High-risk Category Research Articles

SCORE2 Screening Tool for Cardiovascular Risk Assessment in Psoriasis-A Case-Control Study.

Background: Psoriasis is a common, T-cell-mediated inflammatory and immune-mediated skin disease. Numerous studies confirmed that patients with psoriasis have a significant frequency of cardiovascular (CV) risk factors and CV diseases (CVDs). Risk stratification is helpful in light of the elevated risk of CVD in psoriasis patients. SCORE2 and SCORE2-OP, a new algorithm derived, calibrated and validated to predict the 10-year risk of first-onset CVD in European populations, enhances the identification of individuals at higher risk of developing CVD across Europe. Objective: Using the SCORE2 and SCORE2-OP scoring systems, the current study objective was to evaluate CV risk in Slovak psoriasis patients and the relationship between CV risk and psoriasis features in a real-world setting. Results: A case-control study was conducted involving 115 outpatients with plaque psoriasis and 66 age- and gender-matched controls with skin conditions other than psoriasis. Patients with psoriasis had significantly higher mean SCORE2 values. In the age group up to 50 years, more psoriasis patients were classified as moderate risk than controls (33.8% vs. 13.6%, p = 0.010); the high-risk category was dominated by psoriasis patients. Analysing the relationship between CV risk and selected variables, we determined, using linear regression, the dependence of the SCORE2 risk score on gender in the age group up to 50 years, on age in both age groups, on waist circumference (WC) in the category up to 50 years and on the duration and severity of psoriasis in both age groups using linear regression. For individuals older than 70, we estimated the SCORE2-OP risk score, with the average risk score being 19.5 ± 4.95. We did not observe controls with a high risk score. Psoriasis patients were more likely to be smokers and had significantly higher mean values for body mass index (BMI), WC, total cholesterol (TC), low-density lipoprotein (LDL) and systolic blood pressure (BP). Conclusions: Because CV risk factors and psoriasis are strongly related, the importance of CV risk stratification is growing, and initiating preventive lifestyle changes or therapeutic interventions in patients with psoriasis is warranted.

Characterizing the Relationship between Expression Quantitative Trait Loci (eQTLs), DNA Methylation Quantitative Trait Loci (mQTLs), and Breast Cancer Risk Variants.

To assess the association of a polygenic risk score (PRS) for functional genetic variants with the risk of developing breast cancer. Summary data-based Mendelian randomization (SMR) and heterogeneity in dependent instruments (HEIDI) were used to identify breast cancer risk variants associated with gene expression and DNA methylation levels. A new SMR-based PRS was computed from the identified variants (functional PRS) and compared to an established 313-variant breast cancer PRS (GWAS PRS). The two scores were evaluated in 3560 breast cancer cases and 3383 non-cancer controls and also in a prospective study (n = 10,213) comprising 418 cases. We identified 149 variants showing pleiotropic association with breast cancer risk (eQTLHEIDI > 0.05 = 9, mQTLHEIDI > 0.05 = 165). The discriminatory ability of the functional PRS (AUCcontinuous [95% CI]: 0.540 [0.526 to 0.553]) was found to be lower than that of the GWAS PRS (AUCcontinuous [95% CI]: 0.609 [0.596 to 0.622]). Even when utilizing 457 distinct variants from both the functional and GWAS PRS, the combined discriminatory performance remained below that of the GWAS PRS (AUCcontinuous, combined [95% CI]: 0.561 [0.548 to 0.575]). A binary high/low-risk classification based on the 80th centile PRS in controls revealed a 6% increase in cases using the GWAS PRS compared to the functional PRS. The functional PRS identified an additional 12% of high-risk cases but also led to a 13% increase in high-risk classification among controls. Similar findings were observed in the SCHS prospective cohort, where the GWAS PRS outperformed the functional PRS, and the highest-performing PRS, a combined model, did not significantly improve over the GWAS PRS. While this study identified potentially functional variants associated with breast cancer risk, their inclusion did not substantially enhance the predictive accuracy of the GWAS PRS.

