Surrogate Indicator Research Articles

Hospital Mortality in Acute Decompensation of Alcoholic Liver Cirrhosis: Can Novel Survival Markers Outperform Traditional Ones?

Background: There is a strong correlation between systemic inflammation intensity and clinical presentation, disease progression, and survival during liver cirrhosis decompensation. This study aimed to evaluate the prognostic performance of blood-based biomarkers as meta-inflammation markers, including NLR, PLR, LMR, INPR, MPR, ALBI, FIB4, and APRI, in predicting hospital mortality in patients with acute decompensation of alcohol-related liver cirrhosis. Methods: Data from 411 patients with their first onset of acute decompensation were analyzed, forming two groups: deceased and survived during hospitalization. Generalized partial least squares regression analysis was applied to explore the effects of surrogate indicators on mortality rates, using mortality rate as the dependent variable. Root Mean Square Error, Akaike's, and Bayesian information criteria determined that four components accounted for most of the variance. Results: Variables with significant negative contributions to the outcome prediction (ranked by standardized regression coefficients) were encephalopathy grade, total bilirubin, Child-Turcotte-Pugh score, MELD, NLR, MPV, FIB4, INR, PLR, and ALT. Coefficient sizes ranged from -0.63 to -0.09, with p-values from 0 to 0.018. Conclusions: NLR, PLR, and FIB4 significantly contribute to hospital mortality prediction in patients with acute decompensation of alcohol-related liver cirrhosis. Conversely, some variables used to predict liver disease severity, including INPR, APRI, LMR, and ALBI score, did not significantly contribute to hospital mortality prediction in this patient population.

Developing Surrogate Indicator for Prompt Adjusting of Ozonation Operation: Insight from Pilot-Scale Treatment Using China’s South-to-North Water Diversion Project Feedwater

Developing Surrogate Indicator for Prompt Adjusting of Ozonation Operation: Insight from Pilot-Scale Treatment Using China’s South-to-North Water Diversion Project Feedwater

Insulin resistance and sarcopenia: a prognostic longitudinal link to stroke risk in middle-aged and elderly Chinese population

BackgroundStroke is the leading cause of death in middle-aged and elderly people in China. Insulin resistance (IR) and sarcopenia are both closely associated with metabolic diseases. However, the relationship between these two indicators and stroke has not been fully investigated. The aim of this study was to investigate the relationship between IR and sarcopenia and the risk of new-onset stroke.MethodsUsing longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018, Cox proportional hazards models were used to determine the association between IR surrogate indicators and sarcopenia status with stroke incidence.ResultsIn the present study, during a median 7 years of follow-up, we included 7009 middle-aged and elderly residents, of whom 515 presented with stroke incidence. After adjustment for potential confounders, both baseline IR surrogates and sarcopenia independently predicted stroke risk. In addition, co-morbidities had a higher risk of stroke than other groups. The positive association between TyG-WC and sarcopenia on stroke risk was particularly significant [HR (95% CI): 2.03 (1.52, 2.70)]. In subgroups of different ages and sexes, the combination of IR and sarcopenia is associated with the highest risk of stroke.ConclusionsWe found that IR and sarcopenia synergistically increase the incidence of stroke in older adults. This finding provides new perspectives for stroke detection and intervention and highlights the importance of early detection and management of IR and sarcopenia in older adults.

Anticipated buffer time – An evasive surrogate safety indicator for risk assessment of unsignalized intersections under heterogeneous traffic and aggressive driving conditions

Risk assessment of unsignalized intersections is particularly challenging when confronted with a combination of factors such as heavy traffic, diverse vehicle types, lane indiscipline, aggressive driving, and evasive manoeuvres. Understanding how people drive in these situations is crucial for accurately assessing the risks at unsignalized intersections. This study introduces a novel surrogate safety indicator, i.e. Anticipated Buffer Time (ABT), designed to account for these various factors. Additionally, three new indicators derived from ABT are introduced, namely ABT Negation Ratio, ABT Extremity Ratio, and ABT Progression Ratio. A risk assessment measure, denoted as UnSigRisk Score, is formulated using these three indicators for unsignalized intersections. Three intersections in Ahmedabad, India, were selected for the study due to their manifestation of these challenging conditions. Spearman Rank Correlation Coefficient was estimated to find out how well can UnSigRisk Score measure is able to quantify evasive behaviour. The results indicate that this score proficiently measures evasive behaviour, exhibiting coefficients exceeding 0.6 in all cases—significantly outperforming the current evasive indicators, Yaw Rate Ratio and Jerk. The proposed risk assessment score could serve as a practical tool for transportation authorities, enabling them to identify the most vulnerable intersections and allocate resources for targeted safety interventions wisely. The study unequivocally demonstrates that the use of ABT paves the way for a thorough examination of safety at unsignalized intersections, regardless of driving behaviour and traffic conditions.

