Tag: pubmed

Transl Vis Sci Technol. 2024 Nov 4;13(11):14. doi: 10.1167/tvst.13.11.14.

ABSTRACT

PURPOSE: To characterize faricimab ocular and systemic pharmacokinetics (PK) in patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) and to assess the effect of faricimab ocular exposure on clinical endpoints.

METHODS: A population PK (popPK) model was developed using pooled data from phase 1 to 3 studies in patients with nAMD/DME. The dataset included 1095 faricimab aqueous humor (AH) concentrations from 284 patients and 8372 faricimab plasma concentrations from 2246 patients.

RESULTS: Following intravitreal administration, faricimab PK was accurately described by a linear three-compartment model with sequential vitreous humor (VH), AH, and plasma compartments. Faricimab VH elimination to AH is the slowest process, with an estimated half-life (t1/2) of 7.5 days. Due to flip-flop kinetics, plasma, AH, and VH concentrations declined in parallel. Disease had no effect on faricimab PK. Plasma exposure was ∼6000-fold lower than VH exposure. Age, anti-drug antibodies, body weight, and sex statistically significantly influenced PK parameters but had no clinically meaningful effect on ocular and systemic exposure. VH t1/2 alone could not explain faricimab dosing frequency. Exposure-response analyses showed similar gains in best-corrected visual acuity across faricimab exposure ranges and dosing regimens.

CONCLUSIONS: Faricimab ocular and systemic pharmacokinetics were quantified and accurately described by the popPK model, developed using a large dataset from patients with nAMD/DME. Exposure-response analyses suggest that faricimab phase 3 dosing algorithms are appropriate to select the most suitable dosing regimen.

TRANSLATIONAL RELEVANCE: The popPK analysis suggested that faricimab dosing frequency was influenced by several factors and not by VH t1/2 alone.

PMID:39535744 | DOI:10.1167/tvst.13.11.14

Oncol Ther. 2024 Nov 13. doi: 10.1007/s40487-024-00313-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Prostate cancer and its treatment, particularly androgen deprivation therapy (ADT), can profoundly impact patients’ quality of life. The aim of the prospective observational study reported here was to evaluate the effects of ADT on various aspects of quality of life in men with prostate cancer at a community-based hospital in Southern Italy.

METHODS: Eligible men initiating hormonal therapy were recruited between December 2021 and December 2023. Data were collected at baseline (T₀) and after 3 months (T₁) and 6 months (T₂) of ADT using standardized questionnaires (European Organization for Research and Treatment of Cancer [EORTC] QLQ-C30, EORTC QLQ-PR25) and semi-structured interviews.

RESULTS: Of the 52 participants, 43 completed all three assessments. The EORTC QLQ-C30 showed a statistically significant worsening in physical functioning (mean score decrease from 83.8 at T₀ to 76.7 at T₂; p < 0.001), increased fatigue (from 23.7 to 35.2; p < 0.001), and insomnia (from 23.7 to 31.8; p = 0.048) following ADT initiation. The QLQ-PR25 revealed a significant decline in sexual functioning (from 59 to 26.9; p < 0.001) and sexual activity (from 27.3 to 12; p = 0.001). Interviews revealed a significant rise in the number of patients reporting depressed mood. Interviews also highlighted a worsening in body image perception and sexuality, increased feelings of dependence, and challenges in the social and relational spheres.

CONCLUSIONS: ADT significantly impacts various aspects of quality of life in men with prostate cancer, particularly physical functioning, fatigue, sexual function, body image, and emotional well-being. These results underscore the critical importance of a comprehensive, patient-centered approach that addresses both the physical and psychosocial aspects of care.

PMID:39535725 | DOI:10.1007/s40487-024-00313-3

MAGMA. 2024 Nov 13. doi: 10.1007/s10334-024-01213-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To optimize high-resolution 7 T MRI of the cochlea and measure normal cochlea and the cochlear nerve morphometry in vivo.

MATERIALS AND METHODS: Eight volunteers with normal hearing were scanned at 7 T using an optimized protocol. Two neuroradiologists independently scored image quality. The basal turn lumen diameter (BTLD), height, width, length and volume of the cochlear, long (LD) and short (SD) diameter the calculated cross-sectional area (CSA) of the cochlear nerve were measured. Intra and inter-observer reliability was assessed using intraclass correlation (ICC).