Molecular characterization, clinical value, and cancer–immune interactions of genes related to disulfidptosis and ferroptosis in colorectal cancer

BackgroundThis research strived to construct a new signature utilizing disulfidptosis-related ferroptosis (SRF) genes to anticipate response to immunotherapy, prognosis, and drug sensitivity in individuals with colorectal cancer (CRC).MethodsThe data for RNA sequencing as well as corresponding clinical information of individuals with CRC, were extracted from The Cancer Genome Atlas (TCGA) dataset. SRF were constructed with the help of the random forest (RF), least absolute shrinkage and selection operator (LASSO), and stepwise regression algorithms. To validate the SRF model, we applied it to an external cohort, GSE38832. Prognosis, immunotherapy response, drug sensitivity, molecular functions of genes, and somatic mutations of genes were compared across the high- and low-risk groups (categories). Following this, all statistical analyses were conducted with the aid of the R (version 4.23) software and various packages of the Cytoscape (version 3.8.0) tool.ResultsSRF was developed based on five genes (ATG7, USP7, MMD, PLIN4, and THDC2). Both univariate and multivariate Cox regression analyses established SRF as an independent, prognosis-related risk factor. Individuals from the high-risk category had a more unfavorable prognosis, elevated tumor mutational burden (TMB), and significant immunosuppressive status. Hence, they might have better outcomes post-immunotherapy and might benefit from the administration of pazopanib, lapatinib, and sunitinib.ConclusionIn conclusion, SRF can act as a new biomarker for prognosis assessment. Moreover, it is also a good predictor of drug sensitivity and immunotherapy response in CRC but should undergo optimization before implementation in clinical settings.

Discovery of a T cell proliferation-associated regulator signature correlates with prognosis risk and immunotherapy response in bladder cancer.

The efficacy of immunotherapy is heavily influenced by T cell activity. This study aimed to examine how T cell proliferation regulators can predict the prognosis and response to immunotherapy in patients with bladder cancer (BCa). T cell proliferation-related subtypes were determined by employing the non-negative matrix factorization (NMF) algorithm that analyzed the expression patterns of T cell proliferation regulators. Subtypes were assessed for variations in prognosis, immune infiltration, and functional behaviors. Subsequently, a risk model related to T cell proliferation was created through Cox and Lasso regression analyses in the TCGA cohort and then confirmed in two GEO cohorts and an immunotherapy cohort. BCa patients were categorized into two subtypes (C1 and C2) according to the expression profiles of 31T cell proliferation-related genes (TRGs) with distinct prognoses and immune landscapes. The C2 subtype had a shorter overall survival (OS), with higher levels of M2 macrophage infiltration, and the activation of cancer-related pathways than the C1 subtype. Following this, thirteen prognosis-related genes that were involved in T cell proliferation were utilized to create the prognostic signature. The model's predictive accuracy was confirmed by analyzing both internal and external datasets. Individuals in the high-risk category experienced a poorer prognosis, increased immunosuppressive factors in the tumor microenvironment, and diminished responses to immunotherapy. Additionally, the immunotherapeutic prediction efficacy of the model was further confirmed by an immunotherapy cohort (anti-PD-L1 in the IMvigor210 cohort). Our study characterized two subtypes linked to T cell proliferation in BCa patients with distinct prognoses and tumor microenvironment (TME) patterns, providing new insights into the heterogeneity of T cell proliferation in BCa and its connection to the immune landscape. The signature has prospective clinical implications for predicting outcomes and may help physicians to select prospective responders who prioritize current immunotherapy.

Effects of Once-Weekly Semaglutide on Kidney Disease Outcomes by KDIGO Risk Category in the SUSTAIN 6 Trial

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended by Kidney Disease: Improving Global Outcomes (KDIGO) as risk-based treatment for hyperglycemia, weight management, and cardiovascular (CV) risk reduction in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). The aim of this post hoc analysis was to assess treatment effects of once weekly semaglutide on kidney disease outcomes by KDIGO risk category and on changes in KDIGO risk category, compared with placebo. Participants with T2D and established CV disease or at high CV risk treated with once weekly semaglutide or placebo in SUSTAIN 6 (NCT01720446) were stratified by baseline KDIGO risk category (low [n= 1596], moderate [n= 831], high [n= 445], very high [n= 366]). Treatment effect was analyzed for a kidney disease composite end point (macroalbuminuria, serum creatinine doubling and estimated glomerular filtration rate [eGFR]< 45 ml/min per 1.73 m2, kidney replacement therapy, or death due to kidney disease) from baseline to 2 years. The treatment effect of semaglutide versus placebo was consistent across KDIGO categories for the kidney disease composite end point (hazard ratio [95% confidence interval (CI)]: 0.35 [0.07-1.72], 0.42 [0.25-0.72], 0.87 [0.45-1.71], and 0.72 [0.42-1.23] for low, moderate, high, and very high risk categories, respectively; P interaction= 0.28). Participants receiving semaglutide were more likely to move to a lower KDIGO risk category (odds ratio: 1.69; 95% CI: [1.32-2.16]) and less likely to move to a higher KDIGO risk category versus placebo (odds ratio: 0.71; 95% CI: [0.59-0.86]). Once weekly semaglutide versus placebo reduced risks of kidney disease end points and improved risk categories irrespective of baseline KDIGO risk.