Epigenetic regulation of cardiovascular diseases induced by behavioral and environmental risk factors: Mechanistic, diagnostic, and therapeutic insights

AbstractBehavioral and environmental risk factors are critical in the development and progression of cardiovascular disease (CVD). Understanding the molecular mechanisms underlying these risk factors will offer valuable insights for targeted preventive and therapeutic strategies. Epigenetic modifications, including DNA methylation, histone modifications, chromatin remodeling, noncoding RNA (ncRNA) expression, and epitranscriptomic modifications, have emerged as key mediators connecting behavioral and environmental risk factors to CVD risk and progression. These epigenetic alterations can profoundly impact on cardiovascular health and susceptibility to CVD by influencing cellular processes, development, and disease risk over an individual's lifetime and potentially across generations. This review examines how behavioral and environmental risk factors affect CVD risk and health outcomes through epigenetic regulation. We review the epigenetic effects of major behavioral risk factors (such as smoking, alcohol consumption, physical inactivity, unhealthy diet, and obesity) and environmental risk factors (including air and noise pollution) in the context of CVD pathogenesis. Additionally, we explore epigenetic biomarkers, considering their role as causal or surrogate indicators, and discuss epigenetic therapeutics targeting the mechanisms through which these risk factors contribute to CVD. We also address future research directions and challenges in leveraging epigenetic insights to reduce the burden of CVD related to behavioral and environmental factors and improve public health outcomes. This review aims to provide a comprehensive understanding of behavioral and environmental epigenetics in CVD and offer valuable strategies for therapeutic intervention.

Association of Short Sleep Duration and Obstructive Sleep Apnea with Central Obesity: A Retrospective Study Utilizing Anthropometric Measures.

Central obesity, as measured by examination instruments, has been shown to be associated with both OSA and short sleep duration. However, objective measurement tools like CT, MRI, and DXA are expensive, cause radiation exposure, and have limited availability, especially in resource-limited settings. Thus, this study aimed to demonstrate the relevance of Body Mass Index (BMI) and Waist-to-Height Ratio (WHtR) as surrogate indicators of visceral obesity in the assessment of OSA and short sleep duration. We also intend to evaluate whether WHtR, in combination with BMI, can be a suitable surrogate marker for visceral adiposity. We recruited 333 adults with complete polysomnographic (PSG) records retrospectively. Logistic regression helped to assess the association of BMI and WHtR as surrogates for central adiposity with OSA and short sleep duration. Moreover, ROC curve analysis was conducted to evaluate the predictive ability of BMI and WHtR. Following the relevant adjustments, logistic regression analysis results showed that the combination of WHtR and BMI acting as central obesity surrogates was significantly associated with OSA and short sleep duration (p<0.05). According to univariate regression analysis, sleep latency and wakeaftersleeponset were independent predictors of the risk of central obesity in patients with short sleep duration and OSA. Additionally, ROC curve analysis demonstrated that the combination of BMI and WHtR provided a better assessment of central adiposity in patients with OSA and short sleep duration, compared to each measure alone. BMI and WHtR are significantly associated with OSA and short sleep duration, and might serve as a potential surrogate marker for central obesity. Sleep latency and wakeaftersleeponset can independently predict the risk of central obesity in patients with short sleep time and OSA. Thus, larger prospective studies are needed to verify our findings.

