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Journal of Personalized Medicine Sep 2023Psychotic disorders, notably schizophrenia, impose a detrimental burden on both an individual and a societal level. The mechanisms leading to psychotic disorders are... (Review)
Review
Psychotic disorders, notably schizophrenia, impose a detrimental burden on both an individual and a societal level. The mechanisms leading to psychotic disorders are multifaceted, with genetics and environmental factors playing major roles. Increasing evidence additionally implicates neuro-inflammatory processes within at least a subgroup of patients with psychosis. While numerous studies have investigated anti-inflammatory add-on treatments to current antipsychotics, the exploration of immunological biomarkers as a predictor of treatment response remains limited. This review outlines the current evidence from trials exploring the potential of baseline inflammatory biomarkers as predictors of the treatment effect of anti-inflammatory drugs as add-ons to antipsychotics and of antipsychotics alone. Several of the studies have found correlations between baseline immunological biomarkers and treatment response; however, only a few studies incorporated baseline biomarkers as a primary endpoint, and the findings thus need to be interpreted with caution. Our review emphasizes the need for additional research on the potential of repurposing anti-inflammatory drugs while utilizing baseline inflammatory biomarkers as a predictor of treatment response and to identify subgroups of individuals with psychotic disorders where add-on treatment with immunomodulating agents would be warranted. Future studies investigating the correlation between baseline inflammatory markers and treatment responses can pave the way for personalized medicine approaches in psychiatry centred around biomarkers such as specific baseline inflammatory biomarkers in psychotic disorders.
PubMed: 37763150
DOI: 10.3390/jpm13091382 -
Machine Learning to Predict Response to Ranibizumab in Neovascular Age-Related Macular Degeneration.Ophthalmology Science Dec 2023Neovascular age-related macular degeneration (nAMD) shows variable treatment response to intravitreal anti-VEGF. This analysis compared the potential of different...
PURPOSE
Neovascular age-related macular degeneration (nAMD) shows variable treatment response to intravitreal anti-VEGF. This analysis compared the potential of different artificial intelligence (AI)-based machine learning models using OCT and clinical variables to accurately predict at baseline the best-corrected visual acuity (BCVA) at 9 months in response to ranibizumab in patients with nAMD.
DESIGN
Retrospective analysis.
PARTICIPANTS
Baseline and imaging data from patients with subfoveal choroidal neovascularization secondary to age-related macular dengeration.
METHODS
Baseline data from 502 study eyes from the HARBOR (NCT00891735) prospective clinical trial (monthly ranibizumab 0.5 and 2.0 mg arms) were pooled; 432 baseline OCT volume scans were included in the analysis. Seven models, based on baseline quantitative OCT features (Least absolute shrinkage and selection operator [Lasso] OCT minimum [min], Lasso OCT 1 standard error [SE]); on quantitative OCT features and clinical variables at baseline (Lasso min, Lasso 1SE, CatBoost, RF [random forest]); or on baseline OCT images only (deep learning [DL] model), were systematically compared with a benchmark linear model of baseline age and BCVA. Quantitative OCT features were derived by a DL segmentation model on the volume images, including retinal layer volumes and thicknesses, and retinal fluid biomarkers, including statistics on fluid volume and distribution.
MAIN OUTCOME MEASURES
Prognostic ability of the models was evaluated using coefficient of determination (R) and median absolute error (MAE; letters).
RESULTS
In the first cross-validation split, mean R (MAE) of the Lasso min, Lasso 1SE, CatBoost, and RF models was 0.46 (7.87), 0.42 (8.43), 0.45 (7.75), and 0.43 (7.60), respectively. These models ranked higher than or similar to the benchmark model (mean R, 0.41; mean MAE, 8.20 letters) and better than OCT-only models (mean R: Lasso OCT min, 0.20; Lasso OCT 1SE, 0.16; DL, 0.34). The Lasso min model was selected for detailed analysis; mean R (MAE) of the Lasso min and benchmark models for 1000 repeated cross-validation splits were 0.46 (7.7) and 0.42 (8.0), respectively.
CONCLUSIONS
Machine learning models based on AI-segmented OCT features and clinical variables at baseline may predict future response to ranibizumab treatment in patients with nAMD. However, further developments will be needed to realize the clinical utility of such AI-based tools.
FINANCIAL DISCLOSURES
Proprietary or commercial disclosure may be found after the references.
PubMed: 37304043
DOI: 10.1016/j.xops.2023.100319 -
Journal of Clinical Medicine Jul 2023The inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure....