ACUTE MYOCARDIAL INFARCTION DURING VRD CHEMOTHERAPY IN A PATIENT WITH MULTIPLE MYELOMA: A CLINICAL CASE

Acute myocardial infarction is a critical condition associated with significant morbidity and mortality rates. Myocardial infarction-related acute myocardial injury is characterized by a rapid elevation and subsequent decline in cardiac troponin concentration. According to the relevant data patients with multiple myeloma are in a high-risk category for venous and arterial thrombosis. Therefore, the incidence of cardiovascular complications, which include myocardial infarction, in these patients is higher than in the general population. The development of metaplastic anemia further compounds this risk by diminishing myocardial oxygen supply. Moreover, chemotherapy for oncohematological diseases carries the potential for cardiotoxic cardiovascular complications. Immunomodulator drugs like Thalidomide and Lenalidomide, frequently utilized in multiple myeloma treatment, have been associated with Lenalidomide-induced myocardial infarction—a prevalent adverse effect. The use of proteasome inhibitors such as Bortezomib and Carfilzomib poses an increased risk for myocardial infarction development. This clinical case presents an instance of acute myocardial infarction in a multiple myeloma patient during low cumulative chemotherapy dosage, comprising Lenalidomide and Bortezomib. It underscores the necessity for enhanced clinical, instrumental, and laboratory monitoring before each specific chemotherapy course in high-risk multiple myeloma patients. Such monitoring facilitates the early detection of chemotherapy-induced cardiotoxic effects, allowing for timely intervention and management.

Update on Renal Cell Carcinoma Diagnosis with Novel Imaging Approaches.

This review highlights recent advances in renal cell carcinoma (RCC) imaging. It begins with dual-energy computed tomography (DECT), which has demonstrated a high diagnostic accuracy in the evaluation of renal masses. Several studies have suggested the potential benefits of iodine quantification, particularly for distinguishing low-attenuation, true enhancing solid masses from hyperdense cysts. By determining whether or not a renal mass is present, DECT could avoid the need for additional imaging studies, thereby reducing healthcare costs. DECT can also provide virtual unenhanced images, helping to reduce radiation exposure. The review then provides an update focusing on the advantages of multiparametric magnetic resonance (MR) imaging performance in the histological subtyping of RCC and in the differentiation of benign from malignant renal masses. A proposed standardized stepwise reading of images helps to identify clear cell RCC and papillary RCC with a high accuracy. Contrast-enhanced ultrasound may represent a promising diagnostic tool for the characterization of solid and cystic renal masses. Several combined pharmaceutical imaging strategies using both sestamibi and PSMA offer new opportunities in the diagnosis and staging of RCC, but their role in risk stratification needs to be evaluated. Although radiomics and tumor texture analysis are hampered by poor reproducibility and need standardization, they show promise in identifying new biomarkers for predicting tumor histology, clinical outcomes, overall survival, and the response to therapy. They have a wide range of potential applications but are still in the research phase. Artificial intelligence (AI) has shown encouraging results in tumor classification, grade, and prognosis. It is expected to play an important role in assessing the treatment response and advancing personalized medicine. The review then focuses on recently updated algorithms and guidelines. The Bosniak classification version 2019 incorporates MRI, precisely defines previously vague imaging terms, and allows a greater proportion of masses to be placed in lower-risk classes. Recent studies have reported an improved specificity of the higher-risk categories and better inter-reader agreement. The clear cell likelihood score, which adds standardization to the characterization of solid renal masses on MRI, has been validated in recent studies with high interobserver agreement. Finally, the review discusses the key imaging implications of the 2017 AUA guidelines for renal masses and localized renal cancer.

