Excellent Negative Predictive Value Research Articles

Enhancing outcome prediction of concurrent chemoradiation treatment in patients with locally advanced cervical cancer through plasma extracellular vesicle proteomics

Most patients with locally advanced cervical cancer (LACC) are primarily treated using concurrent chemoradiation (CCRT); however, LACC lacks reliable predictive biomarkers. Extracellular vesicles (EVs) could define the dynamic biological response to CCRT. However, the relationship between EVs and the therapeutic response to LACC is unestablished. Thus, we aimed to determine the relationship of plasma EVs pre- and post-CCRT in 62 patients with LACC. For proteomic analyses, EVs were isolated using ultracentrifugation (UC) with size exclusion chromatography or UC alone. We found that plasma particle concentration was significantly increased post-treatment in non-responders. After CCRT, there was a decrease in proteins related to serine protease and fibrinogen, which contribute to tumor microenvironment alteration. This reduction also extended to proteins involved in innate immune and viral immune responses, correlating with reduced tumor burden. Sparse partial least squares discriminant analysis revealed 8, 13, and 19 proteins at diagnosis, one month, and three months, respectively, influencing the CCRT response. Among these, FIBG, TFR1, HBA, and FINC are prognostic markers according to The Cancer Genome Atlas tissue gene expression database. Our discriminant model demonstrated excellent specificity and negative predictive value, underscoring the model's reliability in determining responsiveness to CCRT and highlighting the potential clinical applicability of EVs in improving outcomes in LACC.

Outcomes of In-Office, High Resolution, Ultrasound Silicone Breast Implant Surveillance by Plastic Surgeons.

Implant rupture is a known complication in cosmetic breast surgery but access and cost barriers hinder proper implant surveillance. This study aims to validate High Resolution Ultrasound (HRUS) for diagnosing silicone implant rupture, and secondarily, explore the predictors of implant rupture in a single-surgeon cohort. A retrospective chart review identified patients who underwent HRUS of silicone breast implants that were placed by the senior author (WPA). HRUS sensitivity/specificity and predictive values were calculated. Multivariable logistic regression assessed predictors of implant rupture. Kaplan-Meier methods estimated 10 and 15-year implant survival. Among 254 patients (508 implants) included, 52 patients (104 implants) underwent operative exploration for various reasons; 20 implants had confirmed ruptures. Examining this operative cohort, HRUS had excellent positive and negative predictive value, respectively, 100% (95% CI 83.1-100%) and 97.6% (95% CI 91.6-99.3%); the sensitivity was 90.9% (95% CI 70.8-98.9%) and specificity was 100% (95% CI 95.6%-100%). The median age of the implant at the time of ultrasound was 119 months (10 years; IQR 79-152 months). After multivariable adjustment, the only the implant age was a significant predictor of implant rupture (p=0.04). Across the entire cohort, Kaplan-Meier methods estimated a 10-year and 15-year implant survival rate of 0.98 (95% CI 0.96-0.99) and 0.80 (95% CI 0.71-0.87), respectively. Subgroup analysis showed 10 and 15-year implant survival rates of 0.99 and 0.92, respectively, for surveillance-only HRUS patients. Plastic surgeon delivered office-based HRUS surveillance is a highly sensitive and specific method to assess silicone breast implant integrity.

Risk score prediction for bacteriologically confirmed tuberculosis among adults with HIV on antiretroviral therapy in northwest Ethiopia: prognostic model development.

This study was aimed at developing a risk score prediction model for bacteriologically confirmed tuberculosis (TB) among adults with HIV receiving antiretroviral therapy in Ethiopia. An institutional-based retrospective follow-up study was conducted among 569 adults with HIV on ART. We used demographic and clinical prognostic factors to develop a risk prediction model. Model performance was evaluated by discrimination and calibration using the area under the receiver operating characteristic (AUROC) curve and calibration plot. Bootstrapping was used for internal validation. A decision curve analysis was used to evaluate the clinical utility. Opportunistic infection, functional status, anemia, isoniazid preventive therapy, and WHO clinical stages were used to develop risk prediction. The AUROC curve of the original model was 87.53% [95% confidence interval (CI): 83.88-91.25] and the calibration plot ( P -value = 0.51). After internal validation, the AUROC curve of 86.61% (95% CI: 82.92-90.29%) was comparable with the original model, with an optimism coefficient of 0.0096 and good calibration ( P -value = 0.10). Our model revealed excellent sensitivity (92.65%) and negative predictive value (NPV) (98.60%) with very good specificity (70.06%) and accuracy (72.76%). After validation, accuracy (74.85%) and specificity (76.27%) were improved, but sensitivity (86.76%) and NPV (97.66%) were relatively reduced. The risk prediction model had a net benefit up to 7.5 threshold probabilities. This prognostic model had very good performance. Moreover, it had very good sensitivity and excellent NPV. The model could help clinicians use risk estimation and stratification for early diagnosis and treatment to improve patient outcomes and quality of life.

