho formalizovaným ekvivalentem. (Dobrá klinická praxe) Doporučujeme na každém pracovišti definování indikátorů kvality diagnostiky a léčby PŽOK a jejich formalizované vyhodnocování v pravidelných intervalech, nejméně jednou ročně. (Dobrá klinická praxe) Diagnostický a léčebný postup při PŽOK Při nálezu hypotonie nebo atonie dělohy doporučujeme používat strukturovaný stupňovitý postup. (Dobrá klinická praxe) Na pracovištích s dostupností endovaskulárních intervencí navrhujeme u stavů PŽOK z důvodu hypotonie nebo atonie dělohy zvážit preferenční využití radiologických intervenčních metod (selektivní embolizace pánevních tepen), pokud to aktuální klinický kontext umožňuje. (Slabé doporučení) U všech stavů rozvoje PPH doporučujeme provedení tzv. předtransfuzního vyšetření. Pro posouzení aktuálního stavu koagulace jsou (kromě standardních laboratorních vyšetření) preferovány metody tzv. point-of-care-testing, zejména viskoelastické metody. (Dobrá klinická praxe) Každé porodnické pracoviště by mělo mít ve spolupráci s transfuzním oddělením a ústavní lékárnou trvale dostatečnou zásobu transfuzních přípravků a krevních derivátů pro jejich bezprostřední dostupnost v režimu 24/7. Doporučujeme u stavů rozvoje PŽOK zajistit iniciálně dostupnost čtyř transfuzních jednotek plazmy (preferována je tzv. solvent/detergent ošetřená plazma), čtyř transfuzních jednotek erytrocytů a 6 g fibrinogenu. Za minimální zásobu fibrinogenu považujeme 8 g fibrinogenu a dostupnost dalších 8 g do 1 hod. (Dobrá klinická praxe) Doporučujeme u všech pacientek s PPH zahájit okamžitou tekutinovou resuscitaci. Pro zahájení tekutinové resuscitace doporučujeme použití balancovaných roztoků krystaloidů. (Silné doporučení) Navrhujeme zvážit použití syntetických koloidních roztoků s obsahem želatiny při nedosažení nebo nedosahování hemodynamických cílů tekutinové resuscitace použitím krystaloidních roztoků a při trvající potřebě tekutin. (Slabé doporučení) Do doby dosažení kontroly zdroje krvácení doporučujeme u pacientek s PŽOK usilovat o dosažení hodnoty systolického krevního tlaku v pásmu 80–90 mmHg. (Silné doporučení) Doporučujeme u PŽOK použít vazopresory co nejdříve při nemožnosti dosažení cílových hodnot arteriálního krevního tlaku probíhající tekutinovou resuscitací. (Silné doporučení) V diagnostice a léčbě koagulopatie u PŽOK nereagujícího na standardní léčebné postupy doporučujeme spolupráci s hematologem. (Dobrá klinická praxe) K identifikaci typu koagulační poruchy u PŽOK, k její monitoraci a pro cílenou léčbu poruchy hemostázy doporučujeme kromě výše uvedených skupinových laboratorních vyšetření (minimálně KO, aPTT, fibrinogen) používat i viskoelastické metody (ROTEM, TEG). (Silné doporučení) K dosažení/obnovení účinnosti endogenních hemostatických mechanismů a léčebných postupů podpory koagulace doporučujeme maximální možnou korekci hypotermie, acidózy a hladiny ionizovaného kalcia. (Silné doporučení) Doporučujeme časné zahájení všech dostupných postupů k prevenci hypotermie a udržení nebo dosažení normotermie. (Silné doporučení) Doporučujeme monitorovat a udržovat hladinu ionizovaného kalcia v normálním referenčním rozmezí při podávání transfuzních přípravků. Ke korekci byl měl být přednostně podáván chlorid vápenatý. (Silné doporučení) Substituci fibrinogenu doporučujeme u pacientek s PPH při poklesu jeho hladiny < 2 g/l a/nebo při nálezu jeho funkčního deficitu zjištěném viskoelastickými metodami a/nebo při odůvodněném klinickém předpokladu deficitu fibrinogenu i bez znalosti jeho hladin. Jako úvodní dávku u PŽOK doporučujeme podání minimálně 4 g fibrinogenu. (Silné doporučení) Doporučujeme podat kyselinu tranexamovou (TXA) v úvodní dávce 1 g i.v. co nejdříve po vzniku PŽOK. Identická dávka může být opakována (nejdříve po 30 min), pokud krvácení pokračuje a je-li současně prokázána hyperfibrinolýza a/nebo je-li v aktuálním klinickém kontextu hyperfibrinolýza vysoce pravděpodobná. (Silné doporučení) Po dosažení kontroly krvácení další podání TXA u pacientek s PŽOK nedoporučujeme. (Silné doporučení) Doporučujeme podání plazmy v dávce 15–20 ml/kg u stavů PPH, kde je předpoklad koagulopatie jiné etiologie, než je nedostatek fibrinogenu a/nebo jsou přítomny abnormální výsledky koagulačních vyšetření, a kdy jejich výsledky neumožní identifikovat spolehlivě převažující mechanizmus koagulační poruchy a její cílenou korekci. (Silné doporučení) Doporučujeme