Diagnostic Work-up Research Articles

Aberrant Cytoplasmic INSM1 Expression in Erythroid Cells: A Potential Diagnostic Pitfall Versus Neuroendocrine Neoplasms.

Insulinoma-associated protein 1 (INSM1) is a relatively new immunostain used in the diagnostic assessment of tumors with neuroendocrine differentiation. While INSM1 positivity has been described in some non-neuroendocrine neoplasms, reactivity in red blood cells (RBCs) has only been anecdotally noted in one prior study without description of the degree/extent of staining. INSM1 staining in nucleated erythroid precursors has not been previously reported. Herein, 100 small biopsy specimens containing RBCs where INSM1 was used for diagnostic workup were reviewed. Additionally, 5 benign bone specimens and 5 adrenal myelolipoma specimens containing nucleated erythroid precursors were stained with INSM1. INSM1 staining intensity (0-3) and staining extent (0-100%) in RBC/erythroid cells was evaluated and an H-score was calculated (0-300). Positive cytoplasmic INSM1 staining in RBCs was observed in 99/100 (99%) specimens, with mean staining intensity of 2.1 (median = 2) and mean staining percent of 59% (median = 70%), with mean H-score of 125 (median = 140). Positive cytoplasmic INSM1 staining was identified in 10/10 (100%) specimens containing nucleated erythroid precursors, with mean staining intensity of 2.7 (median = 3) and mean staining percent of 53% (median = 50%), with mean H-score of 132 (median = 120). INSM1 is frequently positive in RBCs and nucleated erythroid precursors, albeit with variable staining intensity and extent. Although the INSM1 staining is cytoplasmic in RBCs (lacking nuclei) and nucleated erythroid precursors, the morphological features can mimic positive nuclear staining of neuroendocrine neoplasms. Particularly in small biopsy samples, which often contain background RBCs, positive INSM1 staining should be reviewed with caution to avoid misdiagnosis of neuroendocrine differentiation.

Optimizing Prostate Cancer Diagnostic Work-Up Through Micro-Ultrasound: Minimizing Unnecessary Procedures and Reducing Overdiagnoses.

We aim to critically assess Microultrasound (mUS) clinical performance in an outpatient setting, focusing on its ability to reduce unnecessary diagnostic procedures, potentially reshape prostate cancer (PCa) diagnostic protocols, and increase the ability to rule out clinically significant (Gleason Score ≥ 3 + 4) PCa (csPCa). Between November 2018 and April 2022, we conducted a prospective study involving men who underwent mUS examination due to clinical symptoms, PSA elevation, or opportunistic early detection of PCa. Experienced urologists performed mUS assessments in an outpatient setting using the prostate risk identification using micro-ultrasound (PRI-MUS) protocol to identify lesions suspicious of csPCa (PRI-MUS score ≥ 3). Men with negative mUS results were followed through consistent phone follow-up calls and visits until October 2023 to assess their diagnostic and therapeutic pathways. Using Cox regression models adjusted for PSA levels, DRE results, age, and previous biopsy history, we calculated the hazard ratio (HR) for biopsy-free (BFS), defined as the time from mUS to biopsy or last follow-up, cancer-free survival (CFS), and clinically significant cancer-free survival (csCFS) within the cohort based on mUS results. Overall, 425 men were enrolled. The median (IQR) age was 66 (59-72) years, PSA levels were 5.7 (4.0-7.9) ng/mL, prostate volume was 44 (31.5-62.1) mL, and the median follow-up was 39 months (27-53). mUS identified lesions suggesting csPCa in 201/425 (47.3%) men. Overall, mUS resulted negative in 224/425 (52.7%) men, of whom 207/224 (92.4%) did not undergo subsequent mpMRI, while 22/224 (9.8%) proceeded with mpMRI according to the referring physician's decision. The latter detected suspicious lesions in 12/22 cases (54.5%), but only 2/12 (16.7%) were confirmed by biopsy as csPCa. Among those with negative mUS results, 192/224 (85.7%) men avoided additional biopsies during follow-up. Men with negative mUS results exhibited superior BFS (aHR: 0.17; p < 0.001), CFS (aHR:0.12; p < 0.001), and csCFS (aHR:0.09; p < 0.001) survival rates compared to their mUS-positive counterparts. Our findings suggest that mUS can potentially refine patient stratification and transform PCa screening and diagnostic protocols. Pending validation by other studies, a wider implementation of mUS could optimize resource allocation, minimize wastage, and reserve additional costly tests.