Non-endoscopic screening for Barrett's esophagus and Esophageal Adenocarcinoma in at risk Veterans.

While rates of Esophageal Adenocarcinoma (EAC) in the US continue to rise, many patients at risk of disease are not screened. EsoCheck (EC), a non-endoscopic esophageal balloon sampling device coupled with EsoGuard (EG), a DNA based screening assay, is an FDA-approved minimally invasive alternative to the traditional screening method of upper endoscopy. To prospectively determine the diagnostic accuracy, tolerance, and acceptability of the EC/EG test in a screening population. We recruited Veterans who met the American College of Gastroenterology (ACG) Guideline criteria for endoscopic Barrett's Esophagus (BE) and EAC screening at Louis Stokes Cleveland Veteran Affairs Medical Center. All study participants completed unsedated EC guided distal esophageal sampling followed by a sedated esophagogastroduodenoscopy (EGD). Diagnostic yield of the EG assay and EGD was recorded and used in calculation of sensitivity and specificity of EC/EG in prospective screening. The abbreviated Spielberger State-Trait Anxiety Inventory (STAI-6) questionnaire was administered before and after completion of EC. Overall tolerance of EC sampling was evaluated on a 10-point Likert scale. Esophageal cancer screening was accepted by 130/782 (16.6%) eligible veterans and we analyzed results of those who completed both screening tests (N = 124). Prevalence of BE/EAC among studied veterans was 12.9% (16/124), based on EGD. Sensitivity and specificity of EC/EG for EGD-detected BE/EAC were 92.9% (95% CI 66.1, 99.8) and 72.2% (95% CI 62.1, 80.8), respectively. Positive and negative predictive values were 32.5% (95% CI 18.6, 49.1) and 98.6% (95% CI 92.4, 100), respectively. Baseline STAI-6 scores were reflective of notable levels of anxiety among veterans in the peri-procedural setting. Mean post-procedure acceptability score for Esocheck test was 7.23 (SD 2.45). Our data suggest excellent sensitivity and negative predictive value of EC/EG in a screening population of veterans, making this modality a powerful screening tool for BE and EAC.

Cardiovascular Imaging for Coronary Artery Disease in Patients with Diabetes Mellitus.

In patients with diabetes mellitus, accelerated progression of atherosclerosis can lead to worse clinical outcomes. Determining the best diagnostic strategy to identify patients with increased cardiovascular risk is challenging. Current guidelines recommend using both functional imaging and CT angiography to detect myocardial ischemia and coronary artery disease based on pre-test probability. Functional imaging is suggested for patients with a higher clinical likelihood due to its higher rule-in diagnostic capacity. On the other hand, CT angiography is preferred for patients with lower pre-test probability because of its excellent negative predictive value. The optimal management strategy for asymptomatic diabetic patients remains unclear. In asymptomatic diabetic patients, previous randomized trials have not shown benefits from diagnostic testing over standard care. However, these trials were methodologically inconsistent and lacked clear stratification of cardiovascular risk. In terms of invasive evaluation, a combined invasive functional and anatomic imaging approach for angiographically intermediate coronary stenosis appears to be the best, most effective decision pathway for managing diabetic patients.