podání faktorů protrombinového komplexu (PCC) u pacientek s PŽOK, kde je laboratorně prokázán deficit faktorů v PCC obsažených. Rutinní podávání PCC u pacientek s PŽOK nedoporučujeme. (Silné doporučení) Navrhujeme zvážit podání rFVIIa v době před rozhodnutím o endovaskulární nebo chirurgické intervenci. (Slabé doporučení) Doporučujeme u pacientek s PŽOK podávání erytrocytárních transfuzních přípravků k dosažení cílové hodnoty hemoglobinu v pásmu 70–80 g/l. (Silné doporučení) Doporučujeme u pacientek s PŽOK podávání trombocytů k dosažení cílové hodnoty minimálně 50 × 109/l a/nebo při předpokladu či průkazu poruchy jejich funkce. (Silné doporučení) Nedoporučujeme rutinní měření hladin antitrombinu III u pacientek s PŽOK. (Silné doporučení) Nedoporučujeme rutinní substituci antitrombinu III u pacientek s PŽOK. (Silné doporučení) Doporučujeme zahájit farmakologickou profylaxi trombembolické nemoci co nejdříve po dosažení kontroly zdroje PPH. Mechanickou tromboprofylaxi (intermitentní pneumatická komprese anebo elastické punčochy) doporučujeme zahájit neprodleně, jakmile to klinický stav dovolí. (Silné doporučení)

Summary of recommendations Preventive measures and procedures We recommend monitoring of blood loss in women with risk factors for PPH during labor using calibrated blood collectors or their equivalents. (Good Clinical Practice) We recommend that women with significant risk factors for PPH (e.g., placenta acrreta spectrum or hematologic disorders requiring consultative hematologic care) deliver in a perinatal intensive care center or perinatal intermediate care center. (Good Clinical Practice) We recommend formulating a plan of care in collaboration with a multidisciplinary team at a reasonable time prior to delivery for patients at high risk of PPH. (Good Clinical Practice) We recommend treating anemia antepartally. Pregnant women should be given iron supplements if the haemoglobin level falls to < 110 g/L in the 1st trimester or < 105 g/L at 28 weeks of pregnancy. (Good Clinical Practice) We suggest considering parenteral iron administration in women with sideropenic anemia unresponsive to oral iron supplementation. The cause of anemia should be identified as soon as possible after termination of pregnancy. (Weak recommendation) If the baby adapts well, we do not recommend cord ligation in less than 1 min. (Strong recommendation) In all vaginal deliveries, we recommend prophylactic administration of uterotonics in the third postpartum period after the delivery of the baby and cord ligation to reduce the risk of PPH. The first-choice drug is oxytocin. (Strong recommendation) If the third stage of labor has not been actively managed, we suggest that uterine massage and controlled umbilical cord traction be considered to shorten the duration of the third stage of labor and to reduce blood loss during vaginal delivery, if performed by a qualified healthcare professional. (Weak recommendation) We recommend the administration of uterotonics to prevent the development of PPH in women after the delivery of a child by caesarean section and umbilical cord ligation. (Strong recommendation) We suggest considering carbetocin administration in women at increased risk of PPH. (Weak recommendation) We recommend a single-dose administration of tranexamic acid (TXA) in women at increased risk of PPH undergoing a caesarean section. Clinical note: The use of TXA prior to the caesarean section is not explicitly stated in the product's SPC. A recent meta-analysis states the most common dosage to be 1 g i.v. (Strong recommendation) Organization of care We recommend that every health care facility with an OB/GYN unit should have the PPH management protocol (guided document is not specific or really used at all, I am not sure if my suggestion is sufficient) defining the organizational and professional procedure for PPH situations. (Good Clinical Practice) We recommend that the PPH management protocol (i.e. the crisis action plan) should clearly define the organizational and professional roles of the individual members of the crisis team in the event of PPH (non-medical staff), obstetrician, anesthetist, hematologist, etc.) and define the minimum scope of equipment for the care of patients with PPH. (Good Clinical Practice) We recommend regular simulation training of PPH crisis by the entire crisis team with a subsequent debriefing or its