Poor Positive Predictive Value Research Articles

Prostate cancer screening: Is it time for a new approach? A review article.

Prostate cancer screening has presented a challenge to clinicians. Although the implementation of screening tests such as prostate-specific antigen (PSA) and digital rectal exam (DRE) has had a significant impact on prostate-cancer-specific mortality, these traditional screening tests have a relatively poor positive predictive value of clinically significant prostate cancer (CSPC), leading to unnecessary biopsies and treatment with a host of potential complications. Fortunately, much research has been done to optimize prostate cancer screening. This includes the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which underwent a secondary analysis to identify an association between PSA level and CSPC, and the IP1-PROSTAGRAM Tri.

Utilization of a Postpartum Fasting Blood Glucose to Predict Impaired Glucose Tolerance in Patients with Gestational Diabetes Mellitus.

The Endocrine Society recommends a postpartum fasting blood glucose (FBG) be performed for patients with gestational diabetes mellitus (GDM) prior to hospital discharge to screen for ongoing hyperglycemia. There are limited data, however, on whether an FBG can screen for glucose intolerance and if it correlates with the gold standard 4- to 12-week 2-hour oral glucose tolerance test (OGTT). Our objective was to evaluate if FBG correlates with the gold standard 2-hour OGTT. This retrospective cohort study of patients with GDM who delivered >20 weeks' gestation at two urban centers from January 2017 to December 2020 included those who completed both a postpartum FBG prior to discharge and a 2-hour 75-g OGTT within 1 year of delivery. Abnormal 2-hour OGTT was defined as fasting value ≥100 mg/dL and/or 2-hour value ≥140 mg/dL. We evaluated test characteristics (e.g., sensitivity, specificity) of postpartum FBG cut-offs to predict an abnormal 2-hour OGTT result. A total of 235 patients met inclusion criteria, of which 63% were diet-controlled and 37% required medical management. FBG ranged from 64 to 134 mg/dL, with 6/235 (2.6%) with values ≥126 mg/dL. A total of 39/235 (16.6%) of patients had an abnormal 2-hour OGTT. Overall, area under the curve for FBG predicting abnormal 2-hour OGTT was 0.65. Traditionally considered high cut-offs (≥126 mg/dL) for predicting persistent impaired glucose intolerance demonstrated poor positive predictive value (PPV; <20%). In contrast, low cut-offs demonstrated excellent NPV (>90%). A postpartum FBG of 88 mg/dL was determined to be the optimal cut-off for FBG with NPV = 92.4% (Youden index = 0.34). In this dataset, if FBG ≥ 88 mg/dL was used to determine if 2-hour OGTT was required, almost half of GDM patients could avoid further glucose tolerance testing. While previously thought of as best utilized for its PPV, the FBG may be best used for its NPV. In our study, clinical application of an FBG < 88 mg/dL was highly correlative with a normal 2-hour OGTT. · Screening for postpartum glucose intolerance is essential for gestational diabetes.. · A promising initiative includes offering screening tests while in the hospital, including an FBG.. · Application of a postpartum FBG < 88 mg/dL is highly correlative with a normal 2-hour OGTT..

The Diagnostic Role of Antinuclear Antibody: A Study of Clinical Utility in a Tertiary Hospital

Abstract Introduction: Various studies reported unnecessary and inappropriate serology testing of rheumatic diseases leading to a significant waste in healthcare utilization. The purpose of this study is to evaluate the clinical utility of antinuclear antibody (ANA) testing in a real-world setting within a tertiary hospital for systemic lupus erythematosus (SLE) and other ANA-associated rheumatic diseases (AARDs), as well as to identify patient characteristics and test results that predict rheumatic disease association. Subjects and Methods: This is a retrospective study of patients aged 15 years or older who underwent ANA testing at Aseer Central Hospital from January 2018 to December 2022. Data collected included patient demographics, clinical presentations, referral physician type, ANA test results, and final diagnoses. Descriptive statistics characterized patient demographics and ANA test results. Sensitivity, specificity, and predictive values of ANA testing were calculated for SLE and AARD diagnoses. Chi-squared test was used to identify the predictive values of AARDs. Results: Of the 2141 patients tested for ANA at Aseer Central Hospital, 583 (27.2%) tested positive, with a higher proportion of females (80.8%). Notably, 85.1% of patients who tested ANA positive were under 55 years old. The highest ANA test-positive proportion was noticed by rheumatologist physician’s referral (67.6%), referral symptoms including joint symptoms (38.3%), mucocutaneous symptoms (19.7%), renal disease symptoms (14.4%), and hematological abnormalities (14.2%). The sensitivity and specificity of ANA for diagnosing SLE were 86.4% and 79.3%, respectively, with a positive predictive value (PPV) of 31.7% and a negative predictive value (NPV) of 98.1%. The sensitivity and specificity of other AARDs were 85.4% and 73.9%, respectively, with a PPV of 6% and an NPV of 99.6%. Significant associated factors with AARDs included younger age (&lt;55 years), female patients, higher ANA titer, rheumatologist referral, and clinical indications such as sicca symptoms, myopathy, mucocutaneous symptoms, and hematological abnormalities (P &lt; 0.001). Conclusion: In this study, ANA testing showed a good sensitivity and NPV in ruling out AARDs; however, its poor specificity and PPV suggest that positive ANA findings should be interpreted cautiously. Younger age, female gender, higher ANA titer, rheumatologist referral, and specific clinical indications were significantly associated with AARDs, suggesting the importance of targeted ANA testing in clinical practice.

Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer

We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively. Univariate and multivariate analyses showed that GCIG CA125 response (n = 32) is associated with improved progression-free survival (PFS) and overall survival (OS) compared to no GCIG CA125 response (n = 40) (median PFS 8.0 vs. 3.5 months [HR: 0.30, 95% CI: 0.18–0.51, p < 0.0001]; median OS 19.8 vs. 10.0 months [HR: 0.38, 95% CI: 0.23–0.64, p < 0.001]) independent of BRCA mutation status, platinum-sensitivity, previous PARP inhibitor therapy, ECOG performance status, and FIGO stage. Notably, GCIG CA125 response had a high negative predictive value (NPV: 93%, 95% CI: 80–98), but poor positive predictive value (PPV: 53%, 95% CI: 35–71) in predicting RECIST response. CA125 PD criteria also showed poor concordance with RECIST PD (PPV 56%, 95% CI: 40–71; NPV 33%, 95% CI: 17–54). Therefore, serum CA125 may be useful as a highly accessible prognostic and predictive biomarker to CHK1i therapy in recurrent HGSOC.

Diagnostic values of inferior Q-waves for myocardial scar identification detected by 3.0 T cardiac MRI

While Q-waves in inferior leads, particularly lead III, can be regarded as a minor abnormality, it can also indicate the presence of myocardial scar. This study assessed the diagnostic value of pathologic inferior Q-waves (lead II, III, aVF) for detecting ischemic scars using a high-resolution 3.0 T cardiac magnetic resonance (CMR). We retrospectively analyzed 1692 patients with suspected or known coronary artery disease who underwent stress CMR perfusion or viability assessment. Pathologic Q-waves were defined as duration of ≥ 30 ms and depth of ≥ 1 mm or QS-complex. Eleven models were created to evaluate the presence of Q-waves in different combinations of inferior leads. Of the 1692 patients, 436 (25.8%) had pathologic Q-waves. Models with Q-waves in leads II + aVF (model 7) and II + III + aVF (model 9) showed high specificity (100% and 99.6%), positive predictive value (PPV) (80.0% and 86.7%), and negative predictive value (NPV) (82.6% and 84.3%) but low sensitivity (1.3% and 13.1%). Other models also maintained high specificity and NPV but poor sensitivity and PPV. Notably, 21% of patients with an isolated pathologic Q-wave in lead III (model 4) exhibited scars. These findings highlight the need for careful clinical assessment when pathologic Q-waves are present.

Discordant Prenatal Cell-Free DNA Screening vs. Diagnostic Results of Sex Chromosome Aneuploidies: Implications for Newborn Screening and Genetic Counseling.

Sex chromosome aneuploidies (SCAs) collectively occur in 1 in 500 livebirths, and diagnoses in the neonatal period are increasing with advancements in prenatal and early genetic testing. Inevitably, SCA will be identified on either routine prenatal or newborn screening in the near future. Tetrasomy SCAs are rare, manifesting more significant phenotypes compared to trisomies. Prenatal cell-free DNA (cfDNA) screening has been demonstrated to have relatively poor positive predictive values (PPV) in SCAs, directing genetic counseling discussions towards false-positive likelihood rather than thoroughly addressing all possible outcomes and phenotypes, respectively. The eXtraordinarY Babies study is a natural history study of children prenatally identified with SCAs, and it developed a longitudinal data resource and common data elements with the Newborn Screening Translational Research Network (NBSTRN). A review of cfDNA and diagnostic reports from participants identified a higher than anticipated rate of discordance. The aims of this project are to (1) compare our findings to outcomes from a regional clinical cytogenetic laboratory and (2) describe discordant outcomes from both samples. Twenty-one (10%), and seven (8.3%) cases were found to be discordant between cfDNA (result or indication reported to lab) and diagnosis for the Babies Study and regional laboratory, respectively. Discordant results represented six distinct discordance categories when comparing cfDNA to diagnostic results, with the largest groups being Trisomy cfDNA vs. Tetrasomy diagnosis (66.7% of discordance in eXtraordinarY Babies study) and Mosaicism (57.1% in regional laboratory). Traditional genetic counseling for SCA-related cfDNA results is inadequate given a high degree of discordance that jeopardizes the accuracy of the information discussed and informed decision making following prenatal genetic counseling.

Predictive values of an immunological fecal occult blood test for the diagnosis of colorectal cancer compared using colonoscopy in symptomatic patients in Yaounde (Cameroon)

IntroductionThe predictive value of immunological fecal occult blood (iFOB) testing for the screening of colorectal cancer has been well described in the Western world. However, its relevance in Sub-Saharan Africa (SSA) is not well evaluated. It could be altered by the other causes of lower gastrointestinal bleeding such as parasitic infections. The aim of this study was to highlight the performance of an iFOB test for the prediction of colorectal cancer (CRC) during colonoscopy in SSA.MethodologyWe conducted an analytical cross-sectional study in two digestive endoscopic centers of Yaoundé (Cameroon) from the 1st July to the 31 November 2022. Patients presenting with an indication for colonoscopy without any overt gastrointestinal bleeding were included. Sociodemographic and clinical data were collected. All consenting patients underwent a qualitative immunologic occult test through the iFOB test before colonoscopy. Data were analyzed using SPSS version 23.0 software. The performance of the iFOB test for the diagnosis of CRC during colonoscopy was evaluated in terms of sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV).ResultsWe included 103 patients during the study period with a male predominance and a sex ratio of 1.7. The median age [IQR] was 52 [38—65] years (range 1 – 84 years). The most common colonoscopic lesions were polyps in 23 patients (22.3%), CRC in 17 patients (16.5%) and hemorrhoids in 15 patients (14.6%). Patients testing positive for iFOB test accounted for 43.7% (45 patients). Among these patients, 31.1% (14 patients) had a CRC. The Se of the occult blood test for CRC detection was calculated to be 82.3% (95%CI: 56.7—96.2); the Sp was 63.9% (95% CI: 53—74); the PPV was 31.1% (95% CI: 24—39) and the NPV was 94.8% (95% CI: 86.6—98.1).ConclusionThe iFOB test has a good NPV, but a poor PPV for the diagnosis of CRC in our study.

Use of Gynecologic Cancer Intergroup (GCIG) CA125 criteria to evaluate cell cycle checkpoint kinase 1 inhibitor (CHK1i) prexasertib response and disease progression (PD) in recurrent high-grade serous ovarian cancer (HGSOC).

e17536 Background: Data suggest discordance between serum biomarker CA125 and Response Evaluation Criteria in Solid Tumors (RECIST) response and/or PD in chemotherapies and PARP inhibitors. Here, we investigated the impact of CA125 on prognosis and its relationship with RECIST response/PD in HGSOC patients treated with a CHK1i, prexasertib. Methods: All relapsed HGSOC patients in this post-hoc analysis were treated with prexasertib at 105 mg/m2 IV every 14 days in a 28-day cycle until RECIST v1.1 PD, unacceptable toxicity, or consent withdrawal (NCT02203513). CA125 was assessed every cycle and CT scans obtained every two cycles. GCIG CA125 response was defined as &gt;50% reduction confirmed after 28 days and PD as &gt; 2X upper limit of normal (ULN) if baseline was normal or doubling of nadir if baseline was elevated. Patients with baseline CA125 &lt; 2X ULN or nadir &gt; 750 units/mL were not eligible for analysis. Clinical benefit rate (CBR; CR + PR + SD ≥ 6 months) was analyzed by Fisher’s exact test. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves and univariate (UV) and multivariate (MV) hazard ratios by Cox regression models. Positive predictive value (PPV) and negative predictive value (NPV) confidence intervals (CI) were estimated by the Wilson-Brown method. Results: Eighty-one patients received at least two cycles of prexasertib between January 2015 and November 2020, out of which 72 were evaluable by both RECIST and GCIG CA125 response criteria. CBR in the CA125 response (CA125-R) group (24/32; 75%) was significantly higher than the CA125 non-responder (CA125-N) group (12/40; 30%; p&lt;0.001). CA125 response tended to occur prior to RECIST response (median: 28 days; IQR: 28, 30). PFS was improved in CA125-R at 8.0 months vs. CA125-N at 3.5 months (UV HR: 0.34, 95% CI: 0.21-0.56; MV HR: 0.35, 95% CI: 0.20-0.59). OS was improved in CA125-R at 19.8 months vs. CA125-N at 10.3 months (HR: 0.43, 95% CI: 0.26-0.71; MV HR: 0.45, 95% CI: 0.27-0.75). No significant differences in PFS or OS were observed between subgroups by BRCA mutation status, platinum-sensitivity, FIGO stage, baseline CA125 value, or previous PARP inhibitor therapy in MV analysis. Out of 70 patients evaluable by RECIST and CA125 PD criteria, 43 patients had CA125 PD and 24 of those had RECIST PD occur within one cycle of CA125 PD (PPV: 59%; 95% CI: 43-72). Of the 27 patients without a CA125 PD, 9 patients also did not have a RECIST PD (NPV: 33%; 95% CI: 19-52). Conclusions: GCIG CA125 response is an independent predictor of response to CHK1i in HGSOC prior to the first restaging scans and is associated with a higher CBR and improved PFS and OS. However, GCIG CA125 PD has poor PPV and NPV within a one cycle window, indicating that CA125 alone is not sufficient in monitoring for PD in HGSOC treated with CHK1i.