Insulin resistance assessed by estimated glucose disposal rate and risk of atherosclerotic cardiovascular diseases incidence: the multi-ethnic study of atherosclerosis

BackgroundTo investigate the relationship between estimated glucose disposal rate (eGDR), a surrogate indicator of insulin resistance, and atherosclerotic cardiovascular diseases (ASCVD) incidence risk.MethodsThis prospective cohort study utilized data from the 6026 participants from the Multi-Ethnic Study of Atherosclerosis. The eGDR (mg/kg/min) was computed as 21.158 − (0.09 × waist circumference [cm]) − (3.407 × hypertension [yes/no]) − (0.551 × HbA1c [%]). The population was categorized into four subgroups according to the quartiles (Q) of eGDR. Cox proportional hazard models were applied to assess the associations between eGDR and ASCVD incidence, and restricted cubic spine (RCS) was employed to examine the dose–response relationship.ResultsThe mean age of participants was 63.6 ± 10.1 years, comprising 3163 (52.5%) women. Over a median follow-up duration of 14.1 years, 565 (9.4%) developed ASCVD, including 256 (4.2%) myocardial infarctions, 234 (3.9%) strokes, and 358 (5.9%) fatal coronary heart disease. Compared to the lowest quartile, the adjusted hazard ratios (95% confidence intervals) for incident ASCVD for Q2–Q4 were 0.87 (0.68−1.10), 0.63 (0.47−0.84), and 0.43 (0.30−0.64), respectively. Per 1 standard deviation increase in eGDR was associated with a 30% (HR: 0.70, 95% CI 0.60−0.80) risk reduction of ASCVD, with the subgroup analyses indicating that age and hypertension modified the association (P for interaction < 0.05). RCS analysis indicated a significant and linear relationship between eGDR and ASCVD incidence risk.ConclusioneGDR level was negatively associated with incident ASCVD risk in a linear fashion among the general population. Our findings may contribute to preventive measures by improving ASCVD risk assessment.

SP3.6 - Do non-colorectal surgeons produce an inferior lymph node yield in emergency colorectal cancer resections?

Abstract Introduction Lymph node yield is a surrogate indicator of adequate resection and yields of 20 or more have been shown to be associated with better survival outcomes. There is controversy as to whether colorectal cancers should be operated on by non-colorectal surgeons in the emergency setting. This study explores whether there are differences in lymph node yield between colorectal and non-colorectal surgeons in the context of emergency Hartmann's procedures performed for malignancy. Methods A retrospective study was conducted at a 3-site Trust in South East England between 2012 and 2022. Theatre and Info flex Cancer records were used to obtain patients who had undergone a Hartmann's procedure for malignancy and their operating surgeon. The histology reports were then reviewed and statistical analysis was undertaken. Results 346 patients were included in the study, in a 197:149 male-to-female ratio. The mean age was 73 (28-92 IQR). Histology confirmed malignancy in all the study participants. 11% (38/346) of the operations were conducted by non-colorectal surgeons (UGI, Breast, and Endocrine). The mean lymph node yield for the non-colorectal surgeons was 28 (24-33 IQR). The mean lymph node yield for colorectal surgeons was 29 (26-34 IQR). There was no statistical difference between the lymph node yield between colorectal and non-colorectal surgeons (p=0.671) Conclusion The study concluded that adequate oncological colonic resections could be conducted safely by non-colorectal surgeons in emergency settings.

Role of Triglyceride-Glucose Index in Type 2 Diabetes Mellitus and Its Complications.

Insulin resistance (IR) is the major mechanism in the pathogenesis of type 2 diabetes mellitus (T2DM). Early identification of IR is of great significance for preventing the onset of T2DM and delaying the progression of the disease. Previous studies have shown that triglyceride-glucose (TyG) index can be used as an effective surrogate marker for IR. There is a significant correlation between TyG index and T2DM and its common complications. In addition, the predictive efficacy of TyG index is better than that of other IR surrogate indicators. TyG index may not only become an important marker to identify people at high risk of T2DM and its complications, but is also expected to become a strong predictor of the prognosis of these diseases. However, there are still some challenges in the widespread application of TyG index in clinical practice. In the future, more high-quality studies are needed to clarify the assessment methods of TyG index for the prognosis of T2DM and its complications. Further investigations of the relationship between TyG index and T2DM and its complications will be expected to provide new ideas and methods for the prevention and treatment of T2DM and its complications.

Evaluation of subclinical left ventricular systolic dysfunction in patients with type 2 diabetes mellitus by combining myocardial work and triglyceride-glucose index.

Type 2 diabetes mellitus (T2DM) frequently presents subclinical left ventricular systolic dysfunction. The TyG index is a surrogate indicator of insulin resistance and is closely related to heart failure (HF). This study aimed to evaluate subclinical systolic dysfunction in T2DM by combining myocardial work (MW) and the TyG index and to investigate the risk factors for MW. This study included 102 diabetic patients and 78 healthy control subjects, and the diabetic group was divided into three subgroups based on the TyG index. LV global longitudinal strain (GLS), global myocardial work index (GWI), global constructive work (GCW), global wasted work (GWW), and global myocardial work efficiency (GWE) were measured in all subjects. GLS and MW were compared between the diabetic and control groups and between subgroups. Regression models were applied to analyze the risk factors for MW in diabetic patients. GLS, GWI, GCW, and GWE significantly increased, and GWW significantly decreased in the diabetic group (all p<.01). GWI and GCW were significantly lower in the T3 subgroup than in the T1 and T2 subgroups (all p<.05). The TyG index, sex (female), BMI, systolic blood pressure (SBP), and total cholesterol (TC) were independent risk factors for GWI and GCW, and HbA1c was an independent risk factor for GWI. MW accurately revealed subtle changes in subclinical LV systolic dysfunction in T2DM patients. An elevated TyG index was strongly associated with decreased GWI and GCW. The TyG index, sex (female), BMI, SBP, and TC were independent risk factors for GWI and GCW, and HbA1c was an independent risk factor for GWI.

Development of an Evidence-Based List of Non-Antineoplastic Vesicants: 2024 Update.

Infiltration of a vesicant, called extravasation, can result in severe patient injuries. Recognition of vesicants and their relative risk of injury is essential to extravasation prevention, early recognition, and appropriate treatment. In this article, the Vesicant Task Force (VTF) updates the previously published Infusion Nurses Society (INS) vesicant list from 2017. The 2024 INS list diverges from earlier vesicant lists, such as the 2017 VTF list, by adopting a risk stratification approach based upon documented patient outcomes, in contrast to the reliance on expert consensus or only surrogate risk indicators, such as pH and osmolarity. The methodology used to create the updated list is explained, and the criteria for high- and moderate-risk vesicants and cautionary vesicants are defined.

Exposure-associated DNA methylation among people exposed to multiple industrial pollutants

BackgroundCurrent research on the epigenetic repercussions of exposure to a combination of pollutants is limited. This study aims to discern DNA methylation probes associated with exposure to multiple pollutants, serving as early effect markers, and single-nucleotide polymorphisms (SNPs) as surrogate indicators for population susceptibility. The investigation involved the analysis of urine exposure biomarkers for 11 heavy metals (vanadium, arsenic, mercury, cadmium, chromium, nickel, lead, manganese, copper, strontium, thallium), polycyclic aromatic hydrocarbon (PAHs) (1-hydroxypyrene), genome-wide DNA methylation sequencing, and SNPs array on all study participants. The data were integrated with metabolomics information and analyzed both at a community level based on proximity to home addresses relative to the complex and at an individual level based on exposure biomarker concentrations.ResultsOn a community level, 67 exposure-related CpG probes were identified, while 70 CpG probes were associated with urine arsenic concentration, 2 with mercury, and 46 with vanadium on an individual level. These probes were annotated to genes implicated in cancers and chronic kidney disease. Weighted quantile sum regression analysis revealed that vanadium, mercury, and 1-hydroxypyrene contributed the most to cg08238319 hypomethylation. cg08238319 is annotated to the aryl hydrocarbon receptor repressor (AHRR) gene, and AHRR hypomethylation was correlated with an elevated risk of lung cancer. AHRR was further linked to deregulations in phenylalanine metabolism, alanine, aspartate, and glutamate metabolism, along with heightened oxidative stress. Additionally, three SNPs (rs11085020, rs199442, and rs10947050) corresponding to exposure-related CpG probes exhibited significant interaction effects with multiple heavy metals and PAHs exposure, and have been implicated in cancer progression and respiratory diseases.ConclusionOur findings underscore the pivotal role of AHRR methylation in gene-environment interactions and highlight SNPs that could potentially serve as indicators of population susceptibility in regions exposed to multiple heavy metals and PAHs.

