BACKGROUND: The carotid bodies primarily serve as oxaemia sensors that affect tidal breathing. Their function has not yet been studied in infants with nocturnal hypoxaemia. This cross-sectional study aimed to characterise the hyperoxic ventilatory response (HVR) in infants and its relationship to nocturnal hypoxaemia. METHODS: The HVR was analysed in term infants aged <24 months with childhood interstitial lung disease (chILD), those with severe recurrent wheezing (wheeze), and nonrespiratory controls. The HVR timing was characterised using hyperoxia response time (HRT1), and HVR magnitude was characterised by the relative change in minute volume between normoxia and 30-s hyperoxia (VE_dH30). Time spent with an arterial haemoglobin oxygen saturation (SpO2) <90% during overnight monitoring (t90) was estimated. RESULTS: HVR data were available for 23 infants with chILD, 24 wheeze and 14 control infants. A significant decrease in minute volume under 30 s of hyperoxia was observed in all patients. HRT1 was shorter in chILD (5.6±1.2 s) and wheeze (5.9±1.5 s) groups than in the controls (12.6±5.5 s) (ANOVA p<0.001). VE_dH30 was increased in the chILD group (24.3±8.0%) compared with that in the controls (14.7±9.2%) (p=0.003). t90 was abnormal in the wheeze (8.0±5.0%) and chILD (32.7±25.8%) groups and higher in the chILD group than in the controls (p<0.001). HRT1 negatively correlated with t90 in all groups. CONCLUSION: Significant differences in HVR timing and magnitude were noted in the chILD, wheeze and control groups. A relationship between nocturnal hypoxaemia and HRT1 was proposed. HVR characterisation may help identify patients with abnormal nocturnal SpO2.
- Publikační typ
- časopisecké články MeSH
Reticular basement membrane (RBM) thickening may occur in children with allergic bronchial asthma (BA), cystic fibrosis (CF), and primary ciliary dyskinesia (PCD). Its functional consequences remain unknown. We investigated the relationship between baseline RBM thickness and subsequent spirometry. In our cohort follow-up study, patients aged 3-18 yr with BA, CF, and PCD and controls underwent baseline lung clearance index (LCI) measurement, spirometry, and endobronchial biopsy sampling. Total RBM and collagen IV-positive layer thickness were measured. Trends in forced vital capacity (FVC), forced expired volume in 1 s (FEV1), and FEV1/FVC were analyzed during follow-up, and their relationship to baseline characteristics was studied using univariate analysis and multiple regression models. Complete baseline data were available in 19 patients with BA, 30 patients with CF, 25 patients with PCD, and 19 controls. The RBM was thicker in patients with BA (6.33 ± 1.22 μm), CF (5.60 ± 1.39 μm), and PCD (6.50 ± 1.87 μm) than in controls (3.29 ± 0.55 μm) (all P < 0.001). The LCI was higher in patients with CF (15.32 ± 4.58, P < 0.001) and PCD (10.97 ± 2.46, P = 0.002) than in controls (7.44 ± 0.43). The median follow-up times were 3.6, 4.8, 5.7, and 1.9 years in patients with BA, CF, PCD, and controls, respectively. The z-scores of FEV1 and FEV1/FVC deteriorated significantly in all groups except in controls. In patients with CF and PCD, trends in FEV1z-scores correlated with baseline LCI and RBM; in BA, it correlated with collagen IV. In multiple regression models, RBM morphology and ventilation inhomogeneity could predict up to 84.4% of variability in spirometry trends. In conclusion, baseline LCI value and RBM morphology may predict trends in subsequent spirometry.NEW & NOTEWORTHY This paper deals with the relationship between reticular basement membrane (RBM) morphology at baseline and follow-up spirometry in children with asthma, cystic fibrosis, and primary ciliary dyskinesia. For the first time, to our knowledge, the possibility to predict subsequent lung function development using selected baseline characteristics (reticular basement membrane morphology from endobronchial biopsy and ventilation inhomogeneity from nitrogen multiple breath washout test) is proposed. Corresponding predictive models are presented.
