Predictor Of Clinical Outcome Research Articles

Unraveling the Predictive Value of the Novel Global Immune-Nutrition-Inflammation Index (GINI) on Survival Outcomes in Patients with Grade 4 Adult-Type Diffuse Gliomas.

This investigation evaluated the predictive and prognostic efficacy of the newly developed global immune-nutrition-inflammation index (GINI) in patients with grade 4 adult-type diffuse gliomas, comparing it with other established indices such as the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune-inflammation value (PIV). A retrospective cohort included 198 patients diagnosed with isocitrate dehydrogenase (IDH)-mutant gr4 (grade 4) astrocytoma and IDH-wt (wilde-type) glioblastoma (GBM) gr4 treated with surgical resection, radiotherapy, and temozolomide. Patients were stratified into two groups based on their GINI values: low GINI (<5815) and high GINI (≥5815). The primary endpoint was overall survival (OS). High GINI was significantly associated with older age, poor performance status, multifocal tumors, and higher SII, SIRI, and PIV values (p < 0.005). The GINI demonstrated strong correlations with SII (r = 0.694), SIRI (r = 0.516), and PIV (r = 0.657) (p < 0.001). Patients with high GINI exhibited poorer OS (5.0 vs. 17.0 months) and PFS (5.0 vs. 13.0 months) in comparison to those with low GINI. Kaplan-Meier survival analysis revealed significantly prolonged OS and PFS among patients with low GINI (p < 0.001). Multivariate analysis identified high GINI as an independent negative risk factor for both PFS and OS. GINI is a robust predictor of clinical outcomes in IDH-mutant gr4 astrocytoma and IDH-wt GBM gr4, highlighting the crucial impact of nutrition and cancer cachexia. It shows superior prognostic value relative to the SII, SIRI, and PIV.

Prediction of clinical prognosis and drug sensitivity in hepatocellular carcinoma through the combination of multiple cell death pathways.

Hepatocellular carcinoma (HCC) is the sixth most common malignant tumor, highlighting a significant need for reliable predictive models to assess clinical prognosis, disease progression, and drug sensitivity. Recent studies have highlighted the critical role of various programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, ferroptosis, cuproptosis, entotic cell death, NETotic cell death, parthanatos, lysosome-dependent cell death, autophagy-dependent cell death, alkaliptosis, oxeiptosis, and disulfidptosis, in tumor development. Therefore, by investigating these pathways, we aimed to develop a predictive model for HCC prognosis and drug sensitivity. We analyzed transcriptome, single-cell transcriptome, genomic, and clinical information using data from the TCGA-LIHC, GSE14520, GSE45436, and GSE166635 datasets. Machine learning algorithms were used to establish a cell death index (CDI) with seven gene signatures, which was validated across three independent datasets, showing that high CDI correlates with poorer prognosis. Unsupervised clustering revealed three molecular subtypes of HCC with distinct biological processes. Furthermore, a nomogram integrating CDI and clinical information demonstrated good predictive performance. CDI was associated with immune checkpoint genes and tumor microenvironment components using single-cell transcriptome analysis. Drug sensitivity analysis indicated that patients with high CDI may be resistant to oxaliplatin and cisplatin but sensitive to axitinib and sorafenib. In summary, our model offers a precise prediction of clinical outcomes and drug sensitivity for patients with HCC, providing valuable insights for personalized treatment strategies.

Complete Blood Count-Based Biomarkers as Predictors of Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients with PD-L1 < 50% Treated with First-Line Chemoimmunotherapy.