Abstract B024: Development of HM-001 as a therapeutic drug for non-muscle invasive bladder cancer

Abstract HM-001 is a drug containing sodium chlorite as the active ingredient that is being developed as a drug for non-muscle invasive bladder cancer (NMIBC), and is currently undergoing physician-led clinical trials. It has been discovered that sodium chlorite generates radicals in an acidic environment, and phosphatidylserine on the surface of tumor cells acts as a Lewis acid to generate radicals. HM-001, like other anticancer drugs and BCG, is intended to be injected into the bladder, retained, and then excreted. GLP studies using the same administration method has been completed, and no toxic changes have been observed in human trial doses. The efficacy of HM-001 against NMIBC was evaluated using an orthotopic transplantation model of UM-UC-3, a bladder cancer cell line. In the model, cells were transplanted into the bladder of SCID mouse after epithelial removal with trypsin, 600, 800, 1,600, and 3,200 ppm of HM-001 were administered once a week, and the weight of the excised bladder was calculated. After 4 weeks, the tumor weight was calculated and the tumor weight suppression rate in the control group was evaluated. As a result, the medicinal efficacy was confirmed at concentrations of 800ppm or higher. On the other hand, the UM-UC-3 model is a commonly used model, but it mimics CIS (carcinoma in situ) and can only partially mimic NMIBC. That is, other models are needed to evaluate efficacy for low- and high-grade NMIBC other than CIS. Therefore, we established high-grade and low-grade PDX and evaluated the effectiveness of HM-001 against low- and high-grade PDX through ex vivo testing. First, patient-derived tissue was transplanted into SCID mice, allowed to grow, and then removed. After extraction, they were cut into 2 mm3 pieces, exposed to HM-001 at 800, 1600, and 3200 ppm for 2 hours, and then transplanted into SCID mice. As a result of comparing the tumor size after transplantation with the control group, a dose-dependent tumor regression effect was confirmed in high-grade and low-grade PDX. NMIBC is divided into low-, medium-, and high-risk categories, with different treatment methods and drugs used for each. In particular, low-grade forms are restricted to low- and intermediate-risk groups. The results of this study show that HM-001 is effective not only for high-risk (including CIS) NMIBC but also for low- and intermediate-risk (low-grade) NMIBC. Citation Format: Shinji Mima, Monta Sakaki, Noriaki Kiya, Atsunari Kawashima, Norio Nonomura, Chihaya Kakinuma. Development of HM-001 as a therapeutic drug for non-muscle invasive bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B024.

Comparative Ergonomic Posture Analysis of CNC Milling Machine Workers through Digital Human Modeling and Artificial Neural Networks

Objectives: To analyze the critical postures of the CNC milling machine operators by RULA (Rapid Upper Limb Assessment) scores and develop an ANN (Artificial Neural Network) prediction model. Methods: The methodology includes a postural analysis of 40 male CNC milling machine operators across Bangladesh, employing both manual (using manual RULA assessment worksheet) and digital (using CATIA V5R21 software) RULA methods complemented by an ANN prediction model. Finally, Digital RULA scores through DHM (Digital Human Modeling) and ANN predicted RULA scores would be compared. Findings: Digital RULA analysis reveals that lifting, carrying, and positioning are the most crucial ergonomic postures, and the most prominent high-risk category limbs are wrist and arm. The overall initial RULA score for lifting, carrying, and positioning are 7, 6, and 7, respectively, and reduced to 3, 3 and 4 respectively for ergonomically designed posture. The ANN model, structured with input, hidden, and output layers of 7, 10, and 1 nodes, significantly refines ergonomic risk prediction by aligning predicted scores closely with actual outcomes during the first stage, emphasized for training. It demonstrates a perfect correlation (R=1) in training, testing, validation, and overall performance for using manual RULA scores. The model's accuracy is further evidenced by minimal prediction offsets across all datasets for digital RULA score in the second stage, with correlation coefficients of 0.87003 (training), 0.93676 (validation), 0.89113 (testing), and (0.88395) for overall. This study contributes significant advancements in ergonomic risk assessment, highlighting the adoption of improved postures to reduce musculoskeletal disorders. Novelty: Employing both manual and DHM methods for RULA score calculation combined with ANN model, which can predict postural risk as floating number and fit a wider range of parameters. Keywords: ANN, CNC, Digital Human Modeling (DHM), Ergonomics, RULA

Effect of high-risk pregnancy on prenatal stress level: a prospective case-control study

The study aimed to determine the effects of high-risk pregnancy on prenatal stress levels. The study was conducted with a case-control design in Turkey in September-December 2019. The sample included pregnant women diagnosed with high-risk pregnancy and were at their 36th or later gestational weeks as the case group (n = 121) and healthy pregnant women as the control group (n = 245). The Antenatal Perceived Stress Inventory (APSI) and the Revised Prenatal Distress Questionnaire (NUPDQ-17 Item Version) were used to assess the stress levels of the participants in the study. It was determined that high-risk pregnancy was associated with higher rates of prenatal stress (APSI: p < 0.001, effect size = 0.388; NUPDQ: p = 0.002, effect size = 0.272) compared to the control group. The results of the linear regression analysis showed that high-risk pregnancy affected APSI (R2 = 0.043, p < 0.001) and NUPDQ (R2 = 0.033, p = 0.009) scores, but education levels, number of pregnancies, and number of abortions did not affect APSI and NUPDQ scores. According to the results of this study, high-risk pregnant women are in a risk group for stress. It is of great importance for the course of a pregnancy that healthcare professionals assess the stress levels of pregnant women in the high-risk pregnancy category and provide psychological support to pregnant women who have high stress levels or are hospitalized.

The Risk of Venous Thromboembolism and Ischemic Stroke Stratified by VTE Risk Following Multiple Myeloma: A Korean Population-Based Cohort Study.

Background: Multiple myeloma (MM) is associated with high morbidity and mortality, with elevated rates of arterial thrombosis and venous thromboembolism (VTE) and ischemic stroke (IS). We aimed to estimate the incidence of VTE and IS categorized by the VTE risk grade among individuals with MM in Korea. Additionally, we explored the potential of the IMPEDE VTE score as a tool for assessing IS risk in patients with MM. Methods: This retrospective cohort study comprised 37,168 individuals aged ≥ 18 years newly diagnosed with MM between January 2008 and December 2021 using the representative claims database of the Korean population. The risk of the incidence of VTE and IS within 6 months after MM diagnosis was stratified based on high-risk (IMPEDE VTE score ≥ 8) and low-risk (<8) categories. The hazard ratios (HRs) were estimated using Cox proportional hazard models. Results: The VTE incidence was 120.4 per 1000 person-years and IS incidence was 149.3 per 1000 person-years. Statistically significant differences were observed in the cumulative incidence rates of VTE between groups with high and low VTE scores (p < 0.001) and between individuals aged ≤ 65 years (p < 0.001) and those with a Charlson comorbidity index (CCI) ≥ 3 compared to lower scores (p < 0.001). Additionally, the cumulative incidence rate of IS differed significantly across all groups (p < 0.001). The HR for the high-risk group in VTE and IS occurrence was 1.59 (95% CI, 1.26-2.00) and 3.47 (95% CI, 2.99-4.02), respectively. Conclusions: It is important to screen and manage high-risk groups for the early development of VTE or IS in patients with newly diagnosed MM.

Laboratory-based surveillance of chronic kidney disease in people with private health coverage in Brazil

BackgroundAlthough approximately 25% of Brazilians have private health coverage (PHC), studies on the surveillance of chronic kidney disease (CKD) in this population are scarce. The objective of this study was to estimate the prevalence of CKD in individuals under two PHC regimes in Brazil, who total 8,335,724 beneficiaries.MethodsOutpatient serum creatinine and proteinuria results of individuals from all five regions of Brazil, ≥ 18 years of age, and performed between 10/01/2021 and 10/31/2022, were analyzed through the own laboratory network database. People with serum creatinine measurements were evaluated for the prevalence and staging of CKD, and those with simultaneous measurements of serum creatinine and proteinuria were evaluated for the risk category of the disease. CKD was classified according to current guidelines and was defined as a glomerular filtration rate (GFR) < 60 ml/min/1.73 m² estimated by the 2021 CKD-EPI equation.ResultsThe number of adults with serum creatinine results was 1,508,766 (age 44.0 [IQR, 33.9–56.8] years, 62.3% female). The estimated prevalence of CKD was 3.8% (2.6%, 0.8%, 0.2% and 0.2% in CKD stages 3a, 3b, 4 and 5, respectively), and it was higher in males than females (4.0% vs. 3.7%, p < 0.001, respectively) and in older age groups (0.2% among 18-29-year-olds, 0.5% among 30-44-year-olds, 2.0% among 45-59-year-olds, 9.4% among 60-74-year-olds, and 32.4% among ≥ 75-year-olds, p < 0.001) Adults with simultaneous results of creatinine and proteinuria were 64,178 (age 57.0 [IQR, 44.8–67.3] years, 58.1% female). After adjusting for age and gender, 70.1% were in the low-risk category of CKD, 20.0% were in the moderate-risk category, 5.8% were in the high-risk category, and 4.1% were in the very high-risk category.ConclusionThe estimated prevalence of CKD was 3.8%, and approximately 10% of the participants were in the categories of high or very high-risk of the disease. While almost 20% of beneficiaries with PHC had serum creatinine data, fewer than 1% underwent tests for proteinuria. This study was one of the largest ever conducted in Brazil and the first one to use the 2021 CKD-EPI equation to estimate the prevalence of CKD.

Clinical and Genomic-Based Decision Support System to Define the Optimal Timing of Allogeneic Hematopoietic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes.

Allogeneic hematopoietic stem-cell transplantation (HSCT) is the only potentially curative treatment for patients with myelodysplastic syndromes (MDS). Several issues must be considered when evaluating the benefits and risks of HSCT for patients with MDS, with the timing of transplantation being a crucial question. Here, we aimed to develop and validate a decision support system to define the optimal timing of HSCT for patients with MDS on the basis of clinical and genomic information as provided by the Molecular International Prognostic Scoring System (IPSS-M). We studied a retrospective population of 7,118 patients, stratified into training and validation cohorts. A decision strategy was built to estimate the average survival over an 8-year time horizon (restricted mean survival time [RMST]) for each combination of clinical and genomic covariates and to determine the optimal transplantation policy by comparing different strategies. Under an IPSS-M based policy, patients with either low and moderate-low risk benefited from a delayed transplantation policy, whereas in those belonging to moderately high-, high- and very high-risk categories, immediate transplantation was associated with a prolonged life expectancy (RMST). Modeling decision analysis on IPSS-M versus conventional Revised IPSS (IPSS-R) changed the transplantation policy in a significant proportion of patients (15% of patient candidate to be immediately transplanted under an IPSS-R-based policy would benefit from a delayed strategy by IPSS-M, whereas 19% of candidates to delayed transplantation by IPSS-R would benefit from immediate HSCT by IPSS-M), resulting in a significant gain-in-life expectancy under an IPSS-M-based policy (P = .001). These results provide evidence for the clinical relevance of including genomic features into the transplantation decision making process, allowing personalizing the hazards and effectiveness of HSCT in patients with MDS.

Enhancing multiple myeloma staging: a novel cell death risk model approach

The prognostication of survival trajectories in multiple myeloma (MM) patients presents a substantial clinical challenge. Leveraging transcriptomic and clinical profiles from an expansive cohort of 2,088 MM patients, sourced from the Gene Expression Omnibus and The Cancer Genome Atlas repositories, we applied a sophisticated nested lasso regression technique to construct a prognostic model predicated on 28 gene pairings intrinsic to cell death pathways, thereby deriving a quantifiable risk stratification metric. Employing a threshold of 0.15, we dichotomized the MM samples into discrete high-risk and low-risk categories. Notably, the delineated high-risk cohort exhibited a statistically significant diminution in survival duration, a finding which consistently replicated across both training and external validation datasets. The prognostic acumen of our cell death signature was further corroborated by TIME ROC analyses, with the model demonstrating robust performance, evidenced by AUC metrics consistently surpassing the 0.6 benchmark across the evaluated arrays. Further analytical rigor was applied through multivariate COX regression analyses, which ratified the cell death risk model as an independent prognostic determinant. In an innovative stratagem, we amalgamated this risk stratification with the established International Staging System (ISS), culminating in the genesis of a novel, refined ISS categorization. This tripartite classification system was subjected to comparative analysis against extant prognostic models, whereupon it manifested superior predictive precision, as reflected by an elevated C-index. In summation, our endeavors have yielded a clinically viable gene pairing model predicated on cellular mortality, which, when synthesized with the ISS, engenders an augmented prognostic tool that exhibits pronounced predictive prowess in the context of multiple myeloma.

Fertility and Pregnancy after Bariatric Surgery: Challenges and Solutions

Abstract Introduction Obesity is increasing worldwide, and bariatric surgery (BS) is increasingly employed for weight management in women of reproductive age. An interplay between pregnancy and BS is very likely. A review of the challenges faced and solutions needed is warranted. Materials and Methods A narrative, nonsystematic review of the international literature from a single online database (PubMed) was performed on July 23, 2023. All articles were included. The retrieved relevant literature is narrated in a concise thematic account. Results BS carries major metabolic, mechanical, and vascular benefits, possibly accompanied by nutritional, vitamins, minerals, and micronutrient deficiencies, which might be clinical or subclinical. A few of the frequently reported postbariatric nutritional jeopardies could be augmented by the physiological changes of pregnancy, which need a different approach to management. Nutritional deficiencies during pregnancy could carry both maternal and fetal short- and long-term risks. Fetal risks may range from miscarriage to low birth weight, neural tube defects, congenital anomalies, cognitive impairment, and internal organ dysplasia. Postbariatric status is, by default, a high-risk pregnancy category, given the altered biochemical, vasomotor, and mechanical indices of any lady treated with BS. Postgastric bypass hypoglycemia (PGBH) is a relatively common phenomenon during pregnancy, and it usually calls for multidisciplinary action to control. A dedicated monitoring protocol before, during, and after pregnancy has been suggested in several guidelines to guard against the potentially devastating consequences to both mother and fetus. Conclusions Weight reduction after BS enhances fertility. The optimum timing for ladies treated with BS to get pregnant is not very well established yet. However, various societies have provided multidisciplinary management guidance of management prior to and during pregnancy. Many nutritional supplements that are not routinely prescribed during pregnancy will be essential for those treated with BS. Further studies are still warranted to ensure the safe interim between BS and conception as well as the safety of various doses of medications used for postbariatric individuals, for instance, medications used for PGBH.