Lesions sub-diagnostic of endometrioid intra-epithelial neoplasia/atypical hyperplasia: value of morphology and immunohistochemistry in predicting neoplastic outcome.

Areas of gland crowding that do not fulfil diagnostic criteria of endometrioid intra-epithelial neoplasia (EIN) are often encountered in endometrial biopsies. In this study, we document the prevalence of neoplastic outcome in patients with these subdiagnostic lesions (SL) and assess the utility of morphological features and a three-marker immunohistochemistry panel (PAX2, PTEN, beta-catenin) to predict outcome. Of 430 women with SL on endometrial sampling at Brigham and Women's Hospital between 2001 and 2021 with available follow-up biopsy, 72 (17%) had a neoplastic outcome (EIN or endometrioid carcinoma). Multilayered epithelium and mitoses in SL were statistically associated with a neoplastic outcome. Abnormal three-marker staining was observed in 93% (53 of 57) of SL with neoplastic outcome and 60% (37 of 62) of a control group with benign outcome. Among the 72 patients with neoplastic outcome, EIN/carcinoma tissue was available in 33; of these, 30 (91%) showed abnormal staining for one or more markers. Remarkably, in 84% of these cases the EIN/carcinoma had the aberrant expression seen in the preceding SL. Based on a prevalence of 17%, the positive and negative predictive values of abnormal staining in one or more markers were 24 and 97%, respectively. The presence of SL warrants clinical surveillance and repeat sampling because it is followed by endometrioid neoplasia in a significant subset of patients. Normal three-marker staining identifies women with a very low risk of neoplastic outcome. Conversely, abnormal staining is frequent in SL with benign outcome leading to poor specificity and positive predictive value.

Performance of Urinalysis Parameters in Predicting Urinary Tract Infection: Does One Size Fit All?

In a multihospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women.

Accuracy of commercial ELISA and ICT for screening schistosomiasis infections at a low endemicity area in Brazil.

Control interventions recommended by the World Health Organization have successfully resulted in low-intensity schistosomiasis transmission areas. To achieve elimination of transmission, new diagnostic screening tools are needed to overcome less than adequate sensitivity of the currently used Kato-Katz faecal thick smear method. Ideally, in-house serological tests should be avoided due to not having a continuous supply of kits as would be necessary for large population studies. Quality assurance provided by manufacturers and proper performance evaluations are also needed. We evaluated the accuracy of two commercially available serology tests as screening methods for detecting light schistosomiasis infections. Serum samples were collected in 2015 from individuals living in a low-endemicity locality in northeastern Brazil and deposited in a biorepository. We evaluated immunoglobulin G (IgG) and IgM enzyme-linked immunosorbent assays (ELISAs) and an immunochromatographic test (ICT). The Helmintex method was used to define true-positive samples. Overall sensitivity was close to 90% for both the IgG ELISA and ICT, yet specificity was 28% and 18%, respectively. For the IgM ELISA, the values were estimated to be 55% and 43%, respectively. Poor specificity and positive predictive values prevent these tests from being recommended for screening populations in low-intensity schistosomiasis-endemic areas.

