BACKGROUND: Exposure of critically ill patients to antibiotics lead to intestinal dysbiosis, which often manifests as antibiotic-associated diarrhoea. Faecal microbiota transplantation restores gut microbiota and may lead to faster resolution of diarrhoea. METHODS: Into this prospective, multi-centre, randomized controlled trial we will enrol 36 critically ill patients with antibiotic-associated diarrhoea. We will exclude patients with ongoing sepsis, need of systemic antibiotics, or those after recent bowel surgery or any other reason that prevents the FMT. Randomisation will be in 1:1 ratio. Patients in the control group will receive standard treatment based on oral diosmectite. In the intervention group, patients will receive, in addition to the standard of care, faecal microbiota transplantation via rectal tube, in the form of a preparation mixed from 7 thawed aliquots (50 mL) made from fresh stool of 7 healthy unrelated donors and quarantined deep frozen for 3 to 12 months. Primary outcome is treatment failure defined as intervention not delivered or diarrhoea persisting at day 7 after randomisation. Secondary outcomes include safety measures such as systemic inflammatory response, adverse events, and also diarrhoea recurrence within 28 days. Exploratory outcomes focus on gut barrier function and composition of intestinal microbiota. DISCUSSION: Faecal microbiota transplantation has been effective for dysbiosis in non-critically ill patients with recurrent C. difficile infections and it is plausible to hypothesize that it will be equally effective for symptoms of dysbiosis in the critically ill patients. In addition, animal experiments and observational data suggest other benefits such as reduced colonization with multi-drug resistant bacteria and improved gut barrier and immune function. The frozen faeces from unrelated donors are immediately available when needed, unlike those from the relatives, who require lengthy investigation. Using multiple donors maximises graft microbiota diversity. Nonetheless, in vulnerable critically ill patients, Faecal microbiota transplantation might lead to bacterial translocation and unforeseen complications. From growing number of case series it is clear that its off label use in the critically ill patients is increasing and that there is a burning need to objectively assess its efficacy and safety, which this trial aims. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT05430269).

• MeSH
• antibakteriální látky * škodlivé účinky   terapeutické užití   MeSH
• dysbióza terapie   mikrobiologie   MeSH
• feces mikrobiologie   MeSH
• fekální transplantace * metody   škodlivé účinky   MeSH
• klinické zkoušky, fáze II jako téma MeSH
• kritický stav * MeSH
• lidé MeSH
• multicentrické studie jako téma MeSH
• prospektivní studie MeSH
• průjem * terapie   mikrobiologie   MeSH
• randomizované kontrolované studie jako téma MeSH
• střevní mikroflóra * účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.

• MeSH
• adrenergní látky MeSH
• ateroskleróza * komplikace   MeSH
• fenotyp MeSH
• feochromocytom * diagnóza   MeSH
• infarkt myokardu * MeSH
• kardiomyopatie * MeSH
• katecholaminy MeSH
• lidé MeSH
• metanefrin MeSH
• nádory nadledvin * patologie   MeSH
• paragangliom * komplikace   MeSH
• retrospektivní studie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Penile squamous cell carcinoma (pSCC) is a rare tumour with a variable prognosis. More prognostic markers linked to mutational signatures and the tumour immune microenvironment are needed. A cohort made up of 165 invasive pSCC was retrospectively analysed using formalin-fixed, paraffin-embedded tumour tissue, focusing on tumour mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, microsatellite instability (MSI), the number of tumour infiltrating lymphocytes (TILs) expressing cytotoxic T-lymphocyte-associated protein 4 (CTLA4), HPV status determined by p16 immunohistochemistry, and several traditional histopathological variables. High TMB (>10 mut/Mb) was associated with high PD-L1 expression (TPS 50-100%), and HPV-negative status. High PD-L1 expression was linked to HPV negativity, a high number of intratumoural CTLA4+ cells, and brisk lymphocytic infiltrate. High TMB was a significant predictor of shorter overall survival (OS) in both univariate and multivariate analysis when using a median cut-off value of 4.3 mut/Mb, but not when using an arbitrary cut-off of 10 mut/Mb. Low CTLA4+ cell infiltration at the tumour invasion front was a marker of shorter OS and cancer-specific survival in both univariate and multivariate analysis. PD-L1 expression had no significant impact on prognosis. Only two cases were MSI high. The results support the hypothesis of two aetiological pathways in pSCC cancerogenesis: (1) SCC linked to HPV infection characterised by low TMB, less common PD-L1 expression, and a lower number of TILs; and (2) SCC linked to chronic inflammation leading to a high number of acquired mutations (high TMB), HPV negativity, increased neoantigen production (i.e., PD-L1), and high immune cell infiltration.