formalized equivalent. (Good Clinical Practice) We recommend defining quality indicators for the diagnosis and treatment of PPH and their formalized evaluation at regular intervals, at least once a year. (Good Clinical Practice) Diagnostic and treatment procedure at PPH When hypotonia or atony of the uterus is found, we recommend using a structured procedure. (Good Clinical Practice) At departments with an option of endovascular interventions, we suggest considering the preferential use of radiological interventional methods (selective pelvic artery embolization) in cases of PPH due to uterine hypotonia or atony, if the current clinical context allows it. (Weak recommendation) For all stages of PPH development, we recommend a pre-transfusion examination. In addition to standard laboratory tests, point-of-care-testing methods, especially viscoelastic methods, are preferred to assess the current coagulation status. (Good Clinical Practice) Each obstetric unit should ensure a sufficient stock of blood products and blood derivatives for their immediate availability 24/7 in collaboration with the transfusion department and the inpatient pharmacy. In case of PPH development, we recommend securing initial availability of 4 units of plasma (solvent/detergent-treated plasma is preferred), 4 units of erythrocytes and 6 g of fibrinogen. We consider 8 g to be a minimum supply of fibrinogen and additional 8 g should be available within 1 h. (Good Clinical Practice) We recommend the initiation of immediate fluid resuscitation in all patients with PPH. We recommend the use of balanced crystalloid solutions to initiate fluid resuscitation. (Strong recommendation) We propose considering the use of synthetic colloid solutions containing gelatin when hemodynamic goals of fluid resuscitation have not been achieved or are not being achieved using crystalloid solutions and when a fluid deficit persists. (Weak recommendation) Until the source of bleeding is controlled, we recommend aiming for a systolic blood pressure in a range of 80–90 mmHg in patients with PPH. (Strong recommendation) We recommend the use of vasopressors as soon as possible in PPH when target arterial blood pressure values cannot be reached by ongoing fluid resuscitation. (Strong recommendation) We recommend cooperation with a hematologist in the diagnosis and treatment of coagulopathy in PPH unresponsive to standard therapies. (Good Clinical Practice) In addition to the above-mentioned panel laboratory tests (at least KO, aPTT, fibrinogen), we also recommend using viscoelastic methods (ROTEM, TEG) to identify the type of coagulation disorder in PPH, to monitor it and for targeted treatment of hemostasis disorders. (Strong recommendation) To achieve/restore the efficacy of endogenous hemostatic mechanisms and coagulation support therapies, we recommend the maximum possible correction of hypothermia, acidosis and ionized calcium levels. (Strong recommendation) Early initiation of all available procedures to prevent hypothermia and maintain or achieve normothermia is recommended. (Strong recommendation) It is recommended monitoring and maintaining ionized calcium levels within the normal range when administering transfusion products. Preferably, calcium chloride should be administered for correction. (Strong recommendation) Fibrinogen replacement is recommended in patients with PPH when fibrinogen levels fall to < 2 g/L and/or when there is a functional fibrinogen deficiency detected by viscoelastic methods and/or when there is a reasonable clinical assumption of fibrinogen deficiency even without knowledge of fibrinogen levels. We recommend a minimum of 4 g of fibrinogen as an initial dose in PPH. (Strong recommendation) It is recommended to administer tranexamic acid (TXA) at an initial dose of 1 g i.v. as soon as possible after the onset of PPH. An identical dose may be repeated (after 30 min at the earliest) if bleeding continues and if hyperfibrinolysis is demonstrated and/or if hyperfibrinolysis is highly likely in the current clinical context. (Strong recommendation) We do not recommend further administration of TXA in patients with PPH after bleeding control has been achieved. (Strong recommendation) We recommend administration of plasma at a dose of 15–20 mL/kg in PPH conditions where coagulopathy of a different etiology than fibrinogen deficiency is suspected and/or abnormal coagulation test results are present, and where the results do not reliably identify the predominant mechanism of the coagulation disorder and its targeted correction. (Strong recommendation) We recommend the administration of prothrombin complex factors (PCC) in patients with PPH where there is a laboratory evidence of a deficiency of PCC factors. We do not recommend routine administration of PCC in patients with PPH. (Strong recommendation) We suggest considering administration of rFVIIa before making a decision on an endovascular or a surgical intervention. (Weak recommendation) In patients with PPH, we recommend administration of erythrocyte blood products to achieve a target hemoglobin value in the range 70–80 g/L. (Strong recommendation) In patients with PPH, we recommend platelet administration to achieve a target value of at least 50 × 109/L and/or when platelet function impairment is suspected or demonstrated. (Strong recommendation) We do not recommend routine measurement of antithrombin III levels in patients with PPH. (Strong recommendation) We do not recommend routine antithrombin III replacement in patients with PPH. (Strong recommendation) We recommend initiating pharmacological prophylaxis for thromboembolic disease as soon as possible after control of the source of PPH is achieved. We recommend initiating mechanical thromboprophylaxis (intermittent pneumatic compression or elastic stockings) as soon as the clinical condition permits. (Strong recommendation)

• Keywords
• profylaxe uterotoniky, peripartální krvácení, tlakové a podlatkové nitroděložní prostředky, hemostatické nitroděložní prostředky, viskoelastické metody, krizový management,
• MeSH
• Uterine Hemorrhage * diagnosis   therapy   MeSH
• Factor VIIa MeSH
• Hemorrhage diagnosis   therapy   MeSH
• Humans MeSH
• Peripartum Period MeSH
• Pregnancy MeSH
• Check Tag
• Humans MeSH
• Pregnancy MeSH
• Female MeSH
• Publication type
• Practice Guideline MeSH

At a population level, the European Society of Gastrointestinal Endoscopy (ESGE), the European Helicobacter and Microbiota Study Group (EHMSG), and the European Society of Pathology (ESP) suggest endoscopic screening for gastric cancer (and precancerous conditions) in high-risk regions (age-standardized rate [ASR] > 20 per 100 000 person-years) every 2 to 3 years or, if cost-effectiveness has been proven, in intermediate risk regions (ASR 10-20 per 100 000 person-years) every 5 years, but not in low-risk regions (ASR < 10).ESGE/EHMSG/ESP recommend that irrespective of country of origin, individual gastric risk assessment and stratification of precancerous conditions is recommended for first-time gastroscopy. ESGE/EHMSG/ESP suggest that gastric cancer screening or surveillance in asymptomatic individuals over 80 should be discontinued or not started, and that patients' comorbidities should be considered when treatment of superficial lesions is planned.ESGE/EHMSG/ESP recommend that a high quality endoscopy including the use of virtual chromoendoscopy (VCE), after proper training, is performed for screening, diagnosis, and staging of precancerous conditions (atrophy and intestinal metaplasia) and lesions (dysplasia or cancer), as well as after endoscopic therapy. VCE should be used to guide the sampling site for biopsies in the case of suspected neoplastic lesions as well as to guide biopsies for diagnosis and staging of gastric precancerous conditions, with random biopsies to be taken in the absence of endoscopically suspected changes. When there is a suspected early gastric neoplastic lesion, it should be properly described (location, size, Paris classification, vascular and mucosal pattern), photodocumented, and two targeted biopsies taken.ESGE/EHMSG/ESP do not recommend routine performance of endoscopic ultrasonography (EUS), computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET)-CT prior to endoscopic resection unless there are signs of deep submucosal invasion or if the lesion is not considered suitable for endoscopic resection.ESGE/EHMSG/ESP recommend endoscopic submucosal dissection (ESD) for differentiated gastric lesions clinically staged as dysplastic (low grade and high grade) or as intramucosal carcinoma (of any size if not ulcerated or ≤ 30 mm if ulcerated), with EMR being an alternative for Paris 0-IIa lesions of size ≤ 10 mm with low likelihood of malignancy.ESGE/EHMSG/ESP suggest