Prevalence of Triggers and Patient Harm Identified by Global Trigger Tool in Specialized Palliative Care.

Background: Global trigger tool (GTT) was developed for identification of patient harm. In palliative patients deterioration can be expected, and there are no data on whether cases classified as "patient harm" actually represents a potential for improved patient safety. Objectives: The primary aim was to test the performance and suitability of GTT in palliative care patients. The secondary aim was to pilot triggers for substandard palliative care. Design and Measurements: GTT was applied in 113 consecutive patients at a palliative ward at a Norwegian university hospital. Cases of patient harm were further evaluated to decide if the case was (a) a natural part of the disease trajectory or (b) a foreseeable consequence of treatment decisions. Potential triggers for substandard palliative care were tested. Results: Two hundred twelve triggers (1.9 per hospitalization) and 26 cases of patient harm were identified. The positive predictive value (PPV) for identifying patient harm was 0.12. The most prevalent harm was pressure ulcers (8.8%). Of the 26 cases of patient harm, 6 cases were a natural part of the disease trajectory and 10 consequences of treatment decisions. In 21 (18%) patients triggers being piloted for substandard palliative care were present, identifying 9 cases of substandard palliative care. The highest PPV (0.67) was observed for "Cessation of antibiotics less than 5 days before death." Conclusions: With the exception of pressure ulcers, GTT triggers were infrequent or had a very poor PPV for patient harm. Triggers related to overtreatment might be suitable for identifying substandard palliative care.

Predictive Value of Methicillin-Resistant Staphylococcus aureus Nasal Swab PCR Assay for MRSA Infection in Critically Ill Pediatric Patients.

Critically ill pediatric patients are frequently initiated methicillin-resistant Staphylococcus aureus (MRSA) active antibiotics during infection evaluation even though MRSA infections are rare in many patient populations. The MRSA nasal swab polymerase chain reaction assay (MRSA-NS-PCR) is a test that has been shown to have a high negative predictive value (NPV) for MRSA infection in adults. This study evaluated the diagnostic test characteristics of the MRSA-NS-PCR in predicting the presence of MRSA infection in critically ill pediatric patients. A retrospective cohort study was performed in a 44-bed pediatric intensive care unit (PICU) between 2013 and 2017. 3860 pediatric patients (54% male, median age 4 years [IQR 1-11 years]) admitted to the PICU who met pediatric systemic inflammatory response syndrome (pSIRS) criteria, were screened with a MRSA-NS-PCR, and had cultures obtained within seven days of MRSA-NS-PCR collection were included. Predictive values and post-test probabilities of the MRSA-NS-PCR for MRSA infection were calculated. MRSA-NS-PCR was positive in 8.6% of patients. MRSA infection was identified in 40 patients, equaling an incidence rate of 2 per 1000 patient days. The MRSA-NS-PCR demonstrated a positive predictive value (PPV) of 9.7%, a NPV of 99.8%, and a post-test probability for a negative test of 0.2% for MRSA infection. The MRSA-NS-PCR has a poor PPV but a high NPV for MRSA infection in PICU patients when the incidence of MRSA infection is low. Creation of protocols to guide antimicrobial selection based on MRSA-NS-PCR results may lead to improved antimicrobial stewardship and significant risk reduction.

Abstract 17700: Double Trouble With Identification of Isolated Sub-Segmental Pulmonary Embolism Using ICD-10 Discharge Diagnosis Codes: The PE-EHR+ Study

Introduction: International Classification of Diseases 10 th revision (ICD-10) discharge diagnosis codes are widely used for research studies that use electronic databases. The accuracy of the codes for identifying patients with isolated sub-segmental pulmonary embolism (issPE) is unknown. Methods: We used data from the Mass General Brigham (MGB) health system (01/2016-12/2021) and included 1,734 patients randomly selected from 3 groups: Patients with ICD-10 Principal Discharge Diagnosis codes for PE, patients with secondary Discharge Diagnosis codes for PE, and patients with no ICD-10 codes for PE. Weighted estimates were obtained by considering the total number of hospitalizations in each category at MGB hospitals. Accuracy of the codes was assessed by two independent physicians who reviewed discharge summaries, daily notes, and radiology reports. Results: Of 1,734 records reviewed, 1,712 were included (age: 60.6±17.8 years, 52.3% female). Manual chart review found 865 patients with acute PE, including 104 (12.0%) with issPE. Of these 104 patients, 103 (98.3%) had ICD-10 codes for PE. However, only in 15 (14.6%) cases, PE codes were specified as being limited to subsegmental vessels (issPE). In turn, in another 43 cases, Principal-or-secondary ICD-10 codes for issPE were listed but the patients did not have acute issPE during index hospitalization per review of records. The sensitivity and specificity for issPE codes in Principal or secondary discharge position were 14.4% and 97.3% (Table, panel A). Positive predictive value in the weighted sample was only 26.2% (Table, panel B). Conclusions: ICD-10 codes are insensitive and have a poor positive predictive value for detection of isolated subsegmental PE and should not be used for case identification for research purposes or quality improvement initiatives.

