Stage Score Research Articles

A Comprehensive Multi-Functional Approach for Measuring Parkinson's Disease Severity.

This research study aims to advance the staging of Parkinson's disease (PD) by incorporating machine learning to assess and include a broader multi-functional spectrum of neurocognitive symptoms in the staging schemes beyond motor-centric assessments. Specifically, we provide a novel framework to modernize and personalize PD staging more objectively by proposing a hybrid feature scoring approach. We recruited thirty-seven individuals diagnosed with PD, each of whom completed a series of tablet-based neurocognitive tests assessing motor, memory, speech, executive functions, and tasks ranging in complexity from single to multi-functional. Then, the collected data was used to develop a hybrid feature scoring system to calculate a weighted vector for each function. We evaluated current PD staging schemes and developed a new approach based on the features selected and extracted using Random Forest and Principal Component Analysis. Our findings indicate a substantial bias in current PD staging systems toward fine-motor skills, i.e., other neurological functions (memory, speech, executive function, etc.) do not map into current PD stages as well as fine-motor skills do. The results demonstrate that a more accurate and personalized assessment of PD severity could be achieved by including a more exhaustive range of neurocognitive functions in the staging systems either by involving multiple functions in a unified staging score or by designing a function-specific staging system. The proposed hybrid feature score approach provides a comprehensive understanding of PD by highlighting the need for a staging system that covers various neurocognitive functions. This approach could potentially lead to more effective, objective, and personalized treatment strategies. Further, this proposed methodology could be adapted to other neurodegenerative conditions such as Alzheimer's disease or ALS.

Abstract A086: Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC)

Abstract Background: Prostate cancer (PCa) survival has improved over the past 20 years due to advancements in treatment and screening. However, racial and ethnic disparities in PCa survival remain. Studying population differences in PCa survival may help identify underlying contributing factors. Methods: We conducted survival analyses among 10,651 African American, Latino, Native Hawaiian, Japanese American, and non-Hispanic White (NHW) men with an incident PCa diagnosis since 1993 who were part of the Multiethnic Cohort Study. Sub- hazard ratios (SHRs) and 95% confidence intervals (CI) were estimated using the Fine and Grey Subdistribution Hazards Model to account for competing risks in PCa-specific mortality, with age since diagnosis as the time metric. Multivariable models included age at PCa diagnosis, Gleason score, stage at diagnosis, and baseline values of education, initial treatment (radiation, surgery, hormone therapy, chemotherapy, or no active treatment), diabetes history, physical activity, BMI, smoking status, and dietary intakes linked to PCa progression (tomatoes, whole milk, fatty fish, processed meat, saturated fat, and alcohol). We also performed stratified analyses by tumor stage (localized or regional/distant) and Gleason score (≤7 or >7). Associations were considered statistically significant at P < 0.05. Results: Of 10,651 men diagnosed with PCa over 27 years of follow-up (mean duration, 8.4 years), 1,324 (12.4%) died of PCa. Those with lower Gleason scores were less likely to die than those with higher scores (6.8% of men with Gleason score ≤7 vs 21.3% of men with Gleason score >7, p<0.001). Likewise, men with localized disease were less likely to die than men with regional/distant disease (7.5% of men with localized disease vs. 29.2% of men with regional/distant disease, p<0.001). Japanese Americans had significantly lower mortality compared with NHWs (SHR=0.63, 95% CI:0.51, 0.79, p<0.001), consistently observed across stage and Gleason score: localized (SHR=0.64, 95% CI: 0.48, 0.87, p<0.001); regional/distant (SHR=0.63, 95% CI: 0.45, 0.88, p=0.01); Gleason ≤7 (SHR=0.61, 95% CI: 0.44, 0.86, p<0.001); and Gleason score >7 (SHR=0.59, 95% CI: 0.43, 0.79, p<0.001). PCa-specific mortality was significantly higher among African Americans compared to NHWs (SHR=1.31, 95% CI: 1.08-1.60, p=0.01). This difference was more pronounced for less aggressive tumors: localized (SHR=1.50, 95% CI: 1.15, 1.96, p<0.001); Gleason ≤7 (SHR=1.28, 95% CI: 0.95, 1.71, p=0.11). Lastly, we did not observe significant differences in PCa mortality for Latinos and Native Hawaiians compared to NHWs overall or by disease severity. Conclusions: Japanese American have ∼40% lower and African Americans have ∼30% higher PCa-specific mortality relative to NHWs, even after accounting for lifestyle/behavioral factors, stage, Gleason score, and treatment. Further investigations are needed to explore social and cultural factors that impact care as well as tumor-based characteristics that may vary between populations to understand these disparities in PCa mortality. Citation Format: Wei Xiong, Fei Chen, Ann S. Hamilton, David Conti, Raymond Hughley, David Bogumil, Anqi Wang, Song-Yi Park, Peggy Wan, Lynne R. Wilkens, Loïc Le Marchand, Brenda Y. Hernandez, Christopher A. Haiman. Racial and ethnic disparities in prostate cancer survival in the Multiethnic Cohort Study (MEC) [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A086.

Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer's disease.

Accumulation of pathological tau isoforms, especially hyperphosphorylated tau at serine 396 (pS396-tau) and tau oligomers, has been demonstrated in the retinas of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Previous studies have noted a decrease in retinal ganglion cells (RGCs) in AD patients, but the presence and impact of pathological tau isoforms in RGCs and RGC integrity, particularly in early AD stages, have not been explored. To investigate this, we examined retinal superior temporal cross-sections from 25 patients with MCI (due to AD) or AD dementia and 16 cognitively normal (CN) controls, matched for age and gender. We utilized the RGC marker ribonucleic acid binding protein with multiple splicing (RBPMS) and Nissl staining to assess neuronal density in the ganglion cell layer (GCL). Our study found that hypertrophic RGCs containing pS396-tau and T22-positive tau oligomers were more frequently observed in MCI and AD patients compared to CN subjects. Quantitative analyses indicated a decline in RGC integrity, with 46-55% and 55-56% reductions of RBPMS+ RGCs (P<0.01) and Nissl+ GCL neurons (P<0.01-0.001), respectively, in MCI and AD patients. This decrease in RGC count was accompanied by increases in necroptotic-like morphology and the cleaved caspase-3 apoptotic marker in RGCs of AD patients. Furthermore, there was a 2.1 to 3.1-fold increase (P<0.05-0.0001) in pS396-tau-laden RGCs in MCI and AD patients, with a greater abundance observed in individuals with higher Braak stages (V-VI), more severe clinical dementia ratings (CDR=3), and lower mini-mental state examination (MMSE) scores. Strong correlations were noted between the decline in RGCs and the total amount of retinal pS396-tau and pS396-tau+ RGCs, with pS396-tau+ RGC counts correlating significantly with brain neurofibrillary tangle scores (r= 0.71, P= 0.0001), Braak stage (r= 0.65, P= 0.0009), and MMSE scores (r= -0.76, P= 0.0004). These findings suggest that retinal tauopathy, characterized by pS396-tau and oligomeric tau in hypertrophic RGCs, is associated with and may contribute to RGC degeneration in AD. Future research should validate these findings in larger cohorts and explore noninvasive retinal imaging techniques that target tau pathology in RGCs to improve AD detection and monitor disease progression.

Identification and validation of diagnostic and prognostic biomarkers in prostate cancer based on WGCNA

BackgroundProstate cancer (PCa) represents a significant health challenge for men, and the advancement of the disease often results in a grave prognosis for patients. Therefore, the identification of biomarkers associated with the diagnosis and prognosis of PCa holds paramount importance in patient health management.MethodsThe datasets pertaining to PCa were retrieved from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was conducted to investigate the modules specifically associated with the diagnosis of PCa. The hub genes were identified using the LASSO regression analysis. The expression levels of these hub genes were further validated by qRT-PCR experiments. Receiver operating characteristic (ROC) curves and nomograms were employed as evaluative measures for assessing the diagnostic value.ResultsThe blue module identified by WGCNA exhibited a strong association with PCa. Six hub genes (SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3) were identified by LASSO regression analysis. Further verification confirmed that these six genes were significantly downregulated in tumor tissues and cells. The six hub genes and the nomogram demonstrated substantial diagnostic value, with area under the curve (AUC) values ranging from 0.754 to 0.961. Moreover, patients with low expression levels of these six genes exhibited elevated T/N pathological stage and Gleason score, implying a more advanced disease state. Meanwhile, their progression-free survival (PFS) was observed to be potentially poorer. Finally, a significant association could be observed between the expression of these genes and the dysregulation of immune cells, along with drug sensitivity.ConclusionsIn summary, our study identified six hub genes, namely SLC14A1, COL4A6, MYOF, FLRT3, KRT15, and LAMB3, which can be utilized to establish a diagnostic model for PCa. The discovery may offer potential molecular targets for clinical diagnosis and treatment of PCa.

Translation, Cross-Cultural Adaptation and Validation of the Lymphedema Quality of Life Questionnaire (LYMQOL) in German-Speaking Patients with Upper Limb Lymphedema.

Objectives: The LYMQOL is the most frequently translated, validated, objective tool for assessing Health-Related Quality of Life (HRQoL) in individuals with upper limb lymphedema (ULL). There have been adaptations and validations in a number of different countries. While a German version of LYMQOL Leg for lower limb lymphedema is available, a validated translation of LYMQOL Arm to German is lacking. We aimed to perform a cross-cultural adaption and translation according to ISPOR principles. Methods: Patients suffering from ULL from Germany, Austria, and Switzerland (n = 52) were questioned twice using the translated LYMQOL Arm, SF-36, and an evaluation questionnaire. The assessment of the content validity and face validity proved this version of LYMQOL Arm to be acceptable for interviewing German-speaking patients with ULL in Germany. Results: Comparison of LYMQOL Arm and SF-36 demonstrated good construct validity. Test-retest reliability was moderate to good (intraclass correlation coefficients 0.66-0.73). Cronbach's alpha values varied between 0.79 and 0.89 in both interviews, indicating good internal consistency. Factor analysis revealed a cumulative variance of 59.5% for the four domains of the questionnaire. Conclusion: There was no significant association between lymphedema stage and LYMQOL Arm score. This trial tested the appropriateness of the German version of the LYMQOL Arm for measuring HRQoL in German-speaking individuals with ULL.

Reliability of self-reported pubertal development scale for girls in early adolescent: a school population-based study.

The study aimed to evaluate the correlation between self-reported pubertal developmental scale (PDS) and physically assessed Tanner staging by an experienced pediatrician among girls. In a school population-based study in Zhongshan, China, we recruited 1,722 girls in grades 1-3 by a multistage stratified cluster random sampling method. Participants completed self-reported PDS questionnaire prior to physical examination. Breast development was evaluated by a female pediatrician combined with ultrasound examination for overweight/obese girls; pubic hair development was evaluated. Otherwise, we tested follicle-stimulating hormone (FSH) and luteinizing hormone (LH) for some participants. We observed a weak association between Tanner-derived composite stage (TDCS) and puberty category scores (PCS) (τ=0.288, p<0.001) among all girls. There was correlation (τ=0.314, p=0.001) between ultrasound-derived composite stage (UDCS) and PCS among overweight/obese girls. Moreover, among overweight/obese girls, PCS was positively correlated with LH (r=0.265, p=0.008), but not FSH (r=0.155, p=0.123), and when the basal LH value was greater than 0.3 mIU/mL, the proportion of PCS stage≥2 (9/18) was higher than the proportion of TDCS≥2 (5/18). As for the determination of pubertal onset, when UDCS was used as the gold standard, the specificity of PCS was 0.86 and positive predictive value was 90.00 %. There was a weak correlation between PCS and TDCS among girls early adolescence. Moreover, among overweight/obese girls, combining hormone values, ultrasonographic stage of breast, and the positive predictive value of PCS, we posit that self-reported PDS might be a more reliable method than TDCS to evaluate pubertal development among overweight/obese girls.

585. COMPREHENSIVE RISK SCORE OF THE E-PASS SERVES A PROGNOSTIC INDICATOR FOR PATIENTS AFTER NEOADJUVANT THERAPY AND CURATIVE ESOPHAGEAL CANCER SURGERY

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) and curative surgery have been recommended as the standard treatments for locally advanced esophageal cancer. In addition, the comprehensive risk score (CRS) of the physiological ability and surgical stress (E-PASS) scoring system, incorporating both clinical and surgical factors, has proven effective in predicting postoperative complications and mortality. However, the impact of E-PASS scoring system on the prognosis of esophageal cancer remains uncertain. This study aimed to evaluate the comprehensive risk score of E-PASS scoring system for predicting the short- and long-term outcomes of patients treated with nCRT and esophageal cancer surgery. Methods Patients with esophageal cancer who underwent curative resection between 2010 and 2022 were retrospectively enrolled in this study. The cohort was divided into the low and high CRS groups. The CRS cutoff value was determined using the Youden index applied to overall survival (OS) curves. Prognostic value was assessed through Cox regression and Kaplan–Meier analyses. Results In total, 814 patients were enrolled, including 556 and 258 patients with low and high CRS, respectively. ROC curve analysis determined that the CRS was a highly specific and sensitive predictive tool for postoperative complication occurrence and severity (AUC=0.889 and 0.838, respectively). When the cutoff value was established using the Youden index applied to overall OS curves, multivariate analysis demonstrated that the CRS was an independent prognostic factor for OS (HR: 1.48; 95% CI 1.14–1.92, P=0.003) and recurrence-free survival (HR: 1.44; 95% CI 1.13–1.82, P=0.002), irrespective of esophageal cancer stage and tumor regression scores. Conclusion The E-PASS scoring system emerges as a visible predictor of short- and long-term outcomes in patients with esophageal cancer undergoing nCRT and curative surgery.

Meyerhold and the Creation of the Stage Score

Meyerhold and the Creation of the Stage Score

265. INITIAL RESULTS FROM RESOLVE, A PHASE 1B DOSE-ESCALATION STUDY OF EP-104GI (EXTENDED-RELEASE FLUTICASONE PROPIONATE INTRA-ESOPHAGEAL INJECTION) FOR EOSINOPHILIC ESOPHAGITIS

Abstract Background Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by inflammation, influx of eosinophils and esophageal remodeling. Therapy for EoE includes swallowed/topical corticosteroids, dupilumab, and dietary elimination; but these are not always effective. EP-104GI is an extended-release fluticasone propionate (FP) intra-esophageal injection being developed as a novel treatment for EoE. EP-104GI consists of coated FP crystals that release locally via diffusion at a pre-defined rate to reduce peak concentrations and prolong therapeutic window. RESOLVE (NCT05608681) is a Phase 1b, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of EP-104GI in patients with EoE. Methods The conservative starting dose of EP-104GI consisted of 1 mg injected at each of 4 sites in 4 quadrants over two ‘rings’ in the esophagus. Dose escalations increase the dose per site and/or number of sites; the second cohort received 1 mg at each of 8 sites. After a single administration of EP-104GI, participants are assessed for up to 24 weeks including adverse events (AEs) and laboratory tests. Efficacy assessments include histological endpoints and patient-reported symptom outcomes including the Straumann Dysphagia Index (SDI). Esophageal biopsies are collected at baseline, Week 4 and Week 12. Results All subjects demonstrated decreased symptom scores compared to baseline, with generally greater responses at the higher EP-104GI dose in Cohort 2 (Fig 1). Histologically, all Cohort 2 patients showed decreases in EoEHSS scores with 2/3 having ≈50% decrease in total grade score and ≈35% decrease in total stage score at Week 4, also, eosinophil counts were reduced by ≈35% at Week 4 and ≈40% at Week 12. Findings from Cohorts 1 and 2 of the ongoing trial include mild-moderate treatment-emergent AEs, the majority occurring on the day of treatment. No AEs were related to EP-104GI. Conclusions The initial results presented here indicate that the novel diffusion-based localized delivery of FP via EP-104GI injection into the esophagus is feasible and safe in patients with EoE and could avoid the side-effects typically associated with swallowed/topical corticosteroids. Efficacy data from the doses studied, although limited at this point, suggest a dose-response relationship with symptom outcomes and also show histologic improvements. These findings support the potential for an interval of at least 6 months between inter-esophageal injections, which may be further extended at the higher doses to be investigated in this study. Recruitment is ongoing.

799. OPTIMUM NUMBERS OF DISSECTED LYMPH NODES FOR ACCURATE NODAL STAGING IN CT1-2N0 ESOPHAGEAL SQUAMOUS CELL CARCINOMA

Abstract Background Patients with esophageal squamous cell carcinoma (ESCC) with lymph node metastasis may be misclassified as pN0 due to an inadequate lymph node dissection. The purpose of this study was to confirm that patients with cT1-2N0 ESCC are indeed pN0 and to propose an adequate number of lymph nodes for correct nodal staging. Methods A total of 1,855 patients who underwent upfront surgery for cT1-2N0 ESCC at two tertiary academic hospital in Korea between 1995 and 2019 were included in the study. The probability of false-negative lymphadenectomy and NSS (nodal staging score) was calculated to assess the probability of pN0 status. Results The mean age was 63.36 ± 8.01 years, with 1,726 (93.05%) male patients. The mean number of dissected lymph nodes was 34.69 ± 13.98. The clinical T stages were as follows: cTis &amp; cT1a 354 (19.08%), cT1b 1,053 (56.77%), and cT2 448 (24.15%). Pathologic nodal upstaging occurred in 443 (23.91%); pN1 352 (19.0%), pN2 78 (4.21%), and pN3 13 (0.7%). By calculating the probability of false-negative lymphadenectomy, removing fewer than 33 lymph nodes was associated with a 20% risk of missing a positive lymph node, whereas removing 53 lymph nodes was associated with a 10% risk of missing a positive lymph node. The NSS, which reflects the probability that a patient with ypN0 status is actually free of occult nodal disease after surgery, increased as the number of dissected lymph nodes increased. Conclusions Extensive lymph node dissection is mandatory for accurate staging and reducing the risk of missing positive lymph nodes in early-stage ESCC. The survival benefits of extensive lymph node dissection need to be evaluated in further analysis.

Prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease in a tertiary health-care center in Turkey.

The objective was to determine the prevalence and clinical correlates of nonmotor symptoms in Parkinson's disease patients in movement disorders outpatient clinics. We enrolled all consecutive PD patients who visited our movement disorders outpatient clinics between January and December 2023; and agreed to participate in the study. In addition to the evaluation of demographic and clinical features, clinical scales, including the MDS-UPDRS, NMSS, and FOOGQ, were performed. Overall, we enrolled 163 PD subjects with a mean age of 63.9 ± 10.4 (F/M = 27/136). The disease duration was 3.5 (20) y [median (range)]. The median score of the NMSS was 41 points. The NMSs burden levels were severe in 25.2%, and very severe in 25.2% of the subjects. The subitems with the highest scores were sleep/fatigue, mood/cognition, urinary, and miscellaneous. The analyses within the patient group with newly diagnosed PD also revealed high NMSS scores. Comparisons of the NMSS between distinct PD stages revealed greater NMSS scores in the severe stage than in the mild stage (p = 0.001). Correlation analyses between the clinical scores and the NMSS scores revealed positive correlations between the NMSS scores and the scores on all the clinical scales including the MDS-UPDRS 1-4, and FOGQ. We reported the first data regarding the NMS burden in PD patients from Turkey. We found a high prevalence and severity of various domains of NMSs, most of which were sleep/fatigue, mood/cognition, urinary, and miscellaneous. More than half of the patients had severe to very severe NMS burden. Although NMSs were more common severe-stage disease, they were also prevalent in the subgroup with newly diagnosed patients.

Identifying prognostic biomarkers in oral squamous cell carcinoma: an integrated single-cell and bulk RNA sequencing study on mitophagy-related genes

Oral squamous cell carcinoma (OSCC) has an extremely poor prognosis. Recent studies have suggested that mitophagy-related genes (MRGs) are closely correlated with the development and occurrence of cancer, but the role they play in oral cancer has not yet been explained.We conducted a comprehensive analysis of integrated single-cell and bulk RNA sequencing (RNA-seq) data retrieved from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. Multiple methods were combined to provide a comprehensive understanding of the genetic expression patterns and biology of OSCC, such as analysis of pseudotime series, CellChat cell communication, immune infiltration, Gene Ontology (GO), LASSO Cox regression, gene set variation analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), Tumor Mutation Burden (TMB) and drug sensitivity assessments. The findings of this study demonstrated significantly greater activity of MRGs in NK cells than in other cells in OSCC. A reliable prognostic model was developed using 12 candidate genes strongly associated with mitochondrial autophagy. T stage, N stage and risk score were revealed as independent prognostic factors. Distinctively enriched pathways and immune cells were observed in different risk groups. Notably, low-risk patients were more responsive to chemotherapy. In addition, a nomogram model with excellent predictive ability was established by combining the risk scores and clinical features. The activity of MRGs suggest the potential for the development of new targeted therapies. The construction of a robust prognostic model also provides reference value for individualized prediction and clinical decision-making in patients with OSCC.

The association between dexterity and upper limb impairment during stroke recovery.

Stroke-induced upper limb disabilities can be characterized by both motor impairments and activity limitations, commonly assessed using Fugl-Meyer Motor Assessment for Upper Extremity (FMMA-UE) and Action Research Arm Test (ARAT), respectively. The relationship between the two assessments during recovery is largely unstudied. Expectedly they diverge over time when recovery of impairment (restitution) plateaus, but compensation-driven improvements still occur. The objective of this study is to evaluate the alignment between FMMA-UE and ARAT in defining upper limb functional recovery categories by ARAT scores. We aimed to establish cut-off scores for both measures from the acute/early subacute, subacute and chronic stages of stroke recovery. Secondary analysis of four prospective cohort studies (acute/early subacute: n = 133, subacute: n = 113, chronic: n = 92) stages post-stroke. Receiver operating characteristic curves calculated the area under the curve (AUC) to establish optimal FMMA-UE cut-offs based on predefined ARAT thresholds distinguishing five activity levels from no activity to full activity. Weighted kappa was used to determine agreement between the two assessments. We used minimally clinically important difference (MCID) and minimal detectable change (MDC95) for comparison. FMMA-UE and ARAT scores showed no relevant divergence across all recovery stages. Results indicated similar cut-off scores in all recovery stages with variability below MCID and MDC95 levels. Cut-off scores demonstrated robust AUC values from 0.77 to 0.86 at every recovery stage. Only in highly functional patients at the chronic stage, we found a reduced specificity of 0.55. At all other times sensitivity ranged between 0.68 and 0.99 and specificity between 0.71 and 0.99. Weighted kappa at the acute/early subacute, subacute and chronic stages was 0.76, 0.83, and 0.81, respectively. Our research shows a strong alignment between FMMA-UE and ARAT cut-off scores throughout stroke recovery, except among the subgroup of highly recovered patients at the chronic stage. Discrepancies in specificity potentially stem from fine motor deficits affecting dexterity outcomes that are not captured by FMMA-UE. Additionally, the high congruence of both measures suggests they are not suited to distinguish between restitution and compensation. Calling for more comprehensive assessment methods to better understand upper limb functionality in rehabilitation.

Global characteristics and outcomes of autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma: A study of the worldwide network for blood and marrow transplantation (WBMT).

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS.

Disaster preparedness perceptions and psychological first-aid competencies of psychiatric nurses.

This study aimed to determine the disaster preparedness perceptions and psychological first-aid competencies of psychiatric nurses. Nurses must recognize the risks before a disaster occurs and have an action plan for providing effective physical and psychological care to patients and other affected individuals during and after the disaster. It is especially important for psychiatric nurses caring for a high-risk group, such as psychiatric patients, to be prepared for disasters and be able to support patients by recognizing the psychological reactions that may occur after a disaster and managing their care accordingly. For this cross-sectional and correlational study, data on 122 nurses were collected using a personal information form, the preparedness perception scale of disaster in nurses, and the psychological first-aid application self-efficacy scale. The mean score for the participants' perception of overall disaster preparedness was 76.70±8.30, the mean score for the preparation stage was 27.02±2.82, the mean score for the intervention stage was 30.40±5.15, the mean score for the post-disaster stage was 19.27±2.88, and the mean score for psychological first-aid application self-efficacy was 140.28±19.17. The findings showed that psychiatric nurses were above the medium level in terms of disaster preparedness perceptions and psychological first-aid application self-efficacy. It is important for nurses caring for high-risk groups, such as psychiatric patients, to be aware of disaster preparedness, to recognize psychological reactions that may be observed after a disaster, and to be aware of psychological first-aid practices that can be used to intervene in a disaster.

A prognostic model constructed by ferroptosis-associated genes (FAGs) in papillary renal cell carcinoma (PRCC) and its association with tumor mutation burden (TMB) and immune infiltration.

This study aimed to identify the prognostic-related differentially expressed ferroptosis-associated genes (DEFAGs) in papillary renal cell carcinoma (PRCC). Data encompassing simple nucleotide variation, transcriptome profiles, and relevant clinical information of PRCC patients were sourced from The Cancer Genome Atlas (TCGA) database. The expression matrix of ferroptosis-associated genes (FAGs) was analyzed using the "limma" package in R to identify differentially expressed DEFAGs. Lasso regression analysis, along with univariate and multivariate Cox proportional hazards regressions, was employed to identify independent prognostic-related DEFAGs and formulate a nomogram. Additionally, we examined potential independent survival-related clinical risk factors and compared immune cell infiltration and tumor mutation burden (TMB) differences between high- and low-risk patient groups. A cohort of 321 patients were analyzed, revealing twelve FAGs significantly influencing the overall survival (OS) of PRCC patients. Among them, two mRNAs (GCLC, HSBP1) emerged as independent prognostic-related DEFAGs. Smoking status, tumor stage, and risk score were identified as independent clinical risk factors for PRCC. Furthermore, notable disparities in immune cell infiltration and function were observed between high- and low-risk groups. GCLC and HSBP1 were associated with various immune cells and functions, TMB, and immune evasion. This finding revealed two independent prognostic-related DEFAGs in PRCC and established a robust prognostic model, offering potential therapeutic targets and promising insights for the management of this disease.

Applications of Artificial Intelligence for Pediatric Cancer Imaging.

Artificial intelligence (AI) is transforming the medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent scarcity of data associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatric patients compared with adult patients could also contribute to this challenge, as market size is a driver of commercialization. This review provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. Although current developments are promising, impediments due to the diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer learning of adult-based AI models to pediatric cancers, multiinstitutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking the full potential of AI for clinical translation and improving outcomes for these young patients.

Cortical inexcitability in ALS: correlating a clinical phenotype

BackgroundCortical inexcitability, a less studied feature of upper motor neuron (UMN) dysfunction in amyotrophic lateral sclerosis (ALS), was identified in a large cross-sectional cohort of ALS patients and their demographic...

Cognitive assessment of a sample of Egyptian patients with amyotrophic lateral sclerosis

BackgroundCognitive and behavioral changes in ALS are featured as an integral part of the disease. A noticeable proportion of ALS patients present with a full-blown picture of frontotemporal dementia, which is considered the most common form of cognitive impairment in ALS.ResultsA total of 30 ALS cases and 30 sex, age and education matched healthy controls were enrolled; their sociodemographic data were statistically insignificant as regards (age, sex, education). Regarding cognitive and behavioral assessment using the ECAS-EG, both ECAS mean total score and subdomains mean scores were significantly lower in ALS patients compared to controls (p-value < 0.001), with statistically significant relation between ALS clinical staging and ECAS total scores (p-value < 0.001). Furthermore, it was found that mean scores of nearly all ECAS domains are lower in early-onset group with longer duration of illness than late onset with short duration of illness but with a non-statistically significant difference.ConclusionALS causes significant cognitive impairment, with relation between functional status and clinical staging of the disease with the severity of cognitive and behavioral dysfunctions and although early-onset cases had lower score on ECAS compared to those with late onset, but it was non-significant.

Emerging multisystem biomarkers in hereditary transthyretin amyloidosis: a pilot study

Hereditary transthyretin (ATTRv) amyloidosis is a rare, adult-onset, progressive, multisystemic condition caused by TTR pathogenic variants. Reliable biomarkers are needed to allow early diagnosis and to monitor disease severity and progression. We measured serum concentrations of growth differentiation factor-15 (GDF-15) and uromodulin (Umod) in ATTRv patients to evaluate correlations with standard markers of disease severity (FAP stage and PND score). Blood samples were collected from 16 patients diagnosed with ATTRv amyloidosis and a verified TTR variant and from 26 healthy controls. ATTRv patients were stratified by clinical phenotype (neurologic vs. mixed), genotype (V30M vs. non-V30M), and disease severity. We found significantly higher levels of serum GDF-15 in ATTRv patients compared with controls. Mean serum Umod levels were significantly lower in patients with ATTRv than controls. A positive correlation was found between serum Umod and estimated glomerular filtration rate (eGFR), while an inverse correlation was found with cystatin C levels. Conversely, GDF-15 showed a negative correlation with eGFR, and a direct correlation with cystatin C levels. No correlation was demonstrated between GDF-15 or Umod levels and traditional cardiac biomarkers. The results identify alteration of serum levels of GDF-15 and Umod in ATTRv amyloidosis.