Background: The aim of the study was to investigate a series of complete blood cell count-based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC and PD-L1 < 50% who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78-10.82 vs. 3.31; IQR: 2.15-4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82-21.20 vs. 9.20; IQR: 7.45-11.20, p = 0.013), and systemic inflammation index (SII, median: 1395; IQR: 929-3334 vs. 945; IQR: 552-1373, p = 0.025), but only NLR and NMR remained independently associated with clinical response in multivariate logistic regression. In the univariate analysis, white blood cells (OR:1.2202; 95% CI: 1.0339-1.4400, p = 0.019), neutrophils (OR:1.2916; 95% CI: 1.0692-1.5604, p = 0.008), NLR (OR:1.3601: 95% CI: 1.0949-1.6896, p = 0.005) and NMR (OR:1.2159; 95% CI: 1.00396-1.4221, p = 0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR, and MLR were independently associated with survival; NLR, at a cut-off value of 4.0, showed the better AUC (0.749) in predicting OS. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

Lemur tail kinase 3 serves as a predictor of patient outcomes and a target for the treatment of ovarian cancer

Lemur tail kinase 3 (LMTK3) belongs to a family of tyrosine kinases that are known to correlate with tumor grade and patient survival in some cancers. Here, we validated LMTK3 as a specific target and a prognostic biomarker in ovarian cancer (OC). In samples from 204 stage I-II OC patients, immunohistochemical studies revealed a higher cytoplasmic-to-nuclear staining intensity of LMTK3, which correlated with worse overall survival (p<0.001). Efficacy studies utilizing novel LMTK3 binding peptides (LMTK3BPs) showed that all chemosensitive and chemoresistant OC cells were killed without affecting normal cells (p<0.005), with synergistic effects shown following cisplatin and docetaxel treatment. In an orthotopic xenograft mouse model of OC, we saw a 35% tumor reduction in response to intravenous injections of 2mg/kg LMTK3BP given three times a week for 3weeks. Furthermore, invivo safety studies showed no signs of toxicity after LMTK3BP treatment, even at doses as high as 40mg/kg. This study highlights LMTK3 as a predictor of patient clinical outcomes. More importantly, novel LMTK3BPs represent potential safe treatment options, either alone or in combination with therapies, for OC.

Ultrasonographic measurements of gastro-soleus fascia thickness in midportion Achilles tendinopathy: A case-control study

BackgroundThe Achilles tendon is one of the thickest, largest, and strongest tendons in the human body. Biomechanically, the AT represents the conjoint tendon of the triceps surae muscle, placed in series with the plantar fascia (PF) to ensure force transmission from the triceps surae toward the toes during walking, running, and jumping. Commonly encountered in the diagnostic evaluation of heel pain, Achilles tendinopathy (AT) refers to a combination of pathological changes affecting the tendon itself often resulting from excessive repetitive stress and overuse. Nevertheless, increasing evidence demonstrates that structural alterations due to overuse or abnormal patterns of skeletal muscle activity are not necessarily restricted to the muscles or tendons but can also affect the fascial tissue. At the same time, there has been recent discussion regarding the role of the fascial tissue as a potential contributor to the pathophysiological mechanisms of the development of several musculoskeletal disorders including tendinopathies. To the best of our knowledge, ultrasound (US) imaging studies on the fascial structures related to the triceps surae complex, as well as their possible correlation with Achillodynia have never been presented in the current literature. MethodsIn the present study, a comparative US imaging evaluation of textural features of the suro-Achilleo-plantar complex was performed in 14 healthy controls and 14 symptomatic subjects complaining of midportion AT. The thickness of the Achilles tendon, paratenon, intermuscular fascia, and PF has been assessed with US. In addition, both groups underwent the Victorian Institute of Sport Assessment-Achilles (VISA-A), a disease-specific questionnaire that measures the severity of symptoms of AT. Correlations between quantitative ultrasound measures and VISA-A scores were determined through Pearson or Spearman's rho correlations. ResultsOur ultrasonographic findings revealed statistically significant differences (p<0.05) in Achilles tendon and paratenon thicknesses between AT patients and controls. No significant differences were observed between groups in PF at the calcaneal insertion as all mean measures were within the expected range of a normal PF on US imaging. In contrast, in tendinopathic subjects, the deep intermuscular fascia between medial gastrocnemius (MG) and soleus (SOL) muscles is significantly (p<0.01) and considerably thickened compared to those of healthy subjects. Moderate correlations exist between tendon and paratenon thicknesses (r= 0.54, p= 0.04) and between MG-SOL fascia and tendon thicknesses (r= 0.58, p= 0.03). Regarding symptom severity and US morphological findings, the Spearman ρ test showed no correlation. ConclusionsOur data demonstrate that, in symptomatic subjects, US alterations are not restricted to paratenon and intratendinous areas, but also affect upstream structures along the myofascial chain, resulting in thickening of the fascia interposed between MG and SOL muscles. Moreover, positive correlations were found between MG-SOL fascia thickening and abnormalities in AT, paratenon, and symptom severity. Thus, US alterations in the fascial system should be interpreted within the clinical context of patients with AT as they may in turn represent important predictors of subsequent clinical outcomes and could help healthcare professionals and clinicians to refine non-operative treatment strategies and rehabilitation protocols for this disease.