- MeSH
- bazální membrána patologie MeSH
- bronchiální astma * patologie MeSH
- cystická fibróza * patologie MeSH
- dítě MeSH
- kolagen MeSH
- lidé MeSH
- následné studie MeSH
- plíce patologie MeSH
- poruchy ciliární motility * MeSH
- spirometrie MeSH
- usilovný výdechový objem MeSH
- zánět patologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Animal models are essential in understanding of the mechanisms of sepsis moreover the development and the assessment of emerging therapies. In clinically relevant porcine model, however, a significant variability in the host response has been observed among animals. Thus, there is a strong demand to better understand the potential sources of this heterogeneity. In this study, we compared faecal microbiome composition of 12 animals. Three samples were collected at different time points from each animal. Bacteriome was subjected to 16S rDNA profiling. A significant difference in bacterial composition was associated with the season (p < 0.001) but not with the sex of the pig (p = 0.28), the timing of sample collection (p = 0.59), or interactions thereof (all p > 0.3). The season batch explained 55% of the total variance in the bacteriome diversity. The season term was highly significant from the high-resolution level of the bacterial amplicon sequencing variants up to the level of phylum. The diversity of the microbiome composition could significantly influence experimental model of sepsis, and studies are warranted to demonstrate the effects of gut microbiome diversity on the host-response. If confirmed, control of the gut microbiome should become a standard part of the pre-clinical sepsis experiments.
BACKGROUND: The long-term respiratory consequences for children with bronchopulmonary dysplasia (BPD) are well known. However, there is little emphasis on monitoring preterm infants without BPD. Few studies have explored the lung function status of infants with the symptoms of chronic lung disease of prematurity (CLD). OBJECTIVE: To evaluate functional lung deficits in preterm infants with CLD, and to assess the perinatal determinants of diminished lung function. METHODS: In our cross-sectional study, 132 preterm infants with symptomatic CLD underwent infant pulmonary function testing (iPFT) at a median post-term age of 0.9 years. The iPFT included bodypletysmography, compliance measurement, tidal breath analysis, and rapid thoracoabdominal compression. The relationships between the respective z scores of the iPFT parameters and perinatal characteristics, postnatal treatment, and BPD status were investigated. RESULTS: Seventy-three patients (55.3%) were born before the 28th week of gestation, and 92 (69.7%) met the BPD criteria. Functional deficits were detected in 85.8%. The obstructive ventilatory pattern was more prevalent than restrictive (36.3 vs. 12.4%, p < 0.001). Infants with restriction had lower birth weight (BW) and required a longer duration of oxygenotherapy. In a univariate model, the lung function correlated with the duration of invasive mechanical ventilation, gestational week, and BW. In a general linear model, BPD status was not an additional determinant of the iPFT results. CONCLUSION: IPFT may reveal significant functional deficits in preterm infants with CLD even without BPD. The current symptoms and perinatal factors may be more important determinants of functional deficits than the BPD status itself.
- MeSH
- bronchopulmonální dysplazie * komplikace MeSH
- dítě MeSH
- gestační stáří MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec nedonošený MeSH
- novorozenec MeSH
- plíce MeSH
- porodní hmotnost MeSH
- průřezové studie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
AIMS: We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes. METHODS: A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent's perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D. RESULTS: Higher age (p=0.004), higher haemoglobin A1c (p=0.026) and medication (p=0.019) were associated with lower general QoL in GCK-MODY patients. In HNF-MODY patients, lower general QoL was associated with a longer time since diagnosis (p=0.005), worse haemoglobin bA1c (p=0.006) and insulin treatment (p=0.019). Similar numbers of participants with GCK- and HNF-MODY considered the genetic diagnosis of MODY to be positive, negative and without significance. The patient with GCK-MODY did not differ from those with T2D in terms of their QoL, but they were less satisfied with their treatment (p<0.001). QoL was better in patients with HNF-MODY compared with patients with T1D (p=0.006), and they did not differ in terms of treatment satisfaction. CONCLUSIONS: QoL was affected in both GCK-MODY and HNF-MODY subjects. Apprehension of genetic diagnosis was not single-valued in MODY respondents.
- MeSH
- diabetes mellitus 1. typu psychologie terapie MeSH
- diabetes mellitus 2. typu psychologie terapie MeSH
- dítě MeSH
- dospělí MeSH
- kvalita života * MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- spokojenost pacientů * MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
- MeSH
- COVID-19 * komplikace MeSH
- dítě MeSH
- incidence MeSH
- lidé MeSH
- SARS-CoV-2 * MeSH
- syndrom systémové zánětlivé reakce MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVES: Suicides of hospitalized patients present rare but very serious adverse events in healthcare settings. The aim of this article is to describe and analyse the facilities and material equipment of acute psychiatric settings in the Czech Republic and contrast these with recommendations for effective prevention of suicidal behaviour. Since there are currently no universally accepted protocols for risk assessment and prevention of suicides in hospital settings in the Czech Republic, these recommendations draw on international guidelines. Based on the outcomes of our study we provide recommendations for risk management and effective prevention of suicidal behaviour of patients hospitalized in acute care settings. METHODS: In order to describe and analyse the environment of acute psychiatric wards in the Czech Republic we have developed a questionnaire based on international recommendations for risk management and prevention of suicidal behaviour. We also collected data on the prevalence of attempted and completed suicides and their respective methods in these hospitals. RESULTS: We have established that acute psychiatric wards in the Czech Republic operate within insufficient safety regimes, especially with respect to the prevention of suicide by hanging and the accessibility of objects for cutting. Our findings demonstrate that only 75% of the wards are equipped with safety glass, and only 50% of the wards with safety mirrors. Only just over 40% of hospitals have safety door handles and shower heads. CONCLUSION: While it is impossible to entirely eliminate the risk of suicidal behaviour it is possible to manage it. The risk reduction is attainable by providing a safe-proofed environment and minimizing opportunities of suicide attempts by hanging and cutting. In order to effectively prevent suicides, it is essential to increase the awareness of the possibilities of safe proofing of the environment as well as standardization of risk assessment of potential suicidal behaviour of patients.
