Indicator Of Progression Research Articles

Keratoconus Detection in High-Astigmatism Pediatric Patients: Optimal Pentacam Indices and Cutoff Points.

To assess the accuracy of various Pentacam indices in distinguishing keratoconus (KC) in pediatric patients with high astigmatism and to establish appropriate cutoff values. This prospective multicenter cross-sectional study included 312 eyes from 167 patients aged 6 to 18 years (mean age, 13.1 ± 3.2 years) evaluated with Oculus Pentacam HR. Patients were categorized into 4 groups: KC, forme fruste keratoconus, astigmatism greater than 2 diopters (Cyl2D), and control. A subgroup of Cyl2D comprised patients with astigmatism greater than 4 diopters (Cyl4D). Twenty-three Pentacam indices were analyzed, and receiver operating characteristic curves determined optimal cutoff points, sensitivity, and specificity. The best indices for distinguishing KC from Cyl2D were high-order aberration root mean square of the anterior corneal surface (area under the receiver operating characteristic curve 0.987), Belin/Ambrosio enhanced ectasia total derivation (0.971), index of vertical asymmetry (0.971), average pachymetric progression index (0.962), maximum Ambrosio relational thickness (0.960), posterior elevation (0.952), and anterior elevation (0.948). The accuracy of these indices was highest in the control group and lowest in the Cyl4D group. Area under the receiver operating characteristic curve was significantly lower for fruste keratoconus than KC. Optimal cutoff values were higher for astigmatic patients than for those with no refractive error. Most indices effectively distinguished between KC and normal pediatric patients. For individuals with high astigmatism, we suggest focusing on specific indices such as high-order aberration root mean square, Belin/Ambrosio enhanced ectasia total derivation value, maximum Ambrosio relational thickness, average pachymetric progression index, and index of vertical asymmetry. Optimal cutoff points for these patients were higher than those for nonastigmatic children and differed from adult populations.

Pentacam and Corvis ST findings in myopic Chinese patients with different corneal diameters in Singapore.

To study the effect of corneal white-to-white diameter on Pentacam Scheimpflug cornea tomography and Corvis ST corneal visualization Scheimpflug technology parameters in myopic eyes. In this retrospective cross-sectional study, 190 eyes of 190 Chinese myopic patients (spherical equivalent range: -1.25 D to -11.00 D) assessed for refractive surgery using Pentacam and Corvis ST devices were included. Patients were divided into groups based on corneal diameter: group A <12 mm, and group B ≥12 mm. Age, gender, spherical equivalent, Pentacam variables, and Corvis ST variables were collected. Statistical analysis was performed using IBM SPSS Statistics (Version 28.0). There were 110 patients in group A and 80 patients in group B, with no statistically significant difference in age, gender, or spherical equivalence. For Pentacam data, group A had significantly higher Belin/Ambrosio Enhanced Ectasia Display (BAD-D) scores than group B (0.88 vs. 0.44) and pachymetric progression index (minimum, average, and maximum), and steeper front keratometric values, whereas group B had larger anterior chamber depth and maximum Ambrosio-relational thickness (ARTmax) (462.54 vs. 503.93). BAD-D indices, pachymetric progression indices, and front keratometric values had negative correlations with corneal diameter, whereas ARTmax and back keratometric values had positive correlations. For Corvis ST data, group A had a significantly higher corneal biomechanical index (CBI) (negatively correlated) while group B had a higher Ambrosio relational thickness to the horizontal profile (ARTh) (473.60 vs. 570.78) (positively correlated). Corneal diameter influences both Pentacam and Corvis ST parameters, with smaller corneal diameters having a higher BAD-D and a lower ARTmax and ARTh. In addition, this is the first study to report a correlation between posterior surface corneal power and corneal diameter. As refractive surgery evaluation relies on these parameters, taking corneal diameter into account would improve both sensitivity and specificity in pre-refractive surgery screening for ectasia/keratoconus.