Exploring genes within the glutathione peroxidase family as potential predictors of prognosis in papillary renal cell carcinoma

Abstract Objectives This research aims to explore the relationship between glutathione peroxidase (GPX) expression variations in papillary renal cell carcinoma (pRCC) and patient survival, while also developing and evaluating a customized survival prediction model based on GPX. Methods The transcriptomic dataset, including clinical parameters and GPX expression levels, is sourced from The Cancer Genome Atlas (TCGA) database, comprising 290 individuals diagnosed with pRCC. We utilized a univariate Cox regression model to select differentially expressed genes. Subsequently, we calculated risk scores through the least absolute shrinkage and selection operator (LASSO) regression. Based on the median risk score, patients were categorized into high and low-risk groups, establishing a prognostic risk model. Following this, the relationship between the risk model and the survival of pRCC patients was revealed through Kaplan–Meier survival curve analysis. The sensitivity and specificity of the predictive model were evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, chemotherapy drug sensitivity analysis was conducted on patients in the high and low-risk groups. Results A risk-scoring model was built by selecting GPX7 and GPX8. Compared to the low-risk group, individuals in the high-risk category showed significantly reduced overall survival rates (p=0.018). Additionally, validation results demonstrated the model’s good predictive accuracy. Conclusions The risk-scoring model constructed based on GPX family genes provides an innovative biomarker for forecasting the prognosis of pRCC and serves as a reference for individualized therapy in pRCC.

Evaluating the efficacy of vermicomposted products in rain-fed wetland rice and predicting potential hazards from metal-contaminated tannery sludge using novel machine learning tactic

The study assessed the ecotoxicity and bioavailability of potential metals (PMs) from tannery waste sludge, alongside addressing the environmental concerns of overuse of chemical fertilizers, by comparing the impacts of organic vermicomposted tannery waste, chemical fertilizers, and sole application of tannery waste on soil and rice (Oryza sativa L.) plants. The results revealed that T3, which received high-quality vermicomposted tannery waste as an amendment, exhibited superior enzymatic characteristics compared to tannery sludge amended (TWS) treatments (T8, T9). After harvesting, vermicomposted tannery waste treatment (T3) showed a more significant decrease in PMs bioavailability. Accumulation of PMs in rice was minimal across all treatments except T8 and T9, where toxic tannery waste was present, resulting in a high-risk classification (class 5 < 0.01) according to the SAMOE risk assessment. Results from Fuzzy-TOPSIS, ANN, and Sobol sensitivity analyses (SSA) further indicated that elevated concentrations of PMs (Ni, Pb, Cr, Cu) adversely impacted soil-plant health synergy, with T3 showing a minimal risk in comparison to T8 and T9. According to SSA, microbial biomass carbon and acid phosphatase activity were the most sensitive factors affected by PMs concentrations in TWS. The results from the ANN assay revealed that the primary contributing factor of toxicity on the TWS was the exchangeable fraction of Cr. Correlation statistics underscored the significant detrimental effect of PMs' bioavailability on microbial and enzymatic parameters. Overall, the findings suggest that vermicomposting of tannery sludge waste shows potential as a viable organic amendment option in the near future.

VALUE OF THE PROGNOSTIC MODEL FOR THE DIAGNOSIS OF HYPERTENSION USING AI ALGORITHMS

Objective: Hypertension is a prevalent cardiovascular condition associated with significant morbidity and mortality. While various prognostic models exist for predicting hypertension, incorporating artificial intelligence (AI) algorithms may enhance diagnostic accuracy and prognostication. However, the value of such AI-based prognostic models in hypertension diagnosis and risk stratification remains to be fully elucidated. This study aimed to evaluate the value of a prognostic model for the diagnosis of hypertension using AI algorithms by assessing biomarkers, predictors for worse prognosis, and clinical outcomes with Kaplan-Meier analysis and Cox regression models. Design and method: A retrospective cohort study was conducted on 256 smoker individulas with a mean age of 56.2 ± 12.8 years. Participants were followed up for a median duration of 6.5±2.6 years. Clinical and laboratory data, including cardiovascular biomarkers and predictors of hypertension, were collected at baseline. An AI-based prognostic model was developed using machine learning algorithms to predict hypertension diagnosis and prognosis. Kaplan-Meier analysis was performed to evaluate the cumulative incidence of hypertension, while Cox regression models were utilized to assess predictors of worse prognosis. Results: During the follow-up period, 42% of patients developed hypertension. The AI-based prognostic model demonstrated excellent diagnostic accuracy in predicting hypertension development, with 78% sensitivity and 75% specificity. Additionally, several predictors were identified for worse prognosis in hypertensive patients, including abdominal obesity, glucose intolerance, dyslipidemia. Cox regression models confirmed the independent association between high-risk classification by the prognostic model and cumulative incidence of hypertension (hazard ratio [HR], [1.15]; 95% confidence interval [CI], [1.05-1.26]; p &lt; 0.05). Conclusions: Our findings suggest that an AI-based prognostic model holds promise for the diagnosis of hypertension and risk stratification. Incorporating AI algorithms into prognostic models may enhance diagnostic accuracy and improve outcomes in patients with hypertension. Further research is warranted to validate these findings in larger cohorts and optimize the AI-based prognostic model for clinical implementation.

A Comprehensive Analysis of Clinical, Biochemical, and Polysomnographic Characteristics in Patients With Type 2 Diabetes Mellitus With and Without Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) has been a significant contributor tomortality all across the globe. The most attributing factors to pathogenesis are metabolic syndrome, obesity, diabetes, and so on,but the indicators of its early detection are still elusive. The study aimed to compare the clinical, biochemical, and polysomnographic characteristics of type 2 diabetes patients with and without OSA. This cross-sectional study was conducted at the Department of Medicine and Endocrinology Unit of Dayanand Medical College and Hospital, Ludhiana. A total of 584 patients with type 2 diabetes were assessed using the Berlin questionnaire, with 302 fulfilling the criteria for a high risk of OSA. Out of 302 patients who met the criteria for the high-risk category, 110 patients underwent a sleep study. Three hundred and two patients satisfying the inclusion and exclusion criteria were enrolled in the study. Atotal of 110 patientsunderwent a sleep study, of which68 (61.8%)had evidence of OSA. The waist-to-hip ratio was considerably higher in the OSA patients than in the non-OSA group (1.09vs 0.930, p = 0.001). HbA1c >7%was found in 58.8% of OSA patients contrary to 38.1% of non-OSA patients. Fasting plasma glucose levels (>126 mg/dl) were identified in a substantially larger proportion of OSA patients than the non-OSA patients (64.7% vs 45.2%, p = 0.04). Similarly, peripheral neuropathy was found more commonly in the OSA patients than in the non-OSA patients (47% vs. 26.1%, p = 0.02). Prevalence of retinopathy, nephropathy, coronary artery disease, stroke, heart failure, and peripheral vascular disease did not differ significantly between the two groups. OSAfrequently occurs among individuals diagnosed with type 2 diabetes mellitus. The prompt identification of OSA within this demographic is imperative to pinpoint those at an elevated risk of succumbing to conditions such as peripheral neuropathy, the exacerbation of glycemic control, and the onset of unmanaged hypertension. Moreover, there exists a positive correlation between the waist-to-hip ratio and the prevalenceof OSAin persons with type 2 diabetes mellitus, highlighting the critical role of waist-to-hip ratio assessments in this patient population.

CCL14 testing to guide clinical practice in patients with AKI: Results from an international expert panel

PurposeUrinary C-C motif chemokine ligand 14 (CCL14) is a strong predictor of persistent stage 3 acute kidney injury (AKI). Multiple clinical actions are recommended for AKI but how these are applied in individual patients and how the CCL14 test results may impact their application is unknown. MethodsWe assembled an international panel of 12 experts and conducted a modified Delphi process to evaluate patients at risk for persistent stage 3 AKI (lasting 72 hours or longer). Using a Likert scale, we rated 11 clinical actions based on international guidelines applied to each case before and after CCL14 testing and analyzed the association between the strength and direction of recommendations and CCL14 results. ResultsThe strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for the interaction). Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results (P < 0.001 comparing low to highest CCL14 risk category). ConclusionsMost recommendations for care of patients with stage 2-3 by an international panel of experts were strongly modified by CCL14 test results. This work should set the stage for clinical practice protocols and studies to determine the effects of recommended actions informed by CCL14.