Mid-Regional Pro-Adrenomedullin Is Associated with Adverse Cardiovascular Outcomes After Cardiac Surgery

Background: In the era of personalized medicine, tools for risk stratification after cardiovascular interventions are crucial to reduce mortality and morbidity, especially in the aging population. Biomarker-based approaches, in particular, have gained significant importance. Mid-regional pro-adrenomedullin (MR-proADM) represents an easily assessable biomarker that mirrors cardiac function and fibrosis. Therefore, we aimed to investigate the prognostic potential of MR-proADM in patients undergoing elective cardiac surgery. Methods: Patients undergoing elective cardiac bypass and/or valve surgery were prospectively enrolled between May 2013 and August 2018. The primary endpoint was the composite of hospitalization for heart failure (HHF) or cardiovascular (CV) mortality. Results: In total, 500 patients (146 female [29.2%]; median age 69.8 years (IQR 60.6–75.5 years) were included. Individuals were stratified into risk categories based on their MR-proADM values (Low Risk ≤ 0.63 nmol/L, Intermediate Risk &gt; 0.63 and ≤0.84, High Risk &gt; 0.84). A significant increase in 5-year event rates for HHF/CV mortality in patients in the high-risk category (Low Risk 8.6% vs. High Risk 37.7%, p &lt; 0.001) was observed. MR-pro ADM showed an independent association with HHF/ CV mortality (adjusted HR of 3.43, 95% CI 1.83–6.42; p &lt; 0.001 comparing the High-Risk group to the Low-Risk group). Conclusions: MR-pro ADM was found to be a strong and independent predictor for HHF/CV mortality in patients undergoing elective cardiac surgery. Considering a personalized diagnostic and prognostic work-up, a standardized preoperative evaluation of MR-proADM levels might help to identify patients at risk for major adverse events and early re-hospitalization.

FAP-positive activated fibroblasts are detectable in the microenvironment of endometriosis and correlate with stroma composition and infiltrating CD8+ and CD68+ cells

