Respiratory medicine, ISSN 0954-6111 vol. 96, suppl. A, February 2002
S35 s. : tab., grafy ; 30 cm
The aim of this study was to find an objective computational approach for phenotype analysis of common variable immunodeficiency (CVID) patients that describes all differences in the six-color space and to form groups of patients using computational methods. CVID is a heterogeneous primary immunodeficiency disorder where molecular defect is recognized in <10% of the cases and is unknown in the majority of patients. The current CVID classification, EUROClass, is based on quantification of selected B-cell subsets. Using six-color polychromatic flow cytometry, we analyzed B-cell phenotypes in a cohort of 48 CVID patients and 49 healthy donors. We used a "probability binning" algorithm to create 1,024 bins (each bin is a six-color gate) that covered the cells' distribution within the entire B-cell compartment. A matrix file recording cellular content in all the bins was made. The hierarchical clustering of the individual samples was analyzed using a Pearson correlation of the bins' values. The Cut tree algorithm found 12 clusters. In six clusters, healthy individuals predominated; in one cluster, smB+CD21low (CVID patients by EUROClass) cells prevailed; in one cluster, smB-CD21norm cells prevailed; in one cluster, smB+CD21low cells prevailed; the remaining cluster was mixed. The overall reproducibility of probability binning clustering was confirmed by matching of replicates to the original cohort using the similarity matrix of the Pearson correlation, 15 replicates matched the same individual, three replicates matched a different individual within the same cluster, and three replicates matched to a different cluster. We were able to define B-cell subsets over- or under-represented in a particular cluster and display them back in the flow cytometry software. We describe a new analytical approach that enables a search in an objective computational environment for patient cohorts that are defined by similar B-cell profiles and thus contribute to the description of differences between CVID patient groups. Copyright 2009 International Society for Advancement of Cytometry.
- MeSH
- Algorithms MeSH
- Principal Component Analysis MeSH
- B-Lymphocytes immunology MeSH
- Common Variable Immunodeficiency diagnosis classification blood MeSH
- Adult MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Probability MeSH
- Flow Cytometry methods MeSH
- Aged MeSH
- Cluster Analysis MeSH
- Case-Control Studies MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
Úvod: Více než 50 % pacientů na světě umírá v nemocničních zařízeních a péče o takové pacienty je finančně náročná. Naším cílem bylo zjistit, zda podpora paliativního týmu může tyto náklady snížit. Metody: Jedná se o retrospektivní case-control studii prováděnou v české fakultní nemocnici. Prozkoumali jsme rozdíly v denních nákladech na péči pacientů, kteří zemřeli s podporou paliativního týmu a těch, kteří zemřeli bez ní, v období od ledna roku 2019 do dubna roku 2020. Data z národních registrů byla použita k párování intervenční a odpovídající kontrolní skupiny. Zároveň jsme porovnávali skupiny dle délky terminální hospitalizace, doby strávené na jednotce intenzivní péče, dávkách i.v. antibiotik, CT a MRI snímků, onkologické léčby v posledním měsíci života a zaznamenání faktu, že se jedná o umírajícího nemocného. Standardní deskriptivní statistika byla použita k popisu dat. Pro porovnání mezi intervenční a kontrolní skupinou bylo využito Fisherova exaktního testu pro kategorické proměnné a Mannova-Whitneyho U testu pro numerická data. Výsledky: Celkem bylo identifikováno 213 párů. Průměrné denní náklady na skupinu pacientů v péči paliativního týmu byly třikrát nižší (4 392,4 Kč/den = 17,3 EUR) než na skupinu pacientů bez paliativního týmu (13 992,8 Kč/den = 545,8 EUR), což bylo pravděpodobně spojeno s kratší dobou hospitalizace na odděleních JIP (16 % proti 33 % dní hospitalizace). Závěr: Ukázali jsme, že integrace paliativního týmu v procesu umírání může vést k významné finanční úspoře. Tato data mohou podpořit zavádění nemocniční paliativní péče v rozvojových zemích.
Background: More than 50% of patients worldwide die in hospitals and end-of-life care is costly. We aimed to explore whether support from the palliative team can influence end-of-life costs. Methods: This was a descriptive retrospective case–control study conducted at a Czech tertiary hospital. We explored the difference in daily hospital costs between patients who died with and without the support of the hospital palliative care team from January 2019 to April 2020. Big data from registries of routine visits were used for case–control matching. As secondary outcomes, we compared the groups over the duration of the terminal hospitalization, intensive care unit (ICU) days, intravenous antibiotics, magnetic resonance imaging/computed tomography scans, oncological treatment in the last month of life, and documentation of the dying phase. Standard descriptive statistics were used to describe the data, and differences between the case and control groups were tested using Fisher's exact test for categorical variables and the Mann–Whitney U test for numerical data. Results: In total, 213 dyads were identified. The average daily costs were three times lower in the palliative group (4392.4 CZK per day = 171.3 EUR) than in the nonpalliative group (13992.8 CZK per day = 545.8 EUR), and the difference was probably associated with the shorter time spent in the ICU (16% vs. 33% of hospital days). Conclusions: We showed that the integration of the palliative care team in the dying phase can be cost saving. These data could support the implementation of hospital palliative care in developing countries.
Východisko. Zvýšení glykémie nad normální mez je u kriticky nemocných pacientů častým jevem. Řada studií dokazuje, že u některých skupin nemocných vede normalizace glykémie intenzifikovanou inzulínovou terapií k výraznému snížení mortality, délky hospitalizace i počtu komplikací. Cílem této pilotní studie bylo porovnat kompenzaci glykémie s použitím počítačového plně automatického prediktivního kontrolního algoritmu s variabilním intervalem zadávání glykémie (eMPC) oproti rutinnímu protokolu pro kontrolu glykémie u kardiochirurgických pacientů (RP) v peri- a pooperačním období. Metody a výsledky. Do studie bylo zařazeno celkem 20 pacientů (14 mužů a 6 žen, průměrný věk 68±10 let, BMI 28,3±5,0 kg/m2). Deset pacientů bylo randomizováno pro léčbu s použitím eMPC protokolu a 10 pacientů za použití RP. Všichni pacienti podstoupili plánovanou kardiochirurgickou operaci a byli léčeni kontinuální infuzí s inzulínem se snahou udržení glykémie v rozmezí 4,4–6,1 mmol/l po dobu 24 hodin. Průměrná hladina glukózy byla signifikantně nižší v eMPC skupině než v RP skupině (5,80±0,45 vs. 7,23±0,84 mmol/l, p<0,05), celková průměrná doba v cílovém rozmezí glykémie byla delší v eMPC než RP skupině (67,6±8,7 % vs. 27,6±15,8 %, p<0,05), zatímco průměrná doba nad cílovým rozmezím byla v eMPC skupině významně kratší. Průměrná rychlost infůze inzulínu byla vyšší u eMPC než u RP skupiny (4,18±1,19 vs. 3,24±1,43 IU/hod., p<0,05). Průměrný interval odběrů glykémie byl signifikantně kratší u eMPC než u RP skupiny (1,51±0,24 vs. 2,03±0,16 hod., p<0,05). V žádné ze skupin se nevyskytla těžší hypoglykémie. Závěry. Výsledky naší pilotní studie dokazují, že eMPC algoritmus je efektivnější při kompenzaci glykémie v peri- a pooperačním období u pacientů po kardiochirurgické operaci a srovnatelně bezpečný oproti rutinnímu protokolu v udržení glykémie.
Background. Increased blood glucose levels are frequently observed in critically ill patients. Recent studies have shown that the normalization of glycemia by intensive insulin therapy decreases mortality, length of the hospitalization and number of complications. Methods and Results. The aim of this pilot study was to compare blood glucose control by an automated model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RP) in peri- and postoperative period in cardiac surgery patients. 20 patients were included into this study (14 men and 6 women, mean age 68±10 let, BMI 28.3±5.0 kg/m2). 10 patients were randomized for treatment using eMPC algorithm and 10 patients for routine protocol. All patients underwent elective cardiac surgery and were treated with continuous insulin infusion to maintain glycemia in target range 4.4–6.1 mmol/l. The study duration was 24 hours. Mean blood glucose was significantly lower in eMPC vs. RP group (5.80±0.45 vs. 7.23±0.84 mmol/l, p<0.05). Percentage of time in target range was significantly higher in eMPC vs. RP group (67.6±8.7 % vs. 27.6±15.8 %, p<0.05). Percentage of time above the target range was higher in RP vs. eMPC group. Average insulin infusion rate was higher in eMPC vs. RP group (4.18±1.19 vs. 3.24±1.43 IU/hour, p<0.05). Average sampling interval was significantly shorter in eMPC vs. RP group (1.51±0.24 vs. 2.03±0.16 hour, p<0.05). No severe hypoglycaemia in either group occurred during the study. Conclusions. The results of our pilot study suggest that eMPC algorithm is more effective in maintaining euglycemia in peri- and post-operative period in patients after cardiac surgery and comparably safe as compared to RP.
- MeSH
- Algorithms MeSH
- Adult MeSH
- Financing, Organized MeSH
- Body Mass Index MeSH
- Data Interpretation, Statistical MeSH
- Insulin administration & dosage pharmacology therapeutic use MeSH
- Insulin Resistance physiology MeSH
- Cardiac Surgical Procedures methods nursing MeSH
- Clinical Protocols MeSH
- Blood Glucose analysis metabolism MeSH
- Humans MeSH
- Mortality MeSH
- Perioperative Care methods MeSH
- Pilot Projects MeSH
- Computers statistics & numerical data trends utilization MeSH
- Postoperative Complications prevention & control therapy MeSH
- Postoperative Care methods MeSH
- Primary Prevention MeSH
- Randomized Controlled Trials as Topic statistics & numerical data MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
Stimulace nervu vagu je nejrozšířenější nefarmakologickou metodou léčby farmakorezistetntní epilepsie. Dvě pacientky s rezistentní epilepsií, kterým byl v roce 2003 implantován vagový stimulátor, sledujeme s ohledem na průběh afektivní symptomatiky a variabilitu srdeční frekvence. Uvádíme výsledky za prvních 20 měsíců sledování.
Vagus nerve stimulation is the most widely used nonpharmacological treatment for drug-resistant epilepsy. We monitor two women with drug-resistant epilepsy implanted by vagus nerve stimulator in year 2003. Now we compare results of affective symptoms and heart rate variable during next 20 months after implantation.
Common Variable Immunodeficiency (CVID) is the most frequent symptomatic immune disorder characterized by reduced serum immunoglobulins. Patients often suffer from infectious and serious non-infectious complications which impact their life tremendously. The monogenic cause has been revealed in a minority of patients so far, indicating the role of multiple genes and environmental factors in CVID etiology. Using 16S and ITS rRNA amplicon sequencing, we analyzed the bacterial and fungal gut microbiota, respectively, in a group of 55 participants constituting of CVID patients and matched healthy controls including 16 case-control pairs living in the same household, to explore possible associations between gut microbiota composition and disease phenotype. We revealed less diverse and significantly altered bacterial but not fungal gut microbiota in CVID patients, which additionally appeared to be associated with a more severe disease phenotype. The factor of sharing the same household impacted both bacterial and fungal microbiome data significantly, although not as strongly as CVID diagnosis in bacterial assessment. Overall, our results suggest that gut bacterial microbiota is altered in CVID patients and may be one of the missing environmental drivers contributing to some of the symptoms and disease severity. Paired samples serving as controls will provide a better resolution between disease-related dysbiosis and other environmental confounders in future studies.