- MeSH
- lidé MeSH
- nemocnice MeSH
- pokus o sebevraždu * MeSH
- psychiatrické oddělení nemocnice * MeSH
- zachování přírodních zdrojů MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Bronchial epithelial reticular basement membrane (RBM) thickening occurs in diseases with both eosinophilic (allergic bronchial asthma [BA]) and neutrophilic (cystic fibrosis [CF] and primary ciliary dyskinesia [PCD]) chronic airway inflammation; however, the lung function and airway remodeling relation remains unclear. The aim of this study was to test whether ventilation inhomogeneity is related to RBM thickening. METHODS: Multiple breath washout test, endobronchial biopsy, and BAL were performed in 24 children with CF, 11 with PCD, 15 with BA, and in 19 control subjects. Lung clearance index at 2.5% (1/40th) of starting nitrogen concentration (LCI2.5), RBM thickness, and lavage fluid cytology were quantified; their mutual associations were studied by using Spearman rank correlations (r). RESULTS: In asthma, ventilation inhomogeneity (mean ± SD) was mild (LCI2.5, 9.3 ± 1.4 vs 7.9 ± 0.9 in control subjects; P = .0391), and the RBM thickened (5.26 ± 0.98 μm vs 3.12 ± 0.62 μm in control subjects; P < .0001). No relation between RBM thickness and ventilation inhomogeneity or lavage cytology was found. In CF and PCD, RBM thickness was similar to that in asthma (4.54 ± 0.66 μm and 5.27 ± 1.11 μm, respectively), but ventilation inhomogeneity was significantly higher (LCI2.5, 12.5 ± 2.4 and 11.8 ± 2.5). Both in CF and PCD, RBM thickness correlated with LCI2.5 (r = 0.594, P = .015; r = 0.821, P = .023). In PCD only, RBM thickness was also related to the number of neutrophils in lavage fluid (r = 0.821; P = .023). CONCLUSIONS: Lung function impairment in relation to RBM thickness was milder in BA than in CF and PCD. In asthma, ventilation inhomogeneity did not correlate with RBM thickness, whereas it did in CF and PCD. This outcome suggests a different structure-function relation in these diseases.
- MeSH
- bazální membrána patologie MeSH
- biopsie metody MeSH
- bronchiální astma * patologie patofyziologie MeSH
- bronchoalveolární lavážní tekutina MeSH
- bronchoskopie MeSH
- bronchy * patologie patofyziologie MeSH
- cystická fibróza * patologie patofyziologie MeSH
- dítě MeSH
- korelace dat MeSH
- lidé MeSH
- mukociliární clearance MeSH
- neutrofily patologie MeSH
- plicní ventilace fyziologie MeSH
- poruchy ciliární motility * patologie patofyziologie MeSH
- remodelace dýchacích cest MeSH
- respirační funkční testy metody MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Úvod: Tofacitinib je léčivo ze skupiny inhibitorů Janusovy kinázy v perorální formě, které je určeno pro léčbu ulcerózní kolitidy (UC – ulcerative colitis). Účinnost přípravku byla prokázána v registračních studiích, avšak data o účinnosti a bezpečnosti z klinické praxe jsou dosud zřídkavá. Cílem této práce bylo posoudit klinickou odpověď na 8týdenní indukční léčbu tofacitinibem u pacientů s UC. Metodika: Do hodnocení byli zařazeni konsekutivní pacienti, u kterých byla zahájena léčba tofacitinibem v dávce 2 × 10 mg denně. Aktivita onemocnění byla posuzována indexem aktivity Mayo vč. endoskopického subskóre na počátku léčby a v týdnu 8, spolu s hodnocením zánětlivých parametrů v podobě C-reaktivního proteinu (CRP) a fekálního kalprotektinu (FC – fecal calprotectin). Jako odpovídající na léčbu byli v týdnu 8 hodnoceni pacienti s celkovým indexem Mayo 0–5 spolu s endoskopickým subskóre 0–1. Při každé návštěvě byly hodnoceny nežádoucí účinky léčby. Výsledky: Hodnocení proběhlo u 24 pacientů (41,7 % muži, 58,3 % ženy) o průměrném stáří 35,3 ± 11,8 let. Průměrná doba trvání choroby byla 8,3 ± 5,2 let. Průměrný pacient souboru byl v minulosti léčen dvěma biologiky, nicméně 25 % bylo zcela naivních k biologické léčbě. V týdnu 0 byla souběžná léčba kortikoidy přítomna u 41,7 % pacientů, jiná imunosupresvní nebo biologická léčba podávána nebyla. Po 8 týdnech odpovědělo na léčbu 52,9 % pacientů. Celkové Mayo skóre pokleslo u respondérů z hodnoty 5,9 ± 3,5 na 1,1 ± 1,3 (p = 0,01), zatímco u nonrespondérů došlo k nesignifikantní změně z 8,0 ± 2,5 na 8,9 ± 2,1 (p = 0,86). Zlepšení endoskopického skóre z 2,0 ± 1,0 na 0,6 ± 0,7 (p = 0,02) u respondérů kontrastuje se zcela nezměněnou hodnotou u pacientů bez odpovědi (2,9). Významný pokles hodnot CRP (6,7 ± 6,2 vs. 2,0 ± 2,2 mg/l; p = 0,04 a FC (1 195 ± 1 189 vs. 578 ± 654 μg/g; p = 0,05) byl zaznamenán rovněž pouze v kohortě s klinickou odpovědí. Všechny hodnocené parametry v týdnu 0 byly v obou kohortách srovnatelné, s výjimkou triacylglycerolů, jejichž vstupní hodnota byla u nonrespondérů vyšší. Léčba byla do 8 týdnů ukončena u 23,5 % pacientů, u všech z důvodu nedostatečné odpovědi. Byly zaznamenány dvě stížnosti na bolesti hlavy po zahájení léčby a po jednom výskytu cytomegalovirové kolitidy, klostridiové kolitidy a orální kandidózy. Závěr: Účinnost indukční fáze léčby tofacitinibem byla pozorována přibližně u poloviny pacientů s UC. S ohledem na omezený vzorek pacientů a délku terapie nutno získat dlouhodobá data o účinnosti a bezpečnosti léku.
Introduction: Tofacitinib is an oral Janus kinase inhibitor approved for the treatment of ulcerative colitis (UC). Its efficiency was proven in registration trials, however data from real clinical practice are still sparse. Our aim was to evaluate efficacy and safety of tofacitinib in UC patients within 8-week induction period. Methods: Data from consecutive UC patients who started tofacitinib 10 mg twice a day were evaluated. Disease activity was assessed by Mayo score including endoscopic Mayo at baseline and week 8 together with C-reactive protein (CRP) and fecal calprotectin (FC). At week 8, patients with total Mayo ≤ 5 with endoscopic subscore ≤ 1 were considered responders. Adverse events were registered at each visit. Results: A total of 24 patients (41.7% males), mean age 35.3 ±11.8 years were included. The mean disease duration was 8.3 ± 5.2 years. In median, the patients were previously treated with two biologic agents, however 25% of the patients were naïve to any biologic therapy. Systemic corticosteroids were present in 41.7% of patients at baseline and no patient had concomitant biologic or immunosuppressive therapy. At week 8, 52.9% of patients responded to treatment. The mean total Mayo decreased in responders from 5.9 ± 3.5 to 1.1 ± 1.3 (p = 0.01), while non-responders it changed from 8.0 ± 2.5 to 8.9 ± 2.1 (p = 0.86). Endoscopic subscore decreased from 2.0 ± 1.0 to 0.6 ± 0.7 (p = 0.02) in responders, however remained stable in non-responders (2.9). CRP and FC dropped significantly in responders (6.7 ± 6.2 vs. 2.0 ± 2.2 mg/L, p = 0.04; 1,195 ± 1,189 vs. 578 ± 654 μg/g, p = 0.05), but not in non-responders. Non-responders had significantly higher baseline triglycerides compared to responders. Tofacitinib was stopped in 23.5% of patients until week 8 due to insufficient response. Two patients reported headaches after treatment initiation and single events of Cytomegalovirus colitis, Clostridium difficile colitis and oral candidiasis occurred. Conclusion: Tofacitinib was efficient in inducing clinical response with mucosal healing in about half of UC patients after 8 weeks of therapy. A need for long-term outcomes and for safety data with emphasis on infectious complications warrant further investigation.
- Klíčová slova
- tofacitinib citrát,
- MeSH
- dospělí MeSH
- hodnocení léčiv MeSH
- Janus kinasa 3 antagonisté a inhibitory farmakologie terapeutické užití MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- ulcerózní kolitida * farmakoterapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
