Stage Of Disease Research Articles

Effect of Difference in Serum Creatinine between Jaffe and Enzymatic Methods in Outpatient Kidney Transplant Recipients

Background: Deviations in serum creatinine (SCr), due to its determination using a Jaffe or an enzymatic method, have an effect on kidney disease detection and staging. It is not yet clear how large this effect is in kidney transplant recipients (KTRs). SCr measurement differences are of particular importance here to evaluate the graft function. Methods: The results of all parallel SCr measurements (Jaffe and enzymatic method) of adult outpatient KTRs in the same serum sample at the University Hospital Essen (Germany) between January 2020 and October 2023 were evaluated. A Bland–Altman plot with 95% limits of agreement (LoA) was used to assess the difference between the Jaffe and the enzymatic SCr (eSCr). For all patients, we used the CKD-EPI 2009 and EKFC formula, and for patients ≥ 70 years, we also used the BIS1 formula for the determination of eGFR. Results: A total of 12,081 parallel SCr measurements from 1243 KTRs were analyzed, where 61% were male and the median age was 53 years. On average, Jaffe SCr was 0.03 mg/dL higher than eSCr (LoA −0.16; 0.21 mg/dL). On average, the eGFR determined by Jaffe SCr was 1.9 mL/min/1.73 m2 lower than the eGFR determined by eSCr (LoA −9.5; 5.7 mL/min/1.73 m2). The comparison of eGFR between the two SCr methods revealed a different CKD stage in 1589 (13%) of all analyzed measurements, most frequently between G2/G3a (41%) and G3a/G3b (24%). When using the EKFC and BIS1 formulas, there were approximately the same number of measurements leading to a different CKD stage. Conclusions: In more than every tenth SCr determination in outpatient KTRs, the difference between the Jaffe and enzymatic methods had an influence on the assignment to a CKD stage. This effect was comparably pronounced for all eGFR formulas applied.

An international field study for the reliability and validity of the EORTC communication questionnaire EORTC QLQ-COMU26

BackgroundThe EORTC Quality of Life Group has developed a questionnaire to evaluate cancer patients’ perception of their communication with healthcare professionals (HCPs): the EORTC QLQ-COMU26. In this study we test the validity and reliability of this novel measure in an international and culturally diverse sample of cancer patients.MethodsCancer patients completed the following EORTC questionnaires at two time points (before and during treatment): the QLQ-COMU26 (including a debriefing questionnaire), the QLQ-C30, and specific IN-PATSAT32 scales. These data were used to assess: the cross-cultural applicability, acceptability, scale structure, reliability, convergent/divergent validity, known-groups validity, and responsiveness to change of the QLQ-COMU26.ResultsData were collected from 498 patients with various cancer diagnoses in 10 European countries, Japan, Jordan and India (overall 5 cultural regions). At most, only 3% of patients identified an item as confusing and 0.6% as upsetting, which indicates that the questionnaire was clear and did not trigger negative emotional responses. Confirmatory factor analysis and multi-trait scaling confirmed the hypothesised QLQ-COMU26 scale structure comprising six multi-item scales and four single items (RMSEA = 0.025). Reliability was good for all scales (internal consistency > 0.70; test–retest reliability > 0.85). Convergent validity was supported by correlations of ≥ 0.50 with related scales of the IN-PATSAT32 and correlations < 0.30 with unrelated QLQ-C30 scales. Known-groups validity was shown according to sex, education, levels of anxiety and depression, satisfaction with communication, disease stage and treatment intention, professional evaluated, and having a companion during the visit. The QLQ-COMU26 captured changes over time in groups that were defined based on changes in the item of satisfaction with communication.ConclusionThe EORTC QLQ-COMU26 is a reliable and valid measure of patients’ perceptions of their communication with HCPs. The EORTC QLQ-COMU26 can be used in daily clinical practice and research and in various cancer patient groups from different cultures. This questionnaire can help to improve communication between patients and healthcare professionals.