Predictive validity of resource-adjusted Korean Triage and Acuity Scale in pediatric gastrointestinal tract foreign body patients

Although paediatric patients with gastrointestinal (GI) foreign bodies require multiple resources, they often present with few or no discernible symptoms and are typically assigned a low acuity level during triage. We compared the predictive accuracy of the revised Korean Triage and Acuity Scale (rKTAS), which elevates acuity by one step in relation to anticipated resource utilization, with that of the conventional KTAS for clinical outcomes. This was a retrospective study of National Emergency Department Information System data. Data on patient and ED characteristics, resources used, and clinical outcomes were collected from January 2018 to December 2021 for patients with GI foreign bodies aged under 19. The primary outcome was rKTAS accuracy in predicting hospitalization, ICU admission, operating room (OR) use, and ED length of stay (EDLOS). The AUROC was used to evaluate the performance via of the KTAS and rKTAS. In total, 25,324 paediatric patients visited the ED for GI tract foreign bodies. The mean age was 3.8 years, and 51% (12,923) were between 1 and 4 year old. Although most (23,658; 93.4%) were discharged, 4.9% required hospitalization. Two or more resources were utilized in 2514 (9.9%) cases, and 3,514 individuals had their triage levels increased by one step. Compared with those of the KTAS, the AUROCs of the rKTAS for predicting overall hospitalization (p < 0.05), admission to general wards (p < 0.05), ICU admission (p = 0.01), and admission via the OR (p < 0.05)were higher than KTAS. Compared with that with the KTAS, the EDLOS with the rKTAS was longer at levels 1, 2, and 3. The adjusted rKTAS is a better predictor of clinical outcomes for paediatric patients with GI tract foreign bodies than the KTAS.

Factors Associated with Clinical Pregnancy following Assisted Reproductive Technology: A Comparative Cross-Sectional Study

Abstract Background: Over the years, the numbers of centres performing assisted reproductive technology (ART) have increased in urban regions of Africa. We reviewed a 10-year record of ART in a public hospital in a bid to determine the pregnancy rate and identify factors associated with achieving clinical pregnancy. Materials and Methods: This was a retrospective, analytical, cross-sectional study of 604 women who had undergone in vitro fertilisation (IVF) or IVF/intra-cytoplasmic sperm injection, over a 10-year period, at the [Institute of Fertility Medicine, Lagos State University Teaching Hospital]. Data were obtained from the medical records of couples who had undergone IVF at the study location and analysed using relevant descriptive and inferential statistics. Regression analysis was used to determine possible predictors of clinical pregnancy outcomes at 95% confidence level and significant P value of &lt;0.05. Results: The clinical pregnancy rate observed was 23.7%. Women aged ≥35 years of age had 2.9 odds of achieving pregnancy compared to women &lt;35 years of age. The quality of embryo and dose of the follicle-stimulating hormone used were not significantly different when compared in pregnant and non-pregnant women (P = 0.612 vs 0.881). Endometrial preparation techniques, number of embryos transferred, types of embryos transferred, sperm quality, and source of gametes used were not significantly different in pregnant and non-pregnant women. There was a 0.77 odds of achieving pregnancy when a day-5 embryo was used compared to a day-3 embryo (P = 0.008). Conclusion: Overall, these results emphasise the multifaceted nature of IVF outcomes, urging further research to elucidate the intricate factors influencing success rates in assisted reproduction.

