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Nature Medicine Aug 2023α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic)...
α-Synuclein aggregates constitute the pathology of Lewy body (LB) disease. Little is known about the effects of LB pathology in preclinical (presymptomatic) individuals, either as isolated pathology or coexisting with Alzheimer's disease (AD) pathology (β-amyloid (Aβ) and tau). We examined the effects of LB pathology using a cerebrospinal fluid α-synuclein-seed amplification assay in 1,182 cognitively and neurologically unimpaired participants from the BioFINDER study: 8% were LB positive, 26% Aβ positive (13% of those were LB positive) and 16% tau positive. LB positivity occurred more often in the presence of Aβ positivity but not tau positivity. LB pathology had independently negative effects on cross-sectional and longitudinal global cognition and memory and on longitudinal attention/executive function. Tau had cognitive effects of a similar magnitude, but these were less pronounced for Aβ. Participants with both LB and AD (Aβ and tau) pathology exhibited faster cognitive decline than those with only LB or AD pathology. LB, but not AD, pathology was associated with reduced sense of smell. Only LB-positive participants progressed to clinical LB disease over 10 years. These results are important for individualized prognosis, recruitment and choice of outcome measures in preclinical LB disease trials, but also for the design of early AD trials because >10% of individuals with preclinical AD have coexisting LB pathology.
Topics: Humans; alpha-Synuclein; Lewy Bodies; tau Proteins; Cross-Sectional Studies; Alzheimer Disease; Lewy Body Disease; Amyloid beta-Peptides; Cognition; Cognitive Dysfunction; Biomarkers; Positron-Emission Tomography
PubMed: 37464059
DOI: 10.1038/s41591-023-02450-0 -
Frontiers in Immunology 2023Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically...
BACKGROUND
Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically to cerebellar degeneration-related protein 2 (CDR2), predominantly affecting women with gynecologic or breast adenocarcinoma. Single-modality CDR2 testing may produce false-positive results. We assessed the performance characteristics of the more recently purported major PCA-1/Yo antigen, CDR2-like (CDR2L), side by side with CDR2, in a line blot format.
METHODS
CDR2 and CDR2L were tested in six specimen groups (serum and cerebrospinal fluid (CSF)). Group 1, PCA-1/Yo mouse brain indirect immunofluorescence assay (IFA) positives; Group 2, PCA-1/Yo IFA mimics; Group 3, suspected CDR2 line blot false positives; Group 4, consecutive patient samples tested for neural antibodies over 1 year; Group 5, healthy subject serums; and Group 6, polyclonal (non-specific) immunoglobulin G (IgG)-positive serums.
RESULTS
Group 1: Of 64 samples tested, all but two were CDR2 positive (both CSF samples) and all were CDR2L positive. In individual patients, CDR2L values were always higher than CDR2. The two "CDR2L-only" positives were CSF samples with low titer PCA-1/Yo by IFA with serum negativity but with typical clinical phenotype. Group 2: All 51 PCA-1/Yo mimics were CDR2/CDR2L negative. Group 3: Nine samples [six of 1289 (0.47%) serums and three of 700 CSF samples (0.43%) were PCA-1/Yo IFA negative/CDR2 positive; two of the six available (serums from the same patient) were also CDR2L positive; the other four CDR2L negative had low CDR2 values (17-22). Group 4: Twenty-two patients had unexpected CDR2 or CDR2L positivity; none had tissue IFA positivity. Eleven of the 2,132 serum (0.5%) and three of the 677 CSF (0.4%) samples were CDR2 positive; median value was 19 (range, 11-48). Seven of the 2,132 serum (0.3%) and three of the 677 CSF (0.4%) samples were CDR2L positive; median value was 18 (range, 11-96). Group 5: All 151 healthy serum samples were negative. Group 6: One of the 46 polyclonal serum samples was CDR2L positive. Optimum overall performance was accomplished by requiring both CDR2 and CDR2L positivity in serum (sensitivity, 100%; and specificity, 99.9%) and positivity for CDR2L in CSF (sensitivity, 100%; and specificity, 99.6%).
CONCLUSION
CDR2L provides additional PCA-1/anti-Yo sensitivity in CSF, and dual positivity with CDR2 provides additional specificity assurance in serum. Combining antigen-specific and tissue-based assays optimizes PCA-1/anti-Yo testing.
Topics: Animals; Mice; Humans; Female; Autoantibodies; Autoimmunity; Paraneoplastic Cerebellar Degeneration; Nerve Tissue Proteins; Cytoplasm; Neurodegenerative Diseases
PubMed: 37841252
DOI: 10.3389/fimmu.2023.1265797 -
Critical Reviews in Oncology/hematology Sep 2023Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Our study aims to evaluate programmed cell death ligand-1 (PD-L1) expression and its prognostic significance in cervical cancer (CC), endometrial cancer (EC) and ovarian cancer (OC).
METHODS
Several electronic databases were searched. Fixed effects models or random effects models were employed to calculate the pooled prevalence of PD-L1 positivity and pooled hazard ratios (HRs) as appropriate. Heterogeneity and publication bias were also assessed.