Next-Generation Sequencing (NGS) for Residual Disease (MRD) Monitoring in T-Lymphoblastic Leukemia (T-ALL)

Background: Flow Cytometry is the current standard for detection of measurable residual disease (MRD) in T-lymphoblastic leukemia (T-ALL) for North America but relies on subjective interpretation of data by a highly trained interpreter, which raises concerns for reproducibility between laboratories. Nevertheless, MRD &amp;gt; 0.01% at End of Induction (EOI) and End of Consolidation (EOC) have been associated with poorer outcome in T-ALL. MRD detection by next-generation sequencing (NGS) offers the potential for reduced subjectivity and increased sensitivity, as has already been demonstrated in B-lymphoblastic leukemia. This study assesses the performance characteristics and potential contribution of NGS for the detection of T-ALL MRD in pediatric patients. Method: Residual patient samples from COG AALL1231 concurrently tested for T-ALL MRD by flow cytometry were tested for the presence of leukemia-associated clonal TCRB sequences at the University of Washington using the immunoSEQ kit from Adaptive Biotechnologies. The sensitivity of the assay for these samples is estimated at 0.002%. The samples included 615 pretreatment samples, 298 EOI samples, and 72 EOC samples. The EOI samples were negative for MRD by flow cytometry (MRD&amp;lt;0.01%). The EOC samples were from patients positive for MRD at EOI, as per the treatment protocol. 111 samples lacking a pretreatment clonal TCRB sequence for which residual material was available were submitted to Adaptive Biotechnologies for TCRG sequencing. ETP status was determined on pre-treatment samples by flow cytometry. A pretreatment clonal sequence representing &amp;gt; 19% of the total T cell sequences was considered leukemia-associated and the presence any leukemia-associated clonal sequence post-treatment was considered MRD positive. The MRD results were correlated with clinical outcome. Results: Clonal TCRB leukemia-associated sequences were identified in 68.5% of pretreatment samples and correlated with ETP status (ETP 3.6% (N=56) , Near-ETP 44.8% (N=96), Not-ETP 82.4% (N=449), unknown 50% (N=14)). Clonal TCRG leukemia-associated sequences were identified in an additional 44.1% of pretreatment samples lacking a clonal TCRB sequence (N=111). EOI MRD was identified in 71.0% of samples assayed for TCRB (ETP not evaluable (N=0), Near-ETP 76.2% (N=21), Not-ETP 70.3% (N=263), Unknown 77.8% (N=9)). Additional EOI samples not informative for TCRB and assayed for TCRG (N=29) identified 89.7% as MRD positive. EOC MRD was identified in 63.9% of samples assayed for TCRB (ETP 66.7% (N=3), Near-ETP 45.5% (N=11), Not-ETP 68.4% (N=57), Unknown 0% (N=1)). Additional EOC samples not informative for TCRB and assayed for TCRG (N=35) identified as 68.6% MRD positive. Correlation of MRD status with clinical outcome data revealed no difference in disease-free survival (DFS) at either EOI or EOC, although all relapses but one at each timepoint (N=15 EOI, N=15 EOC) occurred in the MRD positive groups. Conclusion: A significant subset of T-ALL samples do not contain clonal leukemia-associated TCRB or TCRG sequences (31.5% for TCRB, 17.6% using both TCRB or TCRG) and cannot be evaluated for MRD using this NGS approach. Samples lacking a clonal leukemia-associated sequence are associated with an immature immunophenotype (ETP or Near-ETP), although 17.6% of Not-ETP samples also lack a clonal sequence, suggesting that flow cytometric classification of maturational stage is likely imperfect. A high frequency of MRD positivity is present at both EOI and EOC that does not reflect the excellent outcome that most patients experience, thus raising concerns about the specificity of these clonal sequences at very low levels of detection. Evaluation of sequence specificity across the cohort and use of higher MRD thresholds to optimize the correlation with clinical outcome is underway. A negative MRD result by NGS has a high negative predictive value for relapse/death at either EOI (95.2%) or EOC (92.9%) but a poor positive predictive value (6.8% at both EOI and EOC).

Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models.

The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse. A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared. Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%). AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.

Predictive Risk Score for Postparathyroidectomy Hungry Bone Syndrome in Patients With Secondary Hyperparathyroidism.

Secondary hyperparathyroidism (SHPT) frequently affects patients with end-stage renal disease. Hungry bone syndrome (HBS) is a common complication among patients who undergo parathyroidectomy for SHPT and may cause prolonged hospitalization or require intensive care. The objective of this study is to develop a scoring system to stratify patients according to their risk of developing HBS. A retrospective cohort study was performed using the US Renal Data System (2010-2021). Univariable and multivariable logistic regression models were developed and weighted β-coefficients from the multivariable model were used to construct a risk score for the development of HBS. Positive and negative predictive values were assessed. Of 17 074 patients who underwent parathyroidectomy for SHPT, 19.4% developed HBS. Intensive care unit admission was more common in patients who developed HBS (33.5% vs 24.6%, P < .001). On multivariable logistic regression analysis, younger age, renal osteodystrophy, longer duration of dialysis, longer duration of kidney transplant, and higher Elixhauser score were significantly associated with HBS. A risk score based on these clinical factors was developed, with a total of 6 possible points. Rates of HBS ranged from 8% in patients with 0 points to 44% in patients with 6 points. The risk score had a poor positive predictive value (20.3%) but excellent negative predictive value (89.3%) for HBS. We developed a weighted risk score that effectively stratifies patients by risk for developing HBS after parathyroidectomy. This tool can be used to counsel patients and to identify patients who may not require postoperative hospitalization.

Neutrophil Elastase as a Predictor of Delivery in Pregnant Women with Preterm Labour.

No previous study has been conducted in Nigeria on the role of neutrophil elastase in predicting preterm birth. The present study aimed to determine the role of the neutrophil elastase test in predicting birth in women with preterm labor. The present prospective cohort study recruited 83 pregnant women with preterm labor between 28 and 36+6 weeks of gestation, and followed up these subjects for 14 days. The controls comprised 85 pregnant women without preterm labor. The cervicovaginal fluid was collected and tested using the neutrophil elastase test. Then, the sensitivity, specificity, and positive and negative predictive parameters were determined. Afterward, the data were scrutinized using the SPSS arithmetic software (Sort23). Among the 168 pregnant women analyzed in the present study, 83 pregnant women were assigned to the preterm labor group, and 85 pregnant women were assigned to the control group. Furthermore, among the 83 pregnant women in the preterm labor group, 11 women had spontaneous preterm delivery, leading to a spontaneous preterm birth proportion of 13.3%. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the neutrophil elastase test within 14 days post-enrollment were 93.8%, 61.2%, 36.6%, 97.6%, and 67.5%, respectively, for the general population, and 87.5%, 66.7%, 35.0%, 96.3%, and 70.2%, respectively, for subjects at <35 weeks of gestation. The positive and negative likelihood ratios for preterm birth prediction were 2.62 and 0.19, respectively. The neutrophil elastase test exhibited high predictive accuracy in pregnant women with preterm labor, when compared to the controls, based on the sensitivity and negative predictive value, but this had poor positive predictive values. The neutrophil elastase test may be used as a screening test, but not as a potential predictive test, in the routine clinical setting.

REM Sleep Behavior Disorder and Its Possible Prodromes in General Population: Prevalence, Polysomnography Findings, and Associated Factors.

To evaluate the prevalence of REM sleep behavior disorder (RBD) and its possible prodromal conditions, isolated dream enactment behavior (DEB) and isolated REM without atonia (RWA), in a general population sample, and the factors associated with diagnosis and symptom frequency. From a population-based prospective cohort in Korea, 1,075 participants (age 60.1 ± 7.0 years; range 50-80 years; men 53.7%) completed the RBD screening questionnaire (RBDSQ), a structured telephone interview for the presence and characteristics of repeated DEB, and home polysomnography (PSG). RWA was measured on submentalis EMG, including 30-second epoch-based tonic and phasic activity as well as 3-second mini-epoch-based phasic and any EMG activities. Based on the presence of repeated DEB and any EMG activity of ≥22.3%, we categorized the participants into no RBD, isolated RWA, isolated DEB, and RBD groups. RBD was diagnosed in 20 participants, isolated RWA in 133 participants, and isolated DEB in 48 participants. Sex and DEB frequency-adjusted prevalence of RBD was 1.4% (95% CI 1.0%-1.8%), isolated RWA was 12.5% (95% CI 11.3%-13.6%), and isolated DEB was 3.4% (95% CI 2.7%-4.1%). Total RBDSQ score was higher in the RBD and isolated DEB groups than in the isolated RWA and no RBD group (median 5 [interquartile range (IQR) 4-6] for RBD, median 4 [IQR 3-6] for isolated DEB, median 2 [IQR 1-3] for isolated RWA, and median 2 [IQR 1-4] for no RBD groups, p < 0.001). RBDSQ score of ≥5 had good specificity but poor positive predictive value (PPV) for RBD (specificity 84.1% and PPV 7.7%) and its prodromal conditions (specificity 85.2% and PPV 29.1%). Among the RWA parameters, any EMG activity showed the best association with the RBD and its possible prodromes (area under the curve, 0.917). Three-second mini-epoch-based EMG activity and phasic EMG activity were correlated with the frequency of DEB (standardized Jonckheere-Terpstra statistic [std. J-T static] for trend = 0.488, p < 0.001, and std. J-T static = 3.265, p = 0.001, respectively). This study provides prevalence estimates of RBD and its possible prodromal conditions based on a structured telephone interview and RWA measurement on PSG from the general population.

SAT308 An Assessment Of Prognostic Markers To Predict Metastatic Pheochromocytoma/Paraganglioma

Abstract Disclosure: M.D. Lundholm: None. E. Berber: None. P.P. Rao: None. Introduction: Pheochromocytoma/paraganglioma (PCC/PGL, or PPGL) are rare neuroendocrine tumors arising from chromaffin cells. Early identification of PPGL with metastatic potential is a diagnostic challenge. More data are needed on features and scoring markers used to predict PPGL metastasis. Methods: A single-center, retrospective observational study was performed of consecutive patients with pathology-confirmed PPGL from 2005 to 2022. Features associated with metastasis were identified and Pheochromocytoma of the Adrenal gland Scaled Score (PASS), Age, Size, Extra-adrenal location and Secretory type (ASES) score, and Size, Genetic, Age, and PASS (SGAP) score were calculated. Results: We identified 371 patients with PPGL (251 PCC, 120 PGL), age 52.2±15.4yrs, 60.6% female, 69.8% incidental. Metastatic disease was reported in 13.2% (N=49; 30 PCC, 19 PGL) associated with younger age (47.3 vs 53.0yrs, p=0.029), larger tumor size (6.3 vs 4.0cm, p&amp;lt;0.001), histologic findings of necrosis (26% vs 2.5%, p&amp;lt;0.001) and vascular invasion (42.1% vs 19.6% p=0.038), hyperadrenergic symptoms at diagnosis (38.8% vs 22.0%, p=0.038), norepinephrine-only secreting tumors (59.6% vs 30.1%, p&amp;lt;0.001), extra-adrenal location (51.0% vs 32.0%, p=0.009), presence of genetic mutations (72.4% vs 38.5%, p&amp;lt;0.001), particularly SDHx (31.0% vs 12.2%, p=0.020) and VHL mutations (24.1% vs 3.8%, p=0.001). There were no significant differences by gender, race, other histologic criteria from PASS, or other mutations such as RET or NF-1. ASES was positive (≥2) in 27.2% (N=100/371) with sensitivity (SN) 79.6%, specificity (SP) 81.1%, positive predictive value (PPV) 39.0%, and negative predictive value (NPV) 96.3% for predicting metastatic disease. PASS and SGAP could only be applied to patients with PCC: PASS was positive (≥4) in 29.7% (N=55/185) with SN 60.0%, SP 73.9%, PPV 21.8%, and NPV 93.8%. SGAP was positive (≥5) in 27.6% (N=32/116) with SN 56.3%, SP 77.0%, PPV 28.1%, and NPV 91.7%. Discussion: Metastatic PPGL is associated with age, tumor size and location, select histologic findings, symptomatic presentation, hormone-secreting pattern, and select genetic mutations. PPGL scoring markers ASES, PASS, and SGAP were all effective at identifying cases with low likelihood of metastasis, but had poor PPV. ASES outperformed PASS and SGAP in test metrics and practicality as the only clinically-derived marker which could be applied to all cases of PPGL. ASES can also be used pre-operatively. Most histologic features and genetic mutations included in PASS and SGAP were not strongly correlated with metastasis, though limited by lower prevalence in the study population. Conclusion: Our data supports the use of ASES alongside data on necrosis, vascular invasion, SDHx and VHL mutations where available to fine-tune our prediction of metastatic potential for PPGL. Presentation: Saturday, June 17, 2023