Long-term clinical recovery and treatment resistance in first-episode psychosis: a 10-year follow-up study

Illness trajectories in people with first-episode psychosis (FEP) vary significantly over time. Identifying early-course parameters predicting outcomes is essential, but long-term data still needs to be provided. We conducted a 10-year follow-up study of a comprehensive first-episode psychosis (FEP) cohort investigating the prevalence of clinical recovery (CR) and treatment resistance (TR) after ten years, as well as clinical, demographic, and pre-illness predictors of long-term outcomes. 102 participants with FEP DSM-IV Schizophrenia spectrum disorders were recruited within their first year of treatment. The Treatment Response and Resistance in Psychosis Working Group (TRRIP) and the Remission in Schizophrenia Working Group (RSWG) criteria were used to define TR and CR, respectively. At 10-year follow-up, 29 (29%) of the participants were classified as in CR, while 32 (31%) were classified as TR. We also identified a larger middle group (n = 41, 40%) consisting of participants in partial recovery. 7% of all participants had tried Clozapine at the 10-year follow-up. Logistic regression analyses identified insidious onset (OR = 4.16) and baseline disorganized symptoms (OR = 2.96) as significantly associated with an increased risk of developing TR. Good premorbid academic adjustment (OR = 1.60) and acute onset (OR = 3.40) were associated with an increased chance of CR. We identified three long-term outcome groups by using recent consensus definitions. We also identified the potential importance of assessing baseline disorganized symptoms and monitoring patients with insidious onset more closely. Further, the findings suggest that clinicians should pay close attention to early-course parameters and provide adequate treatment to improve long-term outcomes of FEP.

Prevalence and incidence measures for schizophrenia among commercial health insurance and medicaid enrollees

Given the chronic nature of schizophrenia, it is important to examine age-specific prevalence and incidence to understand the scope of the burden of schizophrenia across the lifespan. Estimates of lifetime prevalence of schizophrenia have varied widely and have often relied upon community-based data estimates from over two decades ago, while more recent studies have shown considerable promise by leveraging pooled datasets. However, the validity of measures of schizophrenia, particularly new onset schizophrenia, has not been well studied in these large health databases. The current study examines prevalence and validity of incidence measures of new diagnoses of schizophrenia in 2019 using two U.S. administrative health databases: MarketScan, a national database of individuals receiving employer-sponsored commercial insurance (N = 16,365,997), and NYS Medicaid, a large state public insurance program (N = 4,414,153). Our results indicate that the prevalence of schizophrenia is over 10-fold higher, and the incidence two-fold higher, in the NYS Medicaid population compared to the MarketScan database. In addition, prevalence increased over the lifespan in the Medicaid population, but decreased in the employment based MarketScan database beginning in early adulthood. Incident measures of new diagnoses of schizophrenia had excellent validity, with positive predictive values and specificity exceeding 95%, but required a longer lookback period for Medicaid compared to MarketScan. Further work is needed to leverage these findings to develop robust clinical outcome predictors for new onset of schizophrenia within large administrative health data systems.

The Infiltrative Margins in Glioblastoma: Important Is What Has Been Left behind.

Supramaximal resection beyond the contrast-enhancing tumor borders represents an emerging surgical strategy for patients with newly diagnosed glioblastoma. A recent study provides evidence detailing the interactive effects of more aggressive surgery on other clinical predictors of outcome, supporting guidance for surgical decision-making and informing clinical trialists about the need to stratify for extent of resection. See related article by Park et al., p. 4866.

Clinical outcomes of reperfusion therapy in patients with site-specific basilar artery occlusion

BackgroundDespite its low incidence, basilar artery occlusion (BAO) remains a major therapeutic challenge since severe disability and death occur in about 80% of patients. Specific site of BAO (proximal, middle,...