RESULTS
The pooled prevalence of PD-L1 positivity was 58.1%, 33.8% and 37.5% for CC, EC and OC patients, respectively. There were significant differences in the pooled estimates after stratification by PD-L1-positive assessment criteria and antibody clones. PD-L1 positivity was associated with worse OS in CC and EC patients and poorer progression-free survival (PFS) in CC patients.
CONCLUSIONS
The prevalence of PD-L1-positive expression was considerably high in CC and modestly high in EC and OC patients. PD-L1 expression has the potential to be a prognostic biomarker for predicting the clinical outcomes of patients with CC and EC but not OC.
Topics: Female; Humans; Prognosis; B7-H1 Antigen; Prevalence; Ovarian Neoplasms; Proportional Hazards Models; Uterine Cervical Neoplasms; Endometrial Neoplasms
PubMed: 37536446
DOI: 10.1016/j.critrevonc.2023.104084 -
Annals of Medicine Dec 2023Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether...
BACKGROUND
Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether stress echocardiography and coronary computed tomography angiography (CCTA) could detect CAD in end-stage liver disease (ESLD) patients without previous evidence of heart disease.
METHODS
LT candidates ≥30 years underwent a cardiovascular (CV) assessment through stress echocardiography. CCTA was performed in patients ≥50 years with two or more CV risk factors (e.g. diabetes, CAD family history, dyslipidaemia). Coronary angiography (CAG) was scheduled when stress echocardiography and/or CCTA were positive. Sensibility, specificity, positive and negative predictive values of stress echocardiography and CCTA were assessed by numbers of coronary revascularization (true positives) and lack of acute coronary events over a mean follow-up of 3 years (true negatives).
RESULTS
Stress echocardiography was performed in 273 patients, CCTA in 34 and CAG in 41. Eight patients had critical coronary lesions, and 19 not-critical lesions. Sensitivity, specificity, positive and negative predictive values were 50.0%, 90.2%, 13.3% and 98.4% for stress echocardiography and 100%, 76.7%, 36.4% and 100% for CCTA. Among 163 patients who underwent LT (57.6%), 16 died and 5 had major adverse CV events over a mean follow-up of 3 years.
CONCLUSIONS
A very low prevalence of CAD in a selected population of ESLD at intermediate to high CV risk was found. A screening based on stress echocardiography and CCTA resulted in low incidence of post-LT acute coronary events in ELSD patients. CAD has no impact on mid-term survival.
Topics: Humans; Coronary Artery Disease; Liver Transplantation; Myocardial Ischemia; Coronary Angiography; Tomography, X-Ray Computed; Predictive Value of Tests
PubMed: 37493458
DOI: 10.1080/07853890.2023.2237521 -
Le Infezioni in Medicina 2023Antibiotic resistance of Gram-positive and Gramnegative bacteria is becoming increasingly prevalent. For this reason, the search for new molecules that can overcome... (Review)
Review
Antibiotic resistance of Gram-positive and Gramnegative bacteria is becoming increasingly prevalent. For this reason, the search for new molecules that can overcome current resistance and also recover antibiotics that are no longer effective is becoming increasingly urgent. Our research group at the 'Polytechnic University of Marche' managed to study the effectiveness of certain antimicrobial peptides (AMPs). We decided to review our experience with AMPs by classifying them according to their origin and evaluating their effect on Gram-negative and Gram-positive bacteria. AMPs can derive from mammals, amphibians, microorganisms, and insects. In conclusion, our research experience shows that the richest source of AMPs are amphibians. However, the studies done are mainly in vitro or in animal models, requiring further human studies to assess the efficacy and safety of these molecules. AMPs may be a new therapeutic option for infections sustained by multi-resistant micro-organisms and for overcoming the mechanisms of resistance to antibiotics currently used. In particular, combining AMPs with antibiotics, including those with limited antimicrobial activity due to antimicrobial resistance, has often shown a synergistic effect, increasing or restoring their efficacy. The possibility of using manageable and relatively safe antibiotics again is crucial, considering the widespread increase in bacterial resistance in hospitals and the community. Despite a plethora of research on AMPs and their application as potential treatment on infectious diseases, this area needs further exploration. There is evidence that the characteristics of AMPs can seriously improve through structural chemical modifications and different delivery systems to become alternatives drugs to conventional antibiotics. The aim is to provide an overview of the possible sources from which AMPs are extracted, evaluating their action exclusively on Gram-positive and negative bacteria. This is to determine, based on our experience, which might be the most promising sources of AMPs for future research as well.
PubMed: 37701381
DOI: 10.53854/liim-3103-5 -
Frontiers in Endocrinology 2023Autoimmune thyroid disease is a prevalent condition affecting women of reproductive age, leading to thyroid dysfunction and impacting pregnancy outcomes. While the...
BACKGROUND
Autoimmune thyroid disease is a prevalent condition affecting women of reproductive age, leading to thyroid dysfunction and impacting pregnancy outcomes. While the critical role of thyroid hormone in pregnancy outcomes is well-established, the potential association between positive anti-thyroid peroxidase antibodies (TPOAb) and adverse pregnancy outcomes in pregnant women with normal thyroid function remains unclear.
