BACKGROUND: The possible clinical utility of endocan, a novel inflammatory biomarker involved in the initiation and progression of atherosclerosis, is largely unknown. We aimed to evaluate its diagnostic and prognostic performance in chest pain patients presenting to the emergency department (ED). METHODS: We prospectively enrolled patients presenting with suspected myocardial infarction (MI) to the ED in an international multicenter study. Endocan, high-sensitivity C-reactive protein (hs-CRP), and high-sensitivity cardiac troponin T (hs-cTnT) were measured in blood samples obtained at presentation. Final diagnoses were centrally adjudicated by two independent cardiologists applying the 4th universal definition of MI and current guidelines. Non-ST-elevation MI (NSTEMI) was the diagnostic endpoint and 5-year cardiovascular death was the primary prognostic endpoint. RESULTS: Among 4728 patients, 843 (17.8 %) had NSTEMI. The diagnostic discrimination of endocan for NSTEMI was low (area under the curve (AUC) 0.585 [95 % CI: 0.563-0.607]. Its combination with hs-cTnT (0.939 [95 % CI: 0.931-0.947]) did not improve the discriminative performance of hs-cTnT alone (0.937 [95 % CI: 0.930-0.950]). Long-term prognostic accuracy of endocan was higher versus hs-CRP, but lower versus hs-cTnT (AUC 0.730 [0.710-0.760] vs 0.650 [0.620-0.680] vs 0.810 [0.790-0.830], respectively). Endocan was associated with an increased 5-year risk for cardiovascular mortality. However, it did not provide relevant incremental prognostic value when added on top of a base model that included SCORE2 risk factors and hs-cTnT. CONCLUSION: Endocan has a low diagnostic accuracy for NSTEMI, and moderate long-term prognostic accuracy for cardiovascular death. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587https://clinicaltrials.gov/ct2/show/NCT00470587.

• Keywords
• Endocan, Inflammatory biomarkers, Myocardial infarction, Troponin,
• MeSH
• Biomarkers blood   MeSH
• Myocardial Infarction * diagnosis   blood   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Proteins * blood   MeSH
• Prognosis MeSH
• Prospective Studies MeSH
• Proteoglycans * blood   MeSH
• Aged MeSH
• Troponin T blood   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers MeSH
• ESM1 protein, human MeSH Browser
• Neoplasm Proteins * MeSH
• Proteoglycans * MeSH
• Troponin T MeSH

Acute appendicitis is a common pediatric surgical emergency, but its clinical presentation can overlap with other conditions, complicating diagnosis. We present a case of a 4-year-old female who initially presented with symptoms suggestive of appendicitis, including right iliac fossa pain, vomiting, and fever. Imaging studies were inconclusive, and a laparoscopic appendectomy was performed. No signs of appendicitis were found, but vasculitic changes were noted in a segment of the ileum. Postoperatively, the patient developed a mild purpuric rash, and elevated C-reactive protein (CRP) levels prompted further investigation. Subsequent laboratory tests and clinical findings led to a diagnosis of Immunoglobulin A (IgA) vasculitis, characterized by a small-vessel vasculitis affecting the gastrointestinal tract. This case highlights the diagnostic challenges when presenting symptoms mimic appendicitis but are ultimately attributed to an atypical presentation of IgA vasculitis. The importance of considering systemic inflammatory conditions like IgA vasculitis in pediatric abdominal pain is emphasized, especially when initial diagnoses do not align with imaging or surgical findings. A multidisciplinary approach, including rheumatological evaluation, was crucial in securing the correct diagnosis and managing the patient's care.

IgA vasculitis (IgAV) is a condition that causes inflammation of small blood vessels. It can often affect the skin, joints, kidneys, and digestive system. This condition usually involves the upper part of the small intestine, but in rare cases, it can affect the very end of the small intestine (terminal ileum). In our case, a patient came to the hospital with sudden, severe abdominal pain and imaging that suggested a localized bowel problem. Surgeons operated urgently, and only later (when a skin rash appeared) IgAV was diagnosed. The patient recovered quickly after starting steroid treatment, without needing further bowel procedures. This case shows that IgAV can sometimes look like a surgical emergency. By being aware of this possibility, we can prevent unnecessary surgery and guide treatment decisions.

• Keywords
• Acute appendicitis, IgA vasculitis, abdominal surgery, diagnostic challenges, gastrointestinal involvement, pediatric abdominal pain, purpura, vasculitis,
• Publication type
• Journal Article MeSH

The structural basis of inhibitory effect of organic solvent dimethyl sulfoxide (DMSO) on human acetylcholinesterase (EC 3.1.1.7; hAChE) was inferred from the effect of DMSO on kinetics of reversible inhibition of uncharged, heterocyclic bis-oximes to hAChE, from DMSO effect on rates of reactivation of inactive organophosphate (OP)-hAChE conjugates by bis-oximes and by X-ray structures of bis-oxime and DMSO binding to hAChE. The reversible inhibition constant of DMSO for hAChE in 0.1 M phosphate buffer pH 7.4 at 22 °C, was Ki= (0.32 ± 0.04) % (or 45 ± 5 mM). The Ki of the bis-oxime LG-703 for hAChE was 3.2-fold larger in 1 % DMSO, consistent with direct competition between LG-703 and DMSO. The X-ray structure of the LG-703∗hAChE complex (PDB ID: 6U3P) shows DMSO and LG-703 bound to individual hAChE monomers, LG-703 in the chain A and DMSO in the chain B. In the co-crystallization both small molecules were present at a similar excess over their corresponding Ki values for hAChE (7.8-fold for DMSO and 6.5-fold for LG-703) and formation of two different complexes (DMSO∗hAChE and LG-703∗hAChE), in the same crystal, appears consistent with inhibition kinetics. Furthermore, rates of reactivation of paraoxon-inhibited hAChE (POX-hAChE) and of VX-hAChE by LG-703 and by a novel heterocyclic bis-oxime LG-1922 were reduced 2 - 3-fold in DMSO, consistent with observation of the active-center-bound DMSO molecules in the newly solved structure of the LG-1922∗POX-hAChE complex presented here and in our POX-hAChE structure (PDB ID: 8DT2) showing obstruction of the reactivator access to the conjugated P atom.

• Keywords
• Acetylcholinesterase inhibition, Acetylcholinesterase reactivation, Antidotes, DMSO, Heterocyclic bis-oximes, Organic solvent, Organophosphorus compounds, Paraoxon, VX,
• MeSH
• Acetylcholinesterase * metabolism   chemistry   MeSH
• Cholinesterase Inhibitors chemistry   pharmacology   metabolism   MeSH
• Dimethyl Sulfoxide * chemistry   pharmacology   metabolism   MeSH
• Kinetics MeSH
• Crystallography, X-Ray MeSH
• Humans MeSH
• Oximes * chemistry   metabolism   pharmacology   MeSH
• Protein Binding MeSH
• Binding Sites MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Acetylcholinesterase * MeSH
• Cholinesterase Inhibitors MeSH
• Dimethyl Sulfoxide * MeSH
• Oximes * MeSH

The lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) is a key scavenger receptor for oxidized low-density lipoprotein cholesterol (oxLDL), which promotes inflammation and atherosclerosis. Here we evaluated MEDI6570, an antibody that acts as a LOX-1 antagonist, in a randomized, double-blind, dose-finding study in patients with myocardial infarction (MI) and residual inflammation (high-sensitivity C-reactive protein ≥ 1 mg l-1). At 30-365 days after MI, 423 patients (75 women, 348 men) were randomly allocated to 50 mg, 150 mg or 400 mg MEDI6570 or placebo treatment subcutaneously every 4 weeks for 32 weeks. The primary endpoint, the change in the noncalcified plaque volume in the most diseased coronary segment (NCPVMD) by computed tomography angiography, was not significantly different between placebo and MEDI6570 at any dose. The secondary endpoints, global NCPV and low-attenuation plaque volume, were also not different between placebo and MEDI6570 at any dose (all placebo-adjusted comparisons, P > 0.05). With regard to exploratory endpoints, there were reductions in free soluble LOX-1 (sLOX-1) from baseline by 44.8%, 85.8%, 94.0% and 96.4% in the placebo, 50 mg, 150 mg and 400 mg dose arms, respectively (all placebo-adjusted comparisons P < 0.001). Interleukin-6 (IL-6) levels decreased by 2.9%, -3.0%, 18.9% and 21.5% in the placebo, 50 mg, 150 mg and 400 mg arms, respectively, with substantial placebo-adjusted reductions observed only at 150 mg and 400 mg (P < 0.05). MEDI6570 was well tolerated and rates of serious adverse events were similar in the MEDI6570 and placebo groups. In summary, despite favorable effects on sLOX-1 and IL-6, a LOX-1 inhibitor did not reduce noncalcified coronary plaque volume in patients with residual inflammation after acute MI. EudraCT registration: 2020-000840-75 .