A deep neural network approach to heart murmur detection using spectrogram and peak interval features

Congenital heart disease affects about 1% of newborns, posing risks like heart failure and mortality. Developing countries often lack resources for diagnosis and treatment. The George B. Moody PhysioNet Challenge 2022 aims to develop systems for detecting murmurs and clinical outcome events using phonocardiogram (PCG) data, offering a cost-effective method for diagnosing cardiac diseases without invasive procedures. We proposed a deep learning model for this task and achieved the 5th rank out of 40 teams in both Track 1 (murmur detection) and Track 2 (clinical outcome prediction). This paper describes our methods and additional experiments. To extract features from the PCG, we employed techniques including Constant Q Transform (CQT) and Mel-scaled spectrogram (Mel-spectrogram) to generate two-dimensional representations in the frequency–time domain. Additionally, we extracted the Peak Interval (PI) feature, which measures the distance between peaks in the PCG data. This feature is useful because the peak intervals should be shorter in PCG recordings with murmurs. We also considered the sequence and mean of PI as additional features. Our proposed system, titled ‘Phonocardiogram-based Heart murmur Detection using Spectrogram and PI features (SpectroHeart),’ employs the Mel-spectrogram and PI features to detect heart murmurs and assess clinical outcomes. We believe that our deep learning-based system has great potential for automatically detecting heart signals from PCG.

Construction of a prognostic model for colon cancer by combining endoplasmic reticulum stress responsive genes

Endoplasmic reticulum stress may affect the occurrence and development of cancer. However, its effect on the prognosis of colon cancer (CC) patients is not clear yet. Herein, based on TCGA database, we screened 15 endoplasmic reticulum stress responsive genes (ERSRGs) associated with the prognosis of CC patients by Cox regression. By LASSO and multivariate Cox regression analyses, a prognostic risk assessment model involving 12 genes (DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, GRIN2B, LRRC59, and RORC) was built. The survival curves indicated that patients in the low-risk group had good prognosis. ROC curves demonstrated a good performance of this 12-gene prognostic model, and the Riskscore could be considered as an independent prognostic factor. Patients in low-risk group benefit more from immune checkpoint inhibitor and immune checkpoint blockade (ICB) treatment. Besides, the enrichment analysis suggested a remarkable difference in Ca2+ signaling in both groups. Finally, based on the cMAP database, we identified several potential drugs that could target high-risk groups, such as Dasatinib, GNF-2, Saracatinib, and WZ-1-84. To sum up, our research constructed an ERSRGs-characteristic prognostic model. The model is a promising biomarker for prediction of clinical outcomes and immune therapy response of CC patients. SignificanceBased on the transcriptomic data of colon cancer in the TCGA database, this study screens 12 endoplasmic reticulum stress-related genes (ERSRGs), including DNAJB2, EIF4A1, YPEL4, COQ10A, IRX3, ASPHD1, NTRK2, TRIM39, XBP1, asphD1, NTRK2. GRIN2B, LRRC59, and RORC, and a prognostic model was constructed. This model can be used as a predictor of prognosis and immunotherapy response in colon cancer patients. At the same time, model-based prediction of drugs can also be a potential option for colon cancer treatment in the future.

Predictors of clinical and functional outcomes of acute ischemic stroke after various types of treatment

Predictors of clinical and functional outcomes of acute ischemic stroke after various types of treatment

Low Levels of Adropin Predict Adverse Clinical Outcomes in Outpatients with Newly Diagnosed Prediabetes after Acute Myocardial Infarction.

Adropin-a multifunctional peptide with tissue-protective capacity that regulates energy homeostasis, sensitivity to insulin and inflammatory response-seems to show an inverse association with the presence of cardiovascular and renal diseases, obesity and diabetes mellitus in the general population. The purpose of the study is to elucidate whether adropin may be a plausible predictive biomarker for clinical outcomes in post-ST elevation of myocardial infarction (STEMI) patients with newly diagnosed prediabetes according to the American Diabetes Association criteria. A total of 1214 post-STEMI patients who received percutaneous coronary intervention were identified in a local database of the private hospital "Vita Center" (Zaporozhye, Ukraine). Between November 2020 and June 2024, we prospectively enrolled 498 patients with prediabetes in this open prospective cohort study and followed them for 3 years. The combined clinical endpoint at follow-up was defined as cardiovascular death due to acute myocardial infarction, heart failure, sudden death due to arrhythmia or cardiac surgery, and/or all-cause death. We identified 126 clinical events and found that serum levels of adropin < 2.15 ng/mL (area under the curve = 0.836; 95% confidence interval = 0.745-0.928; sensitivity = 84.9%; specificity = 72.7%; likelihood ratio = 3.11; p = 0.0001) predicted clinical outcomes. Multivariate logistic regression showed that a Gensini score ≥ 32 (Odds ratio [OR] = 1.07; p = 0.001), adropin ≤ 2.15 ng/mL (OR = 1.18; p = 0.001), use of SGLT2i (OR = 0.94; p = 0.010) and GLP-1 receptor agonist (OR = 0.95; p = 0.040) were independent predictors of clinical outcome. Kaplan-Meier plots showed that patients with lower adropin levels (≤2.15 ng/mL) had worse clinical outcomes compared to patients with higher adropin levels (>2.15 ng/mL). In conclusion, low levels of adropin (≤2.15 ng/mL) independently predicted clinical outcomes in post-STEMI patients with newly detected prediabetes and improved the discriminative ability of the Gensini score for 3-year follow-up events. Future clinical studies are needed to clarify whether adropin is a promising molecule to be incorporated into conventional risk scores for the prediction of MACCEs after STEMI.

Circulating interleukin-8 and osteopontin are promising biomarkers of clinical outcomes in advanced melanoma patients treated with targeted therapy

BackgroundCirculating cytokines can represent non-invasive biomarkers to improve prediction of clinical outcomes of cancer patients. Here, plasma levels of IL-8, CCL4, osteopontin, LIF and BDNF were determined at baseline (T0), after 2 months of therapy (T2) and, when feasible, at progression (TP), in 70 melanoma patients treated with BRAF and MEK inhibitors. The association of baseline cytokine levels with clinical response, progression-free survival (PFS) and overall survival (OS) was evaluated.MethodsCytokine concentrations were measured using the xMAP technology. Their ability to discriminate between responding (Rs) and non-responding (NRs) patients was assessed by Receiver Operating Characteristics analysis. PFS and OS were estimated with the Kaplan–Meier method. The Cox proportional hazard model was used in the univariate and multivariate analyses to estimate crude and adjusted hazard ratios with 95% confidence intervals.ResultsCCL4 and LIF were undetectable in the majority of samples. The median osteopontin concentration at T0 and T2 was significantly higher in NRs than in Rs. The median T0 and T2 values of IL-8 were also higher in NRs than in Rs, although the statistical significance was not reached. No differences were detected for BDNF. In 39 Rs with matched T0, T2, and TP samples, osteopontin and IL-8 significantly decreased from T0 to T2 and rose again at TP, while BDNF levels remained unchanged. In NRs, none of the cytokines showed a significant decrease at T2. Only osteopontin demonstrated a good ability to discriminate between Rs and NRs. A high IL-8 T0 level was associated with significantly shorter PFS and OS and higher risk of progression and mortality, and remained an independent negative prognostic factor for OS in multivariate analysis. An elevated osteopontin T0 concentration was also significantly associated with worse OS and increased risk of death. Patients with high IL-8 and high osteopontin showed the lowest PFS and OS, and in multivariate analysis this cytokine combination remained independently associated with a three- to six-fold increased risk of mortality.ConclusionCirculating IL-8 and osteopontin appear useful biomarkers to refine prognosis evaluation of patients undergoing targeted therapy, and deserve attention as potential targets to improve its clinical efficacy.

Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson’s disease

Several prior studies have proposed the involvement of various brain regions and cell types in Parkinson’s disease (PD) pathology. Here, we performed snRNA-seq on the prefrontal cortex and anterior cingulate regions from a small cohort of post-mortem control and PD brain tissue. We found a significant association of oligodendrocytes (ODCs) and oligodendrocyte precursor cells (OPCs) with PD-linked risk loci and report several dysregulated genes and pathways, including regulation of tau-protein kinase activity, regulation of inclusion body assembly and protein processing involved in protein targeting to mitochondria. In an independent PD cohort with clinical measures (681 cases and 549 controls), polygenic risk scores derived from the dysregulated genes significantly predicted Montreal Cognitive Assessment (MoCA)-, and Beck Depression Inventory-II (BDI-II)-scores but not motor impairment (UPDRS-III). We extended our analysis of clinical outcome prediction by incorporating differentially expressed genes from three separate datasets that were previously published by different laboratories. In the first dataset from the anterior cingulate cortex, we identified an association between ODCs and BDI-II. In the second dataset obtained from the substantia nigra (SN), OPCs displayed an association with UPDRS-III. In the third dataset from the SN region, a distinct subtype of OPCs, labeled OPC_ADM, exhibited an association with UPDRS-III. Intriguingly, the OPC_ADM cluster also demonstrated a significant increase in PD samples. These results suggest that by expanding our focus to glial cells, we can uncover region-specific molecular pathways associated with PD symptoms.

Ensuring Neurosurgical Equity: Setup for Safe Ventricular Endoscopy and Predictors of Clinical Outcome in a Resource-Limited Health Care System

Background/ObjectiveNeuroendoscopic surgeries require specialized equipment, which may not be universally available or equitably distributed in most neurosurgical units of resource-limited healthcare systems. This review reports on the use of locally available resources to perform safe ventricular endoscopic surgeries in patients with hydrocephalus and cystic craniopharyngioma, in a resource-limited health care system. MethodsThis study, described the use of locally available resources to perform intraventricular endoscopic surgeries, and retrospectively reviewed a three-year outcome of these surgeries, The authors, used a 24Fr, 2-way Foley's catheter, that served as an endoscopic working sheet. A transparent 9mm naso-tracheal tube, that served as a retractor and a peel-away sheet. An intravenous fluid (IVF) giving set, was used for irrigation, and a metallic stylet of External ventricular drain(EVD) was used for third ventricular floor or cyst wall fenestration. ResultsTwenty-one intraventricular endoscopic surgeries were performed, consisting; of endoscopic third ventriculostomy (ETV), septostomies, cystostomies, and intraventricular biopsies. Mortality occurred in four patients, with one of the mortality, directly related to intraoperative hemorrhage. Most (3/21) of the complications were post-operative CSF leakage and partial wound dehiscence. Of the 17 surviving patients, the ETV success rate was 82.4% (14/17). Logistic regression analysis revealed that the patient's age, etiology, ETV success score (ETVSS) and procedure performed were not predictive of ETV success or mortality. ConclusionsPatients accessing neurosurgical care in resource-limited healthcare systems can benefit from safe and successful intraventricular endoscopy. However, this may require the innovative use of locally available resources that can be adapted to local neurosurgical needs.

Early circulating tumor DNA (ctDNA) changes during treatment with immune checkpoint inhibitors (ICI) as a predictor of clinical outcomes in patients (pts) with advanced stage melanoma/skin cancer.

