A public, cross-reactive glycoprotein epitope confounds Ebola virus serology.

Ebola disease (EBOD) in humans is a severe disease caused by at least four related viruses in the genus Orthoebolavirus, most often by the eponymous Ebola virus. Due to human-to-human transmission and incomplete success in treating cases despite promising therapeutic development, EBOD is a high priority in public health research. Yet despite almost 50 years since EBOD was first described, the sources of these viruses remain undefined and much remains to be understood about the disease epidemiology and virus emergence and spread. One important approach to improve our understanding is detection of antibodies that can reveal past human infections. However, serosurveys routinely describe seroprevalences that imply infection rates much higher than those clinically observed. Proposed hypotheses to explain this difference include existence of common but less pathogenic strains or relatives of these viruses, misidentification of EBOD as something else, and a higher proportion of subclinical infections than currently appreciated. The work presented here maps B-cell epitopes in the spike protein of Ebola virus and describes a single epitope that is cross-reactive with an antigen seemingly unrelated to orthoebolaviruses. Antibodies against this epitope appear to explain most of the unexpected reactivity towards the spike, arguing against common but unidentified infections in the population. Importantly, antibodies of cross-reactive donors from within and outside the known EBOD geographic range bound the same epitope. In light of this finding, it is plausible that epitope mapping enables broadly applicable specificity improvements in the field of serology.

DeepResBat: Deep residual batch harmonization accounting for covariate distribution differences.

Pooling MRI data from multiple datasets requires harmonization to reduce undesired inter-site variabilities, while preserving effects of biological variables (or covariates). The popular harmonization approach ComBat uses a mixed effect regression framework that explicitly accounts for covariate distribution differences across datasets. There is also significant interest in developing harmonization approaches based on deep neural networks (DNNs), such as conditional variational autoencoder (cVAE). However, current DNN approaches do not explicitly account for covariate distribution differences across datasets. Here, we provide mathematical results, suggesting that not accounting for covariates can lead to suboptimal harmonization. We propose two DNN-based covariate-aware harmonization approaches: covariate VAE (coVAE) and DeepResBat. The coVAE approach is a natural extension of cVAE by concatenating covariates and site information with site- and covariate-invariant latent representations. DeepResBat adopts a residual framework inspired by ComBat. DeepResBat first removes the effects of covariates with nonlinear regression trees, followed by eliminating site differences with cVAE. Finally, covariate effects are added back to the harmonized residuals. Using three datasets from three continents with a total of 2787 participants and 10,085 anatomical T1 scans, we find that DeepResBat and coVAE outperformed ComBat, CovBat and cVAE in terms of removing dataset differences, while enhancing biological effects of interest. However, coVAE hallucinates spurious associations between anatomical MRI and covariates even when no association exists. Future studies proposing DNN-based harmonization approaches should be aware of this false positive pitfall. Overall, our results suggest that DeepResBat is an effective deep learning alternative to ComBat. Code for DeepResBat can be found here: https://github.com/ThomasYeoLab/CBIG/tree/master/stable_projects/harmonization/An2024_DeepResBat.

Exploring strategies to rapidly identify false positives in high-sensitivity cardiac troponin I assay: A prospective study.

BACKGROUND: Cardiac troponin is the pivotal biomarker of myocardial injury, playing a central role in the diagnosis of acute coronary syndrome and various clinical situations. Nevertheless, challenges arise when patients exhibit elevated cardiac troponin levels in the absence of evident cardiac origin, as evidenced by extensive cardiac exploration, which suggests the presence of an interfering factor. Despite the high performance of high-sensitive cardiac troponin immunoassays, these tests remain susceptible to interferences that may lead to false-positives. METHODS: In the period between July 2021 and July 2024, 8129 patients were hospitalized in the cardiology departments of Bordeaux University Hospital with positive results for high-sensitivity cardiac troponin I. Among them, 15 patients were suspected of having false-positive results, based on clinical and biological observations. RESULTS: In this subpopulation, we evaluated prospectively various techniques, including serial dilutions, antibody-binding tubes, and alternative immunoassays (for cardiac troponin I and T) with the objective of identifying any potential analytical interference in their high-sensitive cardiac troponin I measurements. Our investigations revealed that 12 out of 15 suspected cases exhibited an interference on the high-sensitive cardiac troponin I assay. CONCLUSION: In conclusion, we propose an original algorithm designed to identify high-sensitive cardiac troponin I false-positives. This algorithm can help clinicians to make prompt and informed decisions about patient care, and to avoid erroneous clinical interventions that may result from such interferences.

