Assessment Of Disease Status Research Articles

Tele-rheumatology for overcoming socioeconomic barriers to healthcare in resource constrained settings: lessons from COVID-19 pandemic.

ObjectivesTo assess acceptability of teleconsultation among the socioeconomically marginalized sections of patients with rheumatic and musculoskeletal diseases (RMDs), to identify the socioeconomic barriers in continuing rheumatology care during the COVID-19 crisis and to identify patients who could benefit by shifting to tele-rheumatology consultations.MethodsThis was a cross sectional analytical study done at a tertiary care teaching hospital in India including patients with RMDs who were not on biological diseases modifying agents. Assessment of disease status, socioeconomic status and economic impact of COVID-19 was done via tele-consultation.ResultsOut of the 680 patients satisfying inclusion criteria, 373 completed the study. The format was found easy by 334 (89.6%) of them and 284 (76.1%) considered tele-rheumatology better than in-person consultation. During the pre-COVID months, the median monthly per capita income of the families of our patients and cost of illness was Indian rupees (INR) 2000 (US$ 26) and INR 1685 (US$ 21.91), respectively. Families whose financial needs were met (OR = 0.38, 95% CI: 0.239, 0.598) or those with schooling upto at least secondary school (OR = 0.442, 95% CI: 0.260, 0.752) (P =0.002) were less likely to stop prescription drugs. In a hypothetical model, 289 (77.4%) could be successfully switched to tele-rheumatology follow-up.ConclusionThe acceptability of tele-rheumatology among socioeconomically marginalized patients with RMDs is good. During times of crisis, patients from poorer strata of society and lower educational background are likely to abruptly stop medications. Switching to a telemedicine-based hybrid model is likely to improve drug adherence with substantial savings on loss of pay and out of pocket expenditure.

Establishing a unique micro RNAs panel with viral load for real-time assessment of disease status, therapeutic response and relapse in HCV patients

Establishing a unique micro RNAs panel with viral load for real-time assessment of disease status, therapeutic response and relapse in HCV patients

Assessment of Minimal Residual Disease in a Phase 1b Study of Once-Weekly Carfilzomib Combined with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma

Assessment of Minimal Residual Disease in a Phase 1b Study of Once-Weekly Carfilzomib Combined with Lenalidomide and Dexamethasone in Patients with Multiple Myeloma

Fibrinogen-Like Protein 1 Is a Novel Biomarker for Predicting Disease Activity and Prognosis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA), afflicting over 1% of the population, is an inflammatory joint disease leading to cartilage damage and ultimately impaired joint function. Disease-modifying anti-rheumatic drugs are considered as the first-line treatment to inhibit the progression of RA, and the treatment depends on the disease status assessment. The disease activity score 28 as clinical gold standard is extensively used for RA assessment, but it has the limitations of delayed assessment and the need for specialized expertise. It is necessary to discover biomarkers that can precisely monitor disease activity, and provide optimized treatment for RA patients. A total of 1,244 participants from two independent centers were divided into five cohorts. Cohorts 1–4 constituted sera samples of moderate to high active RA, low active RA, RA in remission and healthy subjects. Cohort 5 consisted of sera of RA, osteoarthritis (OA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), primary Sjogren's syndrome (pSS) and healthy subjects. Biomarkers were found from cohorts 1–2 (screening sets), cohort 3 (discovery and external validation sets), cohort 4 (drug intervention set) and cohort 5 (biomarker-specific evaluation set). We found 68 upregulated and 74 downregulated proteins by TMT-labeled proteomics in cohort 1, and fibrinogen-like protein 1 (FGL1) had the highest area under the receiver operating characteristic curve (AUC) values in cohort 2. In cohort 3, in cross-comparison among moderate/high active RA, low active RA, RA in remission and healthy subjects, FGL1 had AUC values of approximately 0.9000 and predictive values of 90%. Additionally, FGL1 had a predictive value of 91.46% for moderate/high active RA vs. remission/low active RA and 80.77% for RA in remission vs. low active RA in cohort 4. Importantly, FGL1 levels had no significant difference in OA and AS compared with healthy persons. The concentrations in SLE and pSS were improved, but approximately 3-fold lower than that in active RA in cohort 5. In summary, FGL1 is a novel and specific biomarker that could be clinically useful for predicting progression of RA.