that a decision about ESD can be considered for malignant lesions clinically staged as having minimal submucosal invasion if differentiated and ≤ 30 mm; or for malignant lesions clinically staged as intramucosal, undifferentiated and ≤ 20 mm; and in both cases with no ulcerative findings.ESGE/EHMSG/ESP recommends patient management based on the following histological risk after endoscopic resection: Curative/very low-risk resection (lymph node metastasis [LNM] risk < 0.5 %-1 %): en bloc R0 resection; dysplastic/pT1a, differentiated lesion, no lymphovascular invasion, independent of size if no ulceration and ≤ 30 mm if ulcerated. No further staging procedure or treatment is recommended.Curative/low-risk resection (LNM risk < 3 %): en bloc R0 resection; lesion with no lymphovascular invasion and: a) pT1b, invasion ≤ 500 μm, differentiated, size ≤ 30 mm; or b) pT1a, undifferentiated, size ≤ 20 mm and no ulceration. Staging should be completed, and further treatment is generally not necessary, but a multidisciplinary discussion is required. Local-risk resection (very low risk of LNM but increased risk of local persistence/recurrence): Piecemeal resection or tumor-positive horizontal margin of a lesion otherwise meeting curative/very low-risk criteria (or meeting low-risk criteria provided that there is no submucosal invasive tumor at the resection margin in the case of piecemeal resection or tumor-positive horizontal margin for pT1b lesions [invasion ≤ 500 μm; well-differentiated; size ≤ 30 mm, and VM0]). Endoscopic surveillance/re-treatment is recommended rather than other additional treatment. High-risk resection (noncurative): Any lesion with any of the following: (a) a positive vertical margin (if carcinoma) or lymphovascular invasion or deep submucosal invasion (> 500 μm from the muscularis mucosae); (b) poorly differentiated lesions if ulceration or size > 20 mm; (c) pT1b differentiated lesions with submucosal invasion ≤ 500 μm with size > 30 mm; or (d) intramucosal ulcerative lesion with size > 30 mm. Complete staging and strong consideration for additional treatments (surgery) in multidisciplinary discussion.ESGE/EHMSG/ESP suggest the use of validated endoscopic classifications of atrophy (e. g. Kimura-Takemoto) or intestinal metaplasia (e. g. endoscopic grading of gastric intestinal metaplasia [EGGIM]) to endoscopically stage precancerous conditions and stratify the risk for gastric cancer.ESGE/EHMSG/ESP recommend that biopsies should be taken from at least two topographic sites (2 biopsies from the antrum/incisura and 2 from the corpus, guided by VCE) in two separate, clearly labeled vials. Additional biopsy from the incisura is optional.ESGE/EHMSG/ESP recommend that patients with extensive endoscopic changes (Kimura C3 + or EGGIM 5 +) or advanced histological stages of atrophic gastritis (severe atrophic changes or intestinal metaplasia, or changes in both antrum and corpus, operative link on gastritis assessment/operative link on gastric intestinal metaplasia [OLGA/OLGIM] III/IV) should be followed up with high quality endoscopy every 3 years, irrespective of the individual's country of origin.ESGE/EHMSG/ESP recommend that no surveillance is proposed for patients with mild to moderate atrophy or intestinal metaplasia restricted to the antrum, in the absence of endoscopic signs of extensive lesions or other risk factors (family history, incomplete intestinal metaplasia, persistent H. pylori infection). This group constitutes most individuals found in clinical practice.ESGE/EHMSG/ESP recommend H. pylori eradication for patients with precancerous conditions and after endoscopic or surgical therapy.ESGE/EHMSG/ESP recommend that patients should be advised to stop smoking and low-dose daily aspirin use may be considered for the prevention of gastric cancer in selected individuals with high risk for cardiovascular events.

• MeSH
• Biopsy MeSH
• Early Detection of Cancer * methods   standards   MeSH
• Gastroscopy * standards   MeSH
• Risk Assessment MeSH
• Helicobacter Infections complications   MeSH
• Humans MeSH
• Stomach Neoplasms * pathology   diagnosis   therapy   MeSH
• Precancerous Conditions * pathology   diagnosis   therapy   MeSH
• Societies, Medical MeSH
• Gastric Mucosa pathology   diagnostic imaging   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Practice Guideline MeSH
• Geographicals
• Europe MeSH