RESULTS: 3D T2W DRIVE combined with dielectric pads, allowed acquisition of high-resolution images showing detailed structures, such as the crista ampullaris in the semicircular canals. The overall grading scores from neuroradiologists were excellent. In the left ear, averaging over all subjects gave BTLD of 2.6 ± 0.05 mm, height of 4.9 ± 0.1 mm, width of 4.4 ± 0.2 mm, length of 36.5 ± 0.4 mm, volume of 0.16 ± 0.02 ml, LD of 1.31 ± 0.1 mm, SD of 1.06 ± 0.1 mm, and CSA of 1.1 ± 0.1 mm². The right ear gave BTLD of 2.6 ± 0.04 mm, height of 4.9 ± 0.1 mm, width of 4.4 ± 0.3 mm, length of 35.5 ± 0.4 mm, volume of 0.16 ± 0.02 ml, LD of 1.29 ± 0.1 mm, SD of 1.07 ± 0.1 mm, and CSA of 1.10 ± 0.2 mm². No statistically significant difference was found between the sides of the head (p-value > 0.05). The intra-observer reliability was high (0.77-0.94), while the inter-observer reliability varied from moderate to high (0.55-0.81).

CONCLUSION: 7 T MRI can provide excellent visualization of the internal structure of the cochlear and of the vestibulocochlear nerve in vivo.

PMID:39535680 | DOI:10.1007/s10334-024-01213-3

Clin Exp Med. 2024 Nov 13;25(1):4. doi: 10.1007/s10238-024-01519-5.

ABSTRACT

Existing challenges in accurately diagnosing various rheumatic diseases (RDs) have stimulated the search for novel biomarkers to aid clinical evaluation and monitoring. We conducted a systematic review and meta-analysis of studies investigating the candidate biomarker endoglin (CD105), a transmembrane glycoprotein expressed in endothelial, myeloid, and lymphoid cells, in RD patients and healthy controls. We searched PubMed, Scopus, and Web of Science from inception to 10 August 2024 to identify relevant studies. We evaluated the risk of bias using the JBI Critical Appraisal Checklist and the certainty of evidence using GRADE (PROSPERO registration number: CRD42023581008). Overall, circulating endoglin concentrations were significantly higher in RD patients compared to controls (13 studies; standard mean difference, SMD = 0.64, 95% CI 0.13 to 1.14, p = 0.014; low certainty of evidence). The effect size of the between-group differences in endoglin concentrations was not significantly associated with age, male-to-female ratio, year of publication, number of participants, or mean RD duration. By contrast, the effect size was statistically significant in studies conducted in the European region (p = 0.033), involving patients with systemic sclerosis (p = 0.032), and measuring serum (p = 0.019). The results of this systematic review and meta-analysis suggest the potential pathophysiological role of endoglin in RDs. This, however, requires further investigation in prospective studies, particularly in patients with systemic sclerosis.

PMID:39535678 | DOI:10.1007/s10238-024-01519-5

Int J Cardiovasc Imaging. 2024 Nov 13. doi: 10.1007/s10554-024-03278-6. Online ahead of print.

ABSTRACT

Left ventricular mechanical dyssynchrony (LVMD) is an important prognostic factor for heart failure (HF). Phase analysis of myocardial perfusion SPECT is actively being researched to evaluate LVMD. We performed a systematic review and meta-analysis on the prognostic significance of LVMD using gated SPECT in HF patient. PubMed, Embase, and the Cochrane library were searched until January 10, 2024, for studies reporting the prognostic value of LVMD in HF patients using gated SPECT for outcomes of all-cause death, cardiac death, or major adverse cardiovascular event (MACE). Hazard ratios (HRs) along with their corresponding 95% confidence intervals (CIs) were combined through meta-analysis employing a random-effects model. Funnel plots and Egger’s tests were utilized to evaluate publication bias, and trim-and-fill method were applied where bias was identified. Ten studies (2585 patients) were included; six on MACE and five on all-cause or cardiac death. Prognoses were worse in patients with LVMD assessed by SPECT than in those without LVMD, with the overall pooled HR for MACE being 2.05 (95% CI, 1.65-2.54). The pooled HR for all-cause or cardiac death was 2.08 (95% CI, 1.10-3.94); however, publication bias was present (p = 0.0024), and after adjustment, the prognostic value of LVMD was not statistically significant (HR, 1.24; 95% CI, 0.68-2.23). Assessing LVMD through myocardial perfusion SPECT proves to be a significant indicator of subsequent adverse cardiac events in HF patients. Utilizing phase analysis of SPECT could offer valuable insights for risk assessment and decision-making regarding therapy in HF patients.

PMID:39535673 | DOI:10.1007/s10554-024-03278-6

Inflammation. 2024 Nov 13. doi: 10.1007/s10753-024-02169-1. Online ahead of print.

ABSTRACT

Our two previous studies observed that cell division cycle 42 (CDC42) was lower and correlated with improved renal function and inflammation in diabetic nephropathy (DN) patients, and CDC42 inhibited renal tubular epithelial cell fibrosis and inflammation under high glucose condition. Sequentially, this current study aimed to investigate the effect of CDC42 on improving renal function, fibrosis, and inflammation in DN mice, and its interaction with T cell receptor (TCR) related pathways. Mice were treated by streptozotocin to construct early-stage DN model, then transfected with CDC42 overexpression adenovirus, followed by simultaneous treatment of LY294002 (PI3K/AKT inhibitor) and CI-1040 (ERK inhibitor), respectively. CDC42 reduced blood glucose, creatinine, and 24 h urine protein in DN mice, but only showed a tendency to decrease blood urea nitrogen without statistical significance. Hematoxylin&eosin staining revealed that CDC42 descended the glomerular volume, basement membrane thickness, and inflammatory cell infiltration in kidney. Meanwhile, CDC42 lowered fibronectin, TGF-β1, and Collagen I expressions in kidney, but not decreased α-SMA significantly. Besides, CDC42 decreased T-helper (Th) 1 and Th17 cells in kidney, and reduced serum IFN-γ, IL-1β, IL-17A, and TNF-α but not IL-6. Regarding TCR-related pathways, CDC42 activated AKT and ERK pathways but not JNK pathway. However, the treatment of LY294002 and CI-1040 had limited effect on attenuating CDC42’s functions on renal function and fibrotic markers. CDC42 improves renal functions, fibrosis, Th1/Th17 infiltration and inflammation to some degree in DN mice, these functions may be independent to AKT and ERK pathways.

PMID:39535664 | DOI:10.1007/s10753-024-02169-1

Eur J Nutr. 2024 Nov 13;64(1):2. doi: 10.1007/s00394-024-03521-9.

ABSTRACT

OBJECTIVES: The potential association between oral health and nutritional status of the very old, has been poorly investigated. Thus, we carried out the cross-sectional study to evaluate the association of oral health with the nutritional status of the older adults.

METHODS: 210 participants aged over 75 years were included in the study. Nutritional status was assessed by the Short-form Mini-Nutritional Assessment (MNA-SF) and body composition measurement. Data were available for self-reported oral health (10-item Eating Assessment Tool (EAT-10) and Chewing Function Questionnaire (CFQ)) and specific experimental tests including salivary flow, tongue and lip pressure, occlusal force, water swallow test and taste test for the detection of oral functions. Spearman rank correlation was used to analyze the correlation between body composition and oral health. Logistic regression and restricted cubic spline models were applied to examine the association of oral health with malnutrition.

RESULTS: The study reveals that poor oral health is related to the malnutrition. The tongue pressure and molar occlusal force were significantly associated with malnutrition in an L-shaped dose-response relationship after adjustment for potential confounding factors. The higher the tongue pressure and molar occlusal force, the lower the risk of malnutrition. Besides, the CFQ score, salty, sour, and bitter taste, are risk factors for malnutrition.

CONCLUSIONS: The presence of malnutrition is significantly associated with poor oral health in older adults. Our study supposes that the design of food suitable for oral conditions of the older adults may be another feasible solution to the nutritional problems among them.

PMID:39535606 | DOI:10.1007/s00394-024-03521-9

West Afr J Med. 2024 Nov 10;41(11 Suppl 1):S19.

ABSTRACT

BACKGROUND: Sickle cell cardiomyopathy is becoming a neglected tropical cardiovascular disease, yet the most common cause of death in HbSS patients. Myocardial strain using speckle tracking has recently been validated as a tool for the detection of subclinical left ventricular systolic dysfunction. Its utility in sickle cell disease in Nigeria is unknown.

OBJECTIVES: The study aims to evaluate global longitudinal left ventricular (GL LV) strain pattern in black SCD patients in steady state, and correlate that with clinico-laboratory and electrocardiographic (ECG) measurements. Furthermore, we will evaluate the timeline for the earliest detectable cardiac changes in SCD detectable by ECG or speckle tracking.

METHOD: 60 sickle cell patients between ages 5 and 40 years will be matched with 60 controls. Baseline clinic-laboratory data will be collected. All participants will have electrocardiography and speckle-tracking echocardiography of the left ventricle. The primary outcome is the global LV longitudinal strain in HBSS and matched control. Secondary outcomes are the clinico-laboratory and electrocardiographic correlates of LV strain in black HBSS patients as well as tracking the earliest detectable cardiovascular change in the life spectrum from childhood to adulthood. Regression analysis and other statistical models will be used.

CONCLUSION: The simplicity of the study design is crafted to spark interest in life-threatening cardiovascular complications of sickle cell disease beyond pulmonary hypertension.

PMID:39535588

Plant Biol (Stuttg). 2024 Nov 7. doi: 10.1111/plb.13735. Online ahead of print.

ABSTRACT

The root system harbours complex bacterial communities, which are critical for plant growth and health. Significant differences exist between bacterial communities in the root compartments; however, limited reports have explored their phylogenetic composition and niche conservatism in the root system of sorghum. We used the sorghum Hongyingzi cultivar as test plant, and applied 16S rRNA high-throughput sequencing and various statistical approaches. Phylogenetic composition of bacterial communities in root compartments were primarily driven by closely related species with similar environmental adaptations. We also found evidence of phylogenetic niche conservatism in bacterial communities for edaphic factors in the various root compartments, with pH and available N playing essential roles in shaping community composition. Environmental threshold analysis revealed threshold ranges of dominant taxa for pH and available N, indicating wider adaptive thresholds for more abundant taxa. Reconstruction of ancestral states suggested evolutionary changes in adaptability of certain bacterial taxa to edaphic factors, suggesting a shift towards slightly acidic, high N environments and reflecting the prolonged mutual interaction between bacteria and plants in cultivated soils. These findings enhance our understanding of environmental responses and evolutionary dynamics of root-associated microbiota in young sorghum plants and provide novel insights into ecological adaptations, shedding light on their responses to environmental factors. Our study contributes to a better understanding of the ecological dynamics of root-associated microbiota and offers analytical pathways for exploring the nutritional regulation of root microbiota.

PMID:39506791 | DOI:10.1111/plb.13735

Epidemiol Psychiatr Sci. 2024 Nov 7;33:e61. doi: 10.1017/S2045796024000623.

ABSTRACT

AIMS: At the basis of many important research questions is causality – does X causally impact Y? For behavioural and psychiatric traits, answering such questions can be particularly challenging, as they are highly complex and multifactorial. ‘Triangulation’ refers to prospectively choosing, conducting and integrating several methods to investigate a specific causal question. If different methods, with different sources of bias, all indicate a causal effect, the finding is much less likely to be spurious. While triangulation can be a powerful approach, its interpretation differs across (sub)fields and there are no formal guidelines. Here, we aim to provide clarity and guidance around the process of triangulation for behavioural and psychiatric epidemiology, so that results of existing triangulation studies can be better interpreted, and new triangulation studies better designed.

METHODS: We first introduce the concept of triangulation and how it is applied in epidemiological investigations of behavioural and psychiatric traits. Next, we put forth a systematic step-by-step guide, that can be used to design a triangulation study (accompanied by a worked example). Finally, we provide important general recommendations for future studies.

RESULTS: While the literature contains varying interpretations, triangulation generally refers to an investigation that assesses the robustness of a potential causal finding by explicitly combining different approaches. This may include multiple types of statistical methods, the same method applied in multiple samples, or multiple different measurements of the variable(s) of interest. In behavioural and psychiatric epidemiology, triangulation commonly includes prospective cohort studies, natural experiments and/or genetically informative designs (including the increasingly popular method of Mendelian randomization). The guide that we propose aids the planning and interpreting of triangulation by prompting crucial considerations. Broadly, its steps are as follows: determine your causal question, draw a directed acyclic graph, identify available resources and samples, identify suitable methodological approaches, further specify the causal question for each method, explicate the effects of potential biases and, pre-specify expected results. We illustrated the guide’s use by considering the question: ‘Does maternal tobacco smoking during pregnancy cause offspring depression?’.

CONCLUSIONS: In the current era of big data, and with increasing (public) availability of large-scale datasets, triangulation will become increasingly relevant in identifying robust risk factors for adverse mental health outcomes. Our hope is that this review and guide will provide clarity and direction, as well as stimulate more researchers to apply triangulation to causal questions around behavioural and psychiatric traits.

PMID:39506622 | DOI:10.1017/S2045796024000623