BACKGROUND: Status epilepticus (SE) is a severe acute condition in neurocritical care with high mortality. Searching for risk factors affecting the prognosis in SE remains a significant issue. The primary study's aim was to test the predictive values of the Clinical Frailty Scale (CFS) and the Modified 11-item Frailty Index (mFI-11), the biomarkers and basic biochemical parameters collected at ICU on the Glasgow Outcome Scale (GOS) assessed at hospital discharge (hosp), and three months later (3 M), in comatose patients with SE. The secondary aim was to focus on the association between the patient's state at admission and the duration of mechanical ventilation, the ICU, and hospital stay. METHODS: In two years single-centre prospective pilot study enrolling 30 adult neurocritical care patients with SE classified as Convulsive SE, A.1 category according to the International League Against Epilepsy (ILAE) Task Force without an-/hypoxic encephalopathy, we evaluated predictive powers of CFS, mFI-11, admission Status Epilepticus Severity Score (STESS), serum protein S100, serum Troponin T and basic biochemical parameters on prognosticating GOS using univariate linear regression, logistic regression and Receiver Operating Characteristic (ROC) analysis. RESULTS: Our study included 60% males, with a mean age of 57 ± 16 years (44-68) and a mean BMI of 27 ± 5.6. We found CFS, mFI-11, STESS, and age statistically associated with GOS at hospital discharge and three months later. Among the biomarkers, serum troponin T level affected GOS hosp (p = 0.027). Serum C-reactive protein significance in prognosticating GOS was found by logistic regression (hosp p = 0.008; 3 M p = 0.004), and serum calcium by linear regression (hosp p = 0.028; 3 M p = 0.015). In relation to secondary outcomes, we found associations between the length of hospital stay and each of the following: age (p = 0.03), STESS (p = 0.009), and serum troponin T (p = 0.029) parameters. CONCLUSIONS: This pilot study found promising predictive powers of two frailty scores, namely CFS and mFI-11, which were comparable to age and STESS predictors regarding the GOS at hospital discharge and three months later in ICU patients with SE. Among biomarkers and biochemical parameters, only serum troponin T level affected GOS at hospital discharge.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- kojenec MeSH
- kóma diagnóza MeSH
- křehkost * MeSH
- lidé středního věku MeSH
- lidé MeSH
- pilotní projekty MeSH
- prognóza MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- status epilepticus * diagnóza MeSH
- stupeň závažnosti nemoci MeSH
- troponin T MeSH
- Check Tag
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Dysfunctional sensory systems, including altered olfactory function, have recently been reported in patients with autism spectrum disorder (ASD). Disturbances in olfactory processing can potentially result from gamma-aminobutyric acid (GABA)ergic synaptic abnormalities. The specific molecular mechanism by which GABAergic transmission affects the olfactory system in ASD remains unclear. Therefore, the present study aimed to evaluate selected components of the GABAergic system in olfactory brain regions and primary olfactory neurons isolated from Shank3-deficient (-/-) mice, which are known for their autism-like behavioral phenotype. Shank3 deficiency led to a significant reduction in GEPHYRIN/GABAAR colocalization in the piriform cortex and in primary neurons isolated from the olfactory bulb, while no change of cell morphology was observed. Gene expression analysis revealed a significant reduction in the mRNA levels of GABA transporter 1 in the olfactory bulb and Collybistin in the frontal cortex of the Shank3-/- mice compared to WT mice. A similar trend of reduction was observed in the expression of Somatostatin in the frontal cortex of Shank3-/- mice. The analysis of the expression of other GABAergic neurotransmission markers did not yield statistically significant results. Overall, it appears that Shank3 deficiency leads to changes in GABAergic synapses in the brain regions that are important for olfactory information processing, which may represent basis for understanding functional impairments in autism.
