Category: Nevin Manimala

Eye (Lond). 2024 Jan 6. doi: 10.1038/s41433-023-02918-w. Online ahead of print.

ABSTRACT

BACKGROUND: To evaluate the long-term anatomical and functional outcomes of anti-Vascular Endothelial Growth Factor intravitreal injections (anti-VEGF IVI) in patients with type 3 macular neovascularisation (MNV) in real-world settings.

METHODS: Retrospective review of patients with type 3 MNV who received anti-VEGF IVI between 2013 and 2020. Primary outcomes were best corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcome was the development of new-onset of foveal-involving geographic atrophy (GA) and disciform scars.

RESULTS: We identified 59 eyes from 48 British patients that met the inclusion criteria. Treatment with anti- VEGF IVI resulted in a statistically significant reduction in median CMT, which was maintained throughout the study period. At 36 months, 24 eyes showed more than 50 μm reduction in CMT, 7 eyes remained stable and only 2 eyes showed an increase in CMT by more than 50μm compared to the baseline. At year three, deterioration was noticed in most eyes (52.78%) and vision remained stable or improved in 47.22% of the eyes. However, the median BCVA was not statistically significant different compared to baseline. During the study period new onset of macula-involving atrophy or scar was noted in 10.2% and 4.3% of the eyes, respectively.

CONCLUSION: In this real-world study, anatomic and functional improvement were recorded 12-months post anti-VEGF IVI in type 3 MNV. Despite sustained anatomical improvement, vision returned back to baseline levels at 36-months. The development of GA and macular scar was only partially responsible for this outcome suggesting a more severe nature of this form of nAMD.

PMID:38184726 | DOI:10.1038/s41433-023-02918-w

Sci Rep. 2024 Jan 6;14(1):738. doi: 10.1038/s41598-024-51498-6.

ABSTRACT

Chronic kidney disease (CKD) imposes a substantial burden, and patient prognosis remains grim. The impact of AST-120 (AST-120) on the survival of CKD patients lacks a consensus. This study aims to investigate the effects of AST-120 usage on the survival of CKD patients and explore the utility of artificial intelligence models for decision-making. We conducted a retrospective analysis of CKD patients receiving care in the pre-end-stage renal disease (ESRD) program at Taichung Veterans General Hospital from 2000 to 2019. We employed Cox regression models to evaluate the relationship between AST-120 use and patient survival, both before and after propensity score matching. Subsequently, we employed Deep Neural Network (DNN) and Extreme Gradient Boosting (XGBoost) models to assess their performance in predicting AST-120’s impact on patient survival. Among the 2584 patients in our cohort, 2199 did not use AST-120, while 385 patients received AST-120. AST-120 users exhibited significantly lower mortality rates compared to non-AST-120 users (13.51% vs. 37.88%, p < 0.0001) and a reduced prevalence of ESRD (44.16% vs. 53.17%, p = 0.0005). Propensity score matching at 1:1 and 1:2 revealed no significant differences, except for dialysis and all-cause mortality, where AST-120 users exhibited significantly lower all-cause mortality (p < 0.0001), with a hazard ratio (HR) of 0.395 (95% CI = 0.295-0.522). This difference remained statistically significant even after propensity matching. In terms of model performance, the XGBoost model demonstrated the highest accuracy (0.72), specificity (0.90), and positive predictive value (0.48), while the logistic regression model showed the highest sensitivity (0.63) and negative predictive value (0.84). The area under the curve (AUC) values for logistic regression, DNN, and XGBoost were 0.73, 0.73, and 0.69, respectively, indicating similar predictive capabilities for mortality. In this cohort of CKD patients, the use of AST-120 is significantly associated with reduced mortality. However, the performance of artificial intelligence models in predicting the impact of AST-120 is not superior to statistical analysis using the current architecture and algorithm.

PMID:38184721 | DOI:10.1038/s41598-024-51498-6

Sci Rep. 2024 Jan 6;14(1):717. doi: 10.1038/s41598-023-50422-8.

ABSTRACT

Correction of leg length discrepancy (LLD) in skeletally mature patients with osteosarcoma was rarely reported and quite challenging. This study aimed to propose a treatment strategy of staged lengthening and reconstruction with a standard static prosthesis to address LLD and restore limb function. It also evaluated the effectiveness of the strategy in terms of leg lengthening, functional outcomes, and complications. The strategy for lengthening included three stages. In stage 1, the previous prosthesis was removed and an external fixator with a temporary rod-cement spacer was placed. In this stage, the external fixator was used to lengthen the limb to the appropriate length. In stage 2, the external fixator was removed and the old rod-cement spacer was replaced with a new one. In stage 3, the rod-cement spacer was removed and the standard static prosthesis was planted. Nine skeletally mature distal femoral osteosarcoma patients with unacceptable LLD were treated in our institution from 2019 to 2021. We performed a chart review on nine patients for the clinical and radiographic assessment of functional outcomes, LLD, and complications. The mean (range) leg lengthening was 7.3 cm (3.6-15.6). The mean (range) LLD of the lower limbs decreased from 7.6 cm (4.1-14.2) before the lengthening to 0.3 cm (- 0.3 to 2.1) at the final follow-up with statistical significance (P = 0.000). The mean (range) Musculoskeletal Tumor Society score improved from 30.3% (16.7%-53.3%) before the lengthening to 96.3% (86.7%-100%) at the final follow-up with statistical significance (P = 0.000). Three patients (33.3%) had a minor complication; none needed additional surgical intervention. In the short term, the current staged lengthening and reconstruction with standard static prosthesis provided satisfactory functional outcomes and LLD correction with few complications. The long-term effects of this method need further exploration.

PMID:38184715 | DOI:10.1038/s41598-023-50422-8

Sci Rep. 2024 Jan 6;14(1):699. doi: 10.1038/s41598-023-49762-2.

ABSTRACT

Lead zirconate titanate (PZT) patches gained popularity in structural health monitoring (SHM) for its sensing and cost effective. However, a robust installation of PZT patches is challenging due to the often-complex geometry and non-accessibility of structural parts. For tubular structures, the curved surface can compromise the perfect bonding of PZT patches. To alleviate the above-mentioned challenges, the non-bonded and reusable configuration of sensor received considerable interest in the field of SHM. However, ensuring the repeatability and reproducibility of Electro-Mechanical Impedance (EMI) measurements is crucial to establish the reliability of these techniques. This work investigated the repeatability and reproducibility measures for one of non-bonded configuration of PZT patch i.e., Metal Foil Based Piezo Sensor (MFBPS). In addition, the concept, application, and suitability of MFBPS for impedance-based monitoring technique of Civil infrastructure are critically discussed. This study evaluates the effect of length of MFBPS on piezo coupled admittance signature. Also, this study evaluates repeatability and reproducibility of EMI measurements via statistical tools such as ANOVA and Gage R&R analysis. The statistical index CCDM was used to quantify the deviations of impedance signals. The overall result shows that the repeatability of the EMI measurements improves with a metal foil length of 500 mm. Overall, this investigation offers a useful point of reference for professionals and scholars to ensure the reliability of MFBPS for EMI techniques, a variant of piezoelectric sensor for SHM applications.

PMID:38184698 | DOI:10.1038/s41598-023-49762-2

Schizophrenia (Heidelb). 2024 Jan 6;10(1):7. doi: 10.1038/s41537-023-00413-5.

ABSTRACT

The mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = -0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.

PMID:38184684 | DOI:10.1038/s41537-023-00413-5

NPJ Syst Biol Appl. 2024 Jan 6;10(1):2. doi: 10.1038/s41540-023-00325-1.

ABSTRACT

Mathematical models are increasingly being developed and calibrated in tandem with data collection, empowering scientists to intervene in real time based on quantitative model predictions. Well-designed experiments can help augment the predictive power of a mathematical model but the question of when to collect data to maximize its utility for a model is non-trivial. Here we define data as model-informative if it results in a unique parametrization, assessed through the lens of practical identifiability. The framework we propose identifies an optimal experimental design (how much data to collect and when to collect it) that ensures parameter identifiability (permitting confidence in model predictions), while minimizing experimental time and costs. We demonstrate the power of the method by applying it to a modified version of a classic site-of-action pharmacokinetic/pharmacodynamic model that describes distribution of a drug into the tumor microenvironment (TME), where its efficacy is dependent on the level of target occupancy in the TME. In this context, we identify a minimal set of time points when data needs to be collected that robustly ensures practical identifiability of model parameters. The proposed methodology can be applied broadly to any mathematical model, allowing for the identification of a minimally sufficient experimental design that collects the most informative data.

PMID:38184643 | DOI:10.1038/s41540-023-00325-1

Trials. 2024 Jan 6;25(1):29. doi: 10.1186/s13063-023-07894-w.

ABSTRACT

This protocol paper presents an updated statistical analysis plan of the protocol of a randomised controlled trial. The randomised controlled trial investigates the effect of integrating smoking cessation interventions at outpatient opioid agonist therapy (OAT) clinics for persons with opioid dependency receiving OAT medication. The intervention group receives weekly follow-up including a short behavioural intervention and provision of nicotine replacement products. The control group receives standard treatment. The duration of the intervention is 16 weeks and the follow-up was completed by the end of October 2023. The primary outcome is defined as the proportion of participants reducing the number of cigarettes smoked by at least a 50% at week 16 of the intervention period. The primary outcome will be analysed according to intention-to-treat principles. Missing outcome data will be set equal to the baseline values. Development and reporting of the statistical analysis plan follow the Guidelines for the Content of Statistical Analysis Plans in Clinical Trials.Trial registration ClinicalTrials.gov NCT05290025. Registered on 22 March 2022.