The inhibition of sodium-glucose co-transporter 2 (SGLT-2) has been shown to be beneficial in the treatment of diabetic and non-diabetic patients with heart failure. The underlying mechanisms are incompletely understood. The present prospective study investigates for the first time the effect of empagliflozin on various soluble markers of inflammation in patients with reduced ejection fraction (HFrEF). We included 50 inpatients with HFrEF and diabetes mellitus type 2. A total of 25 patients received a therapy with the SGLT-2-inhibitor empagliflozin in addition to standard medication; the other 25 patients did not receive empagliflozin and were considered the control group. Quality of life, functional status and soluble immunological parameters in serum were assessed at baseline and after 3 months. The baseline characteristics of both groups revealed no significant differences. Patients on empagliflozin demonstrated a significant improvement in the Minnesota living with heart failure questionnaire (baseline 44.2 ± 20.2 vs. 24 ± 17.7; < 0.001), in distance in the 6-min walk test (baseline 343 ± 145 m vs. 450 ± 115 m; < 0.001) and in soluble interleukin-6 level (baseline 21.7 ± 21.8 pg/mL vs. 13.7 ± 15.8 pg/mL; = 0.008). There was no significant change of these or other parameters in the control group ( > 0.05 each). The empagliflozin-induced improvement of quality of life and functional capacity in patients with HFrEF and type 2 diabetes mellitus is accompanied by a substantial reduction of interleukin-6 levels. Thus, anti-inflammatory effects may contribute to the benefits of SGLT-2-inhibitors in heart failure.
PubMed: 37445494
DOI: 10.3390/jcm12134458 -
Respiratory Medicine 2023The Severe Asthma Registry, founded by German Asthma Net (GAN) in 2011, is a prospective registry recording clinical parameters from participating centers in Germany,...
INTRODUCTION
The Severe Asthma Registry, founded by German Asthma Net (GAN) in 2011, is a prospective registry recording clinical parameters from participating centers in Germany, Austria and Switzerland. This article presents the baseline characteristics of severe asthma patients from Austrian centers.
METHODS
We analyzed the baseline visit data of all patients recruited to the GAN Severe Asthma Registry from participating Austrian centers.
RESULTS
Baseline visit data were available for 214 Austrian severe asthma patients from 6 Austrian centers from 2013 to 2022. Mean age was 53.7 years. Mean BMI was 26.4 kg/m2. More than a third (37.4%) of all patients had daily daytime asthma symptoms at baseline and had to use their reliever medication at least once per day. Forty-one percent of patients were classified as uncontrolled according to GINA and 24.8% as partially controlled at baseline visit. The median annual exacerbation frequency was 3 in the previous 12 months. At the time of baseline visit, 23.4% of all patients had regular treatment with oral corticosteroids. Furthermore, 23.9% had received any severe asthma monoclonal antibody prior to the baseline visit. There were no notable differences in baseline characteristics between patients categorized by smoking history or measurable type 2 inflammation.
CONCLUSIONS
This study provides the first multi-center characterization of Austrian severe asthma patients. Patients in this cohort had better asthma control and less frequent exacerbations compared to most international registries.
Topics: Humans; Middle Aged; Austria; Anti-Asthmatic Agents; Asthma; Adrenal Cortex Hormones; Antibodies, Monoclonal
PubMed: 37827294
DOI: 10.1016/j.rmed.2023.107427 -
Annual Review of Genetics Nov 2023Coral reefs are both exceptionally biodiverse and threatened by climate change and other human activities. Here, we review population genomic processes in coral reef... (Review)
Review
Coral reefs are both exceptionally biodiverse and threatened by climate change and other human activities. Here, we review population genomic processes in coral reef taxa and their importance for understanding responses to global change. Many taxa on coral reefs are characterized by weak genetic drift, extensive gene flow, and strong selection from complex biotic and abiotic environments, which together present a fascinating test of microevolutionary theory. Selection, gene flow, and hybridization have played and will continue to play an important role in the adaptation or extinction of coral reef taxa in the face of rapid environmental change, but research remains exceptionally limited compared to the urgent needs. Critical areas for future investigation include understanding evolutionary potential and the mechanisms of local adaptation, developing historical baselines, and building greater research capacity in the countries where most reef diversity is concentrated.
Topics: Animals; Humans; Coral Reefs; Anthozoa; Metagenomics; Genome; Biological Evolution; Climate Change; Ecosystem
PubMed: 37384733
DOI: 10.1146/annurev-genet-022123-102748 -
Frontiers in Endocrinology 2023This study aimed to assess the association of baseline insulin resistance (IR) surrogates and their longitudinal trajectories with cardiovascular diseases (CVD) to...
Impact of the baseline insulin resistance surrogates and their longitudinal trajectories on cardiovascular disease (coronary heart disease and stroke): a prospective cohort study in rural China.
BACKGROUND
This study aimed to assess the association of baseline insulin resistance (IR) surrogates and their longitudinal trajectories with cardiovascular diseases (CVD) to provide a useful reference for preventing CVD.