Diagnostic performance of MRI in detecting prostate cancer in patients with prostate-specific antigen levels of 4–10 ng/mL: a systematic review and meta-analysis

ObjectiveTo investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific antigen (PSA) levels of 4–10 ng/mL.MethodsA computerized search of PubMed, Embase, Cochrane Library, Medline, and Web of Science was conducted from inception until October 31, 2023. We included articles on the use of MRI to detect csPCa or PCa at 4–10 ng/mL PSA. The primary and secondary outcomes were MRI performance in csPCa and PCa detection, respectively; the estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were pooled in a bivariate random-effects model.ResultsAmong the 19 studies (3879 patients), there were 10 (2205 patients) and 13 studies (2965 patients) that reported MRI for detecting csPCa or PCa, respectively. The pooled sensitivity and specificity for csPCa detection were 0.84 (95% confidence interval [CI], 0.79–0.88) and 0.76 (95%CI, 0.65–0.84), respectively, for PCa detection were 0.82 (95%CI, 0.75–0.87) and 0.74 (95%CI, 0.65–0.82), respectively. The pooled NPV for csPCa detection was 0.91 (0.87–0.93). Biparametric magnetic resonance imaging also showed a significantly higher sensitivity and specificity relative to multiparametric magnetic resonance imaging (both p < 0.01).ConclusionProstate MRI enables the detection of csPCa and PCa with satisfactory performance in the PSA gray zone. The excellent NPV for csPCa detection indicates the possibility of biopsy decision-making in patients in the PSA gray zone, but substantial heterogeneity among the included studies should be taken into account.Clinical relevance statementProstate MRI can be considered a reliable and satisfactory tool for detecting csPCa and PCa in patients with PSA in the “gray zone”, allowing for reducing unnecessary biopsy and optimizing the overall examination process.Key PointsProstate-specific antigen (PSA) is a common screening tool for prostate cancer but risks overdiagnosis.MRI demonstrated excellent negative predictive value for prostate cancer in the PSA gray zone.MRI can influence decision-making for these patients, and biparametric MRI should be further evaluated.Graphical

Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis.

The 2021 European Society of Cardiology (ESC) screening recommendations for individuals carrying a pathogenic transthyretin amyloidosis variant (ATTRv) are based on expert opinion. We aimed to (i) determine the penetrance of ATTRv cardiomyopathy (ATTRv-CM) at baseline; (ii) examine the value of serial evaluation; and (iii) establish the yield of first-line diagnostic tests (i.e. electrocardiogram, echocardiogram, and laboratory tests) as per 2021 ESC position statement. We included 159 relatives (median age 55.6 [43.2-65.9] years, 52% male) at risk for ATTRv-CM from 10 centres. The primary endpoint, ATTRv-CM diagnosis, was defined as the presence of (i) cardiac tracer uptake in bone scintigraphy; or (ii) transthyretin-positive cardiac biopsy. The secondary endpoint was a composite of heart failure (New York Heart Association class ≥II) and pacemaker-requiring conduction disorders. At baseline, 40/159 (25%) relatives were diagnosed with ATTRv-CM. Of those, 20 (50%) met the secondary endpoint. Indication to screen (≤10 years prior to predicted disease onset and absence of extracardiac amyloidosis) had an excellent negative predictive value (97%). Other pre-screening predictors for ATTRv-CM were infrequently identified variants and male sex. Importantly, 13% of relatives with ATTRv-CM did not show any signs of cardiac involvement on first-line diagnostic tests. The yield of serial evaluation (n = 41 relatives; follow-up 3.1 [2.2-5.2] years) at 3-year interval was 9.4%. Screening according to the 2021 ESC position statement performs well in daily clinical practice. Clinicians should adhere to repeating bone scintigraphy after 3 years, as progressing to ATTRv-CM without signs of ATTRv-CM on first-line diagnostic tests or symptoms is common.

Coronary atherosclerosis among symptomatic patients with zero coronary artery calcium score in computed tomography coronary angiography

BackgroundComputed tomographic coronary angiography has been recognized as a reliable imaging modality with excellent negative predictive value and a good negative likelihood ratio to exclude coronary artery disease in stable, symptomatic patients with intermediate or high risk. 1) Coronary calcium scoring has been extensively shown to be an invaluable tool to exclude the presence of coronary artery disease in low-risk patients. 2) Our aim was to identify the presence and extent of coronary atherosclerosis in computed tomographic coronary angiography in stable symptomatic patients with a zero Coronary Calcium score. ResultsThree hundred and eighty-three (383) consecutive patients aged ≥ 18 years fulfilling the criteria were enrolled as of January 1, 2021; 165 (43.1%) were male and 218 (56.9%) were female, with a mean age of 57.8 ± 4.9 years and a zero coronary artery calcium score. Two hundred and twenty-six (226) (59.0%) were hypertensive, followed by 125 (32.6%) who were smokers, and 117 (30.5%) who were diabetic. The frequency of atherosclerotic plaque in coronary arteries was 34 (8.9%), with 16 (47.1%) being male and 18 (52.9%) being female. The mean age of patients with atherosclerosis was 54.9 ± 3.3 years; among them, 13 (38.2%) were between the ages of 45 and 54, and 10 (29.4%) were between the ages of 55 and 64. Nineteen (19) (55.9%) were hypertensive, followed by 10 (29.4%) with dyslipidemia. Twenty-three (23) (67.6%) had non-obstructive plaque, and 11 (32.3%) had obstructive plaque. In the subgroup of patients with non-obstructive plaque, 13 (56.5%) were hypertensive, 8 (34.8%) were diabetic, and 16 (69.6%) had single vessel disease, while among patients with obstructive plaque, 6 (54.5%) were hypertensive, 5 (45.5%) were smokers, and all of them had single vessel disease. The most affected artery was the left anterior descending artery. ConclusionAs the frequency of atherosclerotic plaque in patients with a zero coronary calcium score is relatively high, computed tomographic coronary angiography is indicated in stable, symptomatic patients with a lower likelihood of coronary artery disease.

Performance of Risk Scores in Predicting Infective Endocarditis in Patients with Staphylococcus aureus Bacteraemia in a Prospective Asian Cohort.

Background: Several risk scores have been derived to predict the risk of infective endocarditis (IE) amongst patients with Staphylococcus aureus bacteraemia (SAB), which helps to guide clinical management. Methods: We prospectively studied 634 patients admitted with SAB. The cohort was stratified into those with or without IE, and the PREDICT Day 1, Day 5 and VIRSTA scores were tabulated. Area under the receiver operating characteristic (AUC) curves were constructed to compare the performance of each score. Results: Of the 634 patients examined, 36 (5.7%) had IE. These patients were younger (51.6 ± 20.1 vs. 59.2 ± 18.0 years, p = 0.015), tended to have community acquisition of bacteraemia (41.7% vs. 17.9%, p < 0.001), and had persistent bacteraemia beyond 72 h (19.4% vs. 6.0%, p = 0.002). The VIRSTA score had the best performance in predicting IE (AUC 0.76, 95%CI 0.66-0.86) compared with PREDICT Day 1 and Day 5. A VIRSTA score of <3 had the best negative predictive value (97.5%), compared with PREDICT Day 1 (<4) and Day 5 (<2) (94.3% and 96.6%, respectively). Conclusions: Overall, the risk scores performed well in our Asian cohort. If applied, 23.5% of the cohort with a VIRSTA ≥ 3 would require TEE, and a score of <3 had an excellent negative predictive value.

MRI of pelvic endometriosis: evaluation of the mr#Enzian classification and the importance of adenomyosis subtypes

PurposeThis study aimed to investigate the utility of the #Enzian classification in magnetic resonance imaging (MRI) for endometriosis assessment, focusing on inter-reader agreement, diagnostic accuracy, and the correlation of adenomyosis with deep endometriosis (DE).MethodsThis IRB- approved retrospective single-center study included 412 women who underwent MRI evaluation for endometriosis between February 2017 and June 2022. Two experienced radiologists independently analyzed MRI images using the #Enzian classification and assessed the type of adenomyosis, if any. The surgical #Enzian classification served as the gold standard for evaluating preoperative MRI results of 45 patients. Statistical analysis was performed to assess inter-reader agreement and diagnostic accuracy.ResultsInter-reader agreement was substantial to excellent (Cohen’s kappa 0.75–0.96) for most compartments except peritoneal involvement (0.39). The preoperative MRI showed mostly substantial to excellent accuracy (0.84–0.98), sensitivity (0.62–1.00), specificity (0.87–1.00), positive (0.58–1.00) and negative predictive values (0.86–1.00) for most compartments, except for peritoneal lesions (0.36, 0.17, 1.00, 1.00, 0.26 respectively). A trend with a higher prevalence of concordant DE in women with MR features of external adenomyosis compared to those with internal adenomyosis was visible (p = 0.067).ConclusionsThe mr#Enzian showed mostly high inter-reader agreement and good diagnostic accuracy for various endometriosis compartments. MRI’s role is particularly significant in the context of the current paradigm shift towards medical endometriosis treatment. The inclusion of information about the type of adenomyosis in the mr#Enzian classification could enhance diagnostic accuracy and inform treatment planning.Graphical