Experimenting with a strong dual necessity approach to social progress

Different social progress indices assess well-being and development differently and thus reflect distinct conceptions of social progress. Broadly, these conceptions fall into two categories: ‘subjective’—the attitudes of individuals; and ‘objective’—external standards. Our starting point is a strong ‘dual necessity’ claim, namely that the two categories of conception have joint-special significance. Such a strong dual necessity conception, when operationalized, demands very low compensability/degree of substitution between the two independent indices, objective and subjective. Experimenting with this idea, we hypothesize that implementing low substitution empirically influences outcomes. Previous research presented this concept and exemplified initial empirical outcomes. The present work enhances and broadens this research by employing the constant elasticity of substitution (CES) function, which allows for the adjustment of substitution levels and comparison of resulting rankings. Furthermore, we demonstrate the results using two different well-known and commonly used indices: Human Development Index (HDI) and Sustainable Development Goals Index (SDGI). Our findings show that using a low substitution approach alters the social progress rankings of many countries in comparison to the original components’ rankings and to a high substitution combination of the two. This holds particularly true for countries in the middle of the original rankings. The paper’s original contribution is that it establishes the CES function as a useful device for implementing the idea of ‘dual necessity.’ Importantly, by experimenting with low substitution, and exemplifying its empirical significance with the CES function, the paper also contributes to further validating a strong dual necessity conception and justifies its own measurement. Such measurement should be of value to social scientists, practitioners and policymakers who care for balanced social progress: social progress that does not neglect either of the two aspects (subjective or objective).

Modified furosemide responsiveness index and biomarkers for AKI progression and prognosis: a prospective observational study.

Modified furosemide responsiveness index (mFRI) is a novel biomarker for assessing diuretic response and AKI progression in patients with early AKI. However, the comparative predictive performance of mFRI and novel renal biomarkers for adverse renal outcomes remains unclear. In a single-center prospective study, we aimed to evaluate the discriminatory abilities of mFRI and other novel renal biomarkers in predicting AKI progression and prognosis in patients with initial mild and moderate AKI (KDIGO stage 1 to 2). Patients with initial mild and moderate AKI within 48h following cardiac surgery were included in this study. The mFRI, renal biomarkers (including serum or urinary neutrophil gelatinase-associated lipocalin [sNGAL or uNGAL], serum cystatin C, urinary N-acetyl-beta-D-glycosaminidase [uNAG], urinary albumin-to-creatinine ratio) and cytokines (TNF, IL-1β, IL-2R, IL-6, IL-8, and IL-10) were measured at AKI diagnosis. The mFRI was calculated for each patient, which was defined as 2-hour urine output divided by furosemide dose and body weight. Of 1013 included patients, 154 (15.2%) experienced AKI progression, with 59 (5.8%) progressing to stage 3 and 33 (3.3%) meeting the composite outcome of hospital mortality or receipt of renal replacement therapy (RRT). The mFRI showed non-inferiority or potential superiority to renal biomarkers and cytokines in predicting AKI progression (area under the curve [AUC] 0.80, 95% confidence interval [CI] 0.77-0.82), progression to stage 3 (AUC 0.87, 95% CI 0.85-0.89), and composite outcome of death and receipt of RRT (AUC 0.85, 95% CI 0.82-0.87). Furthermore, the combination of a functional biomarker (mFRI) and a urinary injury biomarker (uNAG or uNGAL) resulted in a significant improvement in the prediction of adverse renal outcomes than either individual biomarker (all P < 0.05). Moreover, incorporating these panels into clinical model significantly enhanced its predictive capacity for adverse renal outcomes, as demonstrated by the C index, integrated discrimination improvement, and net reclassification improvement (all P < 0.05). As a rapid, cost-effective and easily accessible biomarker, mFRI, exhibited superior or comparable predictive capabilities for AKI progression and prognosis compared to renal biomarkers in cardiac surgical patients with mild to moderate AKI. Clinicaltrials.gov, NCT04962412. Registered July 15, 2021, https://clinicaltrials.gov/ct2/show/NCT04962412?cond=NCT04962412&draw=2&rank=1 .