- MeSH
- GABA metabolismus MeSH
- lidé MeSH
- mikrofilamentové proteiny metabolismus MeSH
- myši MeSH
- neurony metabolismus MeSH
- olfaktoriální kortex * metabolismus MeSH
- poruchy autistického spektra * metabolismus MeSH
- proteiny nervové tkáně genetika metabolismus MeSH
- synapse metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: We aimed to assess the diagnostic utility of the Dimension EXL LOCI High-Sensitivity Troponin I (hs-cTnI-EXL) assay. METHODS: This multicenter study included patients with chest discomfort presenting to the emergency department. Diagnoses were centrally and independently adjudicated by two cardiologists using all available clinical information. Adjudication was performed twice including serial measurements of high-sensitivity cardiac troponin (hs-cTn) I-Architect (primary analysis) and serial measurements of hs-cTnT-Elecsys (secondary analysis) in addition to the clinically used (hs)-cTn. The primary objective was to assess and compare the discriminatory performance of hs-cTnI-EXL, hs-cTnI-Architect and hs-cTnT-Elecsys for acute myocardial infarction (MI). Furthermore, we derived and validated a hs-cTnI-EXL-specific 0/1h-algorithm. RESULTS: Adjudicated MI was the diagnosis in 204/1454 (14%) patients. The area under the receiver operating characteristics curve for hs-cTnI-EXL was 0.94 (95%CI, 0.93-0.96), and comparable to hs-cTnI-Architect (0.95; 95%CI, 0.93-0.96) and hs-cTnT-Elecsys (0.93; 95%CI, 0.91-0.95). In the derivation cohort (n = 813), optimal criteria for rule-out of MI were <9ng/L at presentation (if chest pain onset >3h) or <9ng/L and 0h-1h-change <5ng/L, and for rule-in ≥160ng/L at presentation or 0h-1h-change ≥100ng/L. In the validation cohort (n = 345), these cut-offs ruled-out 56% of patients (negative predictive value 99.5% (95%CI, 97.1-99.9), sensitivity 97.8% (95%CI, 88.7-99.6)), and ruled-in 9% (positive predictive value 83.3% (95%CI, 66.4-92.7), specificity 98.3% (95%CI, 96.1-99.3)). Secondary analyses using adjudication based on hs-cTnT measurements confirmed the findings. CONCLUSIONS: The overall performance of the hs-cTnI-EXL was comparable to best-validated hs-cTnT/I assays and an assay-specific 0/1h-algorithm safely rules out and accurately rules in acute MI. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587.
- MeSH
- biologické markery MeSH
- infarkt myokardu * diagnóza MeSH
- lidé MeSH
- prospektivní studie MeSH
- ROC křivka MeSH
- troponin I * MeSH
- troponin T MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVE: To investigate the structural bases of human oocytes' cytoplasmic abnormalities and the causative mechanism of their emergence. Knowledge of an abnormal oocyte's intracellular organization is vital to establishing reliable criteria for clinical evaluation of oocyte morphology. DESIGN: Laboratory-based study on experimental material provided by a private assisted reproduction clinic. SETTING: University laboratory and imaging center. PATIENTS: A total of 105 women undergoing hormonal stimulation for in vitro fertilization (IVF) donated their spare oocytes for this study. INTERVENTIONS: Transmission electron microscopy (TEM) was used to analyze the fine morphology of 22 dysmorphic IVF oocytes exhibiting different types of cytoplasmic irregularities, namely, refractile bodies; centrally located cytoplasmic granularity (CLCG); smooth endoplasmic reticulum (SER) disc; and vacuoles. A total of 133 immature oocytes were exposed to cytoskeleton-targeting compounds or matured in control conditions, and their morphology was examined using fluorescent and electron microscopy. MAIN OUTCOME MEASURES: The ultrastructural morphology of dysmorphic oocytes was analyzed. Drug-treated oocytes had their maturation efficiency, chromosome-microtubule configurations, and fine intracellular morphology examined. RESULTS: TEM revealed ultrastructural characteristics of common oocyte aberrations and indicated that excessive organelle clustering was the underlying cause of 2 of the studied morphotypes. Inhibition experiments showed that disruption of actin, not microtubules, allows for inordinate aggregation of subcellular structures, resembling the ultrastructural pattern seen in morphologically abnormal oocytes retrieved in IVF cycles. These results imply that actin serves as a regulator of organelle distribution during human oocyte maturation. CONCLUSION: The ultrastructural analogy between dysmorphic oocytes and oocytes, in which actin network integrity was perturbed, suggests that dysfunction of the actin cytoskeleton might be implicated in generating common cytoplasmic aberrations. Knowledge of human oocytes' inner workings and the origin of morphological abnormalities is a step forward to a more objective oocyte quality assessment in IVF practice.