Elevated serum lactate dehydrogenase aids prediction of mortality in Pneumocystis jirovecii pneumonia without underlying human immunodeficiency virus infection – Derivation of a clinical risk score

Pneumocystis jirovecii pneumonia (PCP) is associated with significant mortality amongst patients without underlying human immunodeficiency virus infection (HIV). We sought to develop a risk score to predict mortality in this population. We reviewed patients with a presumed or confirmed PCP and a negative HIV test from 2006–2023. We constructed a multivariable model to identify parameters independently associated with mortality and the adjusted odds ratios were converted to weights to derive a risk score. Subsequently, we compared the performance of our score to the CURB-65 score by means of area under receiver operating characteristic curve (AUC). In total, we examined 93 patients with PCP without HIV. Mortality was 31.2%. Risk factors for mortality included older age, male sex and high serum lactate dehydrogenase levels (LDH) and C-reactive protein levels. A risk score was derived comprising age> 65 years (2 points), male sex (2 points) and LDH> 770 U/L (3 points). Our risk score (AUC 0.71, 95%CI 0.60–0.82) performed better than the CURB-65 score (AUC 0.53, 95%CI 0.41–0.66). A low-risk score of 0–1 had excellent negative predictive value for mortality (97.5%). In conclusion, a risk score comprising age, sex and LDH can predict mortality in PCP without underlying HIV and help with prognostication.

Development of a Non-Invasive Machine-Learned Point-of-Care Rule-Out Test for Coronary Artery Disease.

The current standard of care for coronary artery disease (CAD) requires an intake of radioactive or contrast enhancement dyes, radiation exposure, and stress and may take days to weeks for referral to gold-standard cardiac catheterization. The CAD diagnostic pathway would greatly benefit from a test to assess for CAD that enables the physician to rule it out at the point of care, thereby enabling the exploration of other diagnoses more rapidly. We sought to develop a test using machine learning to assess for CAD with a rule-out profile, using an easy-to-acquire signal (without stress/radiation) at the point of care. Given the historic disparate outcomes between sexes and urban/rural geographies in cardiology, we targeted equal performance across sexes in a geographically accessible test. Noninvasive photoplethysmogram and orthogonal voltage gradient signals were simultaneously acquired in a representative clinical population of subjects before invasive catheterization for those with CAD (gold-standard for the confirmation of CAD) and coronary computed tomographic angiography for those without CAD (excellent negative predictive value). Features were measured from the signal and used in machine learning to predict CAD status. The machine-learned algorithm achieved a sensitivity of 90% and specificity of 59%. The rule-out profile was maintained across both sexes, as well as all other relevant subgroups. A test to assess for CAD using machine learning on a noninvasive signal has been successfully developed, showing high performance and rule-out ability. Confirmation of the performance on a large clinical, blinded, enrollment-gated dataset is required before implementation of the test in clinical practice.

Association between vessel-specific coronary Aggregated plaque burden, Agatston score and hemodynamic significance of coronary disease (The CAPTivAte study)

BackgroundCT coronary angiography (CTCA) is a guideline-endorsed assessment for patients with stable angina and suspected coronary disease. Although associated with excellent negative predictive value in ruling out obstructive coronary disease, there are limitations in the ability of CTCA to predict hemodynamically significant coronary disease. The CAPTivAte study aims to assess the utility of Aggregated Plaque Burden (APB) in predicting ischemia based on Fractional Flow Reserve (FFR). MethodsIn this retrospective study, patients who had a CTCA and invasive FFR of the LAD were included. The entire length of the LAD was analyzed using semi-automated software which characterized total plaque burden and plaque morphological subtype (including Low Attenuation Plaque (LAP), Non-calcific plaque (NCP) and Calcific Plaque (CP). Aggregated Plaque Burden (APB) was calculated. Univariate and multivariate analysis were performed to assess the association between these CT-derived parameters and invasive FFR. ResultsThere were 145 patients included in this study. 84.8 % of patients were referred with stable angina. There was a significant linear association between APB and FFR in both univariate and multivariate analysis (Adjusted R-squared = 0.0469; p = 0.035). Mean Agatston scores are higher in FFR positive vessels compared to FFR negative vessels (371.6 (±443.8) vs 251.9 (±283.5, p = 0.0493). ConclusionCTCA-derived APB is a reliable predictor of ischemia assessed using invasive FFR and may aid clinicians in rationalizing invasive vs non-invasive management strategies. Vessel-specific Agatston scores are significantly higher in FFR-positive vessels than in FFR-negative vessels. Associations between HU-derived plaque subtype and invasive FFR were inconclusive in this study.