• MeSH
• antigen CTLA-4 MeSH
• antigeny CD274 metabolismus   MeSH
• infekce papilomavirem * komplikace   MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory penisu * genetika   MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• blokáda Tawarova raménka etiologie   terapie   MeSH
• elektrokardiografie MeSH
• funkce levé komory srdeční MeSH
• Hisův svazek * MeSH
• kardiomyopatie * etiologie   terapie   MeSH
• kardiostimulace umělá škodlivé účinky   MeSH
• lidé MeSH
• srdeční komory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Pulsed-field ablation (PFA) represents a new, nonthermal ablation energy for the ablation of atrial fibrillation (AF). Ablation energies producing thermal injury are associated with an inflammatory response, platelet activation, and coagulation activation. OBJECTIVES: This study aimed to compare the systemic response in patients undergoing pulmonary vein isolation (PVI) using pulsed-field and radiofrequency (RF) energy. METHODS: Patients with AF indicated for PVI were enrolled and randomly assigned to undergo PVI using RF (CARTO Smart Touch, Biosense Webster) or pulsed-field (Farapulse, Boston-Scientific) energy. Markers of myocardial damage (troponin I), inflammation (interleukin-6), coagulation (D-dimers, fibrin monomers, von Willebrand antigen and factor activity), and platelet activation (P-selectin, activated GpIIb/IIIa antigen) were measured before the procedure (T1), after trans-septal puncture (T2), after completing the ablation in the left atrium (T3), and 1 day after the procedure (T4). RESULTS: A total of 65 patients were enrolled in the pulsed-field ablation (n = 33) and RF ablation (n = 32) groups. Both groups were similar in baseline characteristics (age 60.5 ± 12.7 years vs 64.0 ± 10.7 years; paroxysmal AF: 60.6% vs 62.5% patients). Procedural and left atrial dwelling times were substantially shorter in the PFA group (55:09 ± 11:57 min vs 151:19 ± 41:25 min; P < 0.001; 36:00 ± 8:05 min vs 115:58 ± 36:49 min; P < 0.001). Peak troponin release was substantially higher in the PFA group (10,102 ng/L [IQR: 8,272-14,207 ng/L] vs 1,006 ng/L [IQR: 603-1,433ng/L]). Both procedures were associated with similar extents (>50%) of platelet and coagulation activation. The proinflammatory response 24 h after the procedure was slightly but nonsignificantly higher in the RF group. CONCLUSIONS: Despite 10 times more myocardial damage, pulsed-field ablation was associated with a similar degree of platelet/coagulation activation, and slightly lower inflammatory response. (The Effect of Pulsed-Field and Radiofrequency Ablation on Platelet, Coagulation and Inflammation; NCT05603637).

• MeSH
• fibrilace síní * MeSH
• katetrizační ablace * škodlivé účinky   metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• venae pulmonales * chirurgie   MeSH
• výsledek terapie MeSH
• zánět MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Colorectal cancer (CRC) is a leading global cause of illness and death. There is a need for identification of better prognostic markers beyond traditional clinical variables like grade and stage. Previous research revealed that abnormal expression of cytokeratin 7 (CK7) and loss of the intestinal-specific Special AT-rich sequence-binding protein 2 (SATB2) are linked to poor CRC prognosis. This study aimed to explore these markers' prognostic significance alongside two extraintestinal mucins (MUC5AC, MUC6), claudin 18, and MUC4 in 285 CRC cases using immunohistochemistry on tissue microarrays (TMAs). CK7 expression and SATB2-loss were associated with MUC5AC, MUC6, and claudin 18 positivity. These findings suggest a distinct "non-intestinal" immunohistochemical profile in CRC, often right-sided, SATB2-low, with atypical expression of CK7 and non-colorectal mucins (MUC5AC, MUC6). Strong MUC4 expression negatively impacted cancer-specific survival (hazard ratio = 2.7, p = 0.044). Genetic analysis via next-generation sequencing (NGS) in CK7 + CRCs and those with high MUC4 expression revealed prevalent mutations in TP53, APC, BRAF, KRAS, PIK3CA, FBXW7, and SMAD4, consistent with known CRC mutation patterns. NGS also identified druggable variants in BRAF, PIK3CA, and KRAS. CK7 + tumors showed intriguingly common (31.6%) BRAF V600E mutations corelating with poor prognosis, compared to the frequency described in the literature and databases. Further research on larger cohorts with a non-colorectal immunophenotype and high MUC4 expression is needed.

• MeSH
• dospělí MeSH
• fenotyp MeSH
• fosfatidylinositol-3-kinasy třídy I genetika   metabolismus   MeSH
• imunohistochemie * MeSH
• keratin-7 metabolismus   genetika   MeSH
• kolorektální nádory * genetika   patologie   metabolismus   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mucin 4 genetika   metabolismus   MeSH
• mucin 5AC genetika   metabolismus   MeSH
• mucin 6 genetika   metabolismus   MeSH
• mutace MeSH
• nádorové biomarkery * genetika   metabolismus   MeSH
• prognóza MeSH
• protoonkogenní proteiny B-Raf genetika   MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transkripční faktory MeSH
• vazebné proteiny DNA v oblastech připojení k matrix * genetika   metabolismus   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Arrhythmias accompany septic shock and their presence is related to patient ́s prognosis. 1C class antiarrhythmics are seldom administered in intensive care due to an alleged dose-dependent toxicity published in case reports and unfavourable outcome reported in a few prospective trials done on cardiology patients. These papers did not take into consideration a complex haemodynamic assessment using echocardiography. The authors have recently published a large retrospective study (J Crit Care 2017) on supraventricular (SV) arrhythmias in septic shock patients demonstrating safety and favourable long term outcome of propafenone compared to amiodarone. The antiarrhythmic efficacy was also by 15% higher than in the amiodarone group. The hypothesis of this prospective research is that propafenone will be more effective than amiodaron in achieving and maintaining sinus rhythm in septic shock patients with new-onset SV arrhythmia without severe LV dysfunction. The available echoparameters of the heart electromechanics could also help to better characterize a septic myocardial involvement.

Poruchy rytmu ve zvýšené míře doprovází septický šok a jejich management je spojen s prognózou pacienta. 1c třída antiarytmik se na většině pracovišť intenzivní péče využívá zřídka díky domnělé, na dávce závislé toxicitě a nepříznivému dopadu na mortalitu publikovaných ve studiích kardiologických pacientů mimo intenzivní péči. Tyto práce nedostatečně zohledňují komplexní hemodynamické vyšetření a výběr vhodných pacientů s pomocí echokardiografie. Autoři recentně provedli rozsáhlou retrospektivní studii (J Crit Care 2017) ukazující na dobrý efekt i bezpečnost používání propafenonu, který je v podmínkách septického šoku o 15% účinnější než amiodaron. Hypotézou této prospektivní studie je ověření efektivity a bezpečnosti propafenonu v kardioverzi a udržení sinus rytmu u nově vzniklé supraventrikulární arytmie s vyloučením těžkých systol dysfunkcí LK. Monitorované echoparametry srdeční elektromechaniky by mohly lépe zachytit postižení myokardu v sepsi a pomoci definovat septickou kardiomyopatii.

• Klíčová slova
• intenzivní péče, intensive care, supraventrikulární arytmie, septický šok, propafenon, amiodaron, supraventricular arrhythmia, septic shock, propafenone, amiodarone,

• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

INTRODUCTION: Patients who have sustained extensive burns frequently exhibit substantial damage to skeletal muscle and associated complications. The rehabilitation of these patients can be challenging due to the nature of the injury and the subsequent complications. Nevertheless, there is a possibility that functional proprioceptive stimulation (illusory movements) may facilitate effective rehabilitation in patients with limited physiotherapy options. Nevertheless, this approach has yet to be tested in patients with burn injuries. MATERIAL AND METHODOLOGY: A prospective, randomised, crossover trial was conducted at a burn centre in a tertiary teaching hospital. The objective was to assess the effects of illusory movements on energy metabolism, insulin sensitivity, and skeletal muscle biology in adult critically ill patients with deep burns covering 30 % or more of the total body surface area. Two 30-minute daily sessions of functional proprioceptive stimulation were administered in addition to the standard physical therapy or physical activity regimen. Subsequently, the patients proceeded to the next stage of the trial, which involved a two-week crossover period. MEASUREMENTS AND MAIN RESULTS: Daily indirect calorimetry and calculation of nitrogen balance. Skeletal muscle biopsies from vastus lateralis for high resolution respirometry and euglycemic clamps to assess whole body glucose disposal were performed three times: at baseline and then fortnightly after each intervention period. The intervention was feasible and well tolerated in both early and late stages of burn disease. It did not change energy expenditure (mean change -33 [95 % CI: -292;+227] kcal .24 h-1, p = 0.79), nitrogen balance (+2.0 [95 % CI: -3.1;+7.1] g N .1.73 m-2 BSA .24 h-1), or insulin sensitivity (mean change of insulin-mediated glucose disposal -0.33 [95 % CI: -1.18;+0.53] mmol.h-1). At the cellular level, the intervention increased the capacity of mitochondria to synthesize ATP by aerobic phosphorylation and tended to increase mitochondrial coupling. Functional capacities of fatty acid oxidation and electron transfer chain complexes I, II, and IV were unaffected. CONCLUSIONS: Compared to physical therapy alone, two daily sessions of functional proprioceptive stimulation in addition to usual physical therapy in patients with extensive burns did not change energy expenditure, insulin sensitivity, nitrogen balance, or energy substrate oxidation. At cellular level, the intervention improved the capacity of aerobic phosphorylation in skeletal muscle mitochondria. Clinical effects remain to be demonstrated in adequately powered trials.

• MeSH
• dospělí MeSH
• energetický metabolismus * fyziologie   MeSH
• inzulinová rezistence fyziologie   MeSH
• klinické křížové studie * MeSH
• kosterní svaly * metabolismus   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nepřímá kalorimetrie MeSH
• popálení * metabolismus   terapie   rehabilitace   patofyziologie   komplikace   MeSH
• povrch těla MeSH
• propriocepce fyziologie   MeSH
• prospektivní studie MeSH
• techniky fyzikální terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: The arteriovenous access stage (AVAS) classification provides evaluation of upper extremity vessels for vascular access (VA) suitability. It divides patients into classes within three main groups: suitable for native fistula (AVAS1) or prosthetic graft (AVAS2), and patients not suitable for conventional native or prosthetic VA (AVAS3). We validated this system on a prospective dataset. METHODS: A prospective, international observational study (NCT04796558) involved 11 centres from 8 countries. Patient recruitment was from March 2021 to January 2024. Demographic data, risk factors, vessels parameters, VA types, AVAS class and early VA failure were collected. Percentage agreement was used to assess predictive ability of AVAS (comparison of AVAS and created VA) and consistency of AVAS assessment between evaluators. Pearson's Chi-squared test was used for comparison of early failure rate of conventional (predicted by AVAS) and unconventional (not predicted by AVAS) VA. RESULTS: From 1034 enrolled patients, 935 had arteriovenous fistula or graft, 99 patients did not undergo VA creation due opting for alternative renal replacement therapies, experiencing health complications, death or non-compliance. AVAS1 had 91.2%, AVAS2 7.2% and AVAS3 1.6% of patients. Agreement between evaluators was 89%. The most frequently created VAs were radial-cephalic (46%) and brachial-cephalic (27%) fistulae. The accuracy of AVAS versus created access was 79%. In comparison, VA predicted by clinicians versus created access was 62.1%. Inaccuracy of AVAS prediction was more common with higher AVAS classes, and the most common reason for inaccuracy was creation of distal VA despite less favourable anatomy (17%). Patients with unconventional VA had higher early failure rate than patients with conventional VA (20% vs 9.3%, respectively, P = .002). CONCLUSION: AVAS is effective in predicting VA creation, but overall accuracy is reduced at higher AVAS classes when the complexity of decision-making increases and proximal vessels require preservation. When AVAS was followed by clinicians, early failure was significantly decreased.

• Publikační typ
• časopisecké články MeSH

AIMS: A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA). METHODS AND RESULTS: Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 mL/m2. The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40 mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year [Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014]. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40 mL/m2 were less favourable with propafenone compared to amiodarone at 1 month [HR 3.6 (95% CI 1.03; 12.5), P = 0.045]; however, it did not reach statistical significance at 1 year [HR 1.9 (95% CI 0.8; 4.4), P = 0.138]. CONCLUSION: Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40 mL/m2. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017.

• MeSH
• amiodaron * terapeutické užití   aplikace a dávkování   MeSH
• antiarytmika * terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• propafenon * terapeutické užití   aplikace a dávkování   MeSH
• senioři MeSH
• septický šok * farmakoterapie   patofyziologie   MeSH
• srdeční síně * patofyziologie   diagnostické zobrazování   účinky léků   MeSH
• supraventrikulární tachykardie * farmakoterapie   patofyziologie   MeSH
• tepový objem fyziologie   účinky léků   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
• srovnávací studie MeSH