- MeSH
- aktiny * MeSH
- cytoplazma MeSH
- cytoskelet MeSH
- lidé MeSH
- mikrotubuly MeSH
- oocyty * ultrastruktura MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Kontext: Při akutní plicní embolii (PE) hrají významnou roli rychlé stanovení diagnózy a naplánování léčby podle klasifikace rizika úmrtí. Cíle: Posoudit přínos znalosti hodnot systolického tlaku v plicnici (systolic pulmonary artery pressure, sPAP) při stratifikaci rizika pacientů s akutní PE. Metody: Naše studie byla retrospektivní, průřezová. Bylo do ní zařazeno celkem 221 pacientů přijatých do naší nemocnice s diagnózou akutní PE, stanovenou CT angiografií plicnice (computed tomography pulmonary angiography, CTPA). Všichni pacienti byli vyšetřeni echokardiograficky (ECHO) a hodnota sPAP byla vypočítána pomocí Bernoulliho rovnice. Vztahy mezi proměnnými, jako jsou stratifikace rizika podle Evropské kardiologické společnosti (European Society of Cardiology, ESC), dysfunkce pravé komory (right ventricular dysfunction, RVD), hodnota troponinu T a sPAP, byly posuzovány pomocí Spearmanových korelačních koeficientů. Výsledky: Mezi hodnotami sPAP na jedné straně a hodnotami troponinu T, RVD a skupinami s vysokým a středně vysokým rizikem podle ESC na straně druhé byla nalezena těsná pozitivní lineární korelace (Spearmanův korelační koeficient r = 0,615; resp. 0,798; 0,411 a 0,408; p < 0,001). Jako optimální mezní hodnota pro sPAP byla stanovena hodnota 41,5 mm Hg s celkovou přesností 0,961 (95% CI 0,937-0,984). Kromě toho se prokázalo, že při mezní hodnotě 41,5 mm Hg dokáže sPAP účinně vyhledávat přítomnost RVD a rizikové skupiny podle ESC (p < 0,0001). Naše studie prokázala 85% senzitivitu a 92% specificitu sPAP při vyhledávání RVD nad mezní hodnotou 41,5 mm Hg. Závěry: I když nelze sPAP považovat za spolehlivý parametr při vyšetření pacientů s akutní PE metodou ECHO, potvrdily výsledky naší studie, že sPAP může představovat užitečný parametr při stratifikaci rizika akutní PE, a hodnotu sPAP by tak bylo vhodné zařadit mezi kritéria RVD ve stratifikaci rizika akutní PE.
Background: In acute pulmonary embolism (PE), rapid diagnosis and treatment planning according to mortality risk classification are important. Objectives: To explore the effectiveness of systolic pulmonary artery pressure (sPAP) values in the risk stratification of the patients with acute PE. Methods: This study is a retrospective, cross-sectional clinical trial design. A total of 221 patients who were admitted to our hospital and diagnosed as acute PE by thorax computed tomography pulmonary angiography (CTPA) was included in the study. All patients were evaluated by echocardiography (ECHO) and sPAP was calculated by Bernoulli equation. The relationships between variables such as the European Society of Cardiology (ESC) risk stratification, right ventricular dysfunction (RVD), troponin T, and sPAP levels were examined with Spearman's correlation coefficients. Results: A strong positive linear correlation was found between sPAP, and troponin T, RVD, ESC high-risk, intermediate-high risk groups (Spearman's r = 0.615, 0.798, 0.411, 0.408, p <0.001, respectively). The optimal cut-off value for sPAP was found as 41.5 mmHg with an overall accuracy of 0.961 (95% CI: 0.937-0.984). Besides, at the cut-off value of 41.5 mmHg, sPAP was found effective in determining RVD and ESC risk groups (p <0.0001). Sensitivity and specificity of sPAP was found as 85%, 92%, respectively in detecting RVD above 41.5 mmHg cut-off value. Conclusions: Although sPAP is not considered as a reliable finding of ECHO in the patients with acute PE, our study results confirmed that it can be valuable in the risk stratification of acute PE. It would be useful to include sPAP to RVD criteria for acute PE risk stratification.
- MeSH
- biologické markery * analýza MeSH
- galektin 3 analýza metabolismus normy MeSH
- lidé MeSH
- natriuretické peptidy analýza metabolismus MeSH
- růstový diferenciační faktor 15 analýza metabolismus normy MeSH
- srdeční selhání * diagnóza MeSH
- troponin analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
AIMS: The presence of accompanying dyspnoea is routinely assessed and common in patients presenting with acute chest pain/discomfort to the emergency department (ED). We aimed to assess the association of accompanying dyspnoea with differential diagnoses, diagnostic work-up, and outcome. METHODS AND RESULTS: We enrolled patients presenting to the ED with chest pain/discomfort. Final diagnoses were adjudicated by independent cardiologists using all information including cardiac imaging. The primary diagnostic endpoint was the final diagnosis. The secondary diagnostic endpoint was the performance of high-sensitivity cardiac troponin (hs-cTn) and the European Society of Cardiology (ESC) 0/1h-algorithms for the diagnosis of myocardial infarction (MI). The prognostic endpoints were cardiovascular and all-cause mortality at two years. Among 6045 patients, 2892/6045 (48%) had accompanying dyspnoea. The prevalence of acute coronary syndrome (ACS) in patients with vs. without dyspnoea was comparable (MI 22.4% vs. 21.9%, P = 0.60, unstable angina 8.7% vs. 7.9%, P = 0.29). In contrast, patients with dyspnoea more often had cardiac, non-coronary disease (15.3% vs. 10.2%, P < 0.001). Diagnostic accuracy of hs-cTnT/I concentrations was not affected by the presence of dyspnoea (area under the curve 0.89-0.91 in both groups), and the safety of the ESC 0/1h-algorithms was maintained with negative predictive values >99.4%. Accompanying dyspnoea was an independent predictor for cardiovascular and all-cause death at two years [hazard ratio 1.813 (95% confidence intervals, 1.453-2.261, P < 0.01)]. CONCLUSION: Accompanying dyspnoea was not associated with a higher prevalence of ACS but with cardiac, non-coronary disease. While the safety of the diagnostic work-up was not affected, accompanying dyspnoea was an independent predictor for cardiovascular and all-cause death. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00470587, number NCT00470587.
- MeSH
- akutní koronární syndrom * MeSH
- biologické markery MeSH
- bolesti na hrudi diagnóza etiologie MeSH
- dyspnoe diagnóza epidemiologie etiologie MeSH
- infarkt myokardu * diagnóza MeSH
- lidé MeSH
- prediktivní hodnota testů MeSH
- prognóza MeSH
- troponin T MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis. METHODS: We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test). RESULTS: Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177, SLC30A8 - ORAA: 1.62, 95% CI: 1.34-1.96; ORAG: 1.41, 95% CI: 1.30-1.54; ORGG: 1.22, 95% CI: 1.13-1.31; p-value3-d.f.: 5.46 × 10-11) and 13q14.13 (rs9526201, LRCH1 - ORGG: 2.11, 95% CI: 1.56-2.83; ORGA: 1.52, 95% CI: 1.38-1.68; ORAA: 1.13, 95% CI: 1.06-1.21; p-value2-d.f.: 7.84 × 10-09). DISCUSSION: These results suggest that variation in genes related to insulin signaling (SLC30A8) and immune function (LRCH1) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.
- MeSH
- celogenomová asociační studie metody MeSH
- diabetes mellitus * genetika MeSH
- genetická predispozice k nemoci MeSH
- interakce genů a prostředí MeSH
- jednonukleotidový polymorfismus MeSH
- kolorektální nádory * genetika MeSH
- lidé MeSH
- mikrofilamentové proteiny genetika MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, P.H.S. MeSH
Kontext: Periprocedurální poškození myokardu a jeho význam pro klinickou praxi u stabilizovaných pa- cientů je stále předmětem diskuse. Tímto tématem se za celé roky zabývala řada studií s různými definicemi, prahovými hodnotami a biomarkery. Cílem naší studie bylo popsat výsledný klinický stav pacientů s periprocedurálním poškozením myokardu pomocí definic nejnovějších, 4. doporučených postupů UDMI. Metody: Do monocentrické studie bylo retrospektivně zařazeno 238 pacientů po elektivní perkutánní koronární intervenci. Pacienti s periprocedurálním poškozením myokardu byli po výkonu srovnáni s pacienty s normálními hodnotami troponinu z hlediska výsledného klinického stavu. Mezi primární sledované parametry patřily úmrtí, infarkt myokardu, cévní mozková příhoda, refrakterní angina pectoris, revaskularizace cílové léze a hospitalizace pro akutní koronární syndrom do jednoho roku. Výsledky: Periprocedurální poškození myokardu bylo zjištěno u 67,2 % (n = 160) pacientů. Počty lézí a stentů, celková délka stentů, celkový průměr stentů, stav po dilataci, počty překrývajících se stentů, stenty na bifurkacích a skóre SYNTAX byly statisticky významně vyšší ve skupině s poškozením myokardu. Uvedené sledované parametry se vyskytly u 16 pacientů (11 ve skupině s poškozením myokardu a 5 v kontrolní skupině). Během sledování nedošlo k žádnému úmrtí. Poprocedurální zvýšení hodnot troponinu nebylo nijak spojeno se sledovanými parametry (11 vs. 5; p = 0,56). V Kaplanově-Meierově analýze se křivky sledovaných parametrů v obou skupinách od sebe nevzdalovaly (log rank test; 95% interval spolehlivosti [CI], p = 0,71). Závěry: Velikost a délka stenu, dilatace po výkonu, překrývání stentů a implantace stentů do lézí v bifurkacích zvyšují riziko poškození myokardu. Periprocedurální poškození myokardu u stabilní anginy pectoris nelze použít k predikci výsledného stavu pacienta po jednom roce.