OBJECTIVE
This study aims to investigate the relationship between maternal TPOAb positivity and adverse pregnancy outcomes with normal thyroid function.
METHODS
We collected baseline information from pregnant women who visited our hospital between February 2009 and June 2012. Blood samples were taken to measure thyroid stimulating hormone (TSH), free thyroxine (FT4), TPOAb, and anti-thyroglobulin antibodies (TGAb). The incidence of adverse pregnancy outcomes was compared between TPOAb-positive and TPOAb-negative groups among participants with normal thyroid function.
RESULTS
A total of 7,046 pregnant women with normal thyroid function were included, comprising 6,700 with negative TPOAb and 346 with positive TPOAb. The TPOAb-positive group exhibited a higher age (26.0 vs. 27.0 years, = 0.02) and greater serum TSH levels (1.72 vs. 1.94 mIU/L, = 0.029), while the gestational week of blood collection was lower (31.9 vs. 26.5 weeks, = 0.001). Univariate analysis revealed a higher incidence of low birth weight (LBW) in offspring of TPOAb-positive women compared to the TPOAb-negative group (3.5% vs. 1.9%, = 0.035). After adjusting for confounding factors such as age, gestational week of blood collection, menstrual history, education level, gestational diabetes, gestational hypertension, TGAb, TSH, and FT4, TPOAb positivity emerged as an independent risk factor for LBW infants (OR: 2.317, 95% CI: 1.057-5.076, = 0.036), while other adverse pregnancy outcomes did not show a significant correlation with TPOAb positivity.
CONCLUSION
Our findings suggest that TPOAb-positive pregnant women with normal thyroid function are more likely to deliver LBW infants. Regular monitoring of TPOAb-positive pregnancies and timely interventions throughout all stages of pregnancy are crucial.
Topics: Infant, Newborn; Female; Pregnancy; Humans; Infant; Iodide Peroxidase; Thyroxine; Incidence; Thyroid Hormones; Thyrotropin; Infant, Low Birth Weight
PubMed: 38047117
DOI: 10.3389/fendo.2023.1285504 -
Clinical and Translational... Sep 2023Helicobacter pylori colonizes the human stomach. Infection causes chronic gastritis and increases the risk of gastroduodenal ulcer and gastric cancer. Its chronic...
INTRODUCTION
Helicobacter pylori colonizes the human stomach. Infection causes chronic gastritis and increases the risk of gastroduodenal ulcer and gastric cancer. Its chronic colonization in the stomach triggers aberrant epithelial and inflammatory signals that are also associated with systemic alterations.
METHODS
Using a PheWAS analysis in more than 8,000 participants in the community-based UK Biobank, we explored the association of H. pylori positivity with gastric and extragastric disease and mortality in a European country.
RESULTS
Along with well-established gastric diseases, we dominantly found overrepresented cardiovascular, respiratory, and metabolic disorders. Using multivariate analysis, the overall mortality of H. pylori -positive participants was not altered, while the respiratory and Coronovirus 2019-associated mortality increased. Lipidomic analysis for H. pylori -positive participants revealed a dyslipidemic profile with reduced high-density lipoprotein cholesterol and omega-3 fatty acids, which may represent a causative link between infection, systemic inflammation, and disease.
DISCUSSION
Our study of H. pylori positivity demonstrates that it plays an organ- and disease entity-specific role in the development of human disease and highlights the importance of further research into the systemic effects of H. pylori infection.
Topics: Humans; Helicobacter pylori; Gastritis; Gastritis, Atrophic; Peptic Ulcer; Stomach Neoplasms; Helicobacter Infections
PubMed: 37367296
DOI: 10.14309/ctg.0000000000000610 -
Frontiers in Immunology 2023Myelin-oligodendrocyte glycoprotein antibody (MOG)-associated disorder (MOGAD) is a recently identified immune-mediated inflammatory disorder of the central nervous...
INTRODUCTION
Myelin-oligodendrocyte glycoprotein antibody (MOG)-associated disorder (MOGAD) is a recently identified immune-mediated inflammatory disorder of the central nervous system (CNS). The significance of oligoclonal bands (OCBs) is not fully elucidated. This study investigated the clinical differences between patients with MOGAD who tested positive or negative for OCBs.
METHODS
The study was conducted on 23 patients with MOG-IgG-seropositivity who presented with central nervous system (CNS) symptoms. The patients were screened and divided into OCB-positive (n=10) and OCB-negative (n=13) groups, and their demographic, clinical, and magnetic resonance imaging (MRI) features were compared.
RESULTS
The results revealed that patients with OCB-positivity had a significantly higher frequency of relapse, and their IgG index was significantly higher.
DISCUSSION
OCBs were common in MOGAD met the consensus criteria. The study concluded that careful treatment decision-making is necessary in MOG antibody-positive cases with OCB-positivity.
Topics: Humans; Oligoclonal Bands; Myelin-Oligodendrocyte Glycoprotein; Chronic Disease; Central Nervous System; Immunoglobulin G
PubMed: 37520579
DOI: 10.3389/fimmu.2023.1211776