• Publication type
• Journal Article MeSH

BACKGROUND: The incidence of squamous cell carcinoma of the oral tongue (SCCOT) among young adults is increasing in several regions of the world. Age-dependent differences in the biology of SCCOT have been suspected. METHODS: We used the Olink Explore 3072 high-throughput platform to comprehensively quantify plasma proteins in 24 young (≤ 40 years of age) and 50 old (> 50 years of age) individuals. Eight young and 20 old individuals were diagnosed with SCCOT, four young and nine old individuals with SCC at other oral subsites (SCCOO), and the remaining 12 young and 21 old individuals were healthy controls. Dimension reduction analysis, differential expression analysis, and functional enrichment analysis were performed to characterize young patient-specific biological signatures. RESULTS: Plasma levels of 2923 proteins were obtained. Principal component analysis indicated age-related expression patterns. Comparing young patients to young controls/old patients/old controls, differential abundance analysis showed that increases in protein levels of Peroxiredoxin 2 (PRDX2) and C-C motif chemokine ligand 26 (CCL26) and a decrease in Kallikrein related peptidase 4 (KLK4) were young patient-specific. Reactome pathway enrichment analysis identified "Cellular response to chemical stress," "Detoxification of reactive oxygen species" and "Cellular responses to stimuli" as the top altered pathways in young patients with SCCOT. CONCLUSIONS: Abnormal cellular stress and aberrant immune regulation could thus be linked to cancer development in young patients. The unique plasma proteomic signature observed in young patients with SCCOT suggests that they constitute a specific group with distinct underlying pathophysiological processes.

• Keywords
• CCL26, ROS, age, oral cancer, plasma, proteomics, tongue,
• MeSH
• Adult MeSH
• Blood Proteins * analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Biomarkers, Tumor * blood   MeSH
• Tongue Neoplasms * blood   pathology   MeSH
• Peroxiredoxins blood   MeSH
• Aged MeSH
• Carcinoma, Squamous Cell * blood   pathology   MeSH
• Case-Control Studies MeSH
• Age Factors MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Blood Proteins * MeSH
• Biomarkers, Tumor * MeSH
• Peroxiredoxins MeSH
• PRDX2 protein, human MeSH Browser

OBJECTIVES: To develop and validate classification criteria for paediatric chronic nonbacterial osteomyelitis (CNO) jointly supported by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR). METHODS: This international initiative had 4 phases: (1) candidate items were proposed in a survey of paediatric rheumatologists, (2) criteria definition and reduction by Delphi and nominal group technique exercises, (3) criteria weighting using multicriteria decision analysis, and (4) refinement of weights and threshold score in a development cohort of 441 patients and validation in another cohort of 514 patients. RESULTS: The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency, and hypophosphatasia, followed by additive weighted criteria in 5 clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions, fever) and 4 pathology/laboratory domains (bone biopsy findings if done, anaemia, C-reactive protein level, and erythrocyte sedimentation rate). A total score ≥55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort. CONCLUSIONS: These new classification criteria for paediatric CNO developed with international input reflect current views about CNO, have high specificity and good sensitivity, and provide a key foundation for future CNO research.

• MeSH
• Chronic Disease MeSH
• Delphi Technique MeSH
• Child MeSH
• Blood Sedimentation MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Osteomyelitis * classification   diagnosis   MeSH
• Child, Preschool MeSH
• Rheumatology standards   MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Validation Study MeSH

Sepsis is a life-threatening condition triggered by a dysregulated immune response to bloodstream infection. Patients with solid and hematologic malignancies are at increased risk of severe infections and the onset of sepsis. Due to the limitations of blood cultures, particularly in culture-negative sepsis, multiple serological biomarkers, such as C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), white blood cells (WBC), lymphocytes (LYM), neutrophils (NEU), and monocytes (MON), are frequently used to diagnose infections. This prospective observational study aims to evaluate the efficacy of these biomarkers in distinguishing sepsis in patients with hematologic and solid tumors. It was observed that hematologic cancer patients exhibited significantly elevated IL-6, PCT, and MON levels, indicating their strong potential for sepsis detection. However, this difference was not statistically significant in patients with solid cancers and sepsis. Specifically, patients with blood cancer at the onset of sepsis have elevated levels of IL-6, PCT and MON, with AUCs exceeding 0.75, indicating strong predictive value. In contrast, patients with solid tumors had a moderate but not statistically significant increase in PCT (AUC = 0.693). Biomarker combinations enhanced the diagnostic power for hematologic cancers, but their performance in solid tumors remained limited. The findings underscore the need for cancer-specific sepsis diagnostic approaches, with a particular focus on the unique immune dynamics of hematologic versus solid tumors.

• Keywords
• Composite biomarker index, Hematologic cancer, Sepsis, Serum biomarkers, Solid cancer,
• MeSH
• Biomarkers * blood   MeSH
• C-Reactive Protein metabolism   MeSH
• Adult MeSH
• Hematologic Neoplasms * complications   blood   MeSH
• Interleukin-6 blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasms * complications   blood   MeSH
• Procalcitonin blood   MeSH
• Prospective Studies MeSH
• Aged MeSH
• Sepsis * diagnosis   blood   etiology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Observational Study MeSH
• Names of Substances
• Biomarkers * MeSH
• C-Reactive Protein MeSH
• Interleukin-6 MeSH
• Procalcitonin MeSH

BACKGROUND: Data on upadacitinib therapy for pediatric acute severe ulcerative colitis (ASC) are scarce. We aimed to evaluate the effectiveness and safety of upadacitinib as a salvage therapy in pediatric ASC. METHODS: Children and adolescents with ASC who were treated with upadacitinib for the induction of remission were enrolled in this retrospective multicenter study. Demographic, clinical, and laboratory data as well as adverse events (AEs) were recorded after the 8-week induction period and throughout 26 weeks of therapy. Analyses were based on the intention-to-treat principal. RESULTS: Twenty-two patients were included (median age 15.7 [interquartile range 13.5-16.6] years, 12 hospitalized), all with anti-tumor necrosis factor (TNF) therapy refractory disease. Ten patients were treated with corticosteroids at baseline, and upadacitinib was added to an ongoing biologic therapy in five patients. At week 8 of therapy, 11 (50%) patients of the cohort remained colectomy-free and in corticosteroid-free clinical remission (CFR), and 17 (77%) patients remained colectomy-free. Normal C-reactive protein (CRP) was achieved in 9 of 11 (82%) patients who were in CFR, and fecal calprotectin <150 mcg/g in 4 of 6 (67%) patients with available data. By week 26, 14 (64%) were in CFR and 16 (73%) patients remained colectomy-free. All these patients had normal CRP levels, and 4 of 7 patients with available data had fecal calprotectin <150 mcg/g. Twelve patients reported AEs, including two serious AEs of an appendiceal neuroendocrine tumor and cytomegalovirus colitis. CONCLUSION: Upadacitinib is an effective induction therapy for children and adolescents with ASC after failing anti-TNF.

This multicenter study describes 22 children with ASC treated with upadacitinib. Clinical remission was observed in 12 (55%) patients, and 11 (50%) were in colectomy-free, corticosteroid-free remission (CFR) after 8 weeks. By week 26, 14 (64%) patients were in CFR.

• Publication type
• Journal Article MeSH

Metabolic syndrome (MetS) is a cluster of risk factors that increase the likelihood of developing cardiovascular, metabolic and other diseases. The pharmacological management of MetS often involves polypharmacy, making it essential to understand how drug-metabolising enzymes, transporters, transcription factors and other proteins involved are affected under different metabolic conditions. This study investigated the relative mRNA expression of key hepatic and intestinal genes involved in drug metabolism, including Cyp1a2, Cyp3a23, Cyp2d1, Cyp2c11, Cyp2c6, Cyp2e1, Cyp7a1, Cyp2b1, Cyp2a1, Abcg5, Abcg8, Abcb1, Nr1i3, Nr1i2, Ahr, Gsta1 and Comt, in four nonobese rat models of MetS: hereditary hypertriglyceridaemic (HHTg), spontaneously hypertensive rat (SHR), SHR expressing transgenic human C-reactive protein (SHR-CRP), and bilaterally ovariectomised Wistar (W-OVX), compared to Wistar controls. Gene expression was quantified by RT-PCR with data normalised using the ΔΔCt method. Between the models studied, measurements showed significant differences in the liver. The upregulation of Cyp2c6 and Cyp3a23 was observed only in SHR; upregulated Cyp2d1 was found in SHR as well as in HHTg rats. The downregulated Cyp1a2 was measured in a condition of hypertriglyceridemia, postmenopause or hypertension. These findings highlight model-specific alterations in gene expression that may affect drug metabolism and interactions. The HHTg may be, in particular, a suitable model for preclinical studies focusing on intestinal drug-drug interactions in MetS-related conditions.

• Keywords
• drug metabolism, metabolic syndrome, rat model,
• MeSH
• Liver metabolism   enzymology   MeSH
• Rats MeSH
• Humans MeSH
• Membrane Transport Proteins * genetics   metabolism   MeSH
• RNA, Messenger * metabolism   genetics   MeSH
• Metabolic Syndrome * genetics   metabolism   MeSH
• Disease Models, Animal MeSH
• Rats, Inbred SHR MeSH
• Rats, Wistar MeSH
• Receptors, Cytoplasmic and Nuclear * genetics   metabolism   MeSH
• Cytochrome P-450 Enzyme System * genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Membrane Transport Proteins * MeSH
• RNA, Messenger * MeSH
• Receptors, Cytoplasmic and Nuclear * MeSH
• Cytochrome P-450 Enzyme System * MeSH

BACKGROUND: Despite all the effort, infections remain one of the major causes of morbidity and mortality in clinically ill patients, and novel diagnostic markers detecting infections in early stages are searched for. Intensive Care Infection Score (ICIS) was developed as such a marker. METHODS: A total of 102 patients admitted to intensive care units (ICU) in the University Hospital Hradec Kralove, Czech Republic were enrolled in this study. ICIS along with relevant biochemical markers (procalcitonin, C-reactive protein and Interleukin 6) was analyzed on the day of the admission. Individual parameters used to calculate ICIS were analyzed too. Infection was subsequently confirmed in 30 patients. RESULTS: ICIS predicted infections with the highest AUC (0.958) of all analyzed markers. The cut-off value (< 4) was selected as the value with the highest Youden index, and it predicted sepsis with high specificity (84.2%) and sensitivity (93.3%). Negative predictive value was very high too (96.8%). Positive predictive value was 71.8%. CONCLUSIONS: ICIS is a reliable, cheap, fast, and simply interpretable score for the early identification of infection in patients admitted to ICUs. ICIS ≥ 4 predicts infection with high sensitivity, specificity, and negative predictive value.

• Keywords
• Sysmex, infection score, infections, prediction,
• MeSH
• Biomarkers blood   MeSH
• C-Reactive Protein MeSH
• Adult MeSH
• Infections * diagnosis   blood   MeSH
• Interleukin-6 blood   MeSH
• Intensive Care Units * MeSH
• Middle Aged MeSH
• Humans MeSH
• Critical Care * MeSH
• Patient Admission MeSH
• Procalcitonin blood   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sepsis * diagnosis   blood   MeSH
• Severity of Illness Index MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Biomarkers MeSH
• C-Reactive Protein MeSH
• Interleukin-6 MeSH
• Procalcitonin MeSH