225 Background: ctDNA monitoring has shown promising results in predicting relapse in resected solid tumors. Its role in treatment response assessment and predicting survival outcomes in the unresectable or metastatic disease setting merits further investigation. In our study, we attempt to assess the role of early ctDNA changes in predicting disease response, progression, and overall survival outcomes in pts with advanced stage melanoma/skin cancer treated with ICI therapy. Methods: A retrospective analysis using a personalized, tumor-informed ctDNA assay (Natera) on prospectively collected plasma samples from pts with unresectable stage III/IV melanoma/skin cancer treated with anti-PD-1 based therapy at the University of Wisconsin (Madison) was performed. Baseline ctDNA levels were assessed prior to the start of treatment and at 3-4 weeks (i.e. prior to the second treatment dose). A logistic regression model was used to evaluate the odds of overall disease control [complete response + partial response + stable disease, per RECIST version 1.1] based on the change in ctDNA levels (decrease vs increase) between both time points. Cox proportional hazard models were used to investigate the effects of ctDNA level change on progression free survival (PFS) and overall survival (OS). Results: 46 pts were evaluated. 82% melanoma, 14% Merkel cell carcinoma, 2% skin adenocarcinoma and 2% squamous cell carcinoma. 77% were treated with dual ICI (anti-PD-1 based) therapy and 23% with anti-PD-1 monotherapy. Median follow up was 12.1 months. Median change in ctDNA levels from baseline were -4.83 MTM/mL among pts with ctDNA decrease and +37.39 MTM/mL among pts with ctDNA increase. A qualitative decrease in ctDNA level was associated with overall disease control (OR 65.00, 95% CI 11.88-587.89, p&lt;0.0001), longer PFS (HR 0.08, 95% CI 0.03-0.22, p&lt;0.0001), and longer OS (HR 0.17, 95% CI 0.05-0.54, p=0.0008) compared to an increase in ctDNA level from baseline to 3-4 weeks after starting ICI therapy. Median PFS was not reached (NR) and 1.63 months; and median OS was NR and 5.57 months among pts with ctDNA decrease and ctDNA increase, respectively. Conclusions: We found that early ctDNA dynamics after 3-4 weeks of ICI initiation in pts with advanced melanoma/skin cancer appears to be a candidate strategy to predict treatment response, risk of progression, and potentially long-term survival. Larger prospective studies are warranted to validate the utility of ctDNA in treatment monitoring.

The candidate novel markers PIV and PILE score to predict survival outcomes and therapeutic response in patients with primary central nervous system lymphoma.

24 Background: Recent studies highlighted the predictive value of easily measurable blood-based biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), the monocyte-to-lymphocyte ratio (MLR), the platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII). Recently, a novel comprehensive marker that represents the pan-immune-inflammation value (PIV) has been proposed as a more reliable predictor of clinical outcomes. We aimed to investigate the prognostic significance of PIV and PILE score (a score based on PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)), in patients with PCNSL. Methods: A total of 109 patients were enrolled. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE score was calculated with the sum of individual values (for PIV &lt; median = 0, ≥ median = 1; for LDH ≤ upper limit of normal (ULN) = 0, &gt; ULN = 1; for ECOG PS &lt; 2 = 0, ≥ 2 = 1). The Kaplan–Meier method and Cox hazards regression models were used for survival analyses. The relationship between PIV, PILE, and therapeutic response was examined. Results: Pretreatment high PIV was confirmed to be an independent significant factor for overall survival (OS) in univariate (HR 3.990, 95%CI 1.778-8.954, p &lt; 0.001) and multivariate (HR 3.047, 95%CI 1.175-7.897, p = 0.022) analyses. Baseline PIV was also associated with worse progression-free survival (PFS). Regarding OS, PIV showed a better predictive performance than other widely used systemic inflammation parameters. Significantly shorter OS and PFS were observed in the high PILE group (median OS: 25.60, 95% CI 15.60-NR vs. NR months, 95% CI 26.10-NR, p = 0.008; median PFS: 26.13, 95% CI 23.30-NR vs. 7.13 months, 95% CI 4.87-NR, p &lt; 0.001). High PILE was associated with primary resistance to therapy (high PILE group: 21/42 patients, 50.00%; low PILE group: 5/45 patients, 11.11%; p &lt; 0.001). A significantly lower response rate to initial treatment was found in patients in the high PILE group (23/42, 54.76%) as compared to patients in the low PILE group (7/45, 15.56%; p &lt; 0.001). PILE was independently associated with therapeutic response to initial treatment (OR 0.17, 95% CI 0.05–0.46; p &lt; 0.001). Conclusions: High PIV and high PILE were correlated with worse clinical outcomes in PCNSL patients, indicating that PIV and PILE might be a powerful predictor of prognosis and a potential predictive indicator for treatment response in PCNSL.