Pitfalls in Photochemical and Photoelectrochemical Reduction of CO2 to Energy Products.

The photochemical and photoelectrochemical reduction of CO2 is a promising approach for converting carbon dioxide into valuable chemicals (materials) and fuels. A key issue is ensuring the accuracy of experimental results in CO2 reduction reactions (CO2RRs) because of potential sources of false positives. This paper reports the results of investigations on various factors that may contribute to erroneous attribution of reduced-carbon species, including degradation of carbon species contained in photocatalysts, residual contaminants from synthetic procedures, laboratory glassware, environmental exposure, and the operator. The importance of rigorous experimental protocols, including the use of labeled 13CO2 and blank tests, to identify true CO2 reduction products (CO2RPs) accurately is highlighted. Our experimental data (eventually complemented with or compared to literature data) underline the possible sources of errors and, whenever possible, quantify the false positives with respect to the effective conversion of CO2 in clean conditions. This paper clarifies that the incidence of false positives is higher in the preliminary phase of photo-material development when CO2RPs are in the range of a few 10s of µg gcat-1 h-1, reducing its importance when significant conversions of CO2 are performed reaching 10s of mol gcat-1 h-1. This paper suggests procedures for improving the reliability and reproducibility of CO2RR experiments, thus validating such technologies.

False-positive Serum Antiglomerular Basement Membrane Antibody due to Bovine Serum Albumin-containing Surgical Adhesive: A Case Report.

Antiglomerular basement membrane (GBM) disease has a poor prognosis. The rapid detection of serum anti-GBM antibody using an enzyme immunoassay, which has a high sensitivity and specificity, leads to an early diagnosis and improved prognosis. We report a case of acute kidney injury with false-positive anti-GBM antibody. A man in his early fifties underwent aortic arch replacement using bovine serum albumin (BSA)-containing surgical adhesion. After intravenous administration of vancomycin for a fever, he developed acute kidney injury without an abnormal urinalysis, and his anti-GBM antibody titer (fluorescence enzyme immunoassay [FEIA]) was 70.4 IU/mL. A kidney biopsy showed acute tubular injury and minor glomerular abnormalities without immunoglobulin G deposits, suggesting no evidence of anti-GBM glomerulonephritis. Consistent with the false-positive anti-GBM antibody test results, anti-GBM antibody determined using a chemiluminescent enzyme immunoassay was negative. A serum sample showed crossbinding to the FEIA plate from which the GBM antigen was removed. This finding indicated a nonspecific reaction to BSA, which contains a coating solution for the FEIA plate. This reaction was likely caused by anti-BSA antibody produced using BSA-containing surgical adhesion. Our findings suggest emerging challenges in diagnosing anti-GBM disease. Nephrologists must remain vigilant regarding false-positive anti-GBM antibody test results, particularly in cases evaluated with immunoassays that contain BSA.

Revisiting ALK (D5F3) immunohistochemistry: Insights into focal staining and neuroendocrine differentiation.

BACKGROUND: Screening for anaplastic lymphoma kinase (ALK) rearranged non-small cell lung cancer (NSCLC) is crucial for identifying patients eligible for targeted therapy. The FDA-approved ALK (D5F3) immunohistochemistry (IHC) assay, used with the OptiView Amplification Kit, demonstrates excellent sensitivity and specificity in detecting these patients. However, the clinical significance of resulting focal positivity remains unclear, and ALK (D5F3) expression unrelated to ALK fusion is observed in some cases of neuroendocrine differentiation. This study aims to validate these findings with molecular testing and contribute to the accurate interpretation of ALK (D5F3) IHC results. METHODS: A total of 1619 patients diagnosed with NSCLC and neuroendocrine carcinoma were evaluated using ALK (D5F3) IHC. For cases with strong but focal expression and those with diffuse strong positivity in neuroendocrine differentiation, ALK fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) tests were performed. RESULTS: Seven out of 1109 adenocarcinomas (0.6%) and six out of 289 squamous cell carcinomas (2.1%) exhibited strong focal ALK (D5F3) expression. Nine out of 209 neuroendocrine carcinomas (4.3%) showed homogeneously strong ALK (D5F3) expression. All these cases, including adenocarcinoma with neuroendocrine differentiation and combined small cell carcinoma, were negative for ALK fusions by FISH and/or NGS. CONCLUSION: This study demonstrates that strong but focal ALK (D5F3) immunostaining and strong expression in neuroendocrine differentiation may not indicate ALK fusion. By considering these findings, we can improve the accuracy of patient selection for targeted therapy by minimizing false-positive interpretations of ALK (D5F3) staining.