- MeSH
- Bacteria classification genetics immunology MeSH
- Common Variable Immunodeficiency immunology microbiology MeSH
- Biodiversity MeSH
- Adult MeSH
- Feces microbiology MeSH
- Fungi classification genetics immunology MeSH
- Immunoglobulin A blood immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mycobiome * MeSH
- Aged MeSH
- Gastrointestinal Microbiome * immunology MeSH
- Case-Control Studies MeSH
- Family Health MeSH
- Health Status MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Common variable immunodeficiency disorders (CVIDs) represent a group of primary immunodeficiency diseases characterized by hypogammaglobulinemia and dysfunctional immune response to invading pathogens. Previous studies have indicated that CVID is associated with microbial translocation and systemic myeloid cell activation. The goal of this study was to determine whether patients with CVID display elevated systemic levels of markers of granulocyte activation and whether the levels are further influenced by intravenous immunoglobulin (IVIg) infusions. The plasma levels of granulocyte activation markers elastase and myeloperoxidase were determined using enzyme-linked immunosorbent assay (ELISA) in 46 CVID patients and 44 healthy controls. All CVID patients were in a stable state with no apparent acute infection. In addition, granulocyte activation markers' plasma levels in 24 CVID patients were determined prior to and 1 h following IVIg administration. Neutrophil elastase and myeloperoxidase plasma levels were significantly higher in CVID patients than in healthy controls. Systemic elastase levels were further increased following IVIg administration. In vitro stimulation of 13 CVID patients' whole blood using IVIg in a therapeutically relevant dose for 2 h resulted in a significant increase in plasma elastase levels compared to unstimulated blood. The data presented here indicate that CVID is associated with chronic granulocytic activation which is further exacerbated by administering IVIg. Increased myeloperoxidase and elastase levels may contribute to associated comorbidities in CVID patients.
- MeSH
- Common Variable Immunodeficiency blood diagnosis drug therapy MeSH
- Biomarkers blood MeSH
- Adult MeSH
- Immunoglobulins, Intravenous administration & dosage MeSH
- Leukocyte Elastase blood MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Peroxidase blood MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Increased proportions of naive B cell subset and B cells defined as CD27(neg)CD21(neg)CD38(neg) are frequently found in patients with common variable immunodeficiency (CVID) syndrome. Current methods of polychromatic flow cytometry and PCR-based detection of k deletion excision circles allow for fine definitions and replication history mapping of infrequent B cell subsets. We have analyzed B cells from 48 patients with CVID and 49 healthy controls to examine phenotype, frequency, and proliferation history of naive B cell subsets. Consistent with previous studies, we have described two groups of patients with normal (CVID-21norm) or increased (CVID-21lo) proportions of CD27(neg)CD21(neg)CD38(neg) B cells. Upon further analyses, we found two discrete subpopulations of this subset based on the expression of CD24. The B cell subsets showed a markedly increased proliferation in CVID-21lo patients as compared with healthy controls, suggesting developmental arrest rather than increased bone marrow output. Furthermore, when we analyzed CD21(pos) naive B cells, we found two different subpopulations based on IgM and CD24 expression. They correspond to follicular (FO) I and FO II cells previously described in mice. FO I subset is significantly underrepresented in CVID-21lo patients. A comparison of the replication history of naive B cell subsets in CVID patients and healthy controls implies refined naive B cell developmental scheme, in which human transitional B cells develop into FO II and FO I. We propose that the CD27(neg)CD21(neg)CD38(neg) B cells increased in some of the CVID patients originate from the two FO subsets after loss of CD21 expression.
- MeSH
- CD24 Antigen * biosynthesis genetics MeSH
- Common Variable Immunodeficiency * immunology metabolism pathology MeSH
- Cell Differentiation immunology MeSH
- Child MeSH
- Adult MeSH
- Phenotype MeSH
- Resting Phase, Cell Cycle * immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Lymphocyte Count MeSH
- B-Lymphocyte Subsets immunology classification pathology MeSH
- Cell Proliferation MeSH
- Gene Expression Regulation * immunology MeSH
- Aged MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH