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
Ultrazvuk plic a hrudních dutin se stal součástí rutinního vyšetření na intenzivních péčích i na příjmových a standardních odděleních. Cílené vyšetření u lůžka nemocného je využíváno především k vyloučení hrudního výpotku, pneumotoraxu, k posouzení hyperemie při plicním edému nebo konsolidace tkáně při pneumonii, a v neposlední řadě jako vodítko k procedurám, především k hrudním punkcím a drenážím.
Lungs and chest cavities ultrasound has become the standard part of the examinations in intensive care as well as in admission and standard wards. The targeted point-of-care examination is mainly used to rule out chest effusion, and pneumothorax, to assess hyperemia in pulmonary edema or tissue consolidation in pneumonia, and last but not least as a guide to procedures, especially chest punctures and drainages.
BACKGROUND: The impact of serial imaging on the outcome of ICU patients has not been studied specifically in patients with high illness severity. METHODS: The authors sought a relationship between the numbers of antero-posterior supine chest X-rays (CXR), computed tomography (CT) examinations, and outcome in a cohort of 292 patients with severe COVID-19 ARDS collected over 24 months in a high-volume ECMO center with established ultrasound and echocardiographic diagnostics. Of the patients, 172 (59%) were obese or morbidly obese, and 119 (41%) were treated with ECMO. RESULTS: The median number of CXRs was eight per 14 days of the length of stay in the ICU. The CXR rate was not related to ICU survival (p = 0.37). Patients required CT scanning in 26.5% of cases, with no relationship to the outcome except for the better ICU survival of the ECMO patients without a need for a CT scan (p = 0.01). The odds ratio for survival associated with ordering a CT scan in an ECMO patient was 0.48, p = 0.01. The calculated savings for not routinely requesting a whole-body CT scan in every patient were 98.685 EUR/24 months. CONCLUSIONS: Serial imaging does not impact the survival rates of patients with severe ARDS. Extracorporeal membrane oxygenation patients who did not need CT scanning had significantly better ICU outcomes.
- Publikační typ
- časopisecké články 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
Zobrazovací metody dostupné u lůžka pacienta se staly nezastupitelnou částí diagnostického procesu u těžkých forem covid-19 v intenzivní péči. Hrudní ultrasonografie se etablovala jako unikátní zobrazovací modalita umožňující záchyt spektra plicních patologií, pleurálního prostoru a funkce bránice, což umožňuje bez prodlení volit adekvátní terapeutické intervence. Vitální informace je možné získat o funkci srdce a hemodynamice, pokud se hrudní ultrazvuk kombinuje s echokardiografií a ultrazvukovým vyšetřením cévního systému. Hrudní rtg u lůžka pacienta má svoje technická omezení, není senzitivní v časných fázích onemocnění a exponuje pacienty radiaci. Computerová tomografie má vynikající prostorové rozlišení s možností vizualizace všech struktur hrudníku a mediastina, nevýhodou je zátěž pacienta a personálu transportem, společně s radiací a vedlejšími efekty podávané kontrastní látky. Hrudní ultrasonografie se ukázala být výhodná během pandemie v diagnostice covid-19 pneumonie a jejích komplikací. Jedním z důvodů je redukce potenciální infekční kontaminace personálu a pacientů při transportu na radiologii a zpět. V tomto review autoři srovnávají tři nejčastější modality zobrazení hrudníku v diagnostice covid-19 v intenzivní péči a diskutují benefity a limitace hrudního ultrazvuku.
Imaging methods available at the bedside have become an indispensable part of the diagnostic process of COVID-19 in the intensive care setting. Chest ultrasound has been established as an exquisite bedside imaging tool to assess and diagnose a myriad of lung pathologies, assess the pleural space and diaphragm, and ultimately gauge therapeutic interventions. Furthermore, vital information can be attained on the haemodynamic status of a patient when chest ultrasound is combined with echocardiography and Doppler vascular assessment. Bedside chest x‐ray has its technical limitations, is not sensitive in early stages of the disease, and exposes patients to radiation. Computed tomography has great spatial resolution and all the structures in the chest can be assessed, but on the other hand, it requires patient transport and exposes them to radiation and the potential side effects of contrast administration. Recently, chest ultrasound has proved to be extremely useful during the COVID-19 pandemic in assessing COVID-19 pneumonia and its complications with a resultant reduction in potential infectious cross‐ contamination of staff and patients due to transport to and from the radiology department. In this review, the authors compare the three most frequent modalities of chest imaging in the diagnosis of COVID-19 in critical care, with a focus on the benefits of chest ultrasound.
Multiple molecular targets have been identified to mediate membrane-delimited and nongenomic effects of natural and synthetic steroids, but the influence of steroid metabolism on neuroactive steroid signaling is not well understood. To begin to address this question, we set out to identify major metabolites of a neuroprotective synthetic steroid 20-oxo-5β-pregnan-3α-yl l-glutamyl 1-ester (pregnanolone glutamate, PAG) and characterize their effects on GABAA and NMDA receptors (GABARs, NMDARs) and their influence on zebrafish behavior. Gas chromatography-mass spectrometry was used to assess concentrations of PAG and its metabolites in the hippocampal tissue of juvenile rats following intraperitoneal PAG injection. PAG is metabolized in the peripheral organs and nervous tissue to 20-oxo-17α-hydroxy-5β-pregnan-3α-yl l-glutamyl 1-ester (17-hydroxypregnanolone glutamate, 17-OH-PAG), 3α-hydroxy-5β-pregnan-20-one (pregnanolone, PA), and 3α,17α-dihydroxy-5β-pregnan-20-one (17-hydroxypregnanolone, 17-OH-PA). Patch-clamp electrophysiology experiments in cultured hippocampal neurons demonstrate that PA and 17-OH-PA are potent positive modulators of GABARs, while PAG and 17-OH-PA have a moderate inhibitory effect at NMDARs. PAG, 17-OH-PA, and PA diminished the locomotor activity of zebrafish larvae in a dose-dependent manner. Our results show that PAG and its metabolites are potent modulators of neurotransmitter receptors with behavioral consequences and indicate that neurosteroid-based ligands may have therapeutic potential.
- MeSH
- dánio pruhované MeSH
- estery MeSH
- GABA MeSH
- krysa rodu rattus MeSH
- kyselina glutamová MeSH
- pregnanolon * farmakologie chemie MeSH
- receptory GABA-A MeSH
- receptory N-methyl-D-aspartátu * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
INTRODUCTION: Imprinting broadly neutralizing antibody (bNAb) paratopes by shape complementary protein mimotopes represents a potential alternative for developing vaccine immunogens. This approach, designated as a Non-Cognate Ligand Strategy (NCLS), has recently been used for the identification of protein variants mimicking CD4 binding region epitope or membrane proximal external region (MPER) epitope of HIV-1 envelope (Env) glycoprotein. However, the potential of small binding proteins to mimic viral glycan-containing epitopes has not yet been verified. METHODS: In this work, we employed a highly complex combinatorial Myomedin scaffold library to identify variants recognizing paratopes of super candidate bNAbs, PGT121 and PGT126, specific for HIV-1 V3 loop epitopes. RESULTS: In the collection of Myomedins called MLD variants targeted to PGT121, three candidates competed with gp120 for binding to this bNAb in ELISA, thus suggesting an overlapping binding site and epitope-mimicking potential. Myomedins targeted to PGT126 designated MLB also provided variants that competed with gp120. Immunization of mice with MLB or MLD binders resulted in the production of anti-gp120 and -Env serum antibodies. Mouse hyper-immune sera elicited with MLB036, MLB041, MLB049, and MLD108 moderately neutralized 8-to-10 of 22 tested HIV-1-pseudotyped viruses of A, B, and C clades in vitro. DISCUSSION: Our data demonstrate that Myomedin-derived variants can mimic particular V3 glycan epitopes of prominent anti-HIV-1 bNAbs, ascertain the potential of particular glycans controlling neutralizing sensitivity of individual HIV-1 pseudoviruses, and represent promising prophylactic candidates for HIV-1 vaccine development.
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
One of the proposed strategies for the development of a more efficient HIV-1 vaccine is based on the identification of proteins binding to a paratope of chosen broadly neutralizing antibody (bNAb) that will mimic cognate HIV-1 Env (glyco)protein epitope and could be used as potent immunogens for induction of protective virus-neutralizing antibodies in the immunized individuals. To verify this "non-cognate ligand" concept, we developed a highly complex combinatorial library designed on a scaffold of human myomesin-1 protein domain and selected proteins called Myomedins specifically binding to variable regions of HIV-1 broadly neutralizing antibody 10E8. Immunization of mice with these Myomedin variants elicited the production of HIV-1 Env-specific antibodies. Hyperimmune sera bound to Env pseudotyped viruses and weakly/moderately neutralized 54% of tested clade A, B, C, and AE pseudotyped viruses variants in vitro. These results demonstrate that Myomedin variants have the potential to mimic Env epitopes and could be used as potential HIV-1 vaccine components.
- MeSH
- epitopy MeSH
- genové produkty env - virus lidské imunodeficience genetika MeSH
- HIV infekce * prevence a kontrola MeSH
- HIV protilátky MeSH
- HIV-1 * genetika MeSH
- myši MeSH
- neutralizující protilátky MeSH
- pseudotypování virů MeSH
- široce neutralizující protilátky MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