METHODS
This study was a prospective cohort study conducted in the 51st Regiment of the Third Division of Xinjiang Corps. A total of 6362 participants were recruited in 2016 to conduct the baseline survey, and the follow-up surveys in 2019, 2020, 2021, and 2022. The Kaplan-Meier method was used to estimate the cumulative incidence of CVD according to the baseline IR surrogates of metabolic insulin resistance score (METS-IR) and triglyceride-glucose (TyG) index. Cox regression models were used to assess the association between the baseline IR surrogates and CVD. The impact of the longitudinal trajectories of the IR surrogates on CVD was analyzed after excluding those with IR surrogate data measured ≤2 times. Based on the group-based trajectory model (GBTM), the trajectory patterns of IR surrogates were determined. The Kaplan-Meier method was used to estimate the cumulative incidence of CVD in each trajectory group of METS-IR and TyG index. Cox regression models were used to analyze the association between different trajectory groups of each index and CVD. In addition, the Framingham model was utilized to evaluate whether the addition of the baseline IR surrogates increased the predictive potential of the model.
RESULTS
Baseline data analysis included 4712 participants. During a median follow-up of 5.66 years, 572 CVD events were recorded (mean age, 39.42 ± 13.67 years; males, 42.9%). The cumulative CVD incidence increased with the ascending baseline METS-IR and TyG index quartiles (Q1-Q4). The hazard ratio and 95% confidence interval for CVD risk in Q4 of the METS-IR and TyG index were 1.79 (1.25, 2.58) and 1.66 (1.28, 2.17), respectively, when compared with Q1. 4343 participants were included in the trajectory analysis, based on the longitudinal change patterns of the METS-IR and TyG index, the following three trajectory groups were identified: low-increasing, moderate-stable, and elevated-increasing groups. Multivariate Cox regression revealed that the hazard ratio (95% confidence interval) for CVD risk in the elevated-increasing trajectory group of the METS-IR and TyG index was 2.13 (1.48, 3.06) and 2.63 (1.68, 4.13), respectively, when compared with the low-rising group. The C-index, integrated discrimination improvement value, and net reclassification improvement value were enhanced after adding the baseline METS-IR and TyG index values to the Framingham model (<0.05).
CONCLUSIONS
Elevated baseline IR surrogates and their higher long-term trajectories were strongly associated with a high risk of CVD incidence in Xinjiang's rural areas. Regular METS-IR and TyG index monitoring can aid in the early detection of CVD-risk groups.
Topics: Adult; Humans; Male; Middle Aged; Cardiovascular Diseases; China; Coronary Disease; Glucose; Insulin; Insulin Resistance; Prospective Studies; Stroke; Female
PubMed: 38189050
DOI: 10.3389/fendo.2023.1259062 -
Alzheimer's Research & Therapy Aug 2023Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD); however, the rates of cognitive decline are variable according to underlying... (Observational Study)
Observational Study
BACKGROUND
Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD); however, the rates of cognitive decline are variable according to underlying pathologies and biomarker status. We conducted an observational study and aimed to investigate baseline characteristics and biomarkers related with cognitive declines in SCD. Our study also assessed whether SCD participants showed different cognitive and biomarker trajectories according to baseline amyloid deposition.
METHODS
This study is a part of a longitudinal cohort study conducted in multi-centers in South Korea between 2018 and 2021. Individuals (≥ 60 years old) with persistent cognitive complaint despite of normal cognitive functions were eligible for the study. All participants underwent neuropsychological tests, florbetaben PET scans, plasma amyloid markers, and brain MRI scans. Annual follow-up evaluations included neuropsychological tests and assessments for clinical progressions. Regional brain volumetry and amyloid burden represented by PET-based standardized uptake value ratio (SUVR) were measured. We compared cognitive and brain atrophic changes over 24 months between amyloid positive-SCD (Aβ + SCD) and amyloid negative-SCD (Aβ-SCD) groups. Baseline factors associated with cognitive outcomes were investigated.
RESULTS
A total of 120 participants with SCD were enrolled and 107 completed follow-up evaluations. Aβ + SCD participants (n = 20, 18.5%) were older and more frequently APOE4 carriers compared with Aβ-SCD participants (n = 87). Baseline cognitive scores were not different between the two groups, except the Seoul Verbal Learning Test (SVLT) scores showing lower scores in the Aβ + SCD group. After 24 months, plasma amyloid markers were higher, and regional volumes (entorhinal, hippocampal, and pallidum) were smaller in the Aβ + SCD participants compared with Aβ-SCD participants adjusted by age, sex, and baseline volumes. SVLT delayed recall and controlled oral word association test (COWAT) scores indicated more declines in Aβ + SCD participants. Baseline left entorhinal volumes were related to verbal memory decline, while baseline frontal volumes and global SUVR values were related to frontal functional decline.
CONCLUSION
Aβ + SCD participants showed more cognitive decline and medial temporal atrophic changes during 24 months. Baseline neurodegeneration and amyloid burden were related with future cognitive trajectories in SCD.
TRIAL REGISTRATION
This study was registered at CRIS (KCT0003397).
Topics: Humans; Middle Aged; Amyloid beta-Peptides; Longitudinal Studies; Prospective Studies; Alzheimer Disease; Cognitive Dysfunction; Positron-Emission Tomography; Cognition; Cohort Studies; Biomarkers
PubMed: 37550761
DOI: 10.1186/s13195-023-01273-y -
The World Allergy Organization Journal Dec 2023H1-antihistamines (H1AH) are the first-line treatment for chronic spontaneous urticaria (CSU), but 50% of patients have inadequate disease control at standard doses.
BACKGROUND
H1-antihistamines (H1AH) are the first-line treatment for chronic spontaneous urticaria (CSU), but 50% of patients have inadequate disease control at standard doses.
OBJECTIVE
To assess the comorbidity burden and healthcare resource utilization (HRU) associated with non-response to H1AH-based treatments; to identify predictors of non-response.
METHODS
Optum® de-identified Electronic Health Record dataset (2007-2020) was used to identify adult patients with CSU who initiated a H1AH, alone or in combination with other oral non-biologics (index treatment). Based on twelve-month treatment patterns observed after index treatment initiation, patients were categorized as responders (continued index treatment or had only 1 next H1AH treatment without corticosteroids) or non-responders (continued corticosteroids or had 2 or more treatment switches). Patient characteristics and HRU were assessed in the 12 months before (baseline) and ≥12 months after (follow-up) index treatment initiation. Baseline predictors associated with non-response were identified using machine learning.
RESULTS
There were 17 062 patients who met inclusion criteria, and 14824 (86.9%) were classified as non-responders. A higher proportion of non-responders had records of CSU-related symptoms, comorbidities, polypharmacy, and certain laboratory tests than responders at baseline. A higher proportion of non-responders than responders visited an allergist or dermatologist during follow-up (59.5% vs 53.0%). Non-responders had a larger increase in hospitalizations (15.7% vs -2.4%) than responders during follow-up vs baseline. Predictors of non-response included index and baseline treatment classes, types of specialists seen, chronic pulmonary disease, depression, and female sex.
CONCLUSION
A large proportion of CSU patients treated with H1AH-based therapies had uncontrolled disease, contributing to increased HRU and patient burden. Non-responders had more comorbidities and HRU at baseline and follow-up, with steep increases in follow-up hospitalizations relative to baseline, highlighting an urgent need for early disease control.
PubMed: 38075554
DOI: 10.1016/j.waojou.2023.100843 -
International Immunopharmacology Oct 2023Systemic inflammation plays a role in carcinogenesis and is related to overall survival in patients with different cancer types, including those treated with immune...
BACKGROUND
Systemic inflammation plays a role in carcinogenesis and is related to overall survival in patients with different cancer types, including those treated with immune checkpoint blockade (ICB). The neutrophil-lymphocyte ratio (NLR) is calculated by circulating neutrophil to lymphocyte counts, which represents an indicator of the balance between the deleterious roles of neutrophilia and the beneficial roles of lymphocyte-mediated immunity. We hypothesized that the NLR may predict outcomes in metastatic colorectal cancer (mCRC) patients treated with immunotherapy.
MATERIALS AND METHODS
This retrospective study included 110 mCRC patients who were treated with immunotherapy at Sun Yat-sen University Cancer Center. Several inflammatory biomarkers were measured at baseline and after two cycles of treatment. The X-tile program was used to obtain the cutoff values. We examined the impact of both baseline and posttreatment inflammatory index levels on overall survival (OS).
RESULTS
In univariate analysis, both a low baseline NLR (P = 0.014) and a decreased NLR after 2 cycles of immunotherapy (P < 0.001) were considerably correlated with better OS. In multivariate analysis, age, liver metastasis, baseline lymphocyte-monocyte ratio (LMR), baseline NLR and early changes in NLR independently predicted OS. Patients with both a low baseline NLR and an early NLR reduction had the longest OS (median, 29.63 months). The best outcomes were remarkably observed in patients who had both an early NLR reduction and a high tumor mutational burden (TMB) (≥10 mut/Mb) (P < 0.0001).
CONCLUSIONS
Both a low baseline NLR and an early NLR reduction are significantly associated with a better prognosis in mCRC patients treated with immunotherapy. Further analysis indicated that the combination of NLR and TMB could obtain additional predictive power.
Topics: Humans; Neutrophils; Retrospective Studies; Lymphocytes; Prognosis; Colorectal Neoplasms; Immunotherapy
PubMed: 37536184
DOI: 10.1016/j.intimp.2023.110703