Diagnostic evaluation of PanBio, and standard Q COVID-19 rapid antigen tests for the detection of SARS-CoV-2: a cross-sectional study from Nepal

Introduction: The diagnosis of COVID-19 infection was time-consuming and costly, contributing to rampant transmission, particularly in developing countries like Nepal. This study aimed to compare the diagnostic performance of two rapid antigen diagnostic tests (RDTs, PanBio and Standard Q) against real-time reverse transcriptase PCR (rRT-PCR). Methods: This retrospective cross-sectional study was conducted among 1171 suspected COVID-19 patients at a provincial hospital in Nepal. Each participant provided two nasopharyngeal swabs, one for RDT and the other for rRT-PCR, spanning a total duration of four months. Sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of each RDT, as well as the combined antigen-RDT, were determined in reference to the rRT-PCR status. Results: The sensitivity and specificity of PanBio were 60.87% (95% CI: 55.84–65.74) and 98.43% (95% CI: 96.80–99.37), respectively, while that of Standard Q was 59.83% (95% CI: 53.16–66.23) and 96.15% (95% CI: 90.44–98.94), respectively. Positive and negative predictive values of PanBio were 97.14 and 74.20%, respectively, and that of Standard Q were 97.16 and 52.08%. The positive likelihood ratio was higher for PanBio (38.87, 95% CI: 18.56–81.41) than for Standard Q (15.55, 95% CI: 5.92–40.90). Meanwhile, the negative likelihood ratio was more than 0.40 for both RDTs. The accuracy for PanBio, Standard Q, and combined RDTs were 80.91% (95% CI: 78.08–83.52), 71.17% (95% CI: 65.98–75.98), and 78.14% (95% CI: 75.66–80.48), respectively. Conclusion: RDTs exhibited unsatisfactory sensitivity and positive predictive value, rendering them ineffective as a screening tool. Nonetheless, they demonstrated excellent specificity and negative predictive value. Hence, a negative test result almost entirely excludes the possibility of infection.

Angiography-Derived Index of Microcirculatory Resistance to Define the Risk of Early Discharge in STEMI.

Patients with ST-segment-elevation myocardial infarction but no coronary microvascular injury are at low risk of early cardiovascular complications (ECC). We aim to assess whether nonhyperemic angiography-derived index of microcirculatory resistance (NH-IMRangio) could be a user-friendly tool to identify patients at low risk of ECC, potentially candidates for expedited care pathway and early hospital discharge. Retrospective analysis of 2 independent, international, prospective, observational cohorts included 568 patients with ST-segment-elevation myocardial infarction. NH-IMRangio was calculated based on standard coronary angiographic views with 3-dimensional-modeling and computational analysis of the coronary flow. Overall, ECC (a composite of cardiovascular death, cardiogenic shock, acute heart failure, life-threatening arrhythmias, resuscitated cardiac arrest, left ventricular thrombus, post-ST-segment-elevation myocardial infarction mechanical complications, and rehospitalization for acute heart failure or acute myocardial infarction at 30 days follow-up), occurred in 54 (9.3%) patients. NH-IMRangio was significantly correlated with pressure/thermodilution-based index of microcirculatory resistance (r=0.607; P<0.0001) and demonstrated good accuracy in predicting ECC (area under the curve, 0.766 [95% CI, 0.706-0.827]; P<0.0001). Importantly, ECC occurred more frequently in patients with NH-IMRangio ≥40 units (18.1% versus 1.4%; P<0.0001). At multivariable analysis, NH-IMRangio provided incremental prognostic value to conventional clinical, angiographic, and echocardiographic features (adjusted-odds ratio, 14.861 [95% CI, 5.177-42.661]; P<0.0001). NH-IMRangio<40 units showed an excellent negative predictive value (98.6%) in ruling out ECC. Discharging patients with NH-IMRangio<40 units at 48 hours after admission would reduce the total in-hospital stay by 943 days (median 2 [1-4] days per patient). NH-IMRangio is a valuable risk-stratification tool in patients with ST-segment-elevation myocardial infarction. NH-IMRangio guided strategies to early discharge may contribute to safely shorten hospital stay, optimizing resources utilization.

FDG PET/CT may replace bone marrow biopsy for the evaluation of bone marrow involvement in selected mature T- and natural killer-cell lymphomas: A meta-analysis

PurposeTo systematically determine the role of FDG PET/CT for the diagnosis of bone marrow involvement in mature T- and natural killer (NK)-cell lymphomas. MethodsThe PubMed, Embase and Cochrane Library databases were searched to identify eligible studies. Data extraction and quality assessment were independently conducted. Then, pooled diagnostic performance with the 95 % confidence interval (CI) was calculated and further analyzed based on different interpretation criteria, tumor type and stage. ResultsFifteen studies were eventually included for quantitative analysis. Overall, the methodological quality of included studies was acceptable. For detecting bone marrow involvement, FDG PET/CT achieved a poor sensitivity of 0.62 (95 % CI, 0.48–0.71) and a reasonable specificity of 0.92 (95 % CI, 0.87–0.96). Similar performance was observed for the specific type of extranodal NK/T‐cell lymphoma (ENKTCL). In early-stage patients revealed by PET/CT, extremely small proportion (2/777) showed positive bone marrow biopsy, especially for the specific type of ENKTCL, whereas in advanced-stage patients, the specificity of FDG PET/CT dropped to 0.77 (95 % CI, 0.72–0.82). Regarding the interpretation, both diffuse and focal increased uptake patterns as positivity may result in increased sensitivity but decreased specificity compared with focal pattern alone as positivity. ConclusionsFDG PET/CT demonstrated excellent negative predictive value for detecting marrow involvement in early-stage patients with mature T- and NK-cell lymphomas, especially the ENKTCL. Conversely, FDG PET/CT showed poor performance for the diagnosis of bone marrow involvement in advanced-stage patients.

Atypical glandular cells in Pap tests: cytology-histology correlation and risk assessment with human papillopmavirus (HPV) testing

Atypical glandular cells (AGC) represent less than 1% of Pap test cases and include a variety of lesions in both the cervix and endometrium. The study aimed to investigate the cytology-histology correlation in AGC patients and to evaluate the clinical utility of hrHPV testing in this diagnostic context. We identified 491 atypical glandular cells (AGC) cases in our quality analysis (QA) database of 336,064 Pap tests interpreted between March 1, 2013 and July 12, 2016. Of these, 251 cases had follow-up biopsies with hrHPV tests in 148 cases. The most common histologic diagnosis associated with AGC was normal/benign or low-grade lesions, comprising 55% of cervical biopsies and 24% of endometrial biopsies. High-grade lesions were identified in 21% of follow-up biopsies. In patients with AGC cytology, a positive hrHPV test significantly increased the likelihood of cervical HSIL or above lesions on biopsy by 26.4 times (OR = 26.4, 95% CI: 5.8-119.4, P < 0.0001). A positive genotyping result for HPV 16 dramatically increased the likelihood of cervical HSIL or above lesions on biopsy (OR = 84, 95% CI: 12.0-590.5, P < 0.0001). The HPV test had a negative predictive value of 97% (CI: 85%-100%). Our study confirms that AGC is a significant diagnosis with an overall risk for high-grade cervical or endometrial lesions as high as 21%. hrHPV testing with genotyping is an effective tool for identifying high-risk individuals within the AGC population, with excellent positive and negative predictive values. This approach is valuable for clinical risk stratification and differential diagnosis in patients with AGC cytology.

Validation of Temperature Sensors to Monitor Thermoplastic Splint Wear in Hand Surgery Patients.

