BACKGROUND: Pivotal studies with dupilumab demonstrated clinically relevant improvements in nasal polyp score, symptom score, and quality-of-life score in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). OBJECTIVE: We evaluated the effectiveness of dupilumab in a large-scale CRSwNP cohort from 6 European tertiary-care centers. METHODOLOGY: Nasal polyp score, Sinonasal Outcome Test 22 score, visual analog scale for total sinus symptoms, loss of smell, and nasal blockage, and Asthma Control Test (ACT) score were collected from hospital records and assessed at baseline and again at 24 and 52 weeks' treatment with dupilumab in CRSwNP patients. Treatment effectiveness was evaluated in relation to demographic and lifestyle factors, sinus surgery history, presence of comorbidities, and blood eosinophil counts (BEC). Treatment response was evaluated according to European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) 2021 criteria. RESULTS: All patient outcomes improved at 24 and 52 weeks' treatment compared to baseline. Dupilumab showed effectiveness independent of age, sex, body mass index, smoking status, prior sinus surgery, presence of asthma, nonsteroidal anti-inflammatory drug-exacerbated respiratory disease, allergy, or baseline BEC. A total of 92.5% and 94.4% showed an improvement in at least 1 EUFOREA criterion at 24 and 52 weeks, respectively; 54.4% and 68.2% met all 4 of the more stringent EUFOREA criteria at 24 and 52 weeks, respectively. CONCLUSIONS: Real-world evaluation of dupilumab effectiveness demonstrates a robust and sustained response in at least two thirds of patients at 52 weeks' treatment. Favorable treatment response was independent of the number of sinus surgery procedures, major comorbidities, or baseline systemic levels of type 2 inflammation.

• MeSH
• chronická nemoc MeSH
• dospělí MeSH
• humanizované monoklonální protilátky * terapeutické užití   MeSH
• kohortové studie MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• nosní polypy * farmakoterapie   imunologie   MeSH
• rinosinusitida MeSH
• rýma * farmakoterapie   MeSH
• senioři MeSH
• sinusitida * farmakoterapie   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
• multicentrická studie MeSH
• Geografické názvy
• Evropa MeSH

Atopic dermatitis (AD) is a chronic inflammatory disease affecting ~ 10% of adults and ~ 20% of children globally. Many patients with moderate-to-severe AD receiving systemic therapies, including biologics and Janus kinase (JAK) inhibitors, fail to reach or maintain treatment goals due to lack of durable response or safety/tolerability issues. Rocatinlimab is a T-cell rebalancing therapy that inhibits and reduces pathogenic T cells by targeting the OX40 receptor. ROCKET, a large, global phase 3 program of eight clinical trials (NCT05398445; NCT05651711; NCT05724199; NCT05899816; NCT05704738; NCT05633355; NCT05882877; NCT06224192), will evaluate the efficacy, durability of response, and long-term safety of rocatinlimab as monotherapy and combination therapy in adult and adolescent patients with moderate-to-severe AD with or without prior exposure to biologics or systemic JAK inhibitors.

• MeSH
• atopická dermatitida * farmakoterapie   MeSH
• dítě MeSH
• dospělí MeSH
• humanizované monoklonální protilátky terapeutické užití   škodlivé účinky   MeSH
• inhibitory Janus kinas terapeutické užití   MeSH
• lidé MeSH
• mladiství MeSH
• receptory OX40 antagonisté a inhibitory   MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH

BACKGROUND: Pulmonary hernia is a rare condition characterized by the protrusion of lung tissue through a chest wall defect. Trauma and thoracic surgery are the most common causes of acquired lung hernias. We present an unusual case of (sequential) bilateral lung herniation with parenchymal infarction after bilateral lobar lung transplantation. CASE PRESENTATION: A 50-year-old female, wait-listed as high-urgency candidate, with a body mass index (BMI) of 29 kg/m2 underwent a bilateral lobar lung transplantation for pulmonary fibrosis through a clamshell thoracotomy approach. Due to a size mismatch, stapler resection of the segment 3 and the middle lobe of the right lung, as well as an upper left lobectomy was required. The chest was closed with 3 braided non-absorbable pericostal sutures on each side. Sternal osteosynthesis was performed with a titanium sternal splint along with 7 self-tapping screws with a length of 18 mm. On the posttransplant day (PTD) 18, patient's clinical condition deteriorated. Physical examination didn't reveal any palpable subcutaneous chest resistance. However, a computed tomography (CT) scan showed a herniation of the segment 6 of the right lung. During acute surgical revision, perioperative finding revealed posterior pericostal suture failure. Therefore, a stapler resection was performed due to the infarction of the herniated segment. On the PTD 36, herniation of the left lung parenchyma was detected by acute CT scan. The protruding vital parenchyma was surgically repositioned without necessity of resection. Two posterior pericostal sutures were broken, and distal part of sternal splint detached. Thoracotomy was closed using 5 braided non-absorbable sutures. Sternum was re-osteosynthesized with the STRATOSTM system. After 3 months of intensive postoperative care, the patient was transferred to the rehabilitation department. She was discharged on the PTD 99. After 20 months of follow-up, lung function remains stable without the need for oxygen support. CONCLUSION: Clamshell incision remains ultimate approach in thoracic surgery. However, pulmonary herniation after clamshell thoracotomy is a rare complication and may manifest as acute respiratory distress syndrome with an inflammatory response. In these cases, CT scan should be always considered, even if no palpable pathology of chest is present.

• MeSH
• hernie * etiologie   MeSH
• infarkt etiologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• operace kýly metody   škodlivé účinky   MeSH
• plíce diagnostické zobrazování   MeSH
• plicní nemoci chirurgie   etiologie   MeSH
• počítačová rentgenová tomografie MeSH
• pooperační komplikace chirurgie   MeSH
• torakotomie * metody   MeSH
• transplantace plic * škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

OBJECTIVES: This study aimed to investigate the associations between radiographic damage, serum biomarkers, and clinical assessments in Czech patients with hand osteoarthritis (HOA) over a five-year follow-up period. METHODS: The study cohort comprised 129 patients diagnosed with HOA, including 72 patients with an erosive subtype and 57 patients with a non-erosive subtype. Radiographs were evaluated using the Kallman scoring system by two independent readers. Blood samples were analysed for markers of dyslipidaemia, bone metabolism, and inflammation. Clinical assessments focused on symptom severity and functional impairment. We employed generalised additive modelling (GAM) to analyse the associations between the Kallman score, serum biomarkers and clinical outcomes. RESULTS: The Kallman score was consistently higher in the erosive subtype compared to the non-erosive subtype across all time points and demonstrated a positive correlation with age in both groups. We demonstrated significant positive associations between radiographic progression and erythrocyte sedimentation rate across both HOA subtypes. Additionally, positive associations with the number of swollen joints and health assessment questionnaire scores were observed in all HOA patients, particularly in those with non-erosive subtypes. In contrast, markers of dyslipidaemia (e.g. LDL‐c or atherogenic index) were negatively associated with radiographic progression. No biomarker reliably differentiated between the erosive and non-erosive subtypes. CONCLUSIONS: Our longitudinal study revealed a significant association between systemic/local inflammation, dyslipidaemia, functional impairment and structural progression in HOA. However, these findings warrant further validation through additional studies to confirm these associations.

• MeSH
• biologické markery * krev   MeSH
• časové faktory MeSH
• dyslipidemie * krev   diagnostické zobrazování   MeSH
• funkční status MeSH
• klouby ruky * diagnostické zobrazování   MeSH
• krevní sedimentace MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mediátory zánětu krev   MeSH
• osteoartróza * diagnostické zobrazování   krev   MeSH
• posuzování pracovní neschopnosti MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci * MeSH
• radiografie MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• zánět krev   diagnostické zobrazování   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The knowledge about the contribution of the innate immune system to health and disease is expanding. However, to obtain reliable results, it is critical to select appropriate mouse models for in vivo studies. Data on genetic and phenotypic changes associated with different mouse strains can assist in this task. Such data can also facilitate our understanding of how specific polymorphisms and genetic alterations affect gene function, phenotypes, and disease outcomes. Extensive information is available on genetic changes in all major mouse strains. However, comparatively little is known about their impact on immune response and, in particular, on innate immunity. Here, we analyzed a mouse model of chronic multifocal osteomyelitis, an autoinflammatory disease driven exclusively by the innate immune system, which is caused by an inactivating mutation in the Pstpip2 gene. We investigated how the genetic background of BALB/c, C57BL/6J, and C57BL/6NCrl strains alters the molecular mechanisms controlling disease progression. While all mice developed the disease, symptoms were significantly milder in BALB/c and partially also in C57BL/6J when compared to C57BL/6NCrl. Disease severity correlated with the number of infiltrating neutrophils and monocytes and with the production of chemokines attracting these cells to the site of inflammation. It also correlated with increased expression of genes associated with autoinflammation, rheumatoid arthritis, neutrophil activation, and degranulation, resulting in altered neutrophil activation in vivo. Together, our data demonstrate striking effects of genetic background on multiple parameters of neutrophil function and activity influencing the onset and course of chronic multifocal osteomyelitis.

• MeSH
• adaptorové proteiny signální transdukční genetika   MeSH
• aktivace neutrofilů genetika   MeSH
• cytoskeletální proteiny MeSH
• genetické pozadí * MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• neutrofily * imunologie   patologie   MeSH
• osteomyelitida * genetika   imunologie   patologie   MeSH
• přirozená imunita genetika   MeSH
• stupeň závažnosti nemoci MeSH
• zánět genetika   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Perivascular adipose tissue (PVAT) envelops the majority of systemic vessels, providing crucial mechanical support and vessel protection. In physiological conditions, PVAT releases various bioactive molecules, contributing to the anti-inflammatory environment around neighboring vessels. However, in conditions like obesity, PVAT can exacerbate cardiovascular issues such as atherosclerosis. Communication between PVAT and nearby vessels is bidirectional, with PVAT responding dynamically to signals from the vasculature. This responsiveness positions PVAT as a promising indicator of vascular inflammation. Recently, the role of PVAT in the CVD risk prediction is also greatly discussed. The objective of this review is to summarize the current state of knowledge about the PVAT function, its role in physiologic and pathophysiologic processes and its potential in CVD risk prediction. Keywords: Perivascular adipose tissue, inflammation, atherogenesis, Fat attenuation index.

• MeSH
• ateroskleróza * metabolismus   patologie   patofyziologie   MeSH
• lidé MeSH
• obezita metabolismus   patofyziologie   patologie   MeSH
• tuková tkáň * metabolismus   patologie   patofyziologie   MeSH
• zánět * metabolismus   patologie   patofyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.

• MeSH
• biologické markery krev   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• glukokortikoidy * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu * krev   metabolismus   MeSH
• revmatoidní artritida * farmakoterapie   krev   imunologie   MeSH
• senioři MeSH
• zánět MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial. METHODS: We retrospectively collected the data of patients with mRCC from 56 centers in 18 countries. SII (Platelet × Neutrophil/Lymphocyte count) was calculated prior to the first systemic treatment and cut-off was defined by a survival receiver operating characteristic (ROC) analysis. The primary objective of our retrospective study was to assess the outcomes of patients treated with first-line immunotherapy. RESULTS: Data from 1034 mRCC patients was collected and included in this analysis. The SII cut-off value was 1265. After a follow-up of 26.7 months, and the overall survival (OS) and progression-free survival (PFS) were 39.8 and 15.7 months, respectively. According to SII (low vs. high), patients with low-SII had longer OS (55.7 vs. 22.2 months, P < .001), better PFS (20.8 vs. 8.5 months, P < .001), and higher overall response rate (52 vs. 37%, P = .033). CONCLUSION: A high SII is associated with poor oncological outcomes in patients with mRCC. SII could be an easily accessible prognostic indicator for use in clinical practice.

• MeSH
• analýza přežití MeSH
• karcinom z renálních buněk * patologie   MeSH
• lidé MeSH
• nádory ledvin * patologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• zánět patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

RATIONALE: Severe alcohol-associated hepatitis (SAH) is the most critical, acute, inflammatory phenotype within the alcohol-associated liver disease (ALD) spectrum, characterized by high 30- and 90-day mortality. Since several decades, corticosteroids (CS) are the only approved pharmacotherapy offering highly limited survival benefits. Contextually, there is an evident demand for 3PM innovation in the area meeting patients' needs and improving individual outcomes. Fecal microbiota transplantation (FMT) has emerged as one of the new potential therapeutic options. In this study, we aimed to address the crucial 3PM domains in order to assess (i) the impact of FMT on mortality in SAH patients beyond CS, (ii) to identify factors associated with the outcome to be improved (iii) the prediction of futility, (iv) prevention of suboptimal individual outcomes linked to increased mortality, and (v) personalized allocation of therapy. METHODS: We conducted a prospective study (NCT04758806) in adult patients with SAH who were non-responders (NR) to or non-eligible (NE) for CS between January 2018 and August 2022. The intervention consisted of five 100 ml of FMT, prepared from 30 g stool from an unrelated healthy donor and frozen at - 80 °C, administered daily to the upper gastrointestinal (GI) tract. We evaluated the impact of FMT on 30- and 90-day mortality which we compared to the control group selected by the propensity score matching and treated by the standard of care; the control group was derived from the RH7 registry of patients hospitalized at the liver unit (NCT04767945). We have also scrutinized the FMT outcome against established and potential prognostic factors for SAH - such as the model for end-stage liver disease (MELD), Maddrey Discriminant Function (MDF), acute-on-chronic liver failure (ACLF), Liver Frailty Index (LFI), hepatic venous-portal pressure gradient (HVPG) and Alcoholic Hepatitis Histologic Score (AHHS) - to see if the 3PM method assigns them a new dimension in predicting response to therapy, prevention of suboptimal individual outcomes, and personalized patient management. RESULTS: We enrolled 44 patients with SAH (NR or NE) on an intention-to-treat basis; we analyzed 33 patients per protocol for associated factors (after an additional 11 being excluded for receiving less than 5 doses of FMT), and 31 patients by propensity score matching for corresponding individual outcomes, respectively. The mean age was 49.6 years, 11 patients (33.3%) were females. The median MELD score was 29, and ACLF of any degree had 27 patients (81.8%). FMT improved 30-day mortality (p = 0.0204) and non-significantly improved 90-day mortality (p = 0.4386). Univariate analysis identified MELD ≥ 30, MDF ≥ 90, and ACLF grade > 1 as significant predictors of 30-day mortality, (p = 0.031; p = 0.014; p = 0.034). Survival was not associated with baseline LFI, HVPG, or AHHS. CONCLUSIONS AND RECOMMENDATIONS IN THE FRAMEWORK OF 3PM: In the most difficult-to-treat sub-cohort of patients with SAH (i.e., NR/NE), FMT improved 30-day mortality. Factors associated with benefit included MELD ≤ 30, MDF ≤ 90, and ACLF < 2. These results support the potential of gut microbiome as a therapeutic target in the context of 3PM research and vice versa - to use 3PM methodology as the expedient unifying template for microbiome research. The results allow for immediate impact on the innovative concepts of (i) personalized phenotyping and stratification of the disease for the clinical research and practice, (ii) multilevel predictive diagnosis related to personalized/precise treatment allocation including evidence-based (ii) prevention of futile and sub-optimally effective therapy, as well as (iii) targeted prevention of poor individual outcomes in patients with SAH. Moreover, our results add to the existing evidence with the potential to generate new research along the SAH's pathogenetic pathways such as diverse individual susceptibility to alcohol toxicity, host-specific mitochondrial function and systemic inflammation, and the role of gut dysbiosis thereof. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13167-024-00381-5.

• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The aim of this study was to evaluate changes in the relative counts of different leukocyte subsets in peripheral and umbilical cord blood in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of intraamniotic inflammation (IAI) and fetal inflammatory response syndrome (FIRS). METHODS: Fifty-two women with singleton pregnancies complicated by PPROM were included in this study. From samples of peripheral and umbilical cord blood, relative counts of these leukocyte subpopulations were determined using multicolor flow cytometry: granulocytes, monocytes, lymphocytes, T cells and their subpopulations, B cells and their subpopulations, and NK cells and their subpopulations. IAI was defined as increased concentrations of interleukin 6 in the amniotic fluid. Amniotic fluid samples were obtained by transabdominal amniocentesis. RESULTS: Women with IAI had higher relative counts of monocytes (p = 0.04) in peripheral blood. There was an increased relative number of granulocytes (p = 0.003) and a decreased number of lymphocytes (p = 0.0048), helper CD4+ T cells (p = 0.019), NK cells (p = 0.0001) within leukocytes, NK cells within lymphocytes (p = 0.003) and CD16+ NK cells within NK cells (p = 0.005) in umbilical cord blood samples of women with FIRS. However, after adjusting the results for gestational age at sampling, all differences disappeared. CONCLUSIONS: The presence of IAI or FIRS is not accompanied by significant changes in the relative counts of immune cells in peripheral blood or umbilical cord blood in pregnancies complicated by PPROM.

• MeSH
• chorioamnionitida imunologie   krev   MeSH
• dospělí MeSH
• fetální krev * imunologie   cytologie   MeSH
• interleukin-6 krev   metabolismus   MeSH
• leukocyty imunologie   MeSH
• lidé MeSH
• plodová voda imunologie   metabolismus   MeSH
• počet leukocytů MeSH
• předčasný odtok plodové vody * imunologie   krev   MeSH
• průtoková cytometrie MeSH
• syndrom systémové zánětlivé reakce imunologie   krev   MeSH
• těhotenství MeSH
• zánět imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH