Prognostic Test Research Articles

Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in a cross-sectional study

Prognostic tests and treatment approaches for optimized clinical care of prostatic neoplasms are an unmet need. Prostate cancer (PCa) and derived extracellular vesicles (EVs) proteome changes occur during initiation and progression of the disease. PCa tissue proteome has been previously characterized, but screening of tissue samples constitutes an invasive procedure. Consequently, we focused this study on liquid biopsies, such as urine samples. More specifically, urinary small extracellular vesicle and particles proteome profiles of 100 subjects were analyzed using liquid chromatography coupled to high-resolution mass spectrometry (LC–MS/MS). We identified 171 proteins that were differentially expressed between intraductal prostate cancer/cribriform (IDC/Crib) and non-IDC/non-Crib after correction for multiple testing. However, the strong correlation between IDC/Crib and Gleason Grade complicates the disentanglement of the underlying factors driving this association. Nevertheless, even after accounting for multiple testing and adjusting for ISUP (International Society of Urological Pathology) grading, two proteins continued to exhibit significant differential expression between IDC/Crib and non-IDC/non-Crib. Functional enrichment analysis based on cancer hallmark proteins disclosed a clear pattern of androgen response down-regulation in urinary EVs from IDC/Crib compared to non-IDC/non-Crib. Interestingly, proteome differences between IDC and cribriform were more subtle, suggesting high proteome heterogeneity. Overall, the urinary EV proteome reflected partly the prostate pathology.

Diagnosis of a suspicious Spitzoid nevus

The mortality rate of cutaneous melanoma in the United States continues to increase year over year. Research supports that the development of melanoma is determined by genetics, the environment, and an individual’s behavior with certain phenotypic features, such as fair skin, red hair, multiple moles, and a prior history of sunburns, placing some individuals at greater risk of developing melanoma. New treatments have improved the survival rate of individuals with melanoma; however, the proper diagnosis of this deadly cancer is imperative. Histopathology remains the gold standard for diagnosing melanoma, sometimes with the help of immunohistochemistry staining. When a clear diagnosis cannot be made, genomic testing can be a helpful tool to differentiate between a benign and malignant lesion. Here, we present the case of a 27-year-old male patient with Fitzpatrick skin type III who presented to the dermatology clinic with a growing pink bump on his left upper arm. After a shave biopsy, the dermatopathologist reported that the lesion was a suspicious-looking Spitzoid nevus, for which a wide excision by surgical oncology was recommended. The immunohistochemistry staining did not secure a diagnosis of benign or malignant. As the diagnosis was inconclusive, the specimen was sent for a gene expression profile test, which came back positive, indicating malignant melanoma. This case illustrates how diagnostic and prognostic genomic testing can be used to identify a malignant melanoma and determine the likelihood of metastasis, thus guiding the patient's follow-up plan. It also illustrates how genomic testing might help the patient avoid unnecessary and costly medical procedures with potential side effects.

Application of a validated prognostic plasma protein biomarker test for renal decline in type 2 diabetes to type 1 diabetes: the Fremantle Diabetes Study Phase II

BackgroundThere are scant data relating to prognostic biomarkers for chronic kidney disease (CKD) complicating type 1 diabetes. The aim of this study was to assess the performance of the plasma protein biomarker-based PromarkerD test developed and validated for predicting renal decline in type 2 diabetes in the context of type 1 diabetes.MethodsThe baseline PromarkerD test score was determined in 91 community-based individuals (mean age 46.2 years, 56.5% males) with confirmed type 1 diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II. The performance of the PromarkerD test in predicting the risk of incident CKD (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 in people without CKD at baseline) or an eGFR decline of ≥ 30% over the next four years was determined. The score can range from 0 to 100%, and is categorized as representing low (< 10%), moderate (10% to < 20%) or high (≥ 20%) risk.ResultsThe area under the receiver operating characteristic curve was 0.93 (95% confidence interval 0.87–0.99) for the composite renal endpoint, indicating strong predictive accuracy. The positive and negative predictive values at moderate (10% to < 20%) and high (≥ 20%) risk PromarkerD cut-offs were 46.7–50.0% and ≥ 92.0%, respectively.ConclusionsThese preliminary data suggest that PromarkerD is at least as good a prognostic test for renal decline in type 1 as type 2 diabetes.