Evaluation of Conventional Surrogate Indicators of Safety for Connected and Automated Vehicles in Car Following at Signalized Intersections

The driving behaviors of connected and automated vehicles (CAVs) will differ from those of human-driven vehicles (HDVs) because the CAVs’ driving decisions are controlled by computers. Because of the limited amount of crash data for CAVs, researchers have relied on surrogate measures of safety to assess their safety impacts. However, they often use the same safety indicators for CAVs that were used for HDVs, raising questions about the adequacy of the safety indicators for CAVs. This study aims to investigate the suitability of using conventional safety indicators for CAVs. To achieve this, we evaluated eight safety indicators used for CAVs in the literature: time-to-collision (TTC), post-encroachment time (PET), time-exposed TTC, time-integrated TTC, deceleration rate to avoid a crash (DRAC), crash-potential index, rear-end-collision risk index, and potential index for collision with urgent deceleration (PICUD). For the evaluation, we first simulate CAVs on an approaching lane of signalized intersections using the acceleration-control algorithm. The algorithm replaces the HDV trajectories with CAVs for mixed simulations where HDVs and CAVs coexist. Analyzing the simulation output, we examined the safety indicators for the various car-following scenarios and the CAV proportions. The findings suggest that PET and PICUD can yield different safety implications for CAVs because of their small-gap car-following characteristics. Ignoring such characteristics may lead to interpreting the small-gap car-following situations as simply dangerous traffic interactions for CAVs. The car-following experiments indicate that TTC, PET, and DRAC are insufficient in measuring the safety implications when successive vehicles operate at similar speeds for CAVs.

Association of triglyceride-glucose index with the risk of incident aortic dissection and aneurysm: a large-scale prospective cohort study in UK Biobank

BackgroundTriglyceride-glucose (TyG) index is an emerging surrogate indicator of insulin resistance, which has been demonstrated as a risk factor for various cardiovascular diseases including coronary syndrome, in-stent restenosis, and heart failure. However, association of TyG index with incident aortic dissection (AD) and aortic aneurysm (AA) remains to be investigated.MethodsThis study included 420,292 participants without baseline AD/AA from the large-scale prospective UK Biobank cohort. The primary outcome was incident AD/AA, comprising AD and AA. Multivariable-adjusted Cox proportional hazards regression models and restricted cubic spline (RCS) analyses were applied to assess the relationship between TyG index and the onset of AD/AA. In addition, the association between TyG index and incident AD/AA was examined within subgroups defined by age, gender, smoking status, drinking status, diabetes, hypertension, and BMI.ResultsOver a median follow-up period of 14.8 (14.1, 15.5) years, 3,481 AD/AA cases occurred. The incidence of AD/AA rose along with elevated TyG index. RCS curves showed a linear trend of TyG index with risk of incident AD/AA. TyG index was positively associated with risk of incident AD/AA after adjusting for age, gender, smoking status, drinking status, BMI, hypertension, LDL-c, and HbA1c, with adjusted HRs of 1.0 (reference), 1.20 (95% CI 1.08–1.35), 1.21 (95% CI 1.08–1.35), and 1.30 (95% CI 1.16–1.45) for TyG index quartiles 2, 3, and 4, respectively. Especially, participants in the highest TyG index quartile had highest risk of developing AA, with an adjusted HR of 1.35 (95% CI 1.20–1.52).ConclusionsTyG index is independently associated with a higher risk of incident AD/AA, indicating the importance of using TyG index for risk assessment of AD/AA, especially for AA.