PMID:38184633 | DOI:10.1186/s13063-023-07894-w

Eur J Med Res. 2024 Jan 6;29(1):31. doi: 10.1186/s40001-023-01596-4.

ABSTRACT

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1-42 in ALS patients and a control group.

METHODS: Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann-Whitney U-test.

RESULTS: Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1-42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS.

CONCLUSION: Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.

PMID:38184629 | DOI:10.1186/s40001-023-01596-4

J Transl Med. 2024 Jan 6;22(1):29. doi: 10.1186/s12967-023-04776-2.

ABSTRACT

BACKGROUND: The current therapeutic algorithm for Advanced Stage Melanoma comprises of alternating lines of Targeted and Immuno-therapy, mostly via Immune-Checkpoint blockade. While Comprehensive Genomic Profiling of solid tumours has been approved as a companion diagnostic, still no approved predictive biomarkers are available for Melanoma aside from BRAF mutations and the controversial Tumor Mutational Burden. This study presents the results of a Multi-Centre Observational Clinical Trial of Comprehensive Genomic Profiling on Target and Immuno-therapy treated advanced Melanoma.

METHODS: 82 samples, collected from 7 Italian Cancer Centres of FFPE-archived Metastatic Melanoma and matched blood were sequenced via a custom-made 184-gene amplicon-based NGS panel. Sequencing and bioinformatics analysis was performed at a central hub. Primary analysis was carried out via the Ion Reporter framework. Secondary analysis and Machine Learning modelling comprising of uni and multivariate, COX/Lasso combination, and Random Forest, was implemented via custom R/Python scripting.

RESULTS: The genomics landscape of the ACC-mela cohort is comparable at the somatic level for Single Nucleotide Variants and INDELs aside a few gene targets. All the clinically relevant targets such as BRAF and NRAS have a comparable distribution thus suggesting the value of larger scale sequencing in melanoma. No comparability is reached at the CNV level due to biotechnological biases and cohort numerosity. Tumour Mutational Burden is slightly higher in median for Complete Responders but fails to achieve statistical significance in Kaplan-Meier survival analysis via several thresholding strategies. Mutations on PDGFRB, NOTCH3 and RET were shown to have a positive effect on Immune-checkpoint treatment Overall and Disease-Free Survival, while variants in NOTCH4 were found to be detrimental for both endpoints.

CONCLUSIONS: The results presented in this study show the value and the challenge of a genomics-driven network trial. The data can be also a valuable resource as a validation cohort for Immunotherapy and Target therapy genomic biomarker research.

PMID:38184610 | DOI:10.1186/s12967-023-04776-2

Cardiovasc Diabetol. 2024 Jan 6;23(1):15. doi: 10.1186/s12933-023-02110-0.

ABSTRACT

BACKGROUND: Insulin resistance (IR), a hallmark of proceeding diabetes and cardiovascular (CV) disease, has been shown to predict prognosis in patients undergoing percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and metabolic score for insulin resistance (METS-IR) have been shown to be simple and reliable non-insulin-based surrogates for IR. However, limited studies have determined the associations between distinct non-insulin-based IR markers and CV outcomes in patients undergoing complex PCI who are at higher risk of CV events after PCI. Therefore, this study aimed to investigate and compare the prognostic value of these markers in patients undergoing complex PCI.

METHODS: This was a descriptive cohort study. From January 2017 to December 2018, a total of 9514 patients undergoing complex PCI at Fuwai Hospital were consecutively enrolled in this study. The 3 IR indices were estimated from the included patients. The primary study endpoint was CV events, defined as a composite of CV death, nonfatal myocardial infarction and nonfatal stroke.

RESULTS: During a median follow-up of 3.1 years, 324 (3.5%) CV events occurred. Multivariable Cox regression models showed per-unit increase in the TyG index (hazard ratio [HR], 1.42; 95% confidence interval [CI] 1.13-1.77), rather than per-unit elevation in either Ln(TG/HDL-C ratio) (HR, 1.18; 95%CI 0.96-1.45) or METS-IR (HR, 1.00; 95%CI 0.98-1.02), was associated with increased risk of CV events. Meanwhile, adding the TyG index to the original model led to a significant improvement in C-statistics (0.618 vs. 0.627, P < 0.001), NRI (0.12, P = 0.031) and IDI (0.14%, P = 0.003), whereas no significant improvements were observed when adding Ln (TG/HDL-C ratio) or METS-IR (both P > 0.05) to the original model.

CONCLUSIONS: The TyG index, not TG/HDL-C ratio and METS-IR, was positively associated with worse CV outcomes in patients undergoing complex PCI. Our study, for the first time, demonstrated that the TyG index can serve as the suitable non-insulin-based IR marker to help in risk stratification and prognosis in this population.

PMID:38184591 | DOI:10.1186/s12933-023-02110-0