Abstract STUDY QUESTION Do activated fibroblasts expressing fibroblast activation protein-α (FAP)—which is traceable in positron emission topography/computed topography (PET/CT)—play a role in the microenvironment of endometriosis? SUMMARY ANSWER Activated fibroblasts expressing FAP are detectable in endometriotic lesions and correlate with iron and collagen content and infiltrating CD8-positive cytotoxic T cells and CD68-positive macrophages in the microenvironment endometriotic lesions. WHAT IS KNOWN ALREADY FAP-positive activated fibroblasts are found in various fibrosis-related pathologies and in the desmoplastic stroma of solid tumors; they can be traced in PET/CT but have not been investigated in the context of endometriosis, a chronic disease involving hormone-mediated repetitive tissue remodelling and fibrosis. STUDY DESIGN, SIZE, DURATION We analysed a cohort of endometriosis patients (n = 159) who had undergone surgery with removal of endometriotic foci at our University Hospital (tertiary care center) between 2018-2024. All patients provided written informed consent. The median age of the patients was 34 years. In total, 245 samples from different locations were analysed retrospectively. PARTICIPANTS/MATERIALS, SETTING, METHODS We investigated the expression of FAP and its relation to stroma composition and the immune microenvironment of endometriosis in 245 specimens from peritoneal lesions, ovarian endometriomas, deep infiltrating endometriosis and extra-abdominal lesions using conventional histology and immunohistochemistry followed by digital image analysis. Tissue within a radius of 500 µm of ectopic endometrium-like epithelium was analysed. To measure FAP expression in the perilesional stroma, a histoscore (H-score) was calculated. Masson trichrome staining was used to determine collagen content. Prussian blue staining for iron was used for age-dating of lesions. The abundance of CD68-positive macrophages and CD8-positive cytotoxic T cells within the microenvironment of ectopic endometriotic glands was analysed. Extra-lesional tissue served as controls. MAIN RESULTS AND THE ROLE OF CHANCE Distinct FAP expression (H-score &amp;gt; 10) was observed in 84% of endometriotic lesions and in only 4% of extra-lesional controls. FAP expression was significantly higher in endometriotic lesions (mean H-score of 61.8) than in extra-lesional tissue (mean H-score 3.8, p &amp;lt; 0.0001). There was a significant (p &amp;lt; 0.05) association with collagen content when comparing samples with low (H-score &amp;lt; 100) and high (H-score ≥ 100) FAP expression, and a significant difference in FAP expression correlating with the tissue iron content when comparing strong staining intensity and negative samples (p &amp;lt; 0.0005) or samples with weak staining intensity (p &amp;lt; 0.005). Moreover, the abundance of CD8+ and CD68+ cells was significantly higher (p &amp;lt; 0.0001) in samples with high FAP expression (H-score ≥ 100). LARGE SCALE DATA The data underlying this article will be shared upon reasonable request to the corresponding author. LIMITATIONS, REASONS FOR CAUTION This study proves the presence of FAP-positive fibroblasts in endometriosis by immunohistological methods. However, to translate targeting FAP into endometriosis diagnostics, these results have to be compared to imaging data and FAP inhibitor (FAPi) PET/CT has to be validated in a structured way on a large patient cohort. Moreover, we show that FAP expression is intertwined with the immune cell infiltrate in the microenvironment of endometriosis. To explore and to understand mechanisms contributing to chronic inflammation, immune evasion and fibrosis, more studies including more immune cell subtypes and functional experiments, are needed. WIDER IMPLICATIONS OF THE FINDINGS FAP-positive activated fibroblasts not only impact the immune microenvironment of endometriosis and are linked to increased macrophage and cytotoxic T cell infiltration, as we showed, but could also provide new options for non-invasive diagnostic methods and an improvement of the diagnostic workup prior to surgery. FAPi PET/CT should be considered when exploring new diagnostic options in endometriosis. STUDY FUNDING/COMPETING INTEREST(S) This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) “Clinician Scientist Program in Evolutionary Medicine” (project number 413490537 to FK). The authors declare that they have no conflicts of interest.

Bilateral Paraneoplastic Optic Neuropathy as the First Presentation of Pre-Clinical Small Cell Lung Cancer: Case Report

Introduction Paraneoplastic optic neuropathy (PON) is a rare immune-mediated optic neuropathy, secondary to an underlying malignancy. This report describes a rare case of bilateral PON as the initial manifestation in a 77-year-old male, leading to the early detection and treatment of pre-clinical small cell lung cancer (SCLC). Case Presentation The patient initially presented with incidental bilateral disc swelling but was asymptomatic, with preserved visual function. Initial investigations, including orbito-cranial imaging, lumbar puncture, temporal artery ultrasound, and serological testing, were inconclusive. Six weeks later, the patient had persistent disc swelling with compromised bilateral visual function and was commenced on oral steroids. Further diagnostic workup identified paraneoplastic antibodies (anti-CV2/CRMP-5 and anti-Hu) and PET scan findings consistent with a nodular SCLC. Following biopsy confirmation, the patient received carboplatin and etoposide chemotherapy, followed by radiotherapy. Initial oral steroids, prior to cancer treatment, resulted in resolution of optic disc swelling and stabilization of visual function. Conclusion This case underscores the importance of a systematic approach to optic neuropathies where an initial diagnosis is not found, revisiting diagnostic pathways when initial findings remain ambiguous, and consideration of PON as a differential – even in the absence of known malignancy or typical cancer symptoms. Timely recognition allows for early intervention, improving patient outcomes. This report contributes to the limited literature on PON and highlights the role of multidisciplinary care in managing complex cases involving paraneoplastic syndromes.

The Impact of Rapid Molecular Diagnostics for Influenza on Antibiotic Stewardship in the Emergency Department—An Observational Retrospective Study

Objective: The clinical diagnosis of respiratory tract infections (RTIs) may result in unnecessary antibiotic treatment due to clinical exams’ low sensitivity and specificity to differentiate viral from bacterial infections and costly diagnostic work-ups. Unnecessary antibiotic consumption drives antibiotic resistance. We explored whether a rapid influenza-specific polymerase chain reaction (PCR) assay reduced antibiotic use in an emergency room before the COVID-19 pandemic. Methods: We conducted an observational retrospective study of patients with RTI symptoms treated in the ER of the University Hospital Basel from September 2014 to June 2015. We evaluated the impact of rapid diagnostic results, such as an influenza-specific PCR, blood sample results, and radiological imaging, on antibiotic prescription rates. Patient-related confounding factors were included since a patient’s clinical condition affects doctors’ clinical decision-making. Results: We included 607 patients with RTIs, tested with PCR for influenza A or B. Logistic regression showed that the odds ratio (OR) of being treated with antibiotics was significantly reduced by more than two-thirds in patients with a positive influenza PCR result (OR = 0.37; 95% CI, 0.22–0.59; p &lt; 0.001). Increasing C-reactive protein (CRP) levels by tenfold (OR = 5.14; 95% CI, 3.34–8.12; p &lt; 0.001) or suspected chest infection on a radiograph (OR = 5.81; 95% CI, 3.23–10.89; p &lt; 0.001) increased the OR of antibiotic treatment by fivefold. The highest OR for antibiotic prescription was due to increased procalcitonin level by tenfold (OR = 10.13; 95% CI, 4.79–23.4; p &lt; 0.001). Conclusions: Our study provides real-world evidence from a pre-COVID-19 ER setting of diagnostic tools used for RTI evaluation and their impact on antibiotic prescriptions. Rapid influenza-specific PCR results may affect the prescription rate of antibiotics but should be seen as part of a comprehensive diagnostic approach to guide clinical decision-making.

Variant cardiac transthyretin amyloidosis presenting as hypertrophic cardiomyopathy with left ventricular outflow tract obstruction, a case report

Abstract Background Left ventricular outflow tract obstruction (LVOTO) is common in hypertrophic cardiomyopathy (HCM), but has not been reported in hereditary transthyretin amyloidosis (ATTRv). Case summary Here, we describe a 67-year old male patient with a hypertrophic phenotype who was initially diagnosed with LVOTO attributed to HCM. Echocardiographic features included a hyperdynamic left ventricular ejection fraction, severe septal hypertrophy and elongated residual mitral leaflets permitting their systolic anterior motion (SAM). The patient was childless and family history was negative for any cardiovascular disease. Significant coronary artery disease was diagnosed. In cardiac magnet resonance imaging (CMR), the concurrent presence of different late-enhancement patterns initially prevented an unequivocal diagnosis. Due to progressive neuropathy genetic testing for ATTRv was performed and identified a pathogenic variant in the TTR gene. Cardiac involvement was confirmed by amyloid scintigraphy with a Perugini score of 3 and treatment with ribonucleinacid (RNA) silencing therapy was commenced. Discussion The present case illustrates that LVOTO can occur in patients with ATTRv. While cardiac imaging pointed towards sarcomeric HCM, the coexisting red flags initiated re-evaluation of the diagnosis suggesting cardiac amyloidosis as a potential cause. The presence of non-cardiac red flags of ATTR amyloidosis should initiate specific diagnostic work-up even if ATTR is unlikely based on cardiac imaging.

P1022 ChatGPT in the management of Inflammatory Bowel Disease, a future or a present reality?