Radiotherapy for prostate cancer: Effect of gold fiducial markers on diffusion-weighted magnetic resonance imaging.

There has been an increase in the use of gold fiducial markers to ensure precise radiotherapy delivery in prostate cancer patients. However, metal artifacts may affect the quality of subsequent imaging used to assess disease status following treatment. In this study, we evaluated the effect of gold fiducial markers on magnetic resonance imaging (MRI), particularly on diffusion-weighted imaging (DWI). Among 57 patients with prostate cancer, 21 patients in whom two gold markers were placed in the prostate tumor with abnormal signal intensity on DWI were evaluated. The effect of the markers on DWI was evaluated on a scale of 1-5, with a high score indicating clinical usefulness. Change inapparent diffusion coefficient (ADC; 10-3 mm2 /s) from before to after marker placement was also evaluated. The mean effect of the markers on DWI was 4.3 (standard deviation [SD] 1.3, range 2-5) points. The mean change in ADC was 0.045 (SD 0.041, range 0.025-0.089) × 10-3 mm2 /s. The gold fiducial markers demonstrated negligible effect on DWI quality. Therefore, gold markers do not affect MRI quality, particularly DWI, and may be used during follow-up in prostate cancer patients.

Abstract 3389: A multi-gene prostate cancer liquid biopsy with > 92% accuracy in diagnosis and assessment of disease status

Abstract Background: There are a paucity of blood-based biomarkers with clinical utility for prostate cancer (PCa). We examined a circulating-free mRNA (27-gene) prostate cancer signature to diagnose PCa. Clinical utility of the assay was then assessed in surgical patients. Methods: Gene identification and validation: Publicly available PCa transcriptome sets (n=5) (E-GEOD-46691, E-GEOD-46602, E-GEOD-62116, E-GEOD-62667, E-GEOD-72220: n=1,159 samples); PCA cell lines (n=7) gene expression in 22Rv1 and E006AA-hT (localized); VCaP; PC-3; LNCaP; DU145 and MDA PCa2b (all metastatic) from two normal prostate epithelial lines: PWR-1E and RWPE-1 and validated in PCa tumor tissue (n=50). Transcriptome analyses: tumor compared with normal blood-based transcriptomes using gene co-expression network enrichment, differential expression and functional enrichment analyses to identify candidate markers. Blood gene expression: PCa set #I: n=132, PCA set #II: n=50 (biochemical recurrence [BCR]), BPH: n=44, controls n=55. We then constructed an artificial intelligence PCa model using classification algorithm analyses. Scoring: normalized algorithmically analyzed gene expression (0 to 100), positive score ≥20. Matched tumor/ blood samples: n=50. PSA: BPH (n=44) and PCa (n=132). Clinical score assessment: Score utility was assessed in surgical cohorts: Surgical: (n=47), scores =pre-surgical and post: 1 week - 14 months. Statistics: Non-parametric (Kruskal-Wallis), Pearson-correlation, Fisher's and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis identified a 27 gene blood signature for PCa. Expression levels were significantly elevated (p<0.001, 2.1-35.8-fold) in cell lines and PCA tumors. The matched tissue/blood correlation was r: 0.56 (p=0.0023). In PCa #I, levels were 47±2 (p<0.0001) compared to BPH (19±1) and controls (18±0.5); AUROC: 0.92 (BPH) and 0.94 (controls), with an accuracy of 85-88%, a sensitivity of 86% and specificities 82 & 93% respectively. For PSA the AUROC (PCa vs. BPH) was 0.51 (p=0.88). PSA was positive in 86% of BPH and was >10ng/ml in 30%. PSA was positive in 83% of PCa and >10ng/ml in 40% (Fisher's exact: p=0.28). PSA accuracy (>10ng/ml) was 48%. Levels in PCA #II (BCR) were 44±3. ProstaTest-was positive in 48 (96%). Surgical cohort (n=47): PCa Prostatest accuracy 100% pre-surgery. Resection significantly decreased levels (KW-statistic: 57.4, p<0.0001) from 52±1 to 23.5±2. Conclusion: The diagnostic accuracy of a PCa molecular blood-signature was 92%; significantly better than PSA (48%, p<0.0001). Surgical resection significantly (p<0.0001) decreased levels. Biochemical recurrence was accurately detected (96%). A multi-gene prostate cancer liquid biopsy seems likely to have clinical utility in the diagnosis and monitoring management of PCa. Citation Format: Kambiz Rahbar, Mark Kidd, Ignat Drozdov, Alexandra Kitz, Anna Malczewska, Pawel Rajwa, Christof Bernemann, Lisa Bodei, Irvin Modlin. A multi-gene prostate cancer liquid biopsy with > 92% accuracy in diagnosis and assessment of disease status [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3389.