Oligoclonal CD4+CXCR5+ T cells with a cytotoxic phenotype appear in tonsils and blood

In clinical situations, peripheral blood accessible CD3+CD4+CXCR5+ T-follicular helper (TFH) cells may have to serve as a surrogate indicator for dysregulated germinal center responses in tissues. To determine the heterogeneity of TFH cells in peripheral blood versus tonsils, CD3+CD4+CD45RA–CXCR5+ cells of both origins were sorted. Transcriptomes, TCR repertoires and cell-surface protein expression were analysed by single-cell RNA sequencing, flow cytometry and immunohistochemistry. Reassuringly, all blood-circulating CD3+CD4+CXCR5+ T-cell subpopulations also appear in tonsils, there with some supplementary TFH characteristics, while peripheral blood-derived TFH cells display markers of proliferation and migration. Three further subsets of TFH cells, however, with bona fide T-follicular gene expression patterns, are exclusively found in tonsils. One additional, distinct and oligoclonal CD4+CXCR5+ subpopulation presents pronounced cytotoxic properties. Those ‘killer TFH (TFK) cells’ can be discovered in peripheral blood as well as among tonsillar cells but are located predominantly outside of germinal centers. They appear terminally differentiated and can be distinguished from all other TFH subsets by expression of NKG7 (TIA-1), granzymes, perforin, CCL5, CCR5, EOMES, CRTAM and CX3CR1. All in all, this study provides data for detailed CD4+CXCR5+ T-cell assessment of clinically available blood samples and extrapolation possibilities to their tonsil counterparts.

Identifying the fate of dissolved organic matter in wastewater treatment plant effluent-dominated urban river based on fluorescence fingerprinting and flux budget approach

Effluent organic matter from wastewater treatment plants (WWTPs) is an important source of dissolved organic matter (DOM) in urban rivers worldwide and is an important water quality factor. Identifying the fate of DOM in urban river is crucial for water quality management. To address this concern, a fluorescent flux budget approach was conducted to probe the fate of DOM in WWTP effluent-dominated urban river, in combination with field measurement and fluorescence fingerprinting. An urban river receiving two WWTP effluents in Hefei City, China was chosen as the study site, where longitudinal measurements of river hydrology and water quality were performed. The fluorescence fingerprinting revealed the presence of two humic-like components (C1, C4), one fulvic-like component (C2) and one protein-like component (C3) in this investigated river, among which C2 and C4 were indicative of anthropogenic influences, closely associated with treated effluents. For each fluorescent component, the WWTP effluent contributed over 80 % of the total fluorescent dissolved organic matter (FDOM) input in this river. Using the developed FDOM flux budget model, it was found that the C1 and C3 were almost conserved within the waterbody, while the C2 and C4 experienced losses due to biogeochemical reactions. The decay rates of C2 and C4 were estimated to be 0.109–0.174 d−1 and 0.096–0.320 d−1, respectively. Spatial heterogeneity of decay rates for C2 and C4 were associated with the varied chemistries of the lateral input sources including two treated effluents and one tributary flow. Our study highlights that after treated effluent is released into the receiving waterbody, the FDOM would undergo loss from the waters particularly for anthropogenic fulvic-like substance C2 and humic-like substance C4. Additionally, the quantified FDOM decay rate in actual urban water environment provides insights for river water quality management, especially when using DOM as the surrogate indicator of organic pollutants.

Reduction in kidney function decline and risk of severe clinical events in agalsidase beta-treated Fabry disease patients: a matched analysis from the Fabry Registry.

Patients with Fabry disease (FD, α-galactosidase A deficiency or absence) accumulate glycosphingolipids, leading to progressive dysfunction of kidneys, heart and nervous system. Generalizable real-world outcomes following agalsidase beta treatment initiation outside trials are limited. We investigated the associations of long-term agalsidase beta treatment with estimated glomerular filtration rate (eGFR) changes over time and the risk of developing a composite clinical event in a matched analysis of treated and untreated patients with FD. Agalsidase beta-treated adult patients (aged ≥16years) from the Fabry Registry and adult untreated patients from a natural history cohort were matched 1:1 and X:X (with one occurrence and multiple occurrences of each untreated patient, respectively) by sex, phenotype, age and (for eGFR slope analysis) baseline eGFR. Outcomes included eGFR slope over 5years and composite clinical event risk (cardiovascular, cerebrovascular or renal event, or death) over 10+years. As a surrogate indicator of therapeutic response in paediatric patients, the percentage experiencing normalization in plasma globotriaosylceramide (GL-3) from treatment initiation was assessed in patients aged 2 to <16years. Overall, eGFR slopes for 1:1-matched untreated and treated adult patients [122 pairs (72.1% male)] were -3.19 and -1.47mL/min/1.73 m2/year, respectively (reduction in rate of decline=53.9%, P=.007), and for X:X-matched [122 untreated/950 treated (59.4% male)] were -3.29 and -1.56mL/min/1.73 m2/year, respectively (reduction in rate of decline=52.6%, P<.001). Agalsidase beta treatment was associated with lower risk of clinical events, with hazard ratios of 0.41 (P=.003) and 0.67 (P=.008) for 1:1-matched and X:X-matched analyses, respectively. Plasma GL-3 declined markedly in paediatric patients and normalized in most within 6months of treatment initiation. Agalsidase beta treatment preserves kidney function and delays progression to severe clinical events among adult patients with FD. Plasma GL-3 levels analysed in paediatric patients showed normalization of elevated pre-treatment levels in most patients.

Evaluation of Three Different Selective Media for Enumeration of Clostridium perfringens in Untreated and Treated Wastewater.

Current and emerging legislation in North Carolina and other regions calls for the enumeration of Clostridium perfringens as a surrogate indicator for protozoan parasites in various types of waters. Past studies that have evaluated selective media for the detection of this bacterium have provided limited, conflicting, and inconclusive results. In this study, membrane filtration was used to enumerate C. perfringens as culturable spores or total culturable cells in 19 samples of untreated and 25 samples of partially treated wastewaters on 3 candidate media, Tryptose Sulfite Cycloserine Agar (TSC), CP ChromoSelect Agar (CPCS), and membrane Clostridium perfringens Agar (m-CP) in parallel, and the results were compared. Presumptive isolates from each agar were further subjected to phenotypic confirmation tests for acid phosphatase production and stormy fermentation to further determine the performance of each agar. The CPCS agar was determined to have the highest enumerative capacity of total C. perfringens cells when compared to both TSC agar and m-CP agar (p-value < 0.05), but there was no significant difference in its ability to detect spores when compared to TSC agar (p-value > 0.05). The overall specificity of CPCS agar as determined by agreement of results from both confirmation tests was 0.81, while the specificity of TSC agar was only 0.28. Based on its performance, ease of preparation and use and consistency of colony characteristics, CPCS agar is recommended as the preferred medium for C. perfringens enumeration in wastewater.

Association of triglyceride-glucose index and its related parameters with atherosclerotic cardiovascular disease: evidence from a 15-year follow-up of Kailuan cohort

BackgroundTriglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared.MethodA total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD.ResultsDuring a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS.ConclusionsBoth the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD.

Vascular regional analysis unveils differential responses to anti-angiogenic therapy in pancreatic xenografts through macroscopic photoacoustic imaging.

Pancreatic cancer (PC) is a highly lethal malignancy and the third leading cause of cancer deaths in the U.S. Despite major innovations in imaging technologies, there are limited surrogate radiographic indicators to aid in therapy planning and monitoring. Amongst the various imaging techniques Ultrasound-guided photoacoustic imaging (US-PAI) is a promising modality based on endogenous blood (hemoglobin) and blood oxygen saturation (StO 2 ) contrast to monitor response to anti-angiogenic therapies. Adaptation of US-PAI to the clinical realm requires macroscopic configurations for adequate depth visualization, illuminating the need for surrogate radiographic markers, including the tumoral microvessel density (MVD). In this work, subcutaneous xenografts with PC cell lines AsPC-1 and MIA-PaCa-2 were used to investigate the effects of receptor tyrosine kinase inhibitor (sunitinib) treatment on MVD and StO 2 . Through histological correlation, we have shown that regions of high and low vascular density (HVD and LVD) can be identified through frequency domain filtering of macroscopic PA images which could not be garnered from purely global analysis. We utilized vascular regional analysis (VRA) of treatment-induced StO 2 and total hemoglobin (HbT) changes. VRA as a tool to monitor treatment response allowed us to identify potential timepoints of vascular remodeling, highlighting its ability to provide insights into the TME not only for sunitinib treatment but also other anti-angiogenic therapies.