Clinical significance of analysis of long non-coding RNA PSMB8-AS1, MBNL1-AS1, and OLMALINC expression by polymerase chain reaction in non-small cell lung cancer

Rationale: Long non-coding RNAs (lncRNAs) influence tumor cell properties during the onset and progression of lung malignancies; however, their diagnostic and prognostic significance has not been determined. We have previously shown that when non-small cell lung cancer (NSCLC) cells acquire a more malignant phenotype (under the influence of macrophagal cytotoxic activity) compared to the original cell lines, the expression of several lncRNAs, in particular PSMB8-AS1, MBNL1-AS1, and OLMALINC, is altered compared to the original cell lines. Aim: A comparative analysis of lncRNAs PSMB8-AS1, MBNL1-AS1, and OLMALINC expression in tissue samples from lung tumors and conditionally normal areas of the lungs and an assessment of the lncRNAs clinical significance. Methods: We have analyzed surgical samples of the tumor and conditionally normal tissue from 16 patients with a verified diagnosis of NSCLC. The expression level of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was assessed by real-time polymerase chain reaction. To analyze the long-term treatment results and clinical significance of the studied genes, the patients were divided into two comparison groups depending on the relative level of lncRNAs expression (above or below the median). Results: The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC in the lung tumor tissue was significantly reduced compared to the conditionally normal tissues (p = 0.0034; p = 0.002 and p = 0.0172, respectively). Analysis of the association between the expression of these lncRNAs with clinical and morphological characteristics, such as disease stage, tumor size, presence of regional and distant metastases was unable to identify any regular patterns. The expression of lncRNAs PSMB8-AS1, MBNL1-AS1 and OLMALINC was not a significant prognostic factor (p = 0.364; p = 0.759 and p = 0.184, respectively). However in the case of high OLMALINC and PSMB8-AS1 expression, median survival was 47 months, while in the case of their low expression, median survival was not achieved during the follow-up. The expression of lncRNA PSMB8-AS1 in NSCLC tumors positively correlated with the expression of lncRNA OLMALINC (r = 0.680, p = 0.007), which may indicate their functional interplay or the presence of common regulatory mechanisms. Conclusion: The NSCLC tumors demonstrated aberrant expression of PSMB8-AS1, MBNL1-AS1, and OLMALINC lncRNAs. A more detailed study of their expression in various cell types and their regulatory role would allow for validation of new therapeutic targets in NSCLC, as well as for development of alternative therapies.

Artificial Intelligence for Optimizing Cancer Imaging: User Experience Study.

The need for increased clinical efficacy and efficiency has been the main force in developing artificial intelligence (AI) tools in medical imaging. The INCISIVE project is a European Union-funded initiative aiming to revolutionize cancer imaging methods using AI technology. It seeks to address limitations in imaging techniques by developing an AI-based toolbox that improves accuracy, specificity, sensitivity, interpretability, and cost-effectiveness. To ensure the successful implementation of the INCISIVE AI service, a study was conducted to understand the needs, challenges, and expectations of health care professionals (HCPs) regarding the proposed toolbox and any potential implementation barriers. A mixed methods study consisting of 2 phases was conducted. Phase 1 involved user experience (UX) design workshops with users of the INCISIVE AI toolbox. Phase 2 involved a Delphi study conducted through a series of sequential questionnaires. To recruit, a purposive sampling strategy based on the project's consortium network was used. In total, 16 HCPs from Serbia, Italy, Greece, Cyprus, Spain, and the United Kingdom participated in the UX design workshops and 12 completed the Delphi study. Descriptive statistics were performed using SPSS (IBM Corp), enabling the calculation of mean rank scores of the Delphi study's lists. The qualitative data collected via the UX design workshops was analyzed using NVivo (version 12; Lumivero) software. The workshops facilitated brainstorming and identification of the INCISIVE AI toolbox's desired features and implementation barriers. Subsequently, the Delphi study was instrumental in ranking these features, showing a strong consensus among HCPs (W=0.741, P<.001). Additionally, this study also identified implementation barriers, revealing a strong consensus among HCPs (W=0.705, P<.001). Key findings indicated that the INCISIVE AI toolbox could assist in areas such as misdiagnosis, overdiagnosis, delays in diagnosis, detection of minor lesions, decision-making in disagreement, treatment allocation, disease prognosis, prediction, treatment response prediction, and care integration throughout the patient journey. Limited resources, lack of organizational and managerial support, and data entry variability were some of the identified barriers. HCPs also had an explicit interest in AI explainability, desiring feature relevance explanations or a combination of feature relevance and visual explanations within the toolbox. The results provide a thorough examination of the INCISIVE AI toolbox's design elements as required by the end users and potential barriers to its implementation, thus guiding the design and implementation of the INCISIVE technology. The outcome offers information about the degree of AI explainability required of the INCISIVE AI toolbox across the three services: (1) initial diagnosis; (2) disease staging, differentiation, and characterization; and (3) treatment and follow-up indicated for the toolbox. By considering the perspective of end users, INCISIVE aims to develop a solution that effectively meets their needs and drives adoption.

Favorable Impact of Azithromycin on Patients in the Intensive Care Unit with Coronavirus Disease 2019: Insights from the First Wave Using a Japanese Database

BackgroundAzithromycin has favorable effects on critical respiratory diseases owing to its antimicrobial and anti-inflammatory properties. During the early stages of the coronavirus disease 2019 (COVID-19) pandemic, azithromycin was frequently administered before specific treatments were developed. However, the efficacy of this treatment has not been verified. We retrospectively investigated the effects of its intravenous (IV) administration in patients with severe/critical COVID-19 using the National Administrative Database of Japan during the first wave (February–April 2020). MethodsPatients were categorized based on whether they received IV azithromycin within three days of hospitalization. An overlap weighting method with estimated propensity scores was used to reduce bias. ResultsAmong the 830 patients with severe/critical COVID-19, 148 (17.8%) received azithromycin, and 682 (82.2%) did not. After adjustment, the use of azithromycin was associated with a shorter duration of intensive care unit (ICU) management (-3.48 days, 95% confidence interval [CI]: -4.59 to -2.38). However, other endpoints, including mortality rate, duration of mechanical ventilation, and duration of hospital stay, did not suggest any associations. Furthermore, of the 115 ICU patients, 27 (23.5%) were treated with IV azithromycin and 88 (76.5%) were not. After adjustment, azithromycin was associated with favorable outcomes, including reduced in-hospital mortality (odds ratio [OR], 0.45, 95% CI: 0.22 to 0.92), 30-day mortality (OR, 0.46, 95% CI: 0.22 to 0.94), and a shorter duration of ICU management (-2.94 days, 95% CI: -5.15 to -0.73). ConclusionWe verified that IV azithromycin was associated with favorable impact in patients with COVID-19 requiring ICU management.

Cognition in (pre)symptomatic Dutch-type hereditary and sporadic cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) is a main cause of cognitive dysfunction in the elderly. We investigated specific cognitive profiles, cognitive function in the stage before intracerebral hemorrhage (ICH), and the association between magnetic resonance imaging (MRI) based cerebral small vessel disease (cSVD) burden in CAA because data on these topics are limited. We included Dutch-type hereditary CAA (D-CAA) mutation carriers with and without ICH, patients with sporadic CAA (sCAA), and age-matched controls. Cognition was measured with a standardized test battery. Linear regression was performed to assess the association between MRI-cSVD burden and cognition. D-CAA ICH- mutation carriers exhibited poorer global cognition and executive function compared to age-matched controls. Patients with sCAA performed worse across all cognitive domains compared to D-CAA ICH+ mutation carriers and age-matched controls. MRI-cSVD burden is associated with decreased processing speed. CAA is associated with dysfunction in multiple cognitive domains, even before ICH, with increased MRI-cSVD burden being associated with slower processing speed. Cognitive dysfunction is present in early disease stages of cerebral amyloid angiopathy (CAA) before the occurrence of symptomatic intracerebral hemorrhage (sICH). Presymptomatic Dutch-type CAA (D-CAA) mutation carriers show worse cognition than age-matched controls. More early awareness of cognitive dysfunction in CAA before first sICH is needed. Increased cerebral small vessel disease CAA-burden on magnetic resonance imaging is linked to a decrease in processing speed.

Usefulness of Native T1 in Cardiac Magnetic Resonance Imaging and Echocardiographic Strain Parameters for Detecting Early Cardiac Involvement in Fabry Cardiomyopathy.

Non-invasive diagnosis of disease stage in Fabry cardiomyopathy with multimodality imaging is pivotal when deciding on the appropriate time to initiate enzyme replacement therapy. However, this approach has not been well established. We enrolled 14 patients with Fabry disease. All patients were evaluated using echocardiography and contrast cardiac magnetic resonance (CMR), and were divided into either an early-stage group without left ventricular hypertrophy (LVH; wall thickness >12 mm) or late gadolinium enhancement (LGE; n=7; median age 37 years; 4 female), or an advanced-stage group with LVH and/or LGE (n=7; median age 66 years; 7 female). Strain data from echocardiography and T1 mapping on CMR were compared between the groups. In the advanced-stage group, all strain data were impaired. In the early-stage group, localized longitudinal strain in the basal posterolateral segment was already reduced but both localized and global circumferential strain remained preserved. On CMR analysis, global and localized native T1 shortening were observed in the early-stage group, but were pseudo-normalized in the advanced-stage group. In logistic regression analysis, localized circumferential strain had significant diagnostic value for differentiating between early- and advanced stage (P=0.037) and significantly improved the predictive power of the model containing localized native T1 in CMR. A combination of localized native T1 in CMR and echocardiographic strain parameters could be useful for staging Fabry cardiomyopathy.

Insights of Expression Profile of Chemokine Family in Inflammatory Bowel Diseases and Carcinogenesis

Chemokines are integral components of the immune system and deeply involved in the pathogenesis and progression of inflammatory bowel disease (IBD) and colorectal cancer (CRC). Although a considerable amount of transcriptome data has been accumulated on these diseases, most of them are limited to a specific stage of the disease. The purpose of this study is to visually demonstrate the dynamic changes in chemokines across various stages of bowel diseases by integrating relevant datasets. Integrating the existing datasets for IBD and CRC, we compare the expression changes of chemokines across different pathological stages. This study collected 11 clinical databases from various medical centers around the world. Patients: Data of patient tissue types were classified into IBD, colorectal adenoma, primary carcinoma, metastasis, and healthy control according to the publisher’s annotation. The expression changes in chemokines in various pathological stages are statistically analyzed. The chemokines were clustered by different expression patterns. The chemokine family was clustered into four distinct expression patterns, which correspond to varying expression changes in different stages of colitis and tumor development. Certain chemokines and receptors associated with inflammation and tumorigenesis have been identified. Furthermore, it was confirmed that the 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis model and the azoxymethane (AOM)/ dextran sulfate sodium (DSS)-induced colon cancer model shows stronger correlations with the clinical data in terms of chemokine expression levels. This study paints a panoramic picture of the expression profiles of chemokine families at multiple stages from IBD to advanced colon cancer, facilitating a comprehensive understanding of the regulation patterns of chemokines and guiding the direction of drug development. This study provides researchers with a clear atlas of chemokine expression in the pathological processes of inflammatory bowel disease and colon cancer.

Relationships Between Quality of Discharge Teaching, Readiness for Hospital Discharge, Self-Efficacy and Self-Management in Patients With First-Episode Stroke: A Cross-Sectional Study.

The study investigated the influence of quality of discharge teaching (QDT) on readiness for hospital discharge (RHD) and pathways involved in patients with first-episode stroke, aiming to provide a theoretical framework for enhancing RHD levels and reducing readmission rates. Cross-sectional study. A total of 372 inpatients completed the Quality of Discharge Teaching Scale, Readiness for Hospital Discharge Scale, Chronic Disease Self-efficacy Scale and Southampton Stroke Self-Management Questionnaire. Structural equation modelling and Pearson's correlation analysis were utilised to elucidate relationships and action pathways among these variables. The correlation analysis demonstrated significant positive pairwise correlations between QDT, RHD, self-efficacy and self-management (r = 0.376-0.678, p < 0.01). The final model exhibited a good fit with the following indices: χ2/df = 3.286, RMSEA = 0.078, SRMR = 0.0303, GFI = 0.984, AGFI = 0.926, CFI = 0.991 and TLI = 0.970. The impact of QDT on RHD in patients with first-episode stroke was observed through one direct and three indirect pathways: (1) QDT exerted a direct influence on RHD (p < 0.001); (2) QDT indirectly influenced RHD via self-efficacy (p < 0.001); (3) QDT indirectly affected RHD through self-management (p < 0.001); and (4) QDT had an indirect effect on RHD via both self-efficacy and self-management (p < 0.05). QDT was found to directly influence RHD in patients with first-episode stroke and also exerted indirect effects through self-efficacy and self-management, either independently or in combination. Early screening of RHD levels in patients before discharge is recommended, along with the enhancement of QDT through the development of tailored guidance plans according to different disease stages, ultimately improving RHD levels and facilitating a safer transition from hospital to home or community. Healthcare professionals should assess both QDT and RHD levels to provide targeted interventions. The establishment of transitional care teams and implementation of long-term poststroke management are essential for reducing stroke recurrence and mortality rates.

Comprehensive Assessment of the Meibomian Glands by Meibography: Why the Upper Eyelids Matter.

The clinical value of upper eyelid meibographic imaging remains relatively underexplored; consequently, it is not commonly used in clinical assessments. However, its significance could be particularly important for the early detection of various ocular diseases and systemic conditions related to the eyes. An analysis of the current literature from the PubMed database, covering the years 2005 to 2023, with additional relevant papers added from cited references was conducted. Failure to diagnose dry eye disease and meibomian gland dysfunction associated with conditions such as Sjögren syndrome or thyroid eye disease in the early stages and taking appropriate action may result in persistent signs and symptoms. This could potentially lead to the development of chronic conditions that directly affect a patient's visual quality, functionality, and overall well-being. Therefore, this review aimed to demonstrate the potential clinical significance of upper eyelid examination as an integral component of comprehensive meibomian gland evaluation.

Factors behind favorable long-term lung cancer survival in Norway compared to Denmark: a retrospective cohort study

ABSTRACT Background Long-term survival of patients with non-small cell lung cancer (NSCLC) is considerably higher in Norway compared to Denmark, even though diagnostic work-up, treatment, and follow-up are comparable. We aim to explore factors behind favorable long-term survival for lung cancer patients in Norway compared to Denmark. Method A retrospective cohort study of patients with NSCLC diagnosed between 2014 and 2016. From the Danish Lung Cancer Registry, 1000 patients were randomly selected, and 974 patients were included. From the Norwegian Vestfold Hospital Trust, 220 patients were randomly selected, and 218 were included. Data from medical records were obtained for all patients. The Danish and Norwegian cohorts were compared using the Pearson chi squared test and multivariate logistic regression analysis. Results The two cohorts were comparable in terms of age, sex, and smoking history. However, the Danish patients had a higher number of pack-years (43.5 vs 34.5 p < 0.001) and more comorbidities. The Norwegian patients had less advanced disease stage (p < 0.001), and a larger proportion was treated with curative intent (90 (41.3%) vs 343 (35.2%), p = 0.063). One-year survival was similar, but the 5-year survival was superior in the Norwegian cohort (58 (26.6%) vs 177 (18.2%), p = 0.005). In a multivariate logistic regression model, adjusted for sex, smoking history, performance status, TNM stage and comorbidity, the odds ratio of being a five-year survivor in Norway was 1.81 (95% CI: 1.11–2.94) compared to Denmark. Conclusions We found a higher proportion of Norwegian patients diagnosed at potential curable stage and fewer heavy smokers compared to Danish patients. This could contribute to the superior long-term survival found in Norwegian NSCLC patients.

Incidence and predictors of common opportunistic infections among children living with HIV at Bahir Dar City, Ethiopia

Despite the dramatic decline in the incidence of common opportunistic infections (OIs) after antiretroviral therapy initiation, they remain a significant cause of morbidity and mortality among children with HIV. For better interventions, information regarding the incidence and predictors of common OIs is essential for Children living with HIV. Still, there is a lack of studies in low and middle-income countries, including Ethiopia. Therefore, this study aims to assess the incidence and predictors of common OIs among Children living with HIV on anti-retroviral therapy (ART) at public health institutions in Bahir Dar City, Northwest Ethiopia. The reasons for excluding children not on ART is we want to study the effectiveness of chronic HIV care service, ART drugs and OIs prophylaxis drugs for the prevention of common OIs because it is obvious that the occurrence of OIs in children not on ART and OIs prophylaxis drugs is high. A health institution-based retrospective cohort study was done among 403 Human Immunodeficiency Virus-infected children at public health institutions in Bahir Dar City from 2010 to 2020. Data was entered using Epi-data version 4.6 and analyzed using STATA 14.0. A bivariable Cox-proportional hazards regression model was employed to appreciate the relationship between each explanatory variable with the outcome variable. In the bivariable analysis, variables with a p-value of less than 0.25 were candidates for the multivariable proportional hazard model. The Cox proportional hazards model was used to determine predictors of common opportunistic infections at a 5% significance level. The overall incidence rate of common opportunistic infections was 7.06 with a 95% confidence interval ((CI) 5.78, 9.75) per 100 person-years of observation. Statically significant predictors were World Health Organization (WHO) clinical stage III and IV (adjusted hazard ratio (AHR) = 1.90; (95% CI 1.34, 2.75), having fair/poor adherence to anti-retroviral therapy (ART) (AHR) = 1.80; (95% CI 1.25, 2.94) and hemoglobin level < 10 g/dl (AHR) = 2.00; (95% CI 1.36, 2.89). The overall incidence rate of common OIs among children living with HIV on ART was high. Independent predictors of common OIs among children on ART were advanced-stage of HIV disease, poor ART adherence, and lower hemoglobin level. Therefore, we recommend strongly working on the prevention of advanced stages of HIV disease and improving poor ART adherence to prevent the incidence of OIs among children living with HIV on ART.

Early detection and lesion visualization of pear leaf anthracnose based on multi-source feature fusion of hyperspectral imaging

Pear anthracnose, caused by Colletotrichum bacteria, is a severe infectious disease that significantly impacts the growth, development, and fruit yield of pear trees. Early detection of pear anthracnose before symptoms manifest is of great importance in preventing its spread and minimizing economic losses. This study utilized hyperspectral imaging (HSI) technology to investigate early detection of pear anthracnose through spectral features, vegetation indices (VIs), and texture features (TFs). Healthy and diseased pear leaves aged 1 to 5 days were selected as subjects for capturing hyperspectral images at various stages of health and disease. Characteristic wavelengths (OWs1 and OWs2) were extracted using the Successive Projection Algorithm (SPA) and Competitive Adaptive Reweighted Sampling (CARS) algorithm. Significant VIs were identified using the Random Forest (RF) algorithm, while effective TFs were derived from the Gray Level Co-occurrence Matrix (GLCM). A classification model for pear leaf early anthracnose disease was constructed by integrating different features using three machine learning algorithms: Support Vector Machine (SVM), Extreme Learning Machine (ELM), and Back Propagation Neural Network (BPNN). The results showed that: the classification identification model constructed based on the feature fusion performed better than that of single feature, with the OWs2-VIs-TFs-BPNN model achieving a highest accuracy of 98.61% in detection and identification of pear leaf early anthracnose disease. Additionally, to intuitively and effectively monitor the progression and severity of anthracnose in pear leaves, the visualization of anthracnose lesions was achieved using Successive Maximum Angle Convex Cone (SMACC) and Spectral Information Divergence (SID) techniques. According to our research results, the fusion of multi-source features based on hyperspectral imaging can be a reliable method to detect early asymptomatic infection of pear leaf anthracnose, and provide scientific theoretical support for early warning and prevention of pear leaf diseases.

A Nitric Oxide-Sensing T1 Contrast Agent for In Vivo Molecular MR Imaging of Inflammatory Disease.

Nitric oxide (NO) is a signaling molecule that not only appears in the very early stage of inflammatory disease but also persists in chronic conditions. Its detection in vivo can, therefore, potentially enable early disease detection and treatment monitoring. Due to its transient nature and low abundance, however, noninvasive and deep-tissue imaging of NO dynamics is challenging. In this study, we present a magnetic resonance imaging (MRI) contrast agent based on a manganese porphyrin for specific imaging of NO. This agent is activated by NO, binds to tissue protein, accumulates so long as NO is actively produced, and confers a substantial bright contrast on T1-weighted MRI. In vitro tests confirm the specificity of activation by NO over other reactive oxygen or nitrogen species, absence of inflammation induced by the contrast agent, and sensitivity to NO levels in the tens of micromolar. In vivo demonstration in a mouse model of stress-induced acute myocardial inflammation revealed an over 2.2-times increase in T1 reduction in the inflamed heart compared to a healthy heart. This new NO-activatable T1 contrast agent holds the potential to provide early diagnosis of inflammatory disease, characterize different stages of inflammation, and ultimately guide the design of novel anti-inflammation therapeutics.

Impact of the COVID-19 Prioritization Recommendations on Pathological Stages of Urologic Malignancies: A Real-World Analysis at a High-Volume Referral Institution

Background: In response to the COVID-19 pandemic, the European Association of Urology (EAU) Guidelines defined priority groups to guide the prioritization of surgery for urological malignancies. The objective of this study was to evaluate the impact of the COVID-19 prioritization recommendations on tumor pathological characteristics in a real-world setting at our academic referral institution. Methods: We compared baseline and pathological tumor features of all patients with urological malignancies treated during the pandemic period (2020–2021) versus in the post-pandemic period (2022–2023). Our institution adhered to the international recommendations and prioritized those cases defined as “high-risk”. Results: Data from 9196 patients treated for urological malignancies were reviewed and grouped according to period of surgery (4401 in the pandemic period vs. 4785 in the post-pandemic period). The overall number of surgical procedures was comparable for all diseases except for the number of radical prostatectomies (1117 vs. 1405; p = 0.03) and partial nephrectomies (609 vs. 759; p = 0.02), which were significantly lower in the pandemic period. Regarding tumor pathological features, none of the recorded variables were found to differ according to period of surgery, including disease stage, tumor grading, presence of necrosis, lymphovascular invasion, and histological variants. Conclusions: A correct policy of prioritization of oncological pathologies during emergency periods and a centralization of oncological cases in reference centers reduce the possible risk of worsening cancer disease features related to the reorganization of healthcare resources.

RUNX2 as a novel biomarker for early identification of patients progressing to advanced-stage mycosis fungoides

IntroductionThe majority of patients with mycosis fungoides (MF) have an indolent disease course, but a substantial fraction (20-30%) of patients progress to advanced stages – usually with a grave prognosis. Early differentiation between indolent and aggressive types of MF is important for the choice of treatment regimen and monitoring of the individual patient. Good biomarkers are therefore desired.MethodsHere, we used spatial transcriptomics on skin samples at time-of-diagnosis to enable prediction of patients who later progressed to advanced stages of MF. Formalin-fixed, paraffin-embedded skin biopsies at time of diagnosis from six patients with MF who progressed to advanced stages of disease within 4 months to 12 years after diagnosis, and nine patients who remained in early-stage disease over 9 to 27 years were analyzed using the GeoMx Digital Spatial Profiler to capture spatially resolved high-plex RNA gene expression data. Five different regions of interest (the epidermis, the basal layer of epidermis, CD4+ T-cells and neighboring cells, and Pautrier’s microabscesses) were profiled for further assessment.Results and discussionInterestingly, RUNX2, SHMT2, and MCM7 were upregulated in the enriched population of malignant T-cells in Pautrier’s microabscesses in patients who later developed advanced stages of disease. Expression of RUNX2, SHMT2 and MCM7 in malignant T-cells was confirmed in a subset of patients in MF skin using scRNA-seq datasets across multiple studies and correlating with stage of disease. Taken together, we provide first evidence that RUNX2 has potential as a biomarker to identify MF patients progressing to advanced stage disease. As RUNX2 has not previously been linked to MF, our data also shows the analytical strength of combining spatial transcriptomics with scRNA-seq analysis.

Evaluating a motor progression connectivity model across Parkinson's disease stages.

Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson's Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot clinicaltrial. Here, subject-level visualizations are presented of this early-stage PD dataset to further describe the relationship between active contacts and motor progression. This study also evaluates whether stimulation of the sweet spot and connectivity model associated with slower motor progression is alsoassociated with improvements in long-term motor outcomes in patients with advanced-stage PD. Active contacts of the early-stage PD cohort (N = 14) were analyzed alongside the degree of two-year motor progression. Sweet spot and connectivity models derived from the early-stage PD cohort were then used to determine how well they can estimate the variance inlong-term motor outcomes in an independent STN-DBS cohort of advanced-stage PD patients (N = 29). In early-stage PD, proximity of stimulation to the dorsolateral STN wasassociated with slower motor progression. In advanced-stage PD, stimulation proximity to the early PD connectivity model and sweet spot were associated with better long-term motor outcomes (R = 0.60, P < 0.001; R = 0.37, P = 0.046, respectively). Results suggest stimulation of a specific site in the dorsolateral STN isassociated with both slower motor progression and long-term motor improvements in PD.

Comparing Machine Learning Techniques for Detecting Chronic Kidney Disease in Early Stage

CKD is a gradual disease that affects millions of people throughout the United States and results in high morbidity and mortality rates. Chronic Kidney Disease is an ailment that culminates in a gradual loss of kidney function over t,ime. Early detection is essential since timely interventions may prevent the progression of CKD, improve outcomes and survival for patients with CKD, and reduce healthcare costs. In the recent decade, machine learning models have emerged as a game-changing tool in medical diagnostics, leveraging big data and complex algorithms to find patterns almost invisible to clinicians and physicians. This study deployed and evaluated various machine learning approaches for the early detection of CKD, focusing on their comparative performance, strengths, and weaknesses. Machine learning transforms medical diagnosis by leveraging big data and sophisticated algorithms to find patterns that might otherwise elude healthcare professionals. The dataset used for this research will be the CKD dataset, which was contributed to by the Cleveland Clinic in 2021. The dataset can be accessed publicly through the University of California, Irvine's UCI Machine Learning Repository. In this project, the analyst compared and contrasted the performance of Logistic Regression, Decision Trees, and Random Forests. Experimentation results demonstrated that logistic regression had the best performance, yielding a perfect F1 score and accuracy, closely followed by random forest. This result showed that the Logistic model ideally classified all the instances in the test set. Consolidating machine learning algorithms into the early detection of Chronic Kidney Disease (CKD) holds substantial promise for transforming clinical practice. Healthcare professionals can enhance diagnostic accuracy and facilitate timely interventions by leveraging proposed algorithms such as logistic regression.

Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach.

Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses.

The effect of knowledge and person-related factors on breast cancer susceptibility genes (BRCA1/2) testing perception in Turkish women.

Genetic testing for breast cancer susceptibility genes (BRCA1/2) plays a pivotal role in risk assessment and preventive interventions. However, individuals' awareness, knowledge, and attitudes toward genetic testing can vary across different societies. This study focuses on understanding Turkish women's knowledge, perceptions, and attitudes toward BRCA1/2 testing, considering demographic factors and awareness. In this cross-sectional study, 301 Turkish participants, including breast/ovarian cancer patients and their first-degree relatives, were surveyed. Information on sociodemographics, cancer history, awareness, knowledge, and perceptions was collected. The study aimed to assess knowledge levels about breast cancer inheritance and BRCA1/2 testing, describe perspectives about testing in women with a family history of breast or ovarian cancer, and determine associations between knowledge, personal factors, anxiety, and genetic testing perspectives. Results showed a wide range in correct responses (31.6%-96.7%) for knowledge items. No significant relationship between knowledge levels and positive perception was observed. However, participants answering a specific question incorrectly showed higher negative perceptions. While most participants recognized the benefits of genetic testing, concerns centered around passing the genes to future generations. Participants who were younger, more educated, had higher income, were employed, at an earlier disease stage, and were social media users demonstrated more positive attitudes. Negative perceptions were higher among younger patients, physicians, and healthcare professionals. Interestingly, anxiety in cancer patients did not correlate with either positive or negative perceptions. In conclusion, this study identifies participant-related factors influencing perceptions of hereditary genetic tests. Understanding these factors and addressing associated issues can enhance the utilization of genetic testing and promote preventive oncology applications.