Application of a Validated Prognostic Protein Biomarker Test for Kidney Decline in Type 2 Diabetes to Type 1 Diabetes

Application of a Validated Prognostic Protein Biomarker Test for Kidney Decline in Type 2 Diabetes to Type 1 Diabetes

Comparison of Risk Stratification by CanAssist Breast Test Performed on Core Needle Biopsies Versus Surgical Specimens in Hormone Receptor-Positive, Her2-Negative Early Breast Cancer.

Introduction Core needle biopsies (CNB) are being increasingly utilized for biomarker, prognostic, and predictive testing in breast cancer (BC).CanAssist Breast (CAB) is a prognostic test performed to assess the 'risk of breast cancer recurrence' in early-stage hormone receptor-positive, Her2-negative BC patients. CAB segregates tumors as 'low risk' or 'high risk' for distant recurrence.Risk assessment done by CAB aids in planning and making adjuvant chemotherapy or hormone therapy decisions.CAB is typically performed on surgical specimens (SS).However, performing it on CNB does offer additional insights into tumor biology leading to different strategies for treatment planning; hence, we aimed to compare the risk stratification performance of CAB using CNB versus SS. Method We analyzed 103 paired formalin-fixed paraffin-embedded CNB and SS samples from hormone receptor-positive, Her2-negative early BC tissue samples submitted for performing CAB at OncoStem Diagnostics between November 2021 and September 2023. Concordance on 'risk categories' of CAB performed on CNB versus SS was reported using overall percentage agreement and Pearson correlation coefficient. Results We found excellent overall concordance of 92.2% for CAB risk stratification between paired CNB and SS tumor samples with a strong Pearson correlation coefficient of r= 0.8351 (p< 0.0001) when either SS or CNB was used as the gold standard.In prognostic testing patients with a 'low risk' of recurrence may avoid chemotherapy and hence it is crucial to assess the accuracy of CAB in the low-risk category. Additionally, in a real-world scenario, it is more likely that CAB will be performed on CNB first. Conclusion CAB when performed on CNB samples showed high concordance with SS thus demonstrating that CNB was a suitable sample for the CanAssist Breast test.The accuracy in the low-risk category is 97.5%, which ensures that physicians can reliably use prognostic information by testing CNB to guide adjuvant therapy decisions.

The GFAP proteoform puzzle: How to advance GFAP as a fluid biomarker in neurological diseases.

Glial fibrillary acidic protein (GFAP) is a well-established biomarker of reactive astrogliosis in the central nervous system because of its elevated levels following brain injury and various neurological disorders. The advent of ultra-sensitive methods for measuring low-abundant proteins has significantly enhanced our understanding of GFAP levels in the serum or plasma of patients with diverse neurological diseases. Clinical studies have demonstrated that GFAP holds promise both as a diagnostic and prognostic biomarker, including but not limited to individuals with Alzheimer's disease. GFAP exhibits diverse forms and structures, herein referred to as its proteoform complexity, encompassing conformational dynamics, isoforms and post-translational modifications (PTMs). In this review, we explore how the proteoform complexity of GFAP influences its detection, which may affect the differential diagnostic performance of GFAP in different biological fluids and can provide valuable insights into underlying biological processes. Additionally, proteoforms are often disease-specific, and our review provides suggestions and highlights areas to focus on for the development of new assays for measuring GFAP, including isoforms, PTMs, discharge mechanisms, breakdown products, higher-order species and interacting partners. By addressing the knowledge gaps highlighted in this review, we aim to support the clinical translation and interpretation of GFAP in both CSF and blood and the development of reliable, reproducible and specific prognostic and diagnostic tests. To enhance disease pathology comprehension and optimise GFAP as a biomarker, a thorough understanding of detected proteoforms in biofluids is essential.

Recent Electrochemical Advancements for Liquid-Biopsy Nucleic Acid Detection for Point-of-Care Prostate Cancer Diagnostics and Prognostics.

Current diagnostic and prognostic tests for prostate cancer require specialised laboratories and have low specificity for prostate cancer detection. As such, recent advancements in electrochemical devices for point of care (PoC) prostate cancer detection have seen significant interest. Liquid-biopsy detection of relevant circulating and exosomal nucleic acid markers presents the potential for minimally invasive testing. In combination, electrochemical devices and circulating DNA and RNA detection present an innovative approach for novel prostate cancer diagnostics, potentially directly within the clinic. Recent research in electrochemical impedance spectroscopy, voltammetry, chronoamperometry and potentiometric sensing using field-effect transistors will be discussed. Evaluation of the PoC relevance of these techniques and their fulfilment of the WHO's REASSURED criteria for medical diagnostics is described. Further areas for exploration within electrochemical PoC testing and progression to clinical implementation for prostate cancer are assessed.

COMPREHENSIVE MOLECULAR PROFILING OF UVEAL MELANOMA EVALUATED WITH GENE EXPRESSION PROFILING, PREFERENTIALLY EXPRESSED ANTIGEN IN MELANOMA EXPRESSION, AND NEXT-GENERATION SEQUENCING.

To determine the association between gene-expression profiling (GEP), next-generation sequencing (NGS), preferentially expressed antigen in melanoma (PRAME) features, and metastatic risk in patients with uveal melanoma (UM). A retrospective analysis of patients with UM treated by brachytherapy or enucleation by a single ocular oncologist was conducted from November 2020 and July 2022. Clinicopathologic features, patient outcomes, GEP classification, NGS, and PRAME results were recorded. Comprehensive GEP, PRAME, and NGS testing was performed on 135 UMs. The presence of eukaryotic translation initiation factor 1A, X-chromosomal and splicing factor 3B subunit 1 mutations was significantly associated with GEP class 1A and GEP class 1B, respectively. The presence of BRCA- associated protein-1 mutation was significantly associated with GEP class 2. The average largest basal diameter for tumors with eukaryotic translation initiation factor 1A, X-chromosomal mutations was significantly smaller than those with splicing factor 3B subunit 1 mutations and BRCA1-associated protein-1 mutations. Class 2 tumors metastasized sooner than GEP class 1 tumors. Tumors with splicing factor 3B subunit 1 and/or BRCA1-associated protein-1 mutations metastasized sooner compared with tumors that had either no driver mutation or no mutations at all. Tumors with splicing factor 3B subunit 1 did not have a significantly different time to metastasis compared with tumors with BRCA1-associated protein-1 (P value = 0.97). Forty tumors (30%) were PRAME positive, and the remaining 95 tumors (70%) were PRAME negative. Tumors with PRAME-positive status did not have a significantly different time to metastasis compared with tumors without PRAME-positive status (P value = 0.11). GEP, NGS, and PRAME expression analysis help determine different levels of metastatic risk in UM. Although other prognostic tests exist, the following study reports on the use of NGS for metastatic prognostication in UM. However, limitations of NGS exist, especially with small lesions that are technically difficult to biopsy.

297P Real-world data on prognostication of early stage breast cancer patients using CanAssist Breast- first immunohistochemistry based prognostic test developed and validated on Asians

297P Real-world data on prognostication of early stage breast cancer patients using CanAssist Breast- first immunohistochemistry based prognostic test developed and validated on Asians

A novel metric-based approach of scoring early host immune response from oro-nasopharyngeal swabs predicts COVID-19 outcome

Unpredictable fatal outcome of COVID-19 is attributed to dysregulated inflammation. Impaired early adaptive immune response leads to late-stage inflammatory outcome. The purpose of this study was to develop biomarkers for early detection of host immune impairment at first diagnosis from leftover RNA samples, which may in turn identify high risk patients. Leftover RNA samples of COVID-19 patients at first diagnosis were stored. Following prospective follow-up, the samples were shorted and categorized into outcome groups. Impaired adaptive T cell response (severity score) and Impaired IL-10 response (undetectable IL-10 in the presence of high expression of a representative interferon response gene) were determined by RT-PCR based assay. We demonstrate that a T cell response based ‘severity score’ comprising rational combination of Ct values of a target genes’ signature can predict high risk noncomorbid potentially critical COVID-19 patients with a sensitivity of 91% (95% CI 58.7–99.8) and specificity of 92.6% (95% CI 75.7–99) (AUC:0.88). Although inclusion of comorbid patients reduced sensitivity to 77% (95% CI 54.6–92.2), the specificity was still 94% (95% CI 79.8–99.3) (AUC:0.82). The same for ‘impaired IL-10 response’ were little lower to predict high risk noncomorbid patients 64.2% (95% CI 35.1–87.2) and 82% (95% CI 65.5–93.2) respectively. Inclusion of comorbid patients drastically reduce sensitivity and specificity51.6% (95% CI 33.1–69.8) and 80.5% (95% CI 64.0–91.8) respectively. As best of our knowledge this is the first demonstration of a metric-based approach showing the ‘severity score’ as an indicator of early adoptive immune response, could be used as predictor of severe COVID-19 outcome at the time of first diagnosis using the same leftover swab RNA. The work flow could reduce expenditure and reporting time of the prognostic test for an earliest clinical decision ensuring possibility of early rational management.

Detection of differentially methylated CpGs between tumour and adjacent benign cells in diagnostic prostate cancer samples

Differentially methylated CpG sites (dmCpGs) that distinguish prostate tumour from adjacent benign tissue could aid in the diagnosis and prognosis of prostate cancer. Previously, the identification of such dmCpGs has only been undertaken in radical prostatectomy (RP) samples and not primary diagnostic tumour samples (needle biopsy or transurethral resection of the prostate). We interrogated an Australian dataset comprising 125 tumour and 43 adjacent histologically benign diagnostic tissue samples, including 41 paired samples, using the Infinium Human Methylation450 BeadChip. Regression analyses of paired tumour and adjacent benign samples identified 2,386 significant dmCpGs (Bonferroni p < 0.01; delta-β ≥ 40%), with LASSO regression selecting 16 dmCpGs that distinguished tumour samples in the full Australian diagnostic dataset (AUC = 0.99). Results were validated in independent North American (npaired = 19; AUC = 0.87) and The Cancer Genome Atlas (TCGA; npaired = 50; AUC = 0.94) RP datasets. Two of the 16 dmCpGs were in genes that were significantly down-regulated in Australian tumour samples (Bonferroni p < 0.01; GSTM2 and PRKCB). Ten additional dmCpGs distinguished low (n = 34) and high Gleason (n = 88) score tumours in the diagnostic Australian dataset (AUC = 0.95), but these performed poorly when applied to the RP datasets (North American: AUC = 0.66; TCGA: AUC = 0.62). The DNA methylation marks identified here could augment and improve current diagnostic tests and/or form the basis of future prognostic tests.

Abstract Tu147: Serial measurement of circulating cardiovascular enriched miR-1 and -34a reflects the changes in cardiac function in patients with ischemic heart disease – a five year follow-up study

Background: Patients with ischemic heart disease (IHD) require frequent monitoring, as the transition from stable disease to acute life-threatening events remains largely unpredictable. Currently available tests are either not sensitive enough to detect early changes or not easily incorporated into routine clinical practice. MicroRNAs (miRNAs), small non-coding RNAs involved in both physiological and pathological processes, are released into circulation and remain stable. Research Question: In this study, we aimed to determine if the serial measurement of cardiovascular-enriched circulating miRNAs could reflect changes in cardiac function in patients with IHD. Methods: Fifty-four new IHD patients joined a 5-year study, providing informed consent for regular echocardiography, blood tests and follow-ups at 12-month intervals. Plasma RNA was extracted and RT-PCR analysis used to assess expression of cardiovascular-enriched miR-1, miR-126, miR-132, and miR-34a. Results: Serial echocardiography analysis showed the development of diastolic dysfunction in the participants starting from 48 months (E/e’-10.7±4.3 vs 9.7±3.6 at baseline, P&lt;0.04). RT-PCR analysis revealed significant downregulation of miR-1 and miR-126 starting from 24 months of follow-up (P&lt;0.03 vs. baseline). Associations between each miRNA and each cardiac function measure were examined using linear mixed models without and with adjustment for changes in BMI and HbA1c during the same period. None of the lagged models found statistically significant associations (all p ≥ 0.126). From the concurrent models, two miRNA were associated with cardiac function: miR-1 and MV E Vel in the unadjusted (p = 0.045) and adjusted models (slope = -0.004, 95% CI -0.007 to -0.000, p = 0.026) models and miR-34a and FS(%) in the adjusted model only (slope = -0.151, 95% CI -0.301 to -0.001, p = 0.048). Conclusion: Results from this first-ever five-year follow-up study have identified a link between cardiovascular enriched miRNAs, miR-1 and -34a and cardiac function in patients with IHD, providing a knowledge platform for prognostic tests for IHD and laying the foundation for further studies in larger population size.

Recombinant proteins as promising antigens applied to the immunodiagnosis of Chagas disease: a scoping review.

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is an important public health problem, occurring mainly in Latin America. The disease has a major social and economical effect, negatively impacting the life of the infected individuals, and bringing great costs to public health. An early and accurate diagnosis is essential for administration of early treatment. In addition, prognostic tests may aid disease management, decreasing hospitalization costs. However, the serological diagnostic scenario for CD still faces several challenges, making the development of new diagnostic kits a pressing matter. Facing this scenario, several researchers have expanded efforts in developing and testing new antigens, such as recombinant proteins and recombinant multiepitope proteins, with promising results. These recombinant antigens offer several advantages, such as improved sensitivity and specificity, in addition to facilitated scaling. Also, it has been possible to observe a rising number of studies using ELISA and point-of-care platforms, employing these antigens in the past few years. Among them, recombinant proteins were the most applied antigens, demonstrating great capacity to discriminate between positive and negative samples. Although fewer in number, recombinant multiepitope proteins also demonstrated an improved diagnostic performance. Indeed, a great number of studies employing these antigens showed sensitivity and specificity values above 90%, greatly impacting diagnostic accuracy. Nevertheless, despite the good results found, it is still possible to observe some bottlenecks in the development of new antigens, such as the scarcity of tests with sera from the acute phase and the variability of results in different geographic areas. In this sense, aiming to contribute to control and health programs, the continuous search for a more accurate serological diagnosis is essential, both for the acute and chronic phases of the disease.

15-Gene Expression Profile and PRAME as Integrated Prognostic Test for Uveal Melanoma: First Report of Collaborative Ocular Oncology Group Study No. 2 (COOG2.1).

Validated and accurate prognostic testing is critical for precision medicine in uveal melanoma (UM). Our aims were to (1) prospectively validate an integrated prognostic classifier combining a 15-gene expression profile (15-GEP) and PRAME RNA expression and (2) identify clinical variables that enhance the prognostic accuracy of the 15-GEP/PRAME classifier. This study included 1,577 patients with UM of the choroid and/or ciliary body who were enrolled in the Collaborative Ocular Oncology Group Study Number 2 (COOG2) and prospectively monitored across 26 North American centers. Test results for 15-GEP (class 1 or class 2) and PRAME expression status (negative or positive) were available for all patients. The primary end point was metastasis-free survival (MFS). 15-GEP was class 1 in 1,082 (68.6%) and class 2 in 495 (31.4%) patients. PRAME status was negative in 1,106 (70.1%) and positive in 471 (29.9%) patients. Five-year MFS was 95.6% (95% CI, 93.9 to 97.4) for class 1/PRAME(-), 80.6% (95% CI, 73.9 to 87.9) for class 1/PRAME(+), 58.3% (95% CI, 51.1 to 66.4) for class 2/PRAME(-), and 44.8% (95% CI, 37.9 to 52.8) for class 2/PRAME(+). By multivariable Cox proportional hazards analysis, 15-GEP was the most important independent predictor of MFS (hazard ratio [HR], 5.95 [95% CI, 4.43 to 7.99]; P < .001), followed by PRAME status (HR, 1.82 [95% CI, 1.42 to 2.33]; P < .001). The only clinical variable demonstrating additional prognostic value was tumor diameter. In the largest prospective multicenter prognostic biomarker study performed to date in UM to our knowledge, the COOG2 study validated the superior prognostic accuracy of the integrated 15-GEP/PRAME classifier over 15-GEP alone and clinical prognostic variables. Tumor diameter was found to be the only clinical variable to provide additional prognostic information. This prognostic classifier provides an advanced resource for risk-adjusted metastatic surveillance and adjuvant trial stratification in patients with UM.