Abstract 3144: Using artificial intelligence and flow cytometry to confirm the need for a prostate biopsy in at-risk men

Abstract The goal of this study was to create a blood based, liquid biopsy test for confirming the need for a prostate biopsy by objectively analyzing flow cytometry-based immunophenotyping data using machine learning (ML) by evaluating whether a patient is at-risk for having intermediate-/high-grade prostate cancer PCa [Gleason score (GS) ≥ 7]. Currently, there is a lack of blood-based biomarkers that can accurately predict high-risk PCa in at-risk men making it difficult for clinicians to assess disease status. Furthermore, a large percentage of men undergo unnecessary prostate biopsy procedures each year since the majority of biopsies return either benign pathologies, such as benign prostatic hyperplasia (BPH), or low-grade PCa [Gleason score (GS) = 6). Flow cytometry-based immunophenotyping of peripheral blood is an accessible and non-invasive technology, but as more biomarkers are included, new methods must be developed for the efficient analysis and utilization of these large datasets for clinical applications. Here, we used ML to create pattern recognition neural networks (PRNNs) to identify patients with intermediate-/high-grade PCa from those that have either low-grade PCa or BPH based upon the immunophenotyping of 27 different myeloid and lymphoid cell populations. A key population of interest are myeloid-derived suppressor cells (MDSCs) since they are known to be key contributors in supporting tumor progression and escape through their ability to suppress anti-tumor responses mediated through T cell and natural killer (NK) cell activity. We used standard multiparametric flow cytometry to measure MDSCs and other immune cell populations found in the peripheral blood of 114 biopsy-confirmed PCa and 58 biopsy-confirmed BPH patients that were collected in Streck Cyto-Chex® BCT. PRNNs were trained with raw flow cytometry from two data sets: 37 patients with PCa GS ≥ 7 and 40 patients with BPH/PCa GS6. Predictions were evaluated using the performance of the trained PRNNs on known PCa GS ≥ 7 and BPH/PCa GS6 not used in the PRNN training set (holdout samples). In the holdout samples, we identified 21 out of 23 patients who were identified as PCa GS ≥ 7 (Sens = 91.3%, 95%CI = 72.0% to 98.9%; PPV = 33.3%, 95%CI = 28.4% to 38.7%) while 30 out of 72 patients were identified as BPH/PCa GS6 (Spec = 41.7%, 95%CI = 30.2% to 53.9%; NPV = 93.8%, 95%CI = 79.5% to 98.3%) for a combined accuracy of 53.7% (95%CI = 43.2% to 64.0%). The PRNN classified 17 out of 33 BPH, 13 out of 26 GS6 PCa, 13 out of 14 GS7 PCa, and 8 out of 9 > GS7 PCa samples correctly. For this study, out of the 112 patients who were ultimately diagnosed with BPH or low-grade PCa, approximately 47 procedures could have been avoided or delayed. In a clinical setting, we believe that this technology, in use with other known clinical factors, would allow for clinicians to have a more informed decision when recommending their patients for a prostate biopsy procedure while reducing the number of unnecessary biopsy procedures performed each year. Citation Format: George A. Dominguez, John Roop, Anthony J. Campisi, Thomas Schlumpberger, Amit Kumar. Using artificial intelligence and flow cytometry to confirm the need for a prostate biopsy in at-risk men [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3144.