The aim of this study was to validate the use of temperature sensors to accurately measure thermoplastic volar forearm splint wear in a healthy cohort of volunteers using 5- and 15-minute temperature measurement intervals. A prospective diagnostic study was performed to evaluate the diagnostic accuracy of temperature sensors in monitoring splint wear in 8 healthy volunteers between December 2022 and June 2023. Temperature sensors were molded into thermoplastic volar forearm splints. Volunteers who were familiar with the study aims were asked to keep an exact log of the time spent wearing the splint ("actual wear time"). Sensors recorded temperatures every 5 or 15 minutes, and separate algorithms were developed to determine the sensor-detected wear time compared with the actual wear time as the gold standard. The algorithms were then externally validated with the total population. The 5-minute and 15-minute algorithms demonstrated excellent sensitivity (99.1% vs 96.6%), specificity (99.9% vs 99.9%), positive (99.4% vs 99.5%) and negative (99.9% vs 99.3%) predictive value, and diagnostic accuracy (99.8% vs 99.3%), respectively. The 5-minute algorithm recorded 99.5% of the total splint hours, whereas the 15-minute algorithm recorded 96.1%. There was no significant difference between the actual time per wear session (5.4 ± 2.7 hours) and the time estimated by the 5-minute algorithm (5.4 ± 2.6 hours; P = .40), but there was a significant difference for the 15-minute algorithm (5.2 ± 2.6 hours; P < .001). Temperature sensors can be used to accurately monitor thermoplastic volar forearm splint wear. Diagnostic II.

A cross-sectional analysis of syncytiotrophoblast membrane extracellular vesicles-derived transcriptomic biomarkers in early-onset preeclampsia.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder affecting 2%-8% of pregnancies worldwide. Biomarker(s) for the disorder exists, but while these have excellent negative predictive value, their positive predictive value is poor. Extracellular vesicles released by the placenta into the maternal circulation, syncytiotrophoblast membrane extracellular vesicles (STB-EVs), have been identified as being involved in PE with the potential to act as liquid biopsies. The objective of this study was to identify the difference in the transcriptome of placenta and STB-EVs between preeclampsia and normal pregnancy (NP) and mechanistic pathways. We performed RNA-sequencing on placental tissue, medium/large and small STB-EVs from PE (n = 6) and NP (n = 6), followed by bioinformatic analysis to identify targets that could be used in the future for EV-based diagnostic tests for preeclampsia. Some of the identified biomarkers were validated with real-time polymerase chain reactions. Our analysis identified a difference in the transcriptomic STB-EV cargo between PE and NP. We then identified and verified the differential expression of FLNB, COL17A1, SLC45A4, LEP, HTRA4, PAPP-A2, EBI3, HSD17B1, FSTL3, INHBA, SIGLEC6, and CGB3. Our analysis also identified interesting mechanistic processes via an in silico prediction of STB-EV-based mechanistic pathways. In this study, using comprehensive profiling of differentially expressed/carried genes of three linked sample subtypes in PE, we identified potential biomarkers and mechanistic gene pathways that may be important in the pathophysiology of PE and could be further explored in future studies.

The added value of abnormal regional myocardial function for risk prediction in arrhythmogenic right ventricular cardiomyopathy

Abstract Background &amp; aims A risk calculator for individualized prediction of first-time sustained ventricular arrhythmia (VA) in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients has recently been developed and validated. This study aimed to investigate whether regional functional abnormalities, measured by echocardiographic deformation imaging, can provide additional prognostic value. Methods &amp; results From two referral centres, 150 consecutive patients with a definite ARVC diagnosis, no prior sustained VA and an echocardiogram suitable for deformation analysis were included (aged 41 ± 17 years, 50% female). During a median follow-up of 6.3 (IQR 3.1-9.8) years, 37 (25%) experienced a first-time sustained VA. All tested left and right ventricular (LV, RV) deformation parameters were univariate predictors for first-time VA. While LV function did not add predictive value in multivariate analysis, two RV deformation parameters did; RV free wall longitudinal strain and regional RV deformation patterns remained independent predictors after adjusting for the calculator-predicted risk (HR 1.07 [1.02-1.11]; p = 0.004 and 4.45 [1.07-18.57]; p = 0.040, respectively) and improved its discriminative value (from C-statistic 0.78 to 0.82 in both. Akaike information criterion change &amp;gt;2). Importantly, all patients who experienced VA within 5 years from the echocardiographic assessment had abnormal regional RV deformation patterns at baseline. Conclusions This study showed that regional functional abnormalities measured by echocardiographic deformation imaging can further refine personalized arrhythmic risk prediction when added to the ARVC risk calculator. The excellent negative predictive value of normal RV deformation could support a watchful waiting strategy regarding ICD implantation in intermediate risk patients.Added value of functional abnormalities