Abstract Background The management of inflammatory bowel disease (IBD) involves complex clinical scenarios, especially when complications arise. Traditionally guided by clinical expertise and established guidelines, artificial intelligence (AI) is now being explored as an adjunct in medical care. This study assesses ChatGPT’s ability to provide IBD management recommendations in both initial and complex cases. By comparing ChatGPT’s responses to both, real-world decisions and medical treatment in European Crohn’s and Colitis Organisation (ECCO) guidelines, the study aims to evaluate AI’s alignment, reliability, and potential in IBD management. Methods A retrospective analysis was conducted of the electronic medical records of IBD patients in both initial and complicated phases. Management recommendations for 19 cases were generated using ChatGPT-4o and then compared with actual treatments and the ECCO guidelines. A gastroenterologist certified by the Mexican Association of Gastroenterology oversaw evaluations across 7 categories: 5-ASA, steroids, antibiotics, thiopurines, anti-TNF agents, anti-integrins, and anti-IL23. Cohen’s Kappa test was used to assess agreement. Results ChatGPT showed perfect agreement (Kappa = 1.000) with healthcare providers and ECCO guidelines for antibiotics, diagnostic workups, symptom management, surgical consultations, monitoring, and anti-IL-23 recommendations. Substantial agreement (Kappa ~0.6–0.8) was observed for 5-ASA and steroids, with minor variations but overall strong alignment. Moderate to fair agreement (Kappa ~0.3–0.5) was noted for anti-TNF and anti-integrins, reflecting variability in complex cases. For thiopurines, agreement was minimal, suggesting differences due to varying thresholds or interpretations (Figure 1). Conclusion ChatGPT displayed a perfect agreement with providers and guidelines in areas such as antibiotics, diagnostic workups, symptom management, surgical consultations, monitoring, and anti-IL-23 therapies, indicating its potential for standardising IBD care. However, discrepancies arise in complex cases involving anti-TNF and anti-integrins, possibly due to the inclusion of newer treatments not yet covered by ECCO guidelines. This underscores the necessity for AI systems to evolve alongside advancing treatment modalities. Differences in thiopurine recommendations highlight the enduring importance of clinical judgement. Notably, there is currently no standardisation in the management of IBD. This study illustrates ChatGPT’s promise as a decision-support tool for standardising IBD care. Future efforts should focus on validating AI to further apply it as an adjuvant in clinical decision-making and tailoring recommendations to individual patients.

Accuracy of transthoracic echocardiography in diagnosis of cardiac myxoma: single center experience.

The differential diagnosis of cardiac myxomas (CM), the most common benign primary cardiac tumors, is broad and a thorough diagnostic workup is required to establish accurate diagnosis prior to surgical resection. Transthoracic echocardiography (TTE) is usually the first imaging modality used for diagnosis of suspected CM. In a single tertiary centre study, we sought to determine the accuracy, sensitivity, and specificity of TTE in the diagnosis of CM and to determine echocardiographic characteristics indicative of CM. We retrospectively analyzed clinical, echocardiographic, and pathohistological findings of 73 patients consecutively admitted for suspected CM. After diagnostic workup, 53 (73%) patients were treated surgically at our institution. Based on preoperative TTE, patients were divided into a CM group (n=45, 85%) and non-myxoma (NM) group. Of the 53 pathohistological specimens obtained during surgery, 39 (73%) were CM. The sensitivity and specificity of preoperative echocardiography were 97% and 50%, respectively. The overall accuracy was 85%. All NM tumors were found in an atypical location and 72% of CM were found in a typical position in the left atrium (p < 0.001). Tumors in NM group were significantly smaller than CM (24.3 ± 13.2 mm vs. 37.9 ± 18.3 mm, p = 0.017). Our study confirms very good accuracy of TTE in the diagnosis of CM. The most important echocardiographic characteristics to differentiate between CM and tumors of different etiology are tumor location and size. Smaller tumors presenting at an atypical location are less likely to be diagnosed as CM, and these require additional imaging modalities for accurate diagnosis.

Case report: A co-existing case of ulcerative colitis and dysferlinopathy in a male patient

Patients with inflammatory bowel disease (IBD) are at risk of developing malnutrition, severe dystrophic muscle weakness, and muscle atrