RESUMO
Severe intestinal mucositis (IM) increases the risk of bloodstream infections (BSI) and inflammatory toxicity during acute lymphoblastic leukaemia (ALL) induction treatment. However, the implications of IM in subsequent ALL therapy phases after achieving remission remain unknown. This study investigated the relationship between IM (measured by plasma citrulline and the chemokine CCL20) and the development of BSI and systemic inflammation (reflected by C-reactive protein, CRP) in children with ALL during high-dose methotrexate (HDMTX) treatment, an important part of ALL consolidation therapy. The study compared patients treated according to the NOPHO ALL 2008 protocol (n = 52) and the ALLTogether1 protocol (n = 42), both with identical HDMTX procedures but different scheduling. One week post-HDMTX, citrulline dropped to median levels of 14.5 and 16.9 µM for patients treated according to the NOPHO ALL 2008 and ALLTogether1 protocols, respectively (p = 0.11). In a protocol and neutrophil count-adjusted analysis, hypocitrullinaemia (<10 µmol/L) was associated with increased odds of BSI within 3 weeks from HDMTX (OR = 26.2, p = 0.0074). Patients treated according to the NOPHO ALL 2008 protocol exhibited increased mucosal- and systemic inflammation post-HDMTX compared to patients treated according to ALLTogether1, with increased CCL20 (14.6 vs. 3.7 pg/mL, p < 0.0001) and CRP levels (10.0 vs. 1.0 mg/L, p < 0.0001). Both citrulline and CCL20 correlated with CRP for these patients (rs = -0.44, p = 0.0016 and rs = 0.35, p = 0.016, respectively). These results suggest that hypocitrullinaemia following HDMTX increases the risk of BSI, confirming previous observations from more intensive treatments. Moreover, these data indicate that the patients' vulnerability to mucositis and inflammatory toxicity after chemotherapy varies with treatment protocol.
RESUMO
Pediatric hematopoietic stem cell transplantation (HSCT) is challenged by chronic graft-versus-host disease (cGvHD) significantly affecting survival and long-term morbidity, but underlying mechanisms including the impact of post-HSCT CMV infection are sparsely studied. We first investigated the impact of CMV infection for development of cGvHD in 322 children undergoing standard myeloablative HSCT between 2000 and 2018. Clinically significant CMV infection (n = 61) was an independent risk factor for chronic GvHD in a multivariable Cox regression analysis (HR = 2.17, 95% CI = 1.18-3.97, P = 0.013). We next explored the underlying mechanisms in a subcohort of 39 children. CMV infection was followed by reduced concentration of recent thymic emigrants (17.5 vs. 51.9 × 106/L, P = 0.048) and naïve CD4+ and CD8+ T cells at 6 months post-HSCT (all P < 0.05). Furthermore, CD25highFOXP3+ Tregs tended to be lower in patients with CMV infection (2.9 vs. 9.6 × 106/L, P = 0.055), including Tregs expressing the naivety markers CD45RA and Helios. CD8+ T-cell numbers rose after CMV infection and was dominated by exhausted PD1-expressing cells (66% vs. 39%, P = 0.023). These findings indicate that post-HSCT CMV infection is a main risk factor for development of chronic GvHD after pediatric HSCT and suggest that this effect is caused by reduced thymic function with a persistently impaired production of naïve and regulatory T cells in combination with increased peripheral T-cell exhaustion.
Assuntos
Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Timo , Humanos , Doença Enxerto-Hospedeiro/imunologia , Infecções por Citomegalovirus/imunologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Criança , Masculino , Feminino , Pré-Escolar , Timo/imunologia , Adolescente , Doença Crônica , Lactente , Citomegalovirus/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T Reguladores/imunologia , Fatores de Risco , Linfócitos T CD4-Positivos/imunologia , Síndrome de Bronquiolite ObliteranteRESUMO
Primary open-angle glaucoma (POAG) is subdivided depending on eye pressure. Patients with normal-tension glaucoma (NTG) have never had high intraocular pressure (IOP) measured while patients with ocular hypertension (OHT) have high eye pressure but no signs of glaucoma. Although IOP is considered to be a risk factor for all glaucoma patients, it is reasonable to assume that other risk factors such as inflammation play a role. We aimed to characterize the proteome and cytokine profile during hypoxia in plasma from patients with NTG (n = 10), OHT (n = 10), and controls (n = 10). Participants were exposed to hypoxia for two hours, followed by 30 min of normoxia. Samples were taken before ("baseline"), during ("hypoxia"), and after hypoxia ("recovery"). Proteomics based on liquid chromatography coupled with mass spectrometry (LC-MS) was performed. Cytokines were measured by Luminex assays. Bioinformatic analyses indicated the involvement of complement and coagulation cascades in NTG and OHT. Regulation of high-density lipoprotein 3 (HDL3) apolipoproteins suggested that changes in cholesterol metabolism are related to OHT. Hypoxia decreased the level of tumor necrosis factor-α (TNF-α) in OHT patients compared to controls. Circulating levels of interleukin-1ß (IL-1ß) and C-reactive protein (CRP) were decreased in NTG patients compared to controls during hypoxia. After recovery, plasma interleukin-6 (IL-6) was upregulated in patients with NTG and OHT. Current results indicate an enhanced systemic immune response in patients with NTG and OHT, which correlates with pathogenic events in glaucoma. Apolipoproteins may have anti-inflammatory effects, enabling OHT patients to withstand inflammation and development of glaucoma despite high IOP.
Assuntos
Citocinas , Glaucoma de Baixa Tensão , Hipertensão Ocular , Proteômica , Humanos , Citocinas/sangue , Masculino , Feminino , Glaucoma de Baixa Tensão/sangue , Proteômica/métodos , Hipertensão Ocular/sangue , Pessoa de Meia-Idade , Idoso , Pressão Intraocular/fisiologiaRESUMO
OBJECTIVE: This study aimed to compare the prevalence and incidence of polyautoimmunity between anticyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative patients with rheumatoid arthritis (RA). METHODS: In a nationwide register-based cohort study, patients with RA (disease duration ≤ 2 yrs) in the DANBIO rheumatology register with an available anti-CCP test in the Register of Laboratory Results for Research were identified. The polyautoimmunity outcome included 21 nonrheumatic autoimmune diseases identified by linkage between the Danish Patient Registry and Prescription Registry. The age- and sex-adjusted prevalence ratio (PR) was calculated by modified Poisson regression to estimate the prevalence at diagnosis in anti-CCP-positive vs anti-CCP-negative patients. The hazard ratio (HR) of polyautoimmunity within 5 years of entry into DANBIO was estimated in cause-specific Cox regression models. RESULTS: The study included 5839 anti-CCP-positive and 3799 anti-CCP-negative patients with RA. At first visit, the prevalence of prespecified polyautoimmune diseases in the Danish registers was 11.1% and 11.9% in anti-CCP-positive and anti-CCP-negative patients, respectively (PR 0.93, 95% CI 0.84-1.05). The most frequent autoimmune diseases were autoimmune thyroid disease, inflammatory bowel disease, and type 1 diabetes mellitus. During a mean follow-up of 3.5 years, only a few (n = 210) patients developed polyautoimmunity (HR 0.6, 95% CI 0.46-0.79). CONCLUSION: Polyautoimmunity as captured through the Danish National Patient Registry occurred in approximately 1 in 10 patients with RA at time of diagnosis regardless of anti-CCP status. In the years subsequent to the RA diagnosis, only a few and mainly anti-CCP-negative patients developed autoimmune disease.
Assuntos
Anticorpos Antiproteína Citrulinada , Artrite Reumatoide , Humanos , Estudos de Coortes , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/epidemiologia , Autoanticorpos , Dinamarca/epidemiologia , Peptídeos , Peptídeos CíclicosRESUMO
BACKGROUND AND PURPOSE: There is a growing need for rehabilitation services beyond hospitals. This study aims to describe challenges faced by cancer survivors (CSs) referred for rehabilitation in primary healthcare, employing standardized scales measuring health-related quality of life (HRQOL) and open-ended questions. Furthermore, the study explores the applicability of patient-reported outcomes (PROs) in comprehensively understanding challenges encountered by CSs. MATERIAL AND METHODS: This cross-sectional study involves CSs referred for cancer rehabilitation in a primary healthcare setting, including those participating in PROs as a part of routine practice. HRQOL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G). The International Classification of Functioning, Disability and Health (ICF) framed the analysis of responses to open-ended questions 'what concerns you the most?' and 'what matters to you?' Results: FACT-G showed the lowest scores for functional well-being (14.4) and emotional well-being (16.6), with higher scores for physical well-being (18.9) and social/family well-being (21.1). Responses to open-ended questions unveiled worries about everyday life and how cancer will impact family well-being presently and in the future. Furthermore, CSs reported a need to maintain normality and proactively address the challenges posed by the disease. INTERPRETATION: CSs referred for rehabilitation in primary healthcare experience comprehensive challenges necessitating a holistic rehabilitation approach. This includes interventions supporting CSs in dealing with uncertainty, regaining a sense of control, and addressing family well-being concerns. When using PROs for need assessment, the combination of validated HRQOL scales and open-ended questions is crucial for an in-depth understanding of CSs' challenges.
Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Qualidade de Vida/psicologia , Estudos Transversais , Atenção Primária à SaúdeRESUMO
AIM: Periodontitis is an inflammatory disease driven by opportunistic bacteria including Porphyromonas gingivalis and Fusobacterium nucleatum, where T-cell and NKT-cell responses to these bacteria in patients with periodontitis grade B or C are not fully elucidated. The objective is to determine if exaggerated proinflammatory Th-cell responses to periodontitis-associated bacteria, but not commensal bacteria, is a characteristic of increased periodontitis grade. METHODS: Mononuclear cells from patients with periodontitis grade C (n = 26) or grade B (n = 33) and healthy controls (HCs; n = 26) were stimulated with P. gingivalis, F. nucleatum or the commensal bacteria, Staphylococcus epidermidis and Cutibacterium acnes. Cytokine production by different T-cell populations and FOXP3-expression by regulatory T cells were assessed by flow cytometry. RESULTS: Compared to HCs, grade C patients had decreased frequencies of interleukin (IL)-10-producing CD4+ T cells before stimulation (p = .02) and increased frequencies of IFN-y-producing CD4+ T cells after stimulation with P. gingivalis (p = .0019). Grade B patients had decreased frequencies of FOXP3+ CD4+ T cells before (p = .030) before and after stimulation with anti-CD2/anti-CD3/anti-CD28-loaded beads (p = .047), P. gingivalis (p = .013) and S. epidermidis (p = .018). Clinical attachment loss correlated with the frequencies of IFN-y-producing Th1 cells in P. gingivalis- and F. nucleatum-stimulated cultures in grade B patients (p = .023 and p = .048, respectively) and with the frequencies of Th17 cells in P. gingivalis-stimulated cultures (p = .0062) in grade C patients. Patients with periodontitis grade C or grade B showed lower frequencies of IL-10-producing NKT cells than HCs in unstimulated cultures (p = .0043 and p = .027 respectively). CONCLUSIONS: Both periodontitis groups showed decreased frequencies of immunoregulatory T-cell and NKT cell subsets at baseline. Clinical attachment loss correlated with P. gingivalis-induced Th17-responses in grade C patients and with Th1-responses in grade B patients when cells were stimulated with P. gingivalis, supporting that dysregulated pro-inflammatory T-cell responses to periodontitis-associated bacteria contribute to the pathogenesis of periodontitis.
RESUMO
The OH-initiated photo-oxidation of piperidine and the photolysis of 1-nitrosopiperidine were investigated in a large atmospheric simulation chamber and in theoretical calculations based on CCSD(T*)-F12a/aug-cc-pVTZ//M062X/aug-cc-pVTZ quantum chemistry results and master equation modeling of the pivotal reaction steps. The rate coefficient for the reaction of piperidine with OH radicals was determined by the relative rate method to be kOH-piperidine = (1.19 ± 0.27) × 10-10 cm3 molecule-1 s-1 at 304 ± 2 K and 1014 ± 2 hPa. Product studies show the piperidine + OH reaction to proceed via H-abstraction from both CH2 and NH groups, resulting in the formation of the corresponding imine (2,3,4,5-tetrahydropyridine) as the major product and in the nitramine (1-nitropiperidine) and nitrosamine (1-nitrosopiperidine) as minor products. Analysis of 1-nitrosopiperidine photolysis experiments under natural sunlight conditions gave the relative rates jrel = j1-nitrosoperidine/jNO2 = 0.342 ± 0.007, k3/k4a = 0.53 ± 0.05 and k2/k4a = (7.66 ± 0.18) × 10-8 that were subsequently employed in modeling the piperidine photo-oxidation experiments, from which the initial branchings between H-abstraction from the NH and CH2 groups, kN-H/ktot = 0.38 ± 0.08 and kC2-H/ktot = 0.49 ± 0.19, were derived. All photo-oxidation experiments were accompanied by particle formation that was initiated by the acid-base reaction of piperidine with nitric acid. Primary photo-oxidation products including both 1-nitrosopiperidine and 1-nitropiperidine were detected in the particles formed. Quantum chemistry calculations on the OH initiated