The Prognostic Test Accuracy of the Short and Standard Forms of the Montreal Cognitive Assessment.

Cognitive impairment is a critical concern in stroke care, and international guidelines recommend early cognitive screening. The aim of this study was to determine the prognostic accuracy of both the short and standard forms of the Montreal Cognitive Assessment (MoCA) in predicting long-term cognitive recovery following a stroke. For this study, we used data from the Efficacy of Fluoxetine - a Randomized Controlled Trial in Stroke (EFFECTS) study, which encompassed stroke patients from 35 Swedish centers over the period from 2014 to 2019. Cognitive assessments were initially conducted at 2-15 days post-stroke, with follow-up data gathered at 6 months. We used the MoCA for objective cognitive evaluation. For assessing subjective cognitive impairment, we used the memory and thinking domain of the Stroke Impact Scale. For psychometric evaluation of the short Swedish version of MoCA (s-MoCA-SWE), we used cross tables and binary logistic regression. The study included 1,141 patients (62.2% men; median [interquartile range; IQR] age, 72.3 [13.2] years; median [IQR] stroke severity, 3.0 [3.0]). At baseline, the prevalence of cognitive impairment was 71.7% according to the s-MoCA-SWE (≤12) and 67.0% according to the MoCA (≤25). The s-MoCA-SWE demonstrated a sensitivity of 92.3% for correctly identifying patients with objective cognitive impairment and 81.5% for identifying those with subjective impairments at 6 months. Although the s-MoCA-SWE had higher sensitivity, the MoCA had a more balanced sensitivity and specificity in detecting both subjective and objective cognitive impairments. In both crude and multivariable models, the s-MoCA-SWE was more strongly associated than the MoCA with cognitive impairment at 6 months. Both the short and standard versions of the MoCA appear to be effective in identifying individuals likely to experience persistent cognitive issues following a stroke. Considering the limited time available in an acute stroke unit, the short-form version may be more practical. Nevertheless, further prospective studies are required to validate these findings.

Assessment of haematological parameters in HIV patients attending Kabutare district Hospital

Background: Human Immunodeficiency virus (HIV) infection is characterized by progressive weakening of the immune system attributed to the decrease in the number of circulating CD4+ T-helper cells. This predisposes HIV patients to a variety of opportunistic infections and neoplastic disorders. also lead to defective hematopoiesis and a decrease in cell lineage. Haematological parameters including red blood cells, white blood cells, platelet and hemoglobin are widely used clinical indicators of health and disease. Aim: The aim of this study was to assess haematological parameters in HIV patients attending Kabutare District hospital. Methodology: This study was a cross-sectional study conducted to assess haematological parameters in HIV patients attending Kabutare District hospital. Venous blood sample were collected for complete blood count which was determined using sysmex 500i machine automation analyser. Results: A total of 80 HIV infected patient participated. 7.5% of the study participants were proven to have white blood cells below the normal range as it was below 4.26.25% of patients were found below the normal range of red blood cells. Hemoglobin and hematocrit levels of 35% patients were found to below their normal ranges. 10% of patient were found to have low platelet and 23.5% were found to have low levels of lymphocytes. Association between CD4 counts and hemoglobin levels was significant with p value of 0.000 as it is less than confidence level of 0.05. Conclusion: This study concluded that haematological parameters are affected by HIV infection and there is association between CD4 counts and hemoglobin concentration levels. I would recommend health practioners to also consider complete blood count as prognostic test of HIV as it is clinical health indicator and diseases. Keywords: Haematological parameters, Human Immunodeficiency virus, CD4 counts, acquired immunodeficiency syndrome.