The utility of cerebrospinal fluid white cell count during the prognostic assessment for cryptococcal meningitis patients: a retrospective study

BackgroundThe incidence of cryptococcal meningitis (CM) has gradually increased in recent years. Cerebrospinal fluid (CSF) cytology and cell count are very important for CM on etiology diagnosis and assessment of disease status and therapeutic response. However, the clinical significance of CSF white cell count (WCC) in CM patients is not fully understood. Using longitudinal data of CSF WCC and its relationship with clinical outcomes in CM patients, we aimed to elucidate the clinical significance of this test.MethodsWe retrospectively analyzed the medical records of 150 CM patients admitted to our hospital between January 2008 and December 2018.ResultsCM patients with lower baseline CSF WCC, CSF protein concentration or CD4/CD8 ratio, and those with altered mentation or HIV coinfection were more likely to have poor clinical outcome (P<0.05). CM patients with triple therapy during the induction period presented with a better clinical outcome (P<0.05). Baseline CSF WCC had a moderate positive correlation with peripheral CD4+ T lymphocyte count (r = 0.738, P < 0.001) and CD4+ T lymphocyte percentage (r = 0.616, P < 0.001). The best cut-off value to predict a poor clinical outcome was 40 cells/μL during baseline CSF WCC. The predictive model incorporating longitudinal data of CSF WCC had better sensitivity, specificity, and accuracy than a model incorporating only baseline CSF WCC data.ConclusionsOur results indicated that baseline CSF WCC and changes in CSF WCC over time could be used to assess the prognosis of CM patients.

Assessing spatial confounding in cancer disease mapping using R.

Exploring spatial patterns in the context of cancer disease mapping (DM) is a decisive approach to bring evidence of geographical tendencies in assessing disease status and progression. However, this framework is not insulated from spatial confounding, a topic of significant interest in cancer epidemiology, where the latent correlation between the spatial random effects and fixed effects (such as covariates), often lead to misleading interpretation. To introduce three popular approaches (RHZ, HH and SPOCK; details in paper) often employed to tackle spatial confounding, and illustrate their implementation in cancer research via the popular statistical software R. As a solution to alleviate spatial confounding, restricted spatial regressions are constructed by either projecting the latent effect onto the orthogonal space of covariates, or by displacing the spatial locations. Popular parametric count data models, such as the Poisson, generalized Poisson and negative binomial, were considered for the areal count responses, while the spatial association is quantified via the conditional autoregressive (CAR) model. Our method of inference in Bayesian, sometimes aided by the integrated nested Laplace approximation (INLA) to accelerate computing. The methods are implemented in the R package RASCO available from the first author's GitHub page. The results reveal that all three methods perform well in alleviating the bias and variance inflation present in the spatial models. The effects of spatial confounding were also explored, which, if ignored in practice, may lead to wrong conclusions. Spatial confounding continues to remain a critical bottleneck in deriving precise inference from spatial DM models. Hence, its effects must be investigated, and mitigated. Several approaches are available in the literature, and they produce trustworthy results. The central contribution of this paper is providing the practitioners the R package RASCO, capable of fitting a large number of spatial models, as well as their restricted versions.

A multi-gene colorectal cancer liquid biopsy with &gt;90% accuracy in diagnosis and assessment of disease status.

e16079 Background: There are few blood-based biomarkers for colorectal cancer (CRC). We report a 13-gene colon cancer circulating-free mRNA to diagnose CRC. Clinical utility was assessed in surgical and chemotherapy patients. Methods: Gene identification/validation: Publicly available colon cancer transcriptomes (E-MTAB-57) to identify candidate markers using gene co-expression network enrichment, differential expression and functional enrichment analyses. Cell line/tumor tissue gene expression: Candidate gene expression was evaluated in 3 CRC cell-lines (LOVO, LS-180 and COLO320DM) and surgical resection samples (CRC adenocarcinomas: n= 33) and biomarkers validated in the TCGA-COAD database ( n= 261 adenocarcinomas, 41 mucinous adenocarcinomas). Blood gene expression: CRC set (cancers: n= 312, controls n= 117) and a CRC artificial intelligence model constructed. Normalized gene expression algorithmically scored (0-100). Matched tumor/ blood samples were available in 33 patients. RECIST criteria Clinical score assessment: Score utility was assessed in surgical and treated cohorts: Surgical: n= 37, follow&gt;7 days. Chemotherapy: n= 75; stable disease (SD): n= 20, progressive disease (PD): n= 55). The relationship to CEA and CA-19-9 were assessed. Statistics: Non-parametric (Mann-Whitney), Pearson-correlation, Fisher’s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis: Thirteen candidate CRC genes blood were identified. Cell lines and tumor tissue: Expression levels were significantly elevated ( p&lt; 0.001, 20-100-fold) in cell lines and CRC tumors. All 13 markers were confirmed in TCGA-COAD samples (average TPM ranged from 692-4405). Blood gene expression: All 13 CRC marker genes were identified in CRC blood. Levels were 54.4±1.5 ( p&lt; 0.0001) compared to controls (9.5±1.7); AUROC:0.91±0.02, accuracy 90.5% (sensitivity 93.1%, specificity 81.2%). The matched tissue/blood correlation was r = 0.80 ( p= 0.002). Clinical Utility: In the surgical cohort, accuracy was 100% vs CEA (35%) or CA-19-9 (17%) (both p&lt; 0.0001). Resection (R0–92%) significantly decreased levels (47±2) at follow-up ( p&lt; 0.006). In the treated cohort, levels were elevated in PD (63±4.1) vs SD (30±3.2, p&lt; 0.0001). Conclusions: A CRC gene marker panel in blood identified colon cancer with a diagnostic accuracy of 91%. This was significantly greater than CEA or CA-19 in CRCs. Surgical resection decreased levels. CRC score was elevated in progressive vs stable disease. A colorectal cancer liquid biopsy will facilitate image-based management.

B-TREUH: A single-arm phase II pilot study of euthyroid hypothyroxinemia in metastatic breast carcinoma.

TPS1115 Background: It is estimated that there are approximately 155,000 people living with metastatic breast cancer in the US. Studies exploring the connection between hypothyroidism or hyperthyroidism and breast cancer have yielded varying results with up to 33% prevalence of thyroid disease in these patients. L-thyroxine (T4) is the most commonly prescribed agent in the US to manage hypothyroidism. However, there are data suggesting that T4 is a pro-oncogenic agent with proposed mechanisms such as stimulation of mitogenesis, angiogenesis, resistance to apoptosis. In addition, T4 May counter anti-PDL-1 and radiation effects. Triiodothyronine (T3), which is deiodinated form of T4 and also commercially available, is felt to be less oncogenic and less mitogenic. Therefore, exogenous supplementation of T3 would decrease the T4 levels creating the desired state of EUTHYROID HYPOTHYROXINEMIA. The study hypothesizes that replacing L-thyroxine (T4) with Triiodothyronine (T3) in hypothyroid patients with metastatic breast carcinoma, while they simultaneously continue to receive standard systemic therapy, with titrating T3 dose to achieve a state of Euthyroid Hypothyroxinemia would result in improved disease outcomes. Methods: Eligible participants are adults with metastatic breast carcinoma with estimated life expectancy of &gt; 3months, hypothyroidism, and with normal TSH on L-thyroxine (T4). Following consent, participants will discontinue L-thyroixne (T4) and initiate Triiodothyronine (T3) dose based on current T4 dose after an appropriate washout period. Drug titration will be in accordance with thyroid function testing to maintain levels of free T4 at &lt; 50% normal range. The treatment period will continue for 9 months with periodic assessment of disease status, quality of life (FACT-B) and laboratory measures. The primary endpoint is the progression free survival at 12 months while the secondary endpoints are prevalence of hypothyroidism in the cohort, overall survival, quality of life, and duration of time to achieve the Euthyroid Hypothyroxinemia state. Given many uncertainties to calculate power precisely, the sample size is estimated to be approximately 30 patients. Clinical trial information: NCT03787303 .

A novel liquid biopsy aid for identifying clinically significant prostate cancer in at-risk men: Combining artificial intelligence with flow cytometry-based immunophenotyping.

e17508 Background: Current screening methods for prostate cancer (PCa) result in a large number of false positives making it difficult for clinicians to assess disease status thus warranting advancements in screening and early detection methods. The goal of this study was to design a liquid biopsy assay that uses flow cytometry-based immunophenotyping and artificial intelligence (AI) analysis to detect clinically significant PCa in at-risk men. Methods: Standard multiparametric flow cytometry techniques were used to immunophenotype 27 different MDSC, myeloid, and lymphocyte cell populations found in the peripheral blood of 114 biopsy-confirmed PCa (GS6 = 54; ≥ GS7 = 60) and 58 biopsy-confirmed benign prostatic hyperplasia (BPH) patients. Pattern recognition neural networks (PRNNs), a type of AI, were trained with flow cytometry data from two data sets: patients with confirmed clinically significant PCa (≥ GS7) versus patients with BPH or clinically insignificant PCa (GS6). Predictions were evaluated using the performance of the trained PRNNs on 37 known ≥ GS7 PCa patients and 40 known BPH/ &lt; GS7 PCa patients not used in the PRNN training set (holdout samples). Results: In the holdout data set, 21 out of the 23 patients with clinically significant PCa were identified correctly (Sens = 91.3%, 95%CI = 72.0%-98.9%; PPV = 33.3%, 95%CI = 28.4%-38.7%) while 30 out of the 72 patients at low-risk or no-risk were identified correctly (Spec = 41.7%, 95%CI = 30.2%-53.9%; NPV = 93.8%, 95%CI = 79.5%-98.3%) for an accuracy of 53.7% (95%CI = 43.2%-64.0%). For all patients in this study, our data suggests that approximately 47 out of the 112 patients with BPH or GS6 PCa could have avoided an unnecessary prostate biopsy procedure. Conclusions: Pairing our PRNN with surface biomarker blood-based analyses of various leukocyte populations has enabled the ability to objectively identify patterns indicative for the existence of clinically significant PCa (≥ GS7). In a clinical setting, we believe that this technology, in use with other known clinical factors, would allow for clinicians to have a more informed decision when recommending their patients for a prostate biopsy procedure.

Evaluation of surgical resection in advanced ovarian, fallopian tube, and primary peritoneal cancer: laparoscopic assessment. A European Network of Gynaecological Oncology Trial (ENGOT) group survey

ObjectiveLaparoscopy is one of the diagnostic tools available for the complex clinical decision-making process in advanced ovarian, fallopian tube, and peritoneal carcinoma. This article presents the results of a survey...

Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection

The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients’ stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.

Gamma Gap: A Point-of-Care Test That Correlates With Disease Burden and Treatment Response in Multiple Myeloma.

We performed a retrospective chart review on 393 patients with multiple myeloma (MM) to determine the utility of the gamma gap (GG). We calculated the difference between a patient's total serum protein and albumin as a point-of-care test for assessing disease status in MM. GG is highly correlated with the level of M-spike, and the change in GG correlates with myeloma treatment response. In addition, fitted linear models were established that allow for the calculation of M-protein level from the GG within hours from blood draw. Our study has important implications in the care of MM, particularly in countries/areas with limited resources.