atmospheric photo-oxidation of piperidine suggest the branching in the initial H-abstraction routes to be â¼35% N1, â¼50% C2, â¼13% C3, and â¼2% C4. The theoretical study produced an atmospheric photo-oxidation mechanism, according to which H-abstraction from the C2 position predominantly leads to 2,3,4,5-tetrahydropyridine and H-abstraction from the C3 position results in ring opening followed by a complex autoxidation, of which the first few steps are mapped in detail. H-abstraction from the C4 position is shown to result mainly in the formation of piperidin-4-one and 2,3,4,5-tetrahydropyridin-4-ol, whereas H-abstraction from N1 under atmospheric conditions primarily leads to 2,3,4,5-tetrahydropyridine and in minor amounts of 1-nitrosopiperidine and 1-nitropiperidine. The calculated rate coefficient for the piperidine + OH reaction agrees with the experimental value within 35%, and aligning the theoretical numbers to the experimental value results in k(T) = 2.46 × 10-12 × exp(486 K/T) cm3 molecule-1 s-1 (200-400 K).
RESUMO
OBJECTIVE: Necrotizing soft-tissue infection (NSTI) in the head and neck area may develop from odontogenic infections. The aim of this study was to characterize patients with NSTI in the head and neck with odontogenic origin in a well-defined prospectively collected cohort. MATERIAL AND METHODS: Patients with NSTI in the head and neck, hospitalized between 2013 and 2017 at Copenhagen University Hospital and registered in the Scandinavian INFECT database were included. Medical records of identified patients and from the INFECT database were screened for a defined set of data including the primary focus of infection, comorbidities, predisposing factors, clinical and radiographic diagnostics, course of treatment, and treatment outcome. RESULTS: Thirty-five patients with NSTI in the head and neck area were included in the study. A total of 54% had odontogenic origin, primarily from mandibular molars, and 94% had radiographic signs of infectious oral conditions. Overall, comorbidities were reported in 51% with cardiovascular disease being the most prevalent. In 20%, no comorbidities or predisposing conditions could be identified. The overall 30-day mortality rate was 9%. CONCLUSIONS: More than half of NSTI cases in the head and neck region had an odontogenic origin, and special attention should be paid to infections related to mandibular molars.
Assuntos
Fasciite Necrosante , Infecções dos Tecidos Moles , Humanos , Infecções dos Tecidos Moles/diagnóstico , Infecções dos Tecidos Moles/terapia , Fasciite Necrosante/diagnóstico , Fasciite Necrosante/terapia , Estudos Retrospectivos , Pescoço , Resultado do TratamentoRESUMO
Genetic biomarkers could potentially lower the risk of treatment failure in chronic inflammatory diseases (CID) like psoriasis, psoriatic arthritis (PsA), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis assessing the association between single nucleotide polymorphisms (SNPs) and response to biologics. Odds ratio (OR) with 95% confidence interval (CI) meta-analyses were performed. In total, 185 studies examining 62,774 individuals were included. For the diseases combined, the minor allele of MYD88 (rs7744) was associated with good response to TNFi (OR: 1.24 [1.02-1.51], 6 studies, 3158 patients with psoriasis or RA) and the minor alleles of NLRP3 (rs4612666) (OR: 0.71 [0.58-0.87], 5 studies, 3819 patients with RA or IBD), TNF-308 (rs1800629) (OR: 0.71 [0.55-0.92], 25 studies, 4341 patients with psoriasis, RA, or IBD), FCGR3A (rs396991) (OR: 0.77 [0.65-0.93], 18 studies, 2562 patients with psoriasis, PsA, RA, or IBD), and TNF-238 (rs361525) (OR: 0.57 [0.34-0.96]), 7 studies, 818 patients with psoriasis, RA, or IBD) were associated with poor response to TNFi together or infliximab alone. Genetic variants in TNFα, NLRP3, MYD88, and FcRγ genes are associated with response to TNFi across several inflammatory diseases. Most other genetic variants associated with response were observed in a few studies, and further validation is needed.
Assuntos
Artrite Psoriásica , Artrite Reumatoide , Produtos Biológicos , Doenças Inflamatórias Intestinais , Polimorfismo de Nucleotídeo Único , Psoríase , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/tratamento farmacológico , Psoríase/genética , Psoríase/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Artrite Reumatoide/genética , Artrite Reumatoide/tratamento farmacológico , Artrite Psoriásica/genética , Artrite Psoriásica/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Fator 88 de Diferenciação Mieloide/genéticaRESUMO
Chemotherapy-induced mucositis increases the risk of blood stream infections (BSI) due to translocation of bacteria across the intestinal epithelium. Our study investigated if quantitative measures of intestinal mucositis severity, including plasma citrulline (a marker of functional enterocytes) and CCL20 (an intestinal immune homeostatic chemokine), could identify patients at risk of BSI. A total of 106 children with ALL undergoing induction treatment (NOPHO ALL 2008) were included and information regarding BSI episodes was collected from the patients' medical records. Twenty-seven patients (25%) developed BSI during induction. Patients with BSI had a larger decrease in citrulline after chemotherapy than patients without BSI, and nearly all BSI episodes (25/27) occurred in the group of patients exhibiting a drop in citrulline (OR = 6.4 [95% CI: 1.4-29.3], P = .008). Patients who developed BSI had higher plasma CCL20 levels on days 8, 15 and 22 than patients without BSI (all P < .05), and elevated CCL20 levels on day 8 increased the risk of subsequent BSI (OR = 1.57 [1.11-2.22] per doubling of CCL20 level, P = .01) in a multivariable logistic regression analysis. These findings suggest that children with ALL who develop BSI during chemotherapy are characterised by more severe intestinal mucositis, as measured by plasma citrulline and CCL20. These markers may be useful in early risk stratification to guide treatment decisions.
Assuntos
Mucosite , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Criança , Mucosite/induzido quimicamente , Citrulina , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Fatores de Risco , InflamaçãoRESUMO
Neutrophil extracellular traps (NETs) may play a pathogenic role in the thrombosis associated with myeloproliferative neoplasms (MPNs). We measured serum NET levels in 128 pretreatment samples from patients with MPNs and in 85 samples taken after 12 months of treatment with interferon alpha-2 (PEG-IFNα-2) formulations or hydroxyurea (HU). No differences in NET levels were observed across subdiagnoses or phenotypic driver mutations. In PV, a JAK2V617F+ allele burden ≥50% associated with increased NET levels (p = 0.006). Baseline NET levels correlated with neutrophil count (r = 0.29, p = 0.001), neutrophil-to-lymphocyte ratio (r = 0.26, p = 0.004) and JAK2V617F allele burden (r = 0.22, p = 0.03), particularly in patients with PV and with allele burden ≥50% (r = 0.50, p = 0.01, r = 0.56, p = 0.002 and r = 0.45, p = 0.03 respectively). In PV, after 12 months of treatment, NET levels decreased on average by 60% in patients with allele burden ≥50%, compared to only 36% in patients with an allele burden <50%. Overall, treatment with PEG-IFNα-2a or PEG-IFNα-2b reduced NETs levels in 77% and 73% of patients, respectively, versus only 53% of HU-treated patients (average decrease across treatments: 48%). Normalization of blood counts did not per se account for these reductions. In conclusion, baseline NET levels correlated with neutrophil count, NLR and JAK2V617F allele burden, and IFNα was more effective at reducing prothrombotic NET levels than HU.
Assuntos
Armadilhas Extracelulares , Transtornos Mieloproliferativos , Neoplasias , Humanos , Interferon alfa-2 , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/genética , Hidroxiureia/uso terapêutico , Janus Quinase 2/genética , MutaçãoRESUMO
Spin relaxation is an important aspect of the spin dynamics of free radicals and can have a significant impact on the outcome of their spin-selective reactions. Examples range from the use of radicals as spin qubits in quantum information processing to the radical pair reactions in proteins that may allow migratory birds to sense the direction of the Earth's magnetic field. Accurate modeling of spin relaxation, however, is non-trivial. Bloch-Redfield-Wangsness theory derives a quantum mechanical master equation from system-bath interactions in the Markovian limit that provides a comprehensive framework for describing spin relaxation. Unfortunately, the construction of the master equation is system-specific and often resource-heavy. To address this challenge, we introduce a generalized and efficient implementation of BRW theory as a new feature of the spin dynamics toolkit MolSpin which offers an easy-to-use approach for studying systems of reacting radicals of varying complexity.
Assuntos
Campos Magnéticos , Radicais LivresRESUMO
The post-translational modification citrullination has been proposed to play a role in the pathogenesis of multiple sclerosis (MS). Myelin basic protein (MBP) is a candidate autoantigen which is citrullinated to a minor extent under physiological conditions and hypercitrullinated in MS. We examined immune cell responses elicited by hypercitrullinated MBP (citMBP) in cultures of mononuclear cells from 18 patients with MS and 42 healthy donors (HDs). The immunodominant peptide of MBP, MBP85-99, containing citrulline in position 99, outcompeted the binding of native MBP85-99 to HLA-DR15, which is strongly linked to MS. Moreover, using the monoclonal antibody MK16 as probe, we observed that B cells and monocytes from HLA-DR15+ patients with MS presented MBP85-99 more efficiently after challenge with citMBP than with native MBP. Both citMBP and native MBP induced proliferation of CD4+ T cells from patients with MS as well as TNF-α production by their B cells and CD4+ T cells, and citrullination of MBP tended to enhance TNF-α secretion by CD4+ T cells from HLA-DR15+ patients. Unlike native MBP, citMBP induced differentiation into Th17 cells in cultures from HDs, while neither form of MBP induced Th17-cell differentiation in cultures from patients with MS. These data suggest a role for citrullination in the breach of tolerance to MBP in healthy individuals and in maintenance of the autoimmune response to MBP in patients with MS.
Assuntos
Esclerose Múltipla , Humanos , Citrulinação , Proteína Básica da Mielina , Células Th17/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
RESEARCH QUESTION: Is anti-Müllerian hormone (AMH) associated with live birth rate (LBR) in women with unexplained recurrent pregnancy loss (RPL)? DESIGN: Cohort study of women with unexplained RPL attending the RPL Unit, Copenhagen University Hospital, Denmark, between 2015 and 2021. AMH concentration was assessed upon referral, and LBR in the next pregnancy. RPL was defined as three or more consecutive pregnancy losses. Regression analyses were adjusted for age, number of previous losses, body mass index, smoking, treatment with assisted reproductive technology (ART) and RPL treatments. RESULTS: A total of 629 women were included; 507 (80.6%) became pregnant after referral. Pregnancy rates were similar for women with low and high AMH compared to women with medium AMH (81.9, 80.3 and 79.7%, respectively) (low AMH: adjusted odds ratio [aOR] 1.44, 95% confidence interval [CI] 0.84-2.47, P = 0.18; high AMH: aOR 0.98, 95% CI 0.59-1.64, P = 0.95). AMH concentrations were not associated with live birth. LBR was 59.5% in women with low AMH, 66.1% with medium AMH and 65.1% with high AMH (low AMH: aOR 0.68, 95% CI 0.41-1.11, P = 0.12, high AMH: aOR 0.96, 95% CI 0.59-1.56, P = 0.87). Live birth was lower in ART pregnancies (aOR 0.57, 95% CI 0.33-0.97, P = 0.04) and with higher numbers of previous losses (aOR 0.81, 95% CI 0.68-0.95, P = 0.01). CONCLUSION: In women with unexplained RPL, AMH was not associated with the chances of live birth in the next pregnancy. Screening for AMH in all women with RPL is not supported by current evidence. The chance of live birth among women with unexplained RPL achieving pregnancy by ART was low and needs to be confirmed and explored in future studies.
Assuntos
Aborto Habitual , Nascido Vivo , Gravidez , Feminino , Humanos , Hormônio Antimülleriano , Estudos de Coortes , Aborto Habitual/epidemiologia , Aborto Habitual/diagnóstico , Gravidez Múltipla , Taxa de Gravidez , Estudos Retrospectivos , Fertilização in vitroRESUMO
BACKGROUND: Although neutropenic fever is frequently observed during chemotherapy, only a minor proportion is caused by blood stream infections (BSI). This study investigated measurements of neutrophil chemotaxis as risk markers for BSI in children with acute lymphoblastic leukemia (ALL). METHODS: The chemokines CXCL1 and CXCL8 were measured weekly in 106 children with ALL during induction treatment. Information regarding BSI episodes was collected from the patients' medical records. RESULTS: During induction treatment, 102 (96%) patients developed profound neutropenia and 27 (25%) were diagnosed with BSI, debuting on median day 12 (range: 4-29). Patients developing BSI had increased levels of CXCL1 on days 8 and 15 as well as increased CXCL8 on days 8, 15, 22, and 29 compared to patients without BSI (all p < 0.05). Patients with BSI < day 12 exhibited increased CXCL1 and CXCL8 levels as early as day 8 (81 vs. 4 pg/mL, p = 0.031 and 35 vs. 10 pg/mL, p < 0.0001, respectively), while CXCL1 and CXCL8 were increased on day 15 (215 vs. 57 pg/mL, p = 0.022 and 68 vs. 17 pg/mL, p = 0.0002) and after (all p < 0.01) in patients with BSI ≥ day 12. CONCLUSION: The markers of neutrophil chemotaxis, CXCL1, and CXCL8 may help to identify patients at increased risk of BSI during chemotherapy-induced neutropenia.
Assuntos
Neutropenia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sepse , Humanos , Criança , Quimiotaxia , Neutrófilos , Quimiotaxia de Leucócito , Neutropenia/diagnóstico , Neutropenia/etiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológicoRESUMO
OBJECTIVES: To compare plasma levels of 92 cardiovascular- and inflammation-related proteins (CIRPs) and to analyse for associations with anti-cyclic citrullinated peptide (anti-CCP) status and disease activity in early and treatment-naive rheumatoid arthritis (RA). METHODS: Olink CVD-III-panel was used to measure 92 CIRP plasma levels in 180 early, treatment-naive, and highly inflamed RA patients from the OPERA trial. CIRP plasma levels as well as correlation between CIRP plasma levels and RA disease activity were compared between anti-CCP groups. CIRP level-based hierarchical cluster analysis was performed in each anti-CCP group separately. RESULTS: The study included 117 anti-CCP-positive and 63 anti-CCP-negative RA patients. Among the 92 CIRPs measured, the levels of chitotriosidase-1 (CHIT1) and tyrosine-protein-phosphatase non-receptor-type substrate-1 (SHPS-1) were increased and those of metalloproteinase inhibitor-4 (TIMP-4) decreased in the anti-CCP-negative group compared to anti-CCP-positive group. The strongest associations with RA disease activity were found for interleukin-2 receptor-subunit-alpha (IL2-RA) and E-selectin levels in the anti-CCP-negative group and for C-C-motif chemokine-16 levels (CCL16) in the anti-CCP-positive group. None of the differences passed the Hochberg sequential multiplicity test, however, the CIPRs were interacting and thus the prerequisites of the Hochberg procedure were not fulfilled. CIRP level-based cluster analysis identified two patient clusters in both anti-CCP groups. Demographic and clinical characteristics were similar in the two clusters for each anti-CCP group. CONCLUSIONS: In active and early RA, the findings regarding CHIT1, SHPS-1 TIMP-4, IL2-RA, E-selectin, and CCL16 differed between the two anti-CCP groups. In addition, we identified two patient clusters that were independent of the anti-CCP status.
Assuntos
Artrite Reumatoide , Selectina E , Humanos , Anticorpos Antiproteína Citrulinada , Interleucina-2 , Autoanticorpos , Artrite Reumatoide/diagnóstico , Inflamação , Peptídeos CíclicosRESUMO
This comment addresses a systematic error in the potential energy surfaces of the title reactions presented in the original article by Alkorta et al. The NO3 radical has D3h symmetry in the electronic ground state while the M08HX functional employed in the original article predicts an incorrect C2v geometry and energy. By combining thermodynamic data for the OH + HNO3 â H2O + NO3 reaction with spectroscopic data and results from M08HX calculations on HNO3, H2O and the OH radical, the ground state NO3 radical energy is estimated to be 37 kJ mol-1 lower than reported for the C2v geometry.
RESUMO
AIM: To investigate the association between previous periodontal treatment and recurrent events after first-time myocardial infarction (MI). MATERIALS AND METHODS: From the Danish nationwide registries, patients with first-time MI between 2000 and 2015 were divided into three groups according to oral health care within 1 year prior to first-time MI. A multiple logistic regression model provided adjusted odds ratios (ORs) with 95% confidence intervals (CIs) to assess the 3-year risk of major adverse cardiovascular events (MACE). RESULTS: A total of 103,949 patients were included. Patients with treated periodontitis (PD) prior to first-time MI had an adjusted 3-year risk of MACE similar to patients presumed periodontally healthy (OR 0.97 [95% CI 0.92-1.03]). Patients with no prior dental visits were significantly older, had more comorbidities and showed significantly increased adjusted 3-year risks of MACE (OR 1.47 [95% CI 1.42-1.52]), cardiovascular death (OR 1.71 [95% CI 1.64-1.78]) and heart failure (OR 1.13 [95% CI 1.07-1.20]) compared with patients presumed periodontally healthy. CONCLUSIONS: Patients with treated PD 1 year prior to first-time MI had a similar risk of recurrent cardiovascular events as patients presumed periodontally healthy. No dental visit prior to first-time MI was an independent risk factor for recurrent events.
Assuntos
Infarto do Miocárdio , Periodontite , Humanos , Estudos de Coortes , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Fatores de Risco , Periodontite/complicações , Periodontite/epidemiologia , Periodontite/terapia , Dinamarca/epidemiologiaRESUMO
OBJECTIVE: To explore rehabilitees' and professionals' experiences of goal-setting in a context of (un)certainty with a progressive neurodegenerative disease and how they navigate this (un)certainty in Parkinson's disease rehabilitation. DESIGN: A long-term multi-sited ethnographic fieldwork (2019-2020) following 20 rehabilitees and their goals over time and settings. Observation at 30 goal-setting meetings. PARTICIPANTS: Rehabilitees and professionals in Danish Parkinson's disease rehabilitation. Two randomly chosen groups of rehabilitees attending a Parkinson's disease course at a rehabilitation centre participated. METHODS: Semi-structured interviews and participant observation. RESULTS: Living with Parkinson's disease holds a certainty that the condition will progress yet an uncertainty regarding the pace and severity, as indicated by the notion (un)certainty. The (un)certainty challenges goal-setting. Reflecting on goal-setting, rehabilitees brought forth existential, economical, and societal considerations. Some expressed an ambivalent view, questioning the value of goal-setting with a progressive condition, yet finding own rehabilitation goals relevant. Others expressed a pragmatic view, attuning goals to fit the situation. Professionals found that the visible and invisible symptoms and the uncertain pace of Parkinson's made goal-setting challenging. They had to strike a balance between mentioning symptoms to come, yet not rendering the future too bleak. CONCLUSIONS: Rehabilitees and professionals found that setting goals in a condition that progresses is no easy task. They made use of strategies such as observation, repetition, future-proofing strategies, and attuning goals to navigate the (un)certainty. In goal-setting, to maintain functioning with progressive Parkinson's disease was a viable goal. Participants found they just do the best they can to navigate (un)certainty.
Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/reabilitação , Objetivos , Centros de Reabilitação , Antropologia CulturalRESUMO
OBJECTIVES: Recent studies have indicated that cerebral abscess (CA) patients with odontogenic origin are on the rise. However, CA patients are often poorly characterized and with an unknown etiologic background. The purpose of this study is to identify and characterize CA patients that may have an odontogenic origin based on microbiologic, radiographic, and/or clinical findings. MATERIALS AND METHODS: This is a population-based cohort study analyzing retrospective and prospective data from CA patients. Radiographic examinations of panoramic radiographs (PRs) or computed tomography (CT) scans were conducted. CA patients characterized with odontogenic origin required the fulfilment of the following criteria on admission: (1) Oral pathologic conditions were the only bacterial infections present, (2) oral microorganisms were isolated in the purulent exudate from the brain, and (3) radiographically and/or clinical recordings of oral pathologic conditions. RESULTS: A total of 44 patients could be included in this study of which 25 (57%) were characterized as having CA with a likely odontogenic origin. Type two diabetes (T2D) (p = 0.014) and microorganisms of the Streptococcus anginosus group (SAG) (p < 0.01) were overrepresented in patients with CAs of odontogenic origin. CONCLUSIONS: Odontogenic infections may cause CAs to a greater extent than previously assumed. T2D was overrepresented among patients with odontogenic CA. When microorganisms of the SAG were isolated from the brain pus, CA patients had a predisposing odontogenic or sinus infection. CLINICAL RELEVANCE: The identification of patients with a likely odontogenic CA will contribute to understanding the etiology of the infectious disease and highlighting the importance of preserving oral health.