Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• MeSH
• antiflogistika farmakologie   chemie   MeSH
• dexamethason * farmakologie   chemie   analogy a deriváty   MeSH
• játra * účinky léků   metabolismus   MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• makrofágy * účinky léků   metabolismus   MeSH
• myši MeSH
• nanokuličky * chemie   MeSH
• nosiče léků chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The sacroiliac joint (SIJ) exhibits significant variation in auricular surface morphology. This variation influences the mechanics of the SIJ, a central node for transmitting mechanical energy from upper body to lower limbs and vice versa. The impact of the auricular surface morphology on stress and deformation in the SIJ remains poorly understood to date. Computed tomography scans obtained from 281 individuals were included to extract the geometry of the pelvic ring. Then, the auricular surface area, SIJ cartilage thickness, and total SIJ cartilage volume were identified. Based on these reconstructions, 281 finite element models were created to simulate SIJ mechanical loading. It was found that SIJ cartilage thickness only weakly depended on age or laterality, while being strongly sex sensitive. Auricular surface area and SIJ cartilage volume depended weakly and non-linearly on age, peaking around menopause in females, but without significant laterality effect. Larger SIJs, characterized by greater auricular area and cartilage volume, exhibited reduced stress and deformation under loading. These findings highlight the significant role of SIJ morphology in its biomechanical response, suggesting a potential link between morphological variations and the risk of SIJ dysfunction. Understanding this relationship could improve diagnosis and targeted treatment strategies for SIJ-related conditions.

• MeSH
• analýza metodou konečných prvků MeSH
• biomechanika fyziologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mechanický stres MeSH
• mladiství MeSH
• mladý dospělý MeSH
• počítačová rentgenová tomografie * MeSH
• sakroiliakální kloub * anatomie a histologie   fyziologie   diagnostické zobrazování   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Necrotizing enterocolitis (NEC) is one of the most devastating intestinal diseases observed in preterm in the first days of life. Researchers have recently focused on potential predictive biomarkers for early and concomitant diagnoses. Thus, we inquired about the linkage of intestinal dysbiosis, one of the most important factors in NEC development to the gut microbiota. In this study, the systematic differences in the bacterial composition between neonates affected by NEC and healthy newborns were highlighted by metagenomic analysis. The next-generation sequencing of the V3-V4 variable region of the 16S rRNA gene and gene-specific qPCR analyzed the untargeted gut microbiota. Total bacteria, total and fecal coliform loads in stool samples with NEC were higher than control. OTU-level relative abundances of NEC infant was characterized by Firmicutes and Bacteroidetes at phylum levels. At the genus level, NEC stool was identified by the lack of Klebsiella and the presence of Roseburia, Blautia, and Parasutterella. Finally, Clostridium fessum was the predominant species of Clostridium genus in disease and healthy specimens at the species level, whereas Clostridium jeddahitimonense was at NEC diagnosis. Despite a strong relationship between pathophysiology and characterization of gut microbiota at a clinical diagnosis of NEC, our results emphasize the broad difficulty in identifying potential biomarkers.

• MeSH
• Bacteria * klasifikace   genetika   izolace a purifikace   MeSH
• DNA bakterií genetika   MeSH
• dysbióza mikrobiologie   MeSH
• feces * mikrobiologie   MeSH
• lidé MeSH
• metagenomika MeSH
• nekrotizující enterokolitida * mikrobiologie   MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• RNA ribozomální 16S * genetika   MeSH
• střevní mikroflóra * MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• autoprotilátky krev   MeSH
• činnosti denního života MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory cholinergní * imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