Delusory Radioiodine Uptake in Endometriotic Ovarian Cyst.

A 25-year-old woman with a known case of papillary thyroid carcinoma conventional type referred to our center for treatment with radioactive iodine after total thyroidectomy. She received 200 mCi of radioiodine, and in the whole-body scan 1 week after the radioiodine therapy, an area of increased absorption was seen on the right side of the pelvis, which was diagnosed as an endometriotic ovarian cyst in the follow-up examinations.

Use of a synthetic oligonucleotide to detect false positives caused by cross-contamination in nested PCR.

Nested PCR is a useful tool for identifying low-abundance target sequences of pathogens and avoiding false negatives. However, it carries an increased risk of cross-contamination, especially with its positive control. Here, we propose using customized synthetic oligonucleotides to detect false positives due to cross-contamination.

Aortic isthmus flow reversal in fetal coarctation of the aorta and the associated factors.

INTRODUCTION: The aim of this study was to investigate the presence of aortic isthmus flow reversal and its associated factors in fetuses with positive and false-positive coarctation of the aorta (CoA) compared with normal controls. MATERIAL AND METHODS: Pregnant women with fetuses suspected of CoA and normal control were enrolled, and these women experienced prenatal ultrasound scan and followed up for 6 months after birth to confirm the presence of CoA. All the ultrasound parameters were analyzed. RESULTS: A total of 134 pregnant women were enrolled, with 43 CoA-positive fetuses and 91 CoA false-positive fetuses, and 334 matched pregnant women were enrolled in the control group. Aortic isthmus flow reversal occurred in 28 (65.1%) fetuses in the CoA-positive group, significantly (p < 0.05) more than in the false-positive (37 or 40.7%) or control group (64 or 19.2%). Aortic isthmus flow reversal was mostly in the full systole (n = 17 or 60.7%) or late systole and early-middle diastole (n = 10 or 35.7%) in the CoA-positive fetuses (n = 27 or 96.4%), significantly (p < 0.001) different from that in the false-positive or control group. The aortic isthmus flow reversal peak systolic velocity (PSV), flow volume, and ratio of reversed flow/forward flow were significantly (p < 0.05) increased in the CoA-positive and false-positive groups than in the control group. The aortic isthmus flow reversal incidence was significantly (p < 0.05) correlated with the middle cerebral artery (MCA) PSV in the total three groups or in the false-positive group but was significantly (p < 0001) negatively correlated with the MCA resistance index (RI) in the CoA-positive group. The incidence of the aortic isthmus flow reversal was significantly (p < 0.05) positively correlated with the umbilical artery (UA) RI in the false-positive group and with the UA RI in the total three groups. Independently associated factors for aortic isthmus flow reversal were isthmic flow volume/CCO (combined cardiac output) in the CoA-positive group. CONCLUSIONS: Reversal of flow in the aortic isthmus is much more common in true-positive cases of CoA as compared to controls, and isthmic flow reversal in the full systolic phase only suggests presence of CoA. The aortic isthmic reversed flow volume accounts for over half of the isthmic forward flow volume in the CoA-positive fetuses than in the normal controls.

The significance of low titer serum cryptococcal antigen testing from 2017 to 2023 performed in a tertiary care center.

Several false positive low serum cryptococcal antigen (SCrAg) reports by lateral flow assay (LFA) were identified in late 2016 at our tertiary care hospital. After the recall and correction of the problem in the reagent, we studied the significance of SCrAg LFA ≤ 1:10 from January 2017 to October 2023. Of 20 patients with 31 samples of SCrAg LFA ≤ 1:10, 14 patients (70%) were classified as true positives, four (20%) were indeterminate, and only two (10%) patients were false positives. If a new SCrAg LFA ≤ 1:10 is detected, it should be repeated, and additional workup should be pursued.

We studied the significance of low serum cryptococcal antigen (SCrAg) titer lateral flow assay (LFA) ≤ 1:10 from January 2017 to October 2023. Of 20 patients with SCrAg LFA ≤ 1:10, only two patients (10%) were false positives. If a new SCrAg ≤ 1:10 is detected, it should be repeated, and additional workup should be done.

Ultrasensitive Analysis of Escherichia coli O157:H7 Based on Immunomagnetic Separation and Labeled Surface-Enhanced Raman Scattering with Minimized False Positive Identifications.

It is a big challenge to monitor pathogens in food with high selectivity. In this study, we reported an ultrasensitive method for Escherichia coli O157:H7 detection based on immunomagnetic separation and labeled surface-enhanced Raman scattering (SERS). The bacterium was identified by heterogeneous recognition elements, monoclonal antibody (mAb), and aptamer. E. coli O157:H7 was separated and enriched by magnetic nanoparticles modified by mAb, and then a plasmonic nanostructure functionalized by aptamers with embedded Raman tags and interior gaps was utilized for further discrimination and detection. The selectivity was enhanced by two binding sites. The higher Raman enhancement was obtained by strong local electromagnetic field oscillation in the gap and the firm embedment of 4-mercaptopyridine (4-Mpy). Optimum experiments created that SERS signals of 4-Mpy at 1010 cm-1 had a good linearity with E. coli O157:H7 at a large range of 10 to 107 CFU/mL with a limit of detection of 2 CFU/mL. This method has great potential for on-site food pathogenic bacterial detection.

Low Diagnostic Accuracy of Transthoracic Ultrasound for the Assessment of Spontaneous Pneumothorax in the Emergency Setting: A Multicentric Study.

Background: Pneumothorax (PNX) represents a common clinical condition in emergency departments (EDs), requiring prompt recognition and treatment. The role of transthoracic ultrasounds (TUSs) in the diagnosis of PNX is still debated. We aimed to prospectively evaluate the accuracy of TUSs in the detection of spontaneous PNX in EDs. Methods: A total of 637 consecutive adult patients who presented to the EDs of four Italian hospitals complaining of acutely onset chest pain and dyspnoea were included in the study. Exclusion criteria were previous traumatic events, cardiogenic causes of pain/dyspnoea and suspected tension PNX. The absence of "lung sliding" (B-mode) and the "bar-code" sign (M-mode) were considered indicative of PNX in a TUS. Accuracy, sensitivity, specificity, and positive and negative predictive values (PPVs, NPVs) were calculated using a chest CT scan as reference. Results: Spontaneous PNX occurred in 93 patients: of those, 83 (89.2%) were correctly identified by TUSs. However, 306 patients with suspected PNX at TUS were not confirmed by chest CTs. The diagnostic accuracy of both the absence of "lung sliding" and "bar-code" sign during TUS was 50.4% (95% CI: 46.4-54.3), sensitivity was 89.2% (95% CI: 81.1-94.7), specificity was 43.8% (95% CI: 39.5-48.0), the PPV was 21.3% (95% CI: 19.7-23.1) and the NPV was 96.0% (95% CI: 92.9-97.7). Conclusions: TUS showed high sensitivity but low specificity in the identification of PNX in EDs. Relying exclusively on TUSs results for patients' management in ED settings is neither suitable nor recommendable. TUS examination can be useful to strengthen the clinical suspicion of PNX, but its results should be confirmed by a chest X-ray or CT scan.

Diagnostic challenges from conflicting results of tests and imaging.

Accurate diagnosis is the foundation of clinical care but accurate diagnosis is not easily reached in some cases. In rare instances, even a sophisticated multidisciplinary team at an academic medical center cannot reliably reach an accurate diagnosis after extensive testing and imaging, and has to wait until histological diagnosis or even autopsy results are available. The underlying reason of challenging diagnoses is mostly conflicting data from history, tests, and imaging that point to different diagnoses. In this issue of World Journal of Clinical Cases, Huffaker et al reported such a challenging case of a tricuspid mass in a patient with Li-Fraumeni syndrome. The case by Huffaker et al powerfully illustrates the occasional diagnostic challenges inherent in our current diagnostic approach and the current technology. Clinicians should realize that in rare situations, agnosticism in diagnosis is unavoidable but a treatment has to be initiated so long as the principle of primum non nocere is upheld.

Towards automated animal density estimation with acoustic spatial capture-recapture.

Passive acoustic monitoring can be an effective way of monitoring wildlife populations that are acoustically active but difficult to survey visually, but identifying target species calls in recordings is non-trivial. Machine learning (ML) techniques can do detection quickly but may miss calls and produce false positives, i.e., misidentify calls from other sources as being from the target species. While abundance estimation methods can address the former issue effectively, methods to deal with false positives are under-investigated. We propose an acoustic spatial capture-recapture (ASCR) method that deals with false positives by treating species identity as a latent variable. Individual-level outputs from ML techniques are treated as random variables whose distributions depend on the latent identity. This gives rise to a mixture model likelihood that we maximize to estimate call density. We compare our method to existing methods by applying it to an ASCR survey of frogs and simulated acoustic surveys of gibbons based on real gibbon acoustic data. Estimates from our method are closer to ASCR applied to the dataset without false positives than those from a widely used false positive "correction factor" method. Simulations show our method to have bias close to zero and accurate coverage probabilities and to perform substantially better than ASCR without accounting for false positives.

Analytical interference in CA 19-9 immunoassay generates false-positive results in a young woman with a low-grade appendiceal tumor: An educational case report and brief literature review.

CA 19-9 (carbohydrate antigen 19-9) is a tumor marker widely used for the follow-up of patients with pancreatic cancer and other digestive neoplasia. This case report describes a discrepancy between the results of serum CA 19-9 analyses using the Alinity analytical platform (Abbott™) and two other techniques, Kryptor Gold (ThermoFisher Scientific™) and Cobas E411 (Roche™), in the context of a young woman with appendiceal mucocele. In this context, when the serum concentration of CA 19-9 is high, it may raise concerns about potential malignancy or rupture of the mucocele that may lead to tumoral dissemination in the abdominal cavity. In the present case, we observed with Alinity a false elevation in CA 19-9 concentration at 190 kU/L (normal range < 37 kU/L) before appendix resection that continued to increase until reaching 619 kU/L six months after surgery. This situation led to unnecessary additional tests, increased hospitalization time and stress for the patient who also had to interrupt her medically assisted reproduction project. We solved this case using new measurements in CA 19-9 concentration with two other techniques, Kryptor Gold and Cobas E411, and we identified an analytical interference caused by the presence of heterophile antibodies. In all cases, abnormal result initially obtained with Alinity was found below normal range not only with the two other techniques but also with Alinity after a neutralisation step by using Heterophile Blocking Tubes (Scantibodies Laboratory™). Analytical interferences in medical tests can lead to inappropriate medical care. It is an important issue requiring a continuing training of biologists who must be aware of these problems, which are recurring concerns and are not always easy to identify in laboratories of medical biology, in particular when immunoassays are used. This case report also provides an opportunity to do a brief review of the literature and to remind some recommendations and actions to take into consideration in the presence of discrepancies between the clinic and the biology, in particular, one of them is to measure the biological analyte with a different technique. Moreover, the use of Heterophile Blocking Tubes neutralizing specifically the heterophile antibodies may be useful. In all cases, dialogue between clinicians and biologists remains essential.

False Positive for Malaria Rapid Test in a Patient With Cytomegalovirus Infection.

There is a growing development of immunochromatographic tests for the detection of specific Plasmodium spp. antigens. These tests rely on capturing antigens from peripheral blood using monoclonal or polyclonal antibodies against specific targets. We present the case of a 28-year-old male patient with a history of two previous episodes of Plasmodium falciparum malaria, treated appropriately seven months and three years ago. He was referred to our institution with a six-day history of fever, epigastric pain, hematuria, and vomiting. Serial thick and thin blood smears were negative for hemoparasites, but a Bioline™ Malaria Ag P.f/Pan rapid test was positive for the Pan (pLDH) band. Given the clinical context and inability to visualize Plasmodium in blood smears, the positive pLDH band on the rapid malaria test was considered a possible false positive. Subsequent tests concluded that the patient was experiencing a cytomegalovirus (CMV) infection, which improved with supportive management, and he was discharged symptom-free. Malaria remains a major public health issue in tropical and subtropical regions. While rapid diagnostic tests are crucial for timely diagnosis, false positives due to cross-reactivity with other infections and conditions are reported. Our case highlights the potential for cross-reactivity with CMV infections, although direct evidence of active viral replication was not obtained. This phenomenon can lead to the overestimation of malaria cases and inappropriate treatment, underscoring the need for careful interpretation of rapid test results.

Diphenhydramine Intoxication With Blood Extended Half-Life and a False Positive Result for Tricyclic Antidepressants.

Diphenhydramine is a first-generation antihistamine medication. Acute intoxication with diphenhydramine can be severe and potentially fatal. The current case is of a 13-year-old girl who presented with central nervous system depression after voluntary intake of unknown drugs. Serum concentration analysis showed diphenhydramine intoxication, blood half-life extension, and a false positive result for tricyclic antidepressants (TCAs) in urine examination. To our knowledge, this is the first reported case of confirmed diphenhydramine overdose with a false positive result for TCAs and measurement of the serum level in a child. Considering the similarities between the clinical symptoms of diphenhydramine and TCA intoxication, this case illustrates that all physicians should consider the possibility of cross-reactivity during the diagnosis of patients with unknown acute drug intoxication who test positive for TCAs.

Case-control study of the characteristics and risk factors of hot clot artefacts on 18F-FDG PET/CT.

INTRODUCTION: The pulmonary Hot Clot artifact (HCa) on 18F-FDG PET/CT is a poorly understood phenomenon, corresponding to the presence of a focal tracer uptake without anatomical lesion on combined CTscan. The hypothesis proposed in the literature is of microembolic origin. Our objectives were to determine the incidence of HCa, to analyze its characteristics and to identify associated factors. METHODS: All 18F-FDG PET/CT retrieved reports containing the keywords (artifact/vascular adhesion/no morphological abnormality) during the period June 2021-2023 at Brest University Hospital were reviewed for HCa. Each case was associated with 2 control patients (same daily work-list). The anatomical and metabolic characteristics of HCa were analyzed. Factors related to FDG preparation/administration, patient and vascular history were investigated. Case-control differences between variables were tested using Chi-2 test and OR (qualitative) or Student's t-test (quantitative). RESULTS: Of the 22,671 18F-FDG PET/CT performed over 2 years, 211 patients (0.94%) showed HCa. The focus was single in 97.6%, peripheral in 75.3%, and located independently in the right or left lung (51.1% vs. 48.9%). Mean ± SD values for SUVmax, SUVmean, MTV and TLG were 11.3 ± 16.5, 5.1 ± 5.0, 0.3 ± 0.3 ml and 1.5 ± 2.1 g respectively. The presence of vascular adhesion (p < 0.001), patient age (p = 0.002) and proximal venous access (p = 0.001) were statistically associated with the presence of HCa. CONCLUSION: HCa is a real but rare phenomenon (incidence around 1%), mostly unique, intense, small in volume (< 1 ml), and associated with the presence of vascular FDG uptake, confirming the hypothesis of a microembolic origin due to probable vein wall trauma at the injection site.

The self-fulfilling prophecy in medicine.

This article first describes the mechanism of any self-fulfilling prophecy through discussion of its four conditions: credibility, employment, employment sensitivity, and realization. Each condition is illustrated with examples specific to the medical context. The descriptive account ends with the definition of self-fulfilling prophecy and an expansion on collective self-fulfilling prophecies. Second, the normative account then discusses the moral relevance of self-fulfilling prophecies in medicine. A self-fulfilling prophecy is typically considered problematic when the prediction itself changes the predicted outcome to match the prediction (transformative self-fulfillment). I argue that also self-fulfilling prophecies that do not change the outcome but change the ways in which the outcome was realized (operative self-fulfillment), have significant ethical and epistemic ramifications. Because it is difficult to distinguish, retrospectively, between a transformative and an operative self-fulfilling prophecy, and thus between a false or true positive, it becomes equally difficult to catch mistakes. Moreover, since the prediction necessarily turns out true, there is never an error signal warning that a mistake might have been made. On the contrary, accuracy is seen as the standard for quality assurance. As such, self-fulfilling prophecies inhibit our ability to learn, inviting repetition and exacerbation of mistakes. With the rise of automated diagnostic and prognostic procedures and the increased use of machine learning and artificial intelligence for the development of predictive algorithms, attention to self-fulfilling feedback loops is especially warranted. This account of self-fulfilling prophecies is practically relevant for medical research and clinical practice. With it, researchers and practitioners can detect and analyze potential self-fulfilling mechanisms in any medical case and take responsibility for their ethical and epistemic implications.

Assessing the Correlation between Allostatic Load and False-Positive Image-Guided Breast Biopsies.

Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer-Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results.