Verification of the Prediction Accuracy of a Biomarker-Based Prognostic for Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) After Hematopoietic Cell Transplantation (HCT)

Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life-threatening complication of hematopoietic cell transplantation (HCT), especially in severe cases. Patient outcomes are improved with prompt treatment; however, diagnosing this disease is challenging as many clinical symptoms of VOD/SOS overlap with other post-HCT complications. A biomarker-based prognostic test for the assessment of VOD/SOS risk, termed "VODCheck" was developed in a previous study but has not yet been validated. This study aimed to validate the accuracy of VODCheck as a prognostic test for VOD/SOS in an independent cohort of patients. VODCheck incorporates hyaluronan (HA), angiopoietin-2 (ANG-2), and thrombomodulin (TM) based on their association with VOD/SOS, their analytical characteristics, and their ability to complement each other in a multivariate prognostic model. To validate VODCheck we measured plasma biomarker levels from a subset of patients enrolled in the control arm of a phase 3 study that tested VOD/SOS prophylaxis. We used a hierarchical design with prespecified primary (day 7), secondary A (day 15), and secondary B (day 1) hypotheses to verify the prognostic accuracy of VODCheck post-HCT. The cases of VOD/SOS (n = 22) were age-matched ∼1:3 with controls (n = 65). VODCheck was prognostic of VOD/SOS risk at all 3 time points with an area under the curve (AUC) of .815 (P < .001) for day 7, .836 (P < .001) for day 15, and .706 (P = .002) for day 1 post-HCT. A multivariate analysis confirmed the prognostic accuracy of VODCheck after adjustment for confounders such as age, VOD/SOS risk status, primary disease, and ozogamicin treatment. VODCheck was validated as an independent predictor of risk for VOD/SOS within 15 days post-HCT and appears to provide clinicians with actionable information to improve patient care.

Optimizing Surgical Treatment for Chronic Low Back Pain Evaluating Prognostic Tests for Patient Selection in Lumbar Spinal Fusion: A Cohort Study

Optimizing Surgical Treatment for Chronic Low Back Pain Evaluating Prognostic Tests for Patient Selection in Lumbar Spinal Fusion: A Cohort Study

Cholangiocarcinoma, sequential chemotherapy, and prognostic tests.

Routine blood tests are prognostic tests for patients with cholangiocarcinoma. New drug regimens may produce a median overall survival of 2 years or more. This single practice, IRB-approved, phase II trial examines prognostic tests, Kaplan-Meier survival, and univariate Cox regression analyses. Eligibility requires: intent-to-treat; signed consent; advanced measurable intrahepatic cholangiocarcinoma, with or without resistance to the test drugs; any adult age; performance status 0-2; and expected survival of ≥ 6 weeks. Biweekly treatment, with 1/3 of standard dosages in mg/M2, includes: Gemcitabine 500; 5-Fluorouracil 1200 over 24 hours; Leucovorin 180; Irinotecan 80; and on day 2, Oxaliplatin 40. On progression, drugs are added on day 2: first, Docetaxel 25 precedes Oxaliplatin, with or without Mitomycin C 6 after Oxaliplatin. The next sequential additions are day 1, Cetuximab 400 total mg, then 200 mg weekly, and then Bevacizumab 10 mg/kg is substituted for Cetuximab (FDA IND# 119005). For 35 patients, 19 with 1-2 lines of prior therapy, resistant tumors, and 16 no prior therapy, survival at 24-months is ≥ 72 and ≥ 58%, respectively. For 14 patients aged ≥ 70 years, ≥ 63% survive 24 months, P = 0.28. Validated tests that predict ≤ 6-month survivals find median survival times of 17-months through > 2-years when compared to patients with favorable tests: Neutrophils lymphocyte ratio > 3.0, HR = 6.54, P < 6.4x10-3; absolute neutrophil count > 8000/μl, HR = 4.95, P < 6.5x10-3; serum albumin < 3.5 g/dl, HR = 4.10, P < 0.03; and lymphocyte monocyte ratio< 2.1, HR = 1.6, P = 0.50. Overall, the 76 (60-90)% of patients with 0-2 out of 4 high risk tests survive ≥ 24 months, (P = 7.1x10-3). Treatments produce neither hospitalization, neutropenic fever, severe enteritis, nor severe neuropathies. Two-year survival is replicable and predictable. Findings warrant phase III validation tests of sequential regimens, re-challenge with recombination, low dosages, and blood tests that are associated with lethal mechanisms that impair response and survival.

Automated Nuclear Morphometry: A Deep Learning Approach for Prognostication in Canine Pulmonary Carcinoma to Enhance Reproducibility.

The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists' NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists' estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required.