Household financial burden associated with out-of-pocket payments for healthcare in Iran: insights from a cross-sectional survey

BackgroundOne of the key functions and ultimate goals of health systems is to provide financial protection for individuals when using health services. This study sought to evaluate the level of financial protection and its inequality among individuals covered by the Social Security Organization (SSO) health insurance between September and December 2023 in Iran.MethodsWe collected data on 1691 households in five provinces using multistage sampling to examine the prevalence of catastrophic healthcare expenditure (CHE) at four different thresholds (10%, 20%, 30%, and 40%) of the household’s capacity to pay (CTP). Additionally, we explored the prevalence of impoverishment due to health costs and assessed socioeconomic-related inequality in OOP payments for healthcare using the concentration index and concentration curve. To measure equity in out-of-pocket (OOP) payments for healthcare, we utilized the Kakwani progressivity index (KPI). Furthermore, we employed multiple logistic regression to identify the main factors contributing to households experiencing CHE.Findings: The study revealed that households in our sample allocated approximately 11% of their budgets to healthcare services. The prevalence of CHE at the thresholds of 10%, 20%, 30%, and 40% was found to be 47.1%, 30.1%, 20.1%, and 15.7%, respectively. Additionally, we observed that about 7.9% of the households experienced impoverishment due to health costs. Multiple logistic regression analysis indicated that the age of the head of the household, place of residence, socioeconomic status, utilization of dental services, utilization of medicine, and province of residence were the main factors influencing CHE. Furthermore, the study demonstrated that while wealthy households spend more money on healthcare, poorer households spend a larger proportion of their total income to healthcare costs. The KPI showed that households with lower total expenditures had higher OOP payments relative to their CTP.ConclusionThe study findings underscore the need for targeted interventions to improve financial protection in healthcare and mitigate inequalities among individuals covered by SSO. It is recommended that these interventions prioritize the expansion of coverage for dental services and medication expenses, particularly for lower socioeconomic status household.

The synergetic effect of economic complexity and governance on quality of life: policy thresholds

This study aims to bridge the empirical research gap in governance-modulating effects on the link between a country’s productive structure and individuals’ well-being. In doing so, this study utilizes the economic complexity index to quantify a country’s productive structure and the social progress index to measure quality of life. The empirical strategy relies on the system-GMM approach, covering 75 developing countries from 2011 to 2021. The following conclusions were drawn from the empirical analysis. (1) Economic complexity and governance consistently and unconditionally improve quality of life. (2) Governance substantially modulates economic complexity to enhance quality of life, generating an overall positive net effect. (3) The results remain robust and consistent across several GMM specifications, regardless of whether the six governance indicators compiled by the World Bank were clustered using principal component analysis into four categories (i.e., general, political, economic, and institutional) or used individually. (4) Of the six governance indicators, government effectiveness, the rule of law, and control of corruption were found to be particularly significant, as were economic and institutional governance. (5) An additional threshold analysis was implemented to identify the critical governance levels that further improve quality of life. The thresholds for complementary policies are then established as follows: 0.8435, 1.846, and 1.717 for government effectiveness, rule of law, and corruption control, respectively, and 5.59, 3.14, and 3.32 for general, institutional, and economic governance, respectively. Consequently, economic complexity and governance are necessary and sufficient to improve well-being below these thresholds. Complementary policies are, however, necessary to sustain the overall positive impact beyond these thresholds. The findings of this study provide insights into complementary policies for leveraging economic development to improve the well-being of developing countries.

Scheimpflug Tomographic Indices for Classifying Normal, Down Syndrome and Clinical Keratoconus in Pediatric Patients.

The study aimed to evaluate the precision of different Pentacam indices in diagnosing keratoconus (KC) in pediatric patients with and without Down Syndrome (DS) and determine suitable cutoff values. This prospective multicenter cross-sectional study evaluated 216 eyes of 131 patients aged 6-18 years (mean age 12.5 ± 3.2 years) using Pentacam. Patients were categorized into four groups: KC, forme fruste keratoconus (FK), DS, and control, excluding DS patients with topographic KC. Receiver operating characteristic curves were generated to determine the optimal cutoff points and compare the accuracy in identifying KC and FK in patients with and without DS. In DS patients, corneal morphology resembled KC features. The most effective indices for distinguishing KC in DS patients were the average pachymetric progression index (AUC = 0.961), higher-order aberration of the anterior cornea (AUC = 0.953), anterior elevation (AUC = 0.946), posterior elevation (AUC = 0.947), index of vertical asymmetry (AUC = 0.943), and Belin/Ambrosio enhanced ectasia total derivation value (AUC = 0.941). None of the indices showed good accuracy for distinguishing FK in DS patients. The thresholds of these indices differed significantly from non-DS patients. The results highlighted the need for DS-specific cutoff values to avoid false-positive or false-negative diagnoses in this population.