Background: Periprocedural myocardial injury and its clinical significance in stable patients are still under discussion. This subject has been assessed in many studies with different definitions, thresholds, and biomarkers for years. This study aimed to determine the clinical outcomes of periprocedural myocardial injury based on latest 4th UDMI guideline definitions. Methods: 238 patients who underwent elective percutaneous coronary intervention at single center were retrospectively enrolled. Patients who developed periprocedural myocardial injury were compared with patients with normal troponin values after the procedure for clinical outcomes. Primary clinical endpoints were death, MI, stroke, refractory angina, target vessel revascularization and hospitalization due to acute coronary syndrome at one year. Results: Periprocedural myocardial injury was observed in 67.2% (n = 160) of patients. Number of lesions and stents, total stent length, total stent diameter, post-dilatation, overlapping stents, bifurcation stenting and SYNTAX score were significantly higher in myocardial injury group. Clinical outcomes occurred in 16 patients, 11 of 16 had myocardial injury group, 5 of 16 had control group. No mortality was seen during the follow-up. Postprocedural troponin elevation was not associated with clinical outcomes (11 vs. 5, p = 0,56). Kaplan-Meier curve of clinical end points did not show any separation between the curves (Log rank test, 95% CI, p = 0,71). Conclusion: Stent size and length, post-dilatation, overlapping stents and stenting of bifurcation lesions lead to increase in myocardial injury. Periprocedural myocardial injury in stable angina does not predict clinical outcomes at one year.
- MeSH
- Kaplanův-Meierův odhad MeSH
- koronární angioplastika MeSH
- lidé středního věku MeSH
- lidé MeSH
- poranění srdce * epidemiologie etiologie komplikace MeSH
- senioři MeSH
- stabilní angina pectoris * komplikace MeSH
- statistika jako téma MeSH
- troponin analýza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
BACKGROUND & AIMS: Lymphedema cholestasis syndrome 1 or Aagenaes syndrome is a condition characterized by neonatal cholestasis, lymphedema, and giant cell hepatitis. The genetic background of this autosomal recessive disease was unknown up to now. METHODS: A total of 26 patients with Aagenaes syndrome and 17 parents were investigated with whole-genome sequencing and/or Sanger sequencing. PCR and western blot analyses were used to assess levels of mRNA and protein, respectively. CRISPR/Cas9 was used to generate the variant in HEK293T cells. Light microscopy, transmission electron microscopy and immunohistochemistry for biliary transport proteins were performed in liver biopsies. RESULTS: One specific variant (c.-98G>T) in the 5'-untranslated region of Unc-45 myosin chaperone A (UNC45A) was identified in all tested patients with Aagenaes syndrome. Nineteen were homozygous for the c.-98G>T variant and seven were compound heterozygous for the variant in the 5'-untranslated region and an exonic loss-of-function variant in UNC45A. Patients with Aagenaes syndrome exhibited lower expression of UNC45A mRNA and protein than controls, and this was reproduced in a CRISPR/Cas9-created cell model. Liver biopsies from the neonatal period demonstrated cholestasis, paucity of bile ducts and pronounced formation of multinucleated giant cells. Immunohistochemistry revealed mislocalization of the hepatobiliary transport proteins BSEP (bile salt export pump) and MRP2 (multidrug resistance-associated protein 2). CONCLUSIONS: c.-98G>T in the 5'-untranslated region of UNC45A is the causative genetic variant in Aagenaes syndrome. IMPACT AND IMPLICATIONS: The genetic background of Aagenaes syndrome, a disease presenting with cholestasis and lymphedema in childhood, was unknown until now. A variant in the 5'-untranslated region of the Unc-45 myosin chaperone A (UNC45A) was identified in all tested patients with Aagenaes syndrome, providing evidence of the genetic background of the disease. Identification of the genetic background provides a tool for diagnosis of patients with Aagenaes syndrome before lymphedema is evident.
- MeSH
- 5' nepřekládaná oblast genetika MeSH
- cholestáza * genetika MeSH
- HEK293 buňky MeSH
- intracelulární signální peptidy a proteiny * genetika MeSH
- lidé MeSH
- lymfedém * diagnóza genetika metabolismus MeSH
- myosiny genetika metabolismus MeSH
- novorozenec MeSH
- transportní proteiny genetika MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