BACKGROUND AND OBJECTIVE: While active surveillance (AS) is an alternative to surgical interventions in patients with small renal masses (SRMs), evidence regarding its oncological efficacy is still debated. We aimed to evaluate oncological outcomes for patients with SRMs who underwent AS in comparison to surgical interventions. METHODS: In April 2024, PubMed, Scopus, and Web of Science were queried for comparative studies evaluating AS in patients with SRMs (PROSPERO: CRD42024530299). The primary outcomes were overall (OS) and cancer-specific survival (CSS). A random-effects model was used for quantitative analysis. KEY FINDINGS AND LIMITATIONS: We identified eight eligible studies (three prospective, four retrospective, and one study based on Surveillance, Epidemiology and End Results [SEER] data) involving 4947 patients. Pooling of data with the SEER data set revealed significantly higher OS rates for patients receiving surgical interventions (hazard ratio [HR] 0.73; p = 0.007), especially partial nephrectomy (PN; HR 0.62; p < 0.001). However, in a sensitivity analysis excluding the SEER data set there was no significant difference in OS between AS and surgical interventions overall (HR 0.84; p = 0.3), but the PN subgroup had longer OS than the AS group (HR 0.6; p = 0.002). Only the study based on the SEER data set showed a significant difference in CSS. The main limitations include selection bias in retrospective studies, and classification of interventions in the SEER database study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients treated with AS had similar OS to those who underwent surgery or ablation, although caution is needed in interpreting the data owing to the potential for selection bias and variability in AS protocols. Our review reinforces the need for personalized shared decision-making to identify patients with SRMs who are most likely to benefit from AS. PATIENT SUMMARY: For well-selected patients with a small kidney mass suspicious for cancer, active surveillance seems to be a safe alternative to surgery, with similar overall survival. However, the evidence is still limited and more studies are needed to help in identifying the best candidates for active surveillance.

• MeSH
• ablace metody   MeSH
• lidé MeSH
• nádory ledvin * chirurgie   mortalita   patologie   MeSH
• nefrektomie * metody   MeSH
• pozorné vyčkávání * MeSH
• tumor burden MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH
• systematický přehled MeSH

BACKGROUND: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses. METHODS: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications. RESULTS: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder. CONCLUSIONS: The proposed NDP constitutes a promising clinical tool for patient stratification in BD.

• MeSH
• bipolární porucha * genetika   MeSH
• dospělí MeSH
• fenotyp * MeSH
• hyperkinetická porucha genetika   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• multifaktoriální dědičnost genetika   MeSH
• neurovývojové poruchy genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• biologické modely MeSH
• dialýza ledvin * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• monitorování léčiv MeSH
• obezita * komplikace   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vankomycin * farmakokinetika   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Každý operačný výkon predstavuje u pacienta určité riziko a možnosť vzniku pooperačných komplikácii, hoci ide o bežne vykonávanú operáciu. Najčastejšie sa komplikácie vyskytujú u obéznych pacientov, kedy aj z banálnej operácie môže pacient skončiť na oddelení poskytujúcom intenzívnu starostlivosť a bojovať tak o svoj život. U obéznych pacientov je poskytovanie intenzívnej starostlivosti náročnejšie, nakoľko je potrebné u nich saturovať všetky základné potreby od prijímania potravy cez hygienu až po vyprázdňovanie. Cieľom príspevku je predstaviť a opísať priebeh liečby a ošetrovateľskej starostlivosti u extrémne obéznej pacientky po cholecystektómii, ktorej stav si vyžadoval intenzívnu starostlivosť z dôvodu rozvíjajúcej sa sepsy v oblasti operačnej rany, kde bolo potrebné využitie inovatívnych liečebných postupov a metód pri jej hojení. Metodika: Pomocou kvalitatívneho výskumu formou kazuistiky, opisujeme zaujímavý prípad pacientky, ktorá si vyžadovala 95 dňovú hospitalizáciu na intenzívnom oddelení s ťažkou sepsou, kardiovaskulárnym zlyhávaním, nutnosťou umelej pľúcnej ventilácie (UVP), s využitím VAC systému (vacuum assisted closure) na hojenie rany, dekubitmi rôznych stupňov, infekčnou hnačkou a syndrómom závislosti od UVP. Výsledky: Pacientka preložená z chirurgickej jednotky intenzívnej starostlivosti (JIS) v poruche vedomia, s potrebou zabezpečenia dýchacích ciest, napojenia na UVP, potrebou vazopresorickej podpory, septickým stavom, rozpadom operačnej rany a potrebou korekcie glykémie inzulínom v lineárnom dávkovači. Po cirkulačnej stabilizácii pacientky na 13. deň hospitalizácie bol naložený chirurgom do operačnej rany VAC systém, ktorý sa v pravidelných intervaloch menil. Počas hospitalizácie stav pacientky komplikovaný vznikom dekubitov a Clostridioides difficile infection (CDI). U pacientky postupne vznikol syndróm závislosti na UVP, preto extubovaná až na 91. deň. Na 95. deň pacientka v stabilizovanom stave so zhojenými dekubitmi, preliečenou CDI infekciou a s VAC systémom preložená na oddelenie dlhodobo chorých. Aj banálna operácia môže skončiť bojom o život. U extrémne obéznych pacientov je riziko komplikácii vyššie, nakoľko trpia viacerými ochoreniami, ktoré spomaľujú proces hojenia rán a zároveň zvyšujú nároky na poskytovanú ošetrovateľskú starostlivosť vo všetkých oblastiach. Zachránený život však prevyšuje všetky nároky a je najväčšou odmenou pre celý personál oddelenia.

Every surgical procedure represents a certain risk and possibility of developing a patient. postoperative complications, although it is a commonly performed operation. Most often, complications occur in obese patients, when even a banal operation can cause a end up in an intensive care unit and fight for their lives. In obese patients, the provision of intensive care is more difficult, as it is necessary to restoreall basic needs from foodintake to hygiene to defecation. The aim of the paper is to present and describe the course of treatment and nursing care in an extremely obese cholecystectomy patient who secondition required intensive care for developing sepsis in the area of the surgical wound, as a result of which the wound It fell apart and it was necessary to use innovative treatments and methods to heal it. Methodology: Using qualitative research in the form of a case report, we describe an interesting the case of a patient who required 95 days of hospitalization in an intensive care unit with severe sepsis, cardiovascular failure, the need for artificial pulmonary ventilation (APV), using the VAC system (vacuum assisted closure) wound healing, pressure ulcers of varying degrees, infectious diarrhea and addictionsyndrome UVP. Results: Patient transferred from the surgical intensive care unit (ICU) in a disorder of consciousness, with a need securing the respiratory tract, connection to UVP, the need for vasopressor support, septic condition, disintegration of the surgical wound and the need for glucose correction with insulin in lineardispenser. After circulatory stabilization of the patient on the 13th day of hospitalization, loaded by the surgeoninto the surgical wound of the VAC system, which at regular intervals Changed. During hospitalization, the patient’s condition is complicated by the development of pressure ulcers and Clostridioides difficile infection (CDI). The patient gradually developed UVP dependence syndrome, so shewasextubated on day 91. At the 95. day a patient in a stablecondition with healed pressure ulcers, retreated CDI infection and with the VAC system transferred to the long-term care unit. Even a banal operation can end in a fight for life. In extremely obese patients, it is the risk of complications is higher, as they suffer from several diseases that slowdown the process of wound healing and at the sametimeincrease the demands on the nursing care provided in the allareas. However, a life saved exceed sall claims and is the grea test reward for the entire staff of the department.

• MeSH
• Clostridioides difficile MeSH
• dehiscence operační rány ošetřování   terapie   MeSH
• dekubity ošetřování   terapie   MeSH
• hojení ran MeSH
• obezita komplikace   MeSH
• ošetřovatelská péče o pacienty v kritickém stavu MeSH
• péče o pacienty v kritickém stavu MeSH
• plicní ventilace MeSH
• pooperační komplikace ošetřování   terapie   MeSH
• sepse MeSH
• terapie ran pomocí řízeného podtlaku MeSH
• výsledek terapie MeSH
• Publikační typ
• kazuistiky MeSH

OBJECTIVE: The aim of the study was the assessment of adherence to antiretroviral (ARV) treatment in a population of people living with HIV (PWH), improving the awareness of PWH, drawing attention to the risk of developing HIV drug resistance and subsequent treatment failure. METHODS: The basic cohort consisted of PWH followed up long-term at the HIV centre of the University Hospital Pilsen. Adherence to treatment was assessed by ARV levels. Nucleoside analogs were determined in urine by high pressure liquid chromatography (HPLC), in relation to clinical data, viral load (HIV RNA), and absolute CD4 and CD8 T cell counts. To assess mental and physical state of the patients, a modified SF-36 questionnaire was used to measure social relationships, education and ability to relax. RESULTS: From a group of 131 PWH, 18 (13.7%) with zero levels and 113 (86.3%) with any detectable ARV levels were followed for 6-12 months. A statistically significant lower viral load was demonstrated in patients who adhered to the treatment at the time of the test as indicated by ARV levels in the urine. CD4 T lymphocyte values in adherent patients were, as expected, statistically significantly higher. A significant difference for CD8 T lymphocyte was not demonstrated. A survey assessed subjective factors influencing the degree of adherence. PWH consider important: quality care enabling trust, low risk of developing opportunistic infections, self-sufficiency, quality of sleep, managing leisure activities, and good family relationships. Quality of life evaluation and satisfaction in the monitored areas were similar in both groups of PWH. CONCLUSIONS: Non-adherence leads to deterioration of CD4 and viral load levels and may be the cause of the development of HIV drug resistance and treatment failure on the part of the patient. PWH with zero or low urinary nucleoside levels were repeatedly instructed about the need for regular and sustained medication use. Regular checks with a laboratory examination service are needed to detect early emergence of resistance and side effects of the treatment, which are initially only detectable in the laboratory.

• MeSH
• adherence k farmakoterapii * psychologie   MeSH
• dospělí MeSH
• HIV infekce * farmakoterapie   psychologie   MeSH
• kohortové studie MeSH
• kvalita života * MeSH
• látky proti HIV * terapeutické užití   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• virová nálož MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Diabetes mellitus (DM) je jedním z výrazně progredujících chronických onemocnění s vysokou celosvětovou prevalencí. Nehledě na typ diabetu je hlavním cílem zdravotnického týmu efektivní kompenzace metabolických abnormalit s cílem zabránit rozvoji pozdních komplikací či zpomalit jejich progresi do stádií výrazně snižujících kvalitu pacientova života. V posledních letech začíná stoupat počet odborných publikací podporujících domněnku, že stabilizace glykemie může mít zdravotní benefity i u zdravých nediabetiků. Tato práce sledovala vliv složení stravy (glykemické nálože) na glykemický profil a subjektivní parametry u mladých zdravých dobrovolníků pomocí kontinuální monitorace glykemie. Dospěli jsme k závěru, že ačkoliv subjektivní dotazníkové hodnocení ukazuje vyšší pocit útlumu po jídle nebo zhoršení dermatologických problémů ve skupině s vyšší glykemickou náloží, objektivní parametry kontinuální glykemické monitorace neukazují žádné významné rozdíly mezi skupinami podle glykemické nálože stravy. Závěrem můžeme předpokládat výraznou kompenzační schopnost regulačních systémů, které udrží glykemii v optimálním rozmezí i při vysoko-glykemické dietě.

Diabetes mellitus (DM) is one of the significantly progressive chronic diseases with high global prevalence. Regardless of the type of diabetes, the primary goal of the healthcare team is the effective management of the patient’s condition. In recent years, the number of scientific publications supporting the assertion that glycemic stabilization can have health benefits even for healthy non-diabetics has been increasing. In this study, we monitored the effect of diet composition (glycemic load) on the glycemic profile and subjective parameters in young healthy non-diabetic patients. We considered the significance of continuous monitoring on the health status of the participants. We concluded that while subjective questionnaire assessments show a higher feeling of postprandial lethargy and worsening of dermatological issues in the group with a higher glycemic load, the objective parameters of continuous glucose monitoring do not indicate any significant differences between the groups based on the glycemic load of their diet. In conclusion, we can assume a significant compensatory ability of regulatory systems to maintain glycemia within an optimal range even with a high-glycemic diet.