Prognostic value of systemic immune-inflammation index in patients with locally advanced renal cell carcinoma

Purpose: To assess the prognostic value of systemic immune-inflammation index (SII) for disease progression in locally advanced renal cell carcinoma (RCC). Materials and methods: A total of 97 patients with locally advanced RCC who underwent curative surgery between January 1, 2010 and December 31, 2018 were included in this retrospective study. The study was approved by the Institutional Review Board of Linkou Chang Gung Memorial Hospital with an IRB number of 202000092B0. Outcomes analyzed were the disease-free survival (DFS) of patients with locally advanced RCC and the prognostic value of SII. Results: Among 97 locally advanced RCC patients, disease progression was noted in 48.5% of the patients. The median DFS was 55.6 months (95% confidence interval: 45.1–66.2 months). An elevated SII greater or equal to 514 was associated with a poorer DFS. After multivariate analyses of possible predictive factors, SII remained statistically associated with a poorer DFS. Conclusion: An elevated SII was associated with a poorer DFS in patients with locally advanced RCC. SII could be used as a prognostic factor to guide the use of adjuvant therapy after curative surgery for patients with locally advanced RCC.

Clinical characteristics and disease burden of African, Caribbean, and Black people with multiple sclerosis in Toronto, Canada

BackgroundDifferent racial and ethnic groups have demonstrated heterogeneity in the clinical course of multiple sclerosis(MS). ObjectiveWe aimed to evaluate disease characteristics in African, Caribbean, and Black people with MS(ACB-MS) followed at a single centre in Toronto, Canada. MethodsACB-MS were compared with age- and sex-matched people with MS (pwMS) of European descent(EUR-MS) identified through the clinic registry. Results344 PwMS were included(n = 172 ACB-MS, n = 172 EUR-MS; mean age 43 years, 68 % female). Baseline mean Expanded disability status scale (EDSS) scores (ACB-MS 2.3 ± 2.3 vs. EUR-MS 2.2 ± 2.0, p = 0.38) and subsequent clinical and radiological measures of disease activity were similar between groups, including annualized relapse rate (ARR)(ACB-MS 0.47 ± 0.47 vs. EUR-MS 0.41 ± 0.34, p = 0.2) and most recent EDSS (ACB-MS 2.7 ± 2.2 vs. EUR-MS 2.3 ± 2.1, p = 0.10). However, the proportion of MRI brain demonstrating new disease activity was higher(37% vs. 26 %, p < 0.05) and disability progression greater in ACB-MS vs. EUR-MS(43% vs. 33 %,p < 0.05) but measures of disease severity including MS Severity Score(3.17 vs. 2.58, p = 0.3) and Progression Index(PI) (0.27 vs. 0.30, p = 0.5) were comparable. Conclusion: Disability progression was seen more commonly in ACB-MS, though clinical disease activity and severity were generally comparable between ACB-MS and EUR-MS patients in Toronto, Canada. These findings partially differ from prior studies demonstrating more overtly aggressive MS disease courses in Black and African American PwMS, necessitating further studies to understand how structural determinants of health drive these disparities.

