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

PURPOSE: Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared. METHODS: In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence. RESULTS: Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3-6.8) and 7.3 h (95% CI 5-11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05). CONCLUSION: Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.

• MeSH
• amiodaron * terapeutické užití   MeSH
• antiarytmika terapeutické užití   MeSH
• fibrilace síní * terapie   MeSH
• funkce levé komory srdeční MeSH
• lidé MeSH
• propafenon terapeutické užití   MeSH
• prospektivní studie MeSH
• septický šok * komplikace   farmakoterapie   MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH

Patients intoxicated with methamphetamine-like substances may present with myoglobinuria but rarely require admission. An 18-year-old female was admitted due to intoxication with pervitin, a methamphetamine derivative. She presented with an altered mental status, fever, and increased heart and respiratory rates. Biomarkers showed leukocytosis and markedly increased procalcitonin levels, suggestive of sepsis. However, blood cultures and infectious disease workup were unrevealing. Clinical course was heralded by rhabdomyolysis and myoglobinuria resulting in multi-organ failure including respiratory failure necessitating mechanical ventilation, hemodynamic compromise with need for inotropic support, and an acute renal failure requiring renal replacement therapy. Surprisingly, after a transient improvement, an unexpected second peak of myoglobin was observed on hospital day 5, controlled by intensifying the elimination methods, and administration of dantrolene. Acute kidney injury resolved by hospital day 15, and the patient could be discharged on day 22. While most patients with intoxications are discharged within 24 hours from emergency departments without being admitted, our case report highlights that the organ injury may evolve beyond the usual observation period, traditional renal-replacement therapies may not be sufficient to mitigate myoglobinemia with resulting acute kidney injury, and that procalcitonin may not be a reliable biomarker of infection in the setting of drug-induced rhabdomyolysis.

• MeSH
• akutní poškození ledvin * chemicky indukované   diagnóza   terapie   MeSH
• biologické markery MeSH
• lidé MeSH
• methamfetamin * MeSH
• mladiství MeSH
• myoglobinurie * komplikace   MeSH
• prokalcitonin MeSH
• rhabdomyolýza * chemicky indukované   diagnóza   komplikace   MeSH
• sepse * diagnóza   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: The role of chest drain (CD) location by bedside imaging methods in the diagnosis of pneumothorax has not been explored in a prospective study yet. METHODS: Covid-19 ARDS patients with pneumothorax were prospectively monitored with chest ultrasound (CUS) and antero-posterior X-ray (CR) performed after drainage in the safe triangle. CD foreshortening was estimated as a decrease of chest drain index (CDI = length of CD in chest taken from CR/depth of insertion on CD scale + 5 cm). The angle of inclination of the CD was measured between the horizontal line and the CD at the point where it enters pleural space on CR. RESULTS: Of the total 106 pneumothorax cases 80 patients had full lung expansion on CUS, the CD was located by CUS in 69 (86%), the CDI was 0.99 (0.88-1.06). 26 cases had a residual pneumothorax after drainage (24.5%), the CD was located by CUS in 31%, the CDI was 0.76 (0.6-0.93),p < 0.01. The risk ratio for a pneumothorax in a patient with not visible CD between the pleural layers on CUS and an associated low CDI on CR was 5.97, p˂0.0001. For the patients with a steep angle of inclination (> 50°) of the CD, the risk ratio for pneumothorax was not significant (p < 0.17). A continued air leak from the CD after drainage is related to the risk for a residual pneumothorax (RR 2.27, p = 0.003). CONCLUSION: Absence of a CD on CUS post drainage, low CDI on CR and continuous air leak significantly associate with residual occult pneumothorax which may evade diagnosis on an antero-posterior CR.

• Publikační typ
• časopisecké články MeSH

• MeSH
• drenáž MeSH
• dýchací soustava MeSH
• lidé MeSH
• mimotělní membránová oxygenace * MeSH
• pleurální výpotek * diagnostické zobrazování   terapie   MeSH
• ultrasonografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH

INTRODUCTION: Supraventricular arrhythmias contribute to haemodynamic compromise in septic shock. A retrospective study generated the hypothesis that propafenone could be more effective than amiodarone in achieving and maintaining sinus rhythm (SR). Certain echocardiographic parameters may predict a successful cardioversion and help in the decision on rhythm or rate control strategy. METHODS AND ANALYSIS: The trial includes septic shock patients with new-onset arrhythmia, but without severe impairment of the left ventricular ejection fraction. After baseline echocardiography, the patient is randomised to receive a bolus and maintenance dose of either amiodarone or propafenone. The primary outcome is the proportion of patients that have achieved rhythm control at 24 hours after the start of the infusion. The secondary outcomes are the percentages of patients that needed rescue treatments (DC cardioversion or unblinding and crossover of the antiarrhythmics), the recurrence of arrhythmias, intensive care unit mortality, 28-day and 1-year mortality. In the posthoc analysis, we separately assess subgroups of patients with pulmonary hypertension and right ventricular dysfunction. In the exploratory part of the study, we assess whether the presence of a transmitral diastolic A wave and its higher velocity-time integral is predictive for the sustainability of mechanical SR and whether the indexed left atrial endsystolic volume is predictive of recurrent arrhythmia. Considering that the restoration of SR within 24 hours occurred in 74% of the amiodarone-treated patients and in 89% of the patients treated with propafenone, we plan to include 200 patients to have an 80% chance to demonstrate the superiority of propafenone at p=0.05. ETHICS AND DISSEMINATION: The trial is recruiting patients according to its second protocol version approved by the University Hospital Ethical Board on the 6 October 2017 (No. 1691/16S-IV). The results will be disseminated through peer reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03029169.

• MeSH
• amiodaron terapeutické užití   MeSH
• antiarytmika terapeutické užití   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• funkce levé komory srdeční účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• propafenon terapeutické užití   MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• septický šok komplikace   farmakoterapie   patofyziologie   MeSH
• supraventrikulární tachykardie komplikace   farmakoterapie   patofyziologie   MeSH
• tepový objem účinky léků   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Cíl studie: Syndrom Noonanové (NS), jedna z nejčastějších RASopatií, má odhadovanou incidenci 1 z 1000 až 2500 živě narozených jedinců. V prenatálním období lze u postižených plodů s tímto syndromem pozorovat zvýšené šíjové projasnění, hygroma colli, hydrops plodu, vrozené srdeční vady, vady ledvin, lymfatické vaky nebo větší množství plodové vody. U plodů s těmito nálezy byla při nálezu normálního karyotypu a po vyloučení mikrodelečních/mikroduplikačních syndromů doplněna prenatální diagnostika i o vyšetření vybraných genů pro RASopatie. Cílem studie bylo zhodnotit klinický přínos masivně paralelního sekvenování (MPS, massively parallel sequencing) DNA plodů suspektních pro NS, tj. diagnostickou výtěžnost na jedné straně a podíl detekovaných variant nejasného významu na straně druhé. Typ studie: Klinicky diagnostická. Název a sídlo pracoviště: Centrum prenatální diagnostiky, Brno, s.r.o.; Cytogenetická laboratoř Brno, s.r.o. Metodika: Analyzovány byly vzorky plodových vod, resp. choriových klků. Z nich izolovaná DNA byla po zjištění normálního karyotypu a array-CGH (aCGH) postoupena k analýze genů asociovaných s RASopatiemi metodou MPS. Výsledky: Ve sledovaném dvouletém období byl NS potvrzen celkem u 10 z 95 vyšetřovaných plodů. To představuje 10,5% diagnostickou výtěžnost metody. Celkem u 10 plodů byla detekována varianta DNA nejasného významu (VOUS, variants of unknown significance), následná segregační analýza pomohla objasnit její význam u šesti plodů. Závěr: MPS umožňuje rychlou molekulárně-genetickou diagnostiku RASopatií již v prenatálním období. Tato metoda tak přispívá k objasnění nejen fenotypových projevů u již narozených jedinců, ale také ultrazvukových nálezů u plodů s normálním karyotypem i aCGH.

Objective: Noonan syndrome (NS), one of the most common RASopathies, has an estimated incidence of 1 in 1,0002,500 live births. In the prenatal period increased nuchal translucency, hygroma colli, hydrops fetus, congenital heart disease, kidney defects, larger amount of amniotic fluid can be observed in affected fetuses with this syndrome. In the fetuses with normal karyotype and no microdeletion/microduplication syndromes the examination of selected genes for RASopathies was added. The aim of the study was to evaluate the clinical benefit of massively parallel sequencing (MPS) of susceptible fetal DNA for NS, i.e., the diagnostic yield on the one hand and the proportion of detected variants of unknown significance (VOUS) on the other. Design: Clinically diagnostic. Setting: Centrum prenatální diagnostiky, Brno, s.r.o; Cytogenetická laboratoř Brno, s.r.o. Methods: Samples of amniotic fluid or chorionic villus were analyzed. Selected genes associated with RASopathies were analyzed in case of the negative result of karyotype and array-CGH. A panel of twenty genes was investigated by MPS. Results: In the two-years period, Noonan syndrome was detected in 10 from 95 investigated fetuses. This represents a 10.5% diagnostic efficiency of the method. DNA variants of unknown significance were detected in 10 fetuses. A segregation analysis helped to clarify their meaning in six fetuses. Conclusion: MPS allows fast molecular-genetic diagnosis of RASopathies already in the prenatal period. This method contributes to the clarification not only of phenotypic manifestations in already born individuals but also of ultrasound findings in fetuses with both normal karyotype and aCGH.

• Klíčová slova
• cystický hygrom,
• MeSH
• hydrops fetalis MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• měření nuchální translucence metody   MeSH
• Noonanové syndrom * diagnóza   MeSH
• prenatální diagnóza * metody   MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• vrozené srdeční vady diagnóza   MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

INTRODUCTION: Data on management of severe accidental hypothermia published from an established high-volume extracorporeal membrane oxygenation centre are scarce. METHODS: A total of 28 patients with intravesical temperature lower than 28°C on admission were either treated with veno-arterial extracorporeal membrane oxygenation or rewarmed conservatively. RESULTS: A total of 10 patients rewarmed on veno-arterial extracorporeal membrane oxygenation (age: 37 ± 12.6 years) and 18 conservatively (age: 55.2 ± 11.2 years) were collected over a course of 5 years. The dominant cause was alcohol intoxication with exposure to cold (39%), 12 patients were resuscitated prior to admission. The admission temperature in the extracorporeal membrane oxygenation group (23.8 ± 2.6°C) was lower than in the non-extracorporeal membrane oxygenation group (26.0 ± 1.5°C, p = 0.01). The peripheral percutaneous veno-arterial extracorporeal membrane oxygenation was always cannulated in malignant arrhythmias causing refractory cardiac arrest. The typical extracorporeal membrane oxygenation blood flow was 3-4 L/minute and sweep gas flow 2 L/minute, the median extracorporeal membrane oxygenation duration was 48.3 (28.1-86.7) hours. The median rates of rewarming did not differ (0.41 (0.35-0.7)°C/hour in extracorporeal membrane oxygenation and 0.77 (0.54-0.98)°C/hour in non-extracorporeal membrane oxygenation, p = 0.46) as well as the admission arterial lactate, pH and potassium. Their development was not different between the groups except for higher pH between the third and ninth hour of rewarming in the extracorporeal membrane oxygenation group. The hospital mortality was 10% in the extracorporeal membrane oxygenation group and 11.1% in the non-extracorporeal membrane oxygenation group with the median last Glasgow Coma Scale 15 and Cerebral Performance Score 1. CONCLUSION: Veno-arterial extracorporeal membrane oxygenation for severe hypothermia shows promising outcome data collected in an extracorporeal membrane oxygenation/extracorporeal cardiopulmonary resuscitation centre located in a European urban area. Except for presence of refractory cardiac arrest, the established hypothermia-related prognostic indicators did not differ between patients in need for extracorporeal membrane oxygenation and those rewarmed without extracorporeal membrane oxygenation.

• MeSH
• dospělí MeSH
• hypotermie etiologie   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mimotělní membránová oxygenace škodlivé účinky   metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

BACKGROUND: There is high medical need for safe long-term immunosuppression monotherapy in kidney transplantation. Selective targeting of post-transplant alloantigen-(re)activated effector-T cells by anti-TNF antibodies after global T cell depletion may allow safe drug minimization, however, it is unsolved what might be the best maintenance monotherapy. METHODS: In this open, prospective observational single-centre trial, 20 primary deceased donor kidney transplant recipients received 2x20 mg Alemtuzumab (d0/d1) followed by 5 mg/kg Infliximab (d2). For 14 days all patients received only tacrolimus, then they were allocated to either receive tacrolimus (TAC, n = 13) or sirolimus (SIR, n = 7) monotherapy, respectively. Protocol biopsies and extensive immune monitoring were performed and patients were followed-up for 60 months. RESULTS: TAC-monotherapy resulted in excellent graft survival (5yr 92%, 95%CI: 56.6-98.9) and function, normal histology, and no proteinuria. Immune monitoring revealed low intragraft inflammation (urinary IP-10) and hints for the development of operational tolerance signature in the TAC- but not SIR-group. Remarkably, the TAC-monotherapy was successful in all five presensitized (ELISPOT+) patients. However, recruitment into SIR-arm was stopped (after n = 7) because of high incidence of proteinuria and acute/chronic rejection in biopsies. No opportunistic infections occurred during follow-up. CONCLUSIONS: In conclusion, our novel fast-track TAC-monotherapy protocol is likely to be safe and preliminary results indicated an excellent 5-year outcome, however, a full-scale study will be needed to confirm our findings. TRIAL REGISTRATION: EudraCT Number: 2006-003110-18.

• MeSH
• antigeny nádorové MeSH
• biologické markery metabolismus   MeSH
• CD antigeny MeSH
• dospělí MeSH
• glykoproteiny antagonisté a inhibitory   MeSH
• imunosupresiva terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• monitorování imunologické MeSH
• prospektivní studie MeSH
• rejekce štěpu farmakoterapie   etiologie   MeSH
• sirolimus terapeutické užití   MeSH
• stanovení celkové genové exprese MeSH
• takrolimus terapeutické užití   MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• transplantace ledvin škodlivé účinky   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
• klinické zkoušky MeSH
• pozorovací studie MeSH