BACKGROUND: Skeletal muscle alterations are associated with higher mortality and morbidity in patients with liver cirrhosis. Assessing these changes seems to be a promising method for identifying patients at a high risk of poor outcomes following liver transplantation (LT). This is particularly important given the current global shortage of organ donors. However, evidence of the impact of these alterations on the prognosis of patients undergoing LT is inconclusive. The aim of our prospective study was to evaluate the impact of skeletal muscle changes, reflected in sarcopenia, myosteatosis and metabolic changes in the calf muscles, on perioperative outcomes and long-term survival after LT. We also sought to determine the posttransplant evolution of the resting muscle metabolism. METHODS: We examined 134 adult LT candidates. Of these, 105 underwent LT. Sarcopenia and myosteatosis were diagnosed by measuring the skeletal muscle index and mean psoas muscle radiation attenuation, respectively, which were obtained from computed tomography (CT) scans taken during pretransplant assessment. Additionally, patients underwent 31P MR spectroscopy (MRS) of the calf muscles at rest before LT and 6, 12 and 24 months thereafter. The median follow-up was 6 years. RESULTS: Patients with abnormal 31P MRS results and CT-diagnosed myosteatosis prior to LT had significantly worse long-term survival after LT (hazard ratio (HR), 3.36; 95% confidence interval (CI), 1.48-7.60; p = 0.0021 and HR, 2.58; 95% CI, 1.06-6.29; p = 0.03, respectively). Multivariable analysis showed that abnormal 31P MR spectra (HR, 3.40; 95% CI, 1.50-7.71; p = 0.003) were a better predictor of worse long-term survival after LT than myosteatosis (HR, 2.78; 95% CI, 1.14-6.78; p = 0.025). Patients with abnormal 31P MR spectra had higher blood loss during LT (p = 0.038), required a higher number of red blood cell transfusions (p = 0.006) and stayed longer in ICU (p = 0.041) and hospital (p = 0.007). Myosteatosis was associated with more revision surgeries following LT (p = 0.038) and a higher number of received red blood cell transfusion units (p = 0.002). Sarcopenia had no significant effect on posttransplant patient survival. An improvement in the resting metabolism of the calf muscles was observed at 12 and 24 months after LT. CONCLUSIONS: Abnormal 31P MRS results of calf muscles were superior to CT-based diagnosis of myosteatosis and sarcopenia in predicting perioperative complications and long-term survival after LT. Resting muscle metabolism normalized 1 year after LT in most recipients.
- MeSH
- dospělí MeSH
- kosterní svaly * diagnostické zobrazování metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční spektroskopie * metody MeSH
- počítačová rentgenová tomografie * metody MeSH
- prognóza MeSH
- prospektivní studie MeSH
- sarkopenie etiologie metabolismus MeSH
- senioři MeSH
- transplantace jater * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
AIMS: Recent-onset dilated cardiomyopathy (RODCM) is characterized by heterogeneous aetiology and diverse clinical outcomes, with scarce data on genotype-phenotype correlates. Our aim was to correlate individual RODCM genotypes with left ventricular reverse remodelling (LVRR) and clinical outcomes. METHODS AND RESULTS: In this prospective study, a total of 386 Czech RODCM patients with symptom duration ≤6 months underwent genetic counselling and whole-exome sequencing (WES). The presence of pathogenic (class 5) or likely pathogenic (class 4) variants in a set of 72 cardiomyopathy-related genes was correlated with the occurrence of all-cause death, heart transplantation, or implantation of a ventricular assist device (primary outcome) and/or ventricular arrhythmia event (secondary outcome). LVRR was defined as an improvement of left ventricular ejection fraction to >50% or ≥10% absolute increase, with a left ventricular end-diastolic diameter ≤33 mm/m2 or ≥10% relative decrease. Median follow-up was 41 months. RODCM was familial in 98 (25%) individuals. Class 4-5 variants of interest (VOIs) were identified in 125 (32%) cases, with 69 (18%) having a single titin-truncating variant (TTNtv) and 56 (14%) having non-titin (non-TTN) VOIs. The presence of class 4-5 non-TTN VOIs, but not of TTNtv, heralded a lower probability of 12-month LVRR and proved to be an independent baseline predictor both of the primary and the secondary outcome. The negative result of genetic testing was a strong protective baseline variable against occurrence of life-threatening ventricular arrhythmias. Detection of class 4-5 VOIs in genes coding nuclear envelope proteins was another independent predictor of both study outcomes at baseline and also of life-threatening ventricular arrhythmias after 12 months. Class 4-5 VOIs of genes coding cytoskeleton were associated with an increased risk of life-threatening ventricular arrhythmias after baseline assessment. A positive family history of dilated cardiomyopathy alone only related to a lower probability of LVRR at 12 months and at the final follow-up. CONCLUSIONS: RODCM patients harbouring class 4-5 non-TTN VOIs are at higher risk of progressive heart failure and life-threatening ventricular arrhythmias. Genotyping may improve their early risk stratification at baseline assessment.
- MeSH
- dilatační kardiomyopatie * genetika patofyziologie MeSH
- dospělí MeSH
- funkce levé komory srdeční fyziologie MeSH
- genotyp * MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- remodelace komor * genetika fyziologie MeSH
- sekvenování exomu MeSH
- tepový objem fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Induced hypothermia post-cardiac arrest is neuroprotective in animal experiments, but few high-quality studies have been performed in larger animals with human-like brains. The neuroprotective effect of postischemic hypothermia has recently been questioned in human trials. Our aim is to investigate whether hypothermia post-cardiac arrest confers a benefit compared to normothermia in large adult animals. Our hypothesis is that induced hypothermia post cardiac arrest is neuroprotective and that the effect diminishes when delayed two hours. METHODS: Adult female pigs were anesthetized, mechanically ventilated and kept at baseline parameters including normothermia (38 °C). All animals were subjected to ten minutes of cardiac arrest (no-flow) by induced ventricular fibrillation, followed by four minutes of cardiopulmonary resuscitation with mechanical compressions, prior to the first countershock. Animals with sustained return of spontaneous circulation (systolic blood pressure >60 mmHg for ten minutes) within fifteen minutes from start of life support were included and randomized to three groups; immediate or delayed (2 h) intravenous cooling, both targeting 33 °C, or intravenously controlled normothermia (38 °C). Temperature control was applied for thirty hours including cooling time, temperature at target and controlled rewarming (0.5 °C/h). Animals were extubated and kept alive for seven days. The primary outcome measure is histological brain injury on day seven. Secondary outcomes include neurological and neurocognitive recovery, and the trajectory of biomarkers of brain injury. CONCLUSION: High-quality animal experiments in clinically relevant large animal models are necessary to close the gap of knowledge regarding neuroprotective effects of induced hypothermia after cardiac arrest.Trial registration:Preclinicaltrials.eu (PCTE0000272), published 2021-11-03.
- Publikační typ
- časopisecké články MeSH
- MeSH
- hemolýza * MeSH
- katetrizační ablace * škodlivé účinky MeSH
- lidé MeSH
- srdeční katétry MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- dopisy MeSH
- MeSH
- krevní tlak MeSH
- nucleus solitarius * MeSH
- receptory muskarinové * MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- práce podpořená grantem MeSH
BACKGROUND: Peroral endoscopic myotomy (POEM) is nowadays a standard method for treatment of achalasia; nevertheless, it remains an invasive intervention with corresponding risk of adverse events (AEs). The classification and grading of AEs are still a matter of discussion. The aim of our retrospective study was to assess the occurrence of all "undesirable" events and "true" adverse events in patients undergoing POEM and to compare the outcomes when either Clavien-Dindo classification (CDC) or American Society of Gastrointestinal Endoscopy (ASGE) lexicon classification applied. METHODS: This was a retrospective analysis of prospectively managed database of all patients who had undergone POEM between December 2012 and August 2018. We assessed the pre-, peri-, and early-postoperative (up to patient's discharge) undesirable events (including those not fulfilling criteria for AEs) and "true" AEs according the definition in either of the classifications. RESULTS: A total of 231 patients have successfully undergone 244 POEM procedures (13 × re-POEM). Twenty-nine procedures (11.9%) passed uneventfully, while in 215 procedures (88.1%), a total of 440 undesirable events occurred. The CDC identified 27 AEs (17 minor, 10 major) occurring in 23/244 (9.4%) procedures. The ASGE lexicon identified identical 27 AEs (21 mild or moderate, 6 severe or fatal) resulting in the severity distribution of AEs being the only difference between the two classifications. Only the absence of previous treatment was found to be a risk factor [p = 0.047, OR with 95% CI: 4.55 (1.02; 20.25)] in the combined logistic regression model. CONCLUSION: Undesirable events are common in patients undergoing POEM but the incidence of true AEs is low according to both classifications. Severe adverse events are infrequent irrespective of the classification applied. CDC may be more appropriate than ASGE lexicon for classifying POEM-related AEs given a surgical nature of this procedure.
- MeSH
- achalázie jícnu * chirurgie MeSH
- chirurgie trávicího traktu * MeSH
- dolní jícnový svěrač chirurgie MeSH
- endoskopické operace přirozenými otvory * metody MeSH
- lidé MeSH
- myotomie * metody MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
There is a clear experience in clinical practice: boys with a diagnosis of ADHD are clearly in greater numbers than girls. It is noteworthy that even in the "older" review articles, the cause of sex-dependent incidence is not mentioned. If we accept the neurodevelopmental hypothesis of such disorder, then the possible genetic predisposition breaks down into two separate groups. On the genome of an individual with ADHD and on the genome of the parents. However, it cannot be overlooked that the incidence of ADHD (3-7%) corresponds to the incidence and sex differences of the number of newborns born at a certain risk (premature birth, immaturity, hypotrophy, hypoxic-ischemic syndrome, low birth weight, etc.). This association of possible genetic predisposition with "external" risks in the genesis of ADHD raises the question of whether a higher incidence of ADHD, as well as higher morbidity and mortality in males, are a) the norm and the female is privileged, or b) the female is the norm and the male is handicapped. The picture of ADHD includes various cognitive dysfunctions with one possible cause in norepinephrine and dopamine insufficiency. Experimental work shows that in response to stress females release more catecholamines in the CNS than males. Since catecholamines stimulate membrane Na+ K+ ATPase activity, this means both the value of the membrane potential and the threshold for activation is increased. Females are more successful in responding to and adapting to a stressful situation due to their higher production of noradrenaline in the CNS.
- MeSH
- genetická predispozice k nemoci MeSH
- hyperkinetická porucha * diagnóza epidemiologie MeSH
- incidence MeSH
- katecholaminy MeSH
- lidé MeSH
- noradrenalin MeSH
- novorozenec MeSH
- pohlavní dimorfismus * MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Atrial fibrillation (AF) is the most common sustained arrhythmia in humans. The onset of the arrhythmia can significantly impair cardiac function. This hemodynamic deterioration has been explained by several mechanisms such as the loss of atrial contraction, shortening of ventricular filling, or heart rhythm irregularity. This study sought to evaluate the relative hemodynamic contribution of each of these components during in vivo simulated human AF. METHODS: Twelve patients undergoing catheter ablation for paroxysmal AF were paced simultaneously from the proximal coronary sinus and the His bundle region according to prescribed sequences of irregular R-R intervals with the average rate of 90 and 130 bpm, which were extracted from the database of digital ECG recordings of AF from other patients. The simulated AF was compared to regular atrial pacing with spontaneous atrioventricular conduction and regular simultaneous atrioventricular pacing at the same heart rate. Beat-by-beat left atrial and left ventricular pressures, including LV dP/dT and Tau index were assessed by direct invasive measurement; beat-by-beat stroke volume and cardiac output (index) were assessed by simultaneous pulse-wave doppler intracardiac echocardiography. RESULTS: Simulated AF led to significant impairment of left ventricular systolic and diastolic function. Both loss of atrial contraction and heart rate irregularity significantly contributed to hemodynamic impairment. This effect was pronounced with increasing heart rate. CONCLUSION: Our findings strengthen the rationale for therapeutic strategies aiming at rhythm control and heart rate regularization in patients with AF.
The objective of the study was to determine the effects of inferior alveolar nerve transection on inorganic components in mandibular molars of the rat. We used 26 male laboratory rats of the Wistar strain for the study, age 7-9 weeks. The rats were divided in three groups. The control group (intact) included 6 rats. The surgery was performed under general anesthesia. The experimental group included (group with the nerve transected on the left) included 12 rats. The sham group (group with the nerve prepared without transection) included 8 rats. The animals were sacrificed after 4 weeks. Molars from the left and right sides of the mandible were extracted. Element content levels were determined using inductively coupled plasma mass spectrometry. The following elements were determined in all samples: magnesium (Mg), sodium (Na), potassium (K), calcium (Ca), zinc (Zn), and strontium (Sr). The nerve transection caused: a reduction of the contents of Ca and Sr in the mandibular molars; an increase in the contents of Mg and Zn; a difference arrangement of both sides for Na. The surgery approach itself caused a decrease in the contents of Na and K in the experimental and sham groups; the difference in K in M3 between the left and right sides disappeared due to the surgery. Our results have confirmed the hypothesis of inferior alveolar nerve transection having an effect on inorganic components in mandibular molars in the rat.
- MeSH
- krysa rodu rattus MeSH
- mandibula * chirurgie MeSH
- moláry chirurgie MeSH
- nervus mandibularis * fyziologie chirurgie MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