Kidney and Cardiovascular Protection Using Dietary Acid Reduction in Primary Hypertension: A Five-Year, Interventional, Randomized, Control Trial

BackgroundHigh fruit and vegetable diets are associated with reduced chronic kidney disease and cardiovascular disease but are infrequently used in hypertension treatment. Low acid diets are also associated with reduced chronic kidney disease and cardiovascular disease, and fruits and vegetables or oral sodium bicarbonate (NaHCO3) lowers dietary acid. MethodsWe randomized 153 hypertensive macroalbuminuric patients receiving pharmacologic chronic kidney disease and cardiovascular disease protection to get fruits and vegetables, oral NaHCO3, or Usual Care. We assessed the course of kidney disease progression and cardiovascular disease risk indices over five years. ResultsChronic kidney disease progression was slower in participants receiving fruits and vegetables or oral NaHCO3 than Usual Care [mean (SE)] [−1.08 (0.06) and −1.17 (0.07) vs. −1.94 (0.11) mL/min/1.73m2/ year, respectively, P’s< .001). Yet, systolic blood pressure was lower, and cardiovascular disease risk indices improved more in participants receiving fruits and vegetables than in those receiving NaHCO3 or Usual Care. These cardiovascular benefits of fruits and vegetables were achieved despite lower doses of pharmacologic chronic kidney disease and cardiovascular disease protection. ConclusionThe trial supports fruits and vegetables as foundational hypertension treatment to reduce chronic kidney disease progression and cardiovascular disease risk.

Executing Ad-Hoc Queries on Large Geospatial Data Sets Without Acceleration Structures

In this case study, we investigate if it is possible to harness the capabilities of modern commodity hardware to perform ad-hoc queries on large raw geospatial data sets. Normally, this requires building an index structure, which is a time-consuming process. We aim to provide means to individual users who receive a new or updated geospatial data set and want to directly start working with it without having to build such an index structure first. To this end, we conduct various experiments on two distinct types of data: 3D building models and point clouds. For the former, we demonstrate that well-known algorithms such as fast string search allow a wide range of queries to be answered in at most a few seconds on data sets with over a million buildings. The usage of progressive indexing additionally improves query run time by more than a factor of two. Regarding point clouds, we achieve similar run times using the popular LAS file format and a query throughput of up to a billion points per second when using a columnar memory layout. The run time of ad-hoc queries is often on par with that of database-driven solutions, sometimes even outperforming them. Considering that ad-hoc queries require no preprocessing, our results show that they are a viable alternative to acceleration structures when working with geospatial data.

Country statistical capacity: A recent assessment tool and further reflections on the way forward

A country’s statistical capacity takes an indispensable part in its development. We offer a comprehensive comparison between the World Bank’s Statistical Performance Indicators and Index (SPI) and its predecessor, the Statistical Capacity Index (SCI) regarding different conceptual and empirical aspects. We further examine the relationships of the two indexes with some agriculture development indicators such as food security, food sustainability and productivity as well as other key indicators including headcount poverty, GDP per capita, and an SDG progress index. Our analysis employs the latest SPI data update in 2022, which were not available in previous studies. We also propose clear guidelines on how the SPI can be maintained and updated in the future to ensure that this process is transparent, replicable, safeguarded with high quality, and provides comparable data over time.

On the robustness of the relationship between tax progressivity, growth, and inequality in the US

We investigate the impact of a shock in tax progressivity on GDP growth and income inequality in the US between 1969 and 2016. Employing various robustness tests, including different imputation methods for the progressivity index, as well as utilizing Vector Autoregressive and Linear Projection models for estimating impulse response functions, we find that both GDP growth and inequality decline in response to more tax progressivity. Nevertheless, only the effect on inequality remains statistically significant across our battery of robustness exercises, while the negative effect on GDP growth is robustly significant only prior to the Great Recession in 2008.

Impact of cryoprotectant-free sperm vitrification in pulled-glass capillary on sperm parameters and DNA integrity: A lab trial study.

Vitrification is a recently introduced yet widely applied assisted reproduction technique. So far, the effects of the chemicals and devices in vitrification on sperm motility and DNA integrity are still unclear. This study aimed to examine sperm quality, as determined by semen analysis and sperm DNA integrity when vitrified with or without cryoprotectant agents (CPAs) using pulled-glass capillaries. Between February and June 2020, 50 infertile men from the Hue Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Vietnam, were enrolled. Sperm samples, prepared using the swim-up technique, were divided into 2 groups: vitrification with CPAs (group 1) and without CPAs (group 2). Vitrified sperm samples were preserved in 10 µL pulled-glass capillaries. Motility, sperm membrane integrity, and the DNA fragmentation index were tested. Sperm motility in vitrified media with CPAs (54.4 11%) was statistically higher than in media without CPAs (51.14 10.6%, p 0.05). CPAs did not affect sperm membrane integrity or large halo ratio (71.34 8.47 vs. 70.38 8.11 and 50.84 18.92 vs. 51.98 19.44, respectively). Group 2 exhibited a lower DNA fragmentation index than group 1 after vitrification (14.2 8.47 vs. 12.60 9.03, p = 0.021). Using a pulled-glass capillary for sperm vitrification, the presence of CPAs in the vitrification medium resulted in higher progressive motility and lower DNA fragmentation index than the medium without CPAs.

The Correlation between Sustainable Development and Digitalization in the Post-Pandemic Era

Abstract This study contains both a qualitative and a quantitative approach regarding the correlation between digitalization and sustainable development and the significance level of the impact that digitalization might have on sustainable development. In order to conduct the research, the dependent and independent variables were selected. We selected as a dependent variable representing the sustainable development, the Social Progress Index and as independent variables, representing the digitalization area, the share of enterprises turnover on e-commerce and share of Individuals who have never used the internet. The database was created for 24 European countries for a period of 6 years (2016, 2017, 2019, 2020, 2021 and 2022). The main conclusion of the study indicates to a strong direct correlation between the Social Progress Index and the share of enterprises turnover on e-commerce and a strong and reverse correlation between the Social Progress Index and the share of Individuals who have never used the internet. Also, based on the linear regression model, we can affirm that for the selected period of time and for the 24 European countries, the increase with one unit of the social progress index, the enterprises turnover on e-commerce (%) increases with 2.06 units. As well, at the increase with one unit of the social progress index, the percentage of the individuals who never used the internet increases with 0.18 (decreases). However, the current model has its own limitations based on the restricted number of variables and time period considered in the database.

Impact of Adverse Childhood Experiences and Mental Health on School Success in Autistic Children: Findings from the 2016-2021 National Survey of Children's Health.

School is an important developmental setting for children. Adverse childhood experiences (ACEs) are linked to overall lower educational attainment and are more prevalent in children with Autism Spectrum Disorder (ASD) than in their neurotypical peers. The aim of this study is to test the association between ACEs and school outcomes among autistic children and whether mental health conditions explain this association. We combined 2016-2021 data from the National Surveys of Children's Health for children, ages 6-17, identified by parents as having ASD (N = 4,997), to examine the relationship between ACEs and school outcomes (grade progression, school attendance, and engagement). We analyzed depression and anxiety variables to investigate the extent to which mental health can explain the relationships between ACEs and school outcomes. ACEs were significantly associated with school outcomes. With increased ACEs, autistic children experienced a significant decrease in the odds of school attendance, grade progression and school engagement (p < .05). Furthermore, although depression and anxiety symptoms were significantly associated with school outcomes, they cannot explain away the enduring, strong relationship between ACEs and level of grade progression, engagement, and school success index. Our findings suggest ACEs predict school success among autistic children, with mental health conditions appearing to mediate the relationship between ACEs and key factors in school success. Efforts should be made to proactively identify and address the impact of ACEs and associated mental health conditions among autistic students.

The use of polyurethane foam-sand mixtures in sandy embankment design- predicting seismic response using FEM, catastrophe theory, B-spline method, and artificial neural networks

High-permeability sand cannot control the water that is stored behind an embankment. In addition, if clay cannot be provided within a reasonable distance of the embankment construction site, an alternative method must be found. The study proposes using a polyurethane foam-sand mixture to construct an impermeable embankment. The main purpose of the paper was to predict the seismic stability of the embankment. The nonlinear finite element models (FEMs) are applied along with artificial neural networks (ANNs), and this research method applied was performed to investigate the main objectives of the research. Catastrophe theory was used to predict the mechanism of differential displacement in the Y direction at selected points of the embankment model. For model smooth functions, the basis spline (B-spline) method was applied to simulate the catastrophe progression index value. Results revealed that the suitability of the polyurethane foam-sand mixture controls the acceleration, displacement, strain, and stress of the model at points selected in different parts of the embankment. Moreover, it was found that the deformation pattern of the model was related to the polyurethane foam-sand mixture ratios. Furthermore, the main contribution was that the seismic response of the embankment model could be improved with the right percentage of polyurethane foam added to the sand. Results were validated by referencing those available in the literature.

Associations between triglyceride-glucose index and risk of diabetic kidney disease progression in type 2 diabetes mellitus

Associations between triglyceride-glucose index and risk of diabetic kidney disease progression in type 2 diabetes mellitus

Interaction between miR-142-3p and BDNF Val/Met Polymorphism Regulates Multiple Sclerosis Severity.

MiR-142-3p has recently emerged as key factor in tailoring personalized treatments for multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS) with heterogeneous pathophysiology and an unpredictable course. With its involvement in a detrimental regulatory axis with interleukin-1beta (IL1β), miR-142-3p orchestrates excitotoxic synaptic alterations that significantly impact both MS progression and therapeutic outcomes. In this study, we investigated for the first time the influence of individual genetic variability on the miR-142-3p excitotoxic effect in MS. We specifically focused on the single-nucleotide polymorphism Val66Met (rs6265) of the brain-derived neurotrophic factor (BDNF) gene, known for its crucial role in CNS functioning. We assessed the levels of miR-142-3p and IL1β in cerebrospinal fluid (CSF) obtained from a cohort of 114 patients with MS upon diagnosis. By stratifying patients according to their genetic background, statistical correlations with clinical parameters were performed. Notably, in Met-carrier patients, we observed a decoupling of miR-142-3p levels from IL1β levels in the CSF, as well as from of disease severity (Expanded Disability Status Score, EDSS; Multiple Sclerosis Severity Score, MSSS; Age-Related Multiple Sclerosis Severity Score, ARMSS) and progression (Progression Index, PI). Our discovery of the interference between BDNF Val66Met polymorphism and the synaptotoxic IL1β-miR-142-3p axis, therefore hampering miR-142-3p action on MS course, provides valuable insights for further development of personalized medicine in the field.

Progressive sarcopenia and myosteatosis predict prognosis of advanced HCC patients treated with immune checkpoint inhibitors.

Immunotherapy stands as a pivotal modality in the therapeutic landscape for the treatment of advanced hepatocellular carcinoma, yet responses vary among patients. This study delves into the potential impact of sarcopenia, myosteatosis and adiposity indicators, as well as their changes during immunotherapy, on treatment response and prognosis in patients with advanced hepatocellular carcinoma treated with immune checkpoint inhibitors. In this retrospective analysis, 116 patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors were recruited. Skeletal muscle, intramuscular, subcutaneous, and visceral adipose tissue were assessed by computed tomography at the level of the third lumbar vertebrae before and after 3 months of treatment. Sarcopenia and myosteatosis were evaluated by skeletal muscle index and mean muscle density using predefined threshold values. Patients were stratified based on specific baseline values or median values, along with alterations observed during the treatment course. Overall survival (OS) and progression-free survival (PFS) were compared using the log-rank test and a multifactorial Cox proportional risk model. A total of 116 patients were recruited and divided into two cohorts, 81 patients for the training set and 35 patients for the validating set. In the overall cohort, progressive sarcopenia (P=0.021) and progressive myosteatosis (P=0.001) were associated with objective response rates, whereas progressive myosteatosis (P<0.001) was associated with disease control rates. In the training set, baseline sarcopenia, myosteatosis, and subcutaneous and visceral adipose tissue were not significantly associated with PFS and OS. In multivariate analysis adjusting for sex, age, and other factors, progressive sarcopenia(P=0.002) and myosteatosis (P=0.018) remained independent predictors of PFS. Progressive sarcopenia (P=0.005), performance status (P=0.006) and visceral adipose tissue index (P=0.001) were all independent predictors of OS. The predictive models developed in the training set also had good feasibility in the validating set. Progressive sarcopenia and myosteatosis are predictors of poor clinical outcomes in patients with advanced hepatocellular carcinoma receiving immune checkpoint inhibitors, and high baseline visceral adiposity is associated with a poorer survival.