Validation of the Angioedema Control Test (AECT)—A Patient-Reported Outcome Instrument for Assessing Angioedema Control

Recurrent angioedema (RA) is an important clinical problem in routine care and emergency medicine. As of recently, the only validated tools to specifically assess disease status in patients with RA were diary-type activity assessments and angioedema-related quality-of-life questionnaires. Although these tools are particularly helpful in clinical studies, they were not designed to determine disease control or to guide treatment decisions. To close this gap, the Angioedema Control Test (AECT) was published recently. To test the AECT for its validity and reliability, and to identify a cutoff value to aid treatment decisions. Two AECT versions with a recall period of 4 weeks (AECT-4wk) and 3 months (AECT-3mo) were tested for their internal consistency and test-retest reliability, convergent and known-groups validity as well as screening accuracy in 81 patients with RA with bradykinin-mediated angioedema, mast cell mediator-mediated angioedema, or idiopathic angioedema. Both AECT versions showed excellent internal consistency reliability with a Cronbach alpha value of more than 0.85 and test-retest reliability with an intraclass correlation coefficient greater than 0.9. The convergent validity of both AECT versions was high. Both tools showed strong correlations with anchors of disease control, angioedema frequency, and health-related quality of life. A stratification of AECT scores into different levels of disease control together with a receiver-operating characteristic curve analysis suggested a cutoff value of 10 or more points to identify patients with well-controlled RA versus less than 10 points to identify patients with poorly controlled disease for both AECT versions. The AECT is the first valid and reliable patient-reported outcome measure to assess disease control in patients with RA.

A 13-gene colorectal cancer liquid biopsy with greater than 90 percent accuracy in diagnosis and assessment of disease status.

18 Background: There are a paucity of blood-based biomarkers with clinical utility for colorectal cancer (CRC) We report the use of a 13-gene colon cancer circulating-free mRNA to diagnose CRC and identify disease burden and status Clinical utility of the assay was assessed in surgical and chemotherapy patients. Methods: Gene identification and validation: Publicly available colon cancer transcriptomes (TTs) (E-MTAB-57); gene expression in 3 CRC cell-lines (LOVO, LS-180 and COLO320DM) and validated in CRC tumors ( n=33). Tumor TT analysis: co-expression network generation and differential expression analysis compared with normal blood-based TT to identify candidate markers. Blood gene expression: CRC set (cancers: n=312, controls n=117) and a CRC artificial intelligence model constructed. Normalized gene expression algorithmically scored (0-100). Matched tumor/ blood samples were available in 33 patients. RECIST criteria Clinical score assessment: Score utility was assessed in surgical and treated cohorts: Surgical: n=37, follow&gt;7 days. Treated chemotherapy: n=75; stable disease (SD): n=20, progressive disease (PD): n=55) The relationship to CEA and CA-19-9 were assessed. Statistics: Non-parametric (Mann-Whitney), Pearson-correlation, Fisher’s and AUROC analyses (Mean±SEM). Results: Transcriptomic analysis identified a13 genes blood signature for CRC. Expression levels were significantly elevated ( p&lt;0.001, 20-100-fold) in cell lines and CRC tumors. The matched tissue/blood correlation r: 0.795 ( p=0.002). In CRC, levels were 54.4±1.5 ( p&lt;0.0001) compared to controls (9.5±1.7); AUROC: 0.91±0.02, accuracy 90.5% (sensitivity 93.1%, specificity 81.2%). Surgical cohort: CRC assay accuracy 100% vs CEA (35%) or CA-19-9 (17%) (both p&lt;0.0001). Resection (R0 – 92%) significantly decreased levels (47±2) at follow-up ( p=0.0055). Treated cohort: Levels were elevated in PD (63±4.1) vs SD (30±3.2, p&lt;0.0001). Conclusions: The diagnostic accuracy of CRC blood-signature was 91%; significantly greater than CEA or CA-19 Surgical resection decreased levels. CRC score was elevated in progressive vs stable disease. A colorectal cancer liquid biopsy has probable clinical utility in management.

Disease detection methodologies in relapsed B-cell acute lymphoblastic leukemia: Opportunities for improvement.

Accurate disease detection is integral to risk stratification in B-cell acute lymphoblastic leukemia (ALL). The gold standard used to evaluate response in the United States includes morphologic evaluation and minimal residual disease (MRD) testing of aspirated bone marrow (BM) by flow cytometry (FC). This MRD assessment is usually made on a single aspirate sample that is subject to variability in collection techniques and sampling error. Additionally, central nervous system (CNS) assessments for ALL include evaluations of cytopathology and cell counts, which can miss subclinical involvement. We retrospectively compared BM biopsy, aspirate, and FC samples obtained from children and young adults with relapsed/refractory ALL to identify the frequency and degree of disease discrepancies in this population. We also compared CNS FC and cytopathology techniques. Sixty of 410 (14.6%) BM samples had discrepant results, 41 (10%) of which were clinically relevant as they resulted in a change in the assignment of marrow status. Discrepant BM results were found in 28 of 89 (31.5%) patients evaluated. Additionally, cerebrospinal fluid (CSF) FC identified disease in 9.7% of cases where cytopathology was negative. These results support further investigation of the role of concurrent BM biopsy, with aspirate and FC evaluations, and the addition of FC to CSF evaluations, to fully assess disease status and response, particularly in patients with relapsed/refractory ALL. Prospective studies incorporating more comprehensive analysis to evaluate the impact on clinical outcomes are warranted.

Eltrombopag May Improve Platelet Recovery in the Outpatient Setting after Allogeneic Stem Cell Transplant

<h3>Introduction</h3> Thrombocytopenia after allogeneic stem cell transplant (HCT) is multifactorial in etiology and may require long term transfusion care support. Eltrombopag (TPO) is sometimes used off-label in the post HCT setting to treat poor graft function and thrombocytopenia, however data is limited to small retrospective cases/series. We present our single institution experience. <h3>Objective</h3> Our objective was to describe the outcomes of pts treated with TPO for post-HCT primary and second failure of platelet recovery (FPR), defined as platelet <30K with transfusion requirements. <h3>Methods</h3> We retrospectively reviewed charts of HCT patients who received TPO post HCT from 1/1/13 to 10/1/19. We excluded patients who had active, identified relapse at the time of TPO initiation. We examined clinical characteristics and outcomes of those receiving TPO. <h3>Results</h3> Thirty-four patients received TPO for primary (22) and secondary (12) FPR. 6 had BM grafts, and 15 had alternative donors (mismatch or haplo). Median time to start of TPO was D+79 (range 21-341). Among 16/34 TPO responders, median time to response was 49 days (range 7-166). In responders, GvHD (10), infection (8) and ITP (6) were well represented as potential etiologies. 18 (53%) patients were started on TPO as inpatients with only 4/18 (22%) responses. Outpatient TPO starts had 12/16 (75%) responses. Relapsed disease was eventually diagnosed after TPO in 9/34 (26%) pts at median 44 days (range 11-280), with full donor chimerism in all relapsed pts prior to TPO. Among those with relapse, 3/9 (33%) patients had response to TPO. <h3>Conclusion</h3> TPO may facilitate platelet recovery, particularly in the outpatient setting. Inpatients had limited benefit from TPO likely due to multiple life threatening infectious and immunologic issues. The frequency of relapses seen after TPO should alert the clinician to assess disease status when considering initiation.

The Utility of the Random Urine Uric Acid-to-Creatinine Ratio for Patients with Gout Who Need Uricosuric Agents: Retrospective Cross-Sectional Study.

BackgroundThe 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid.MethodsThis was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups.ResultsThe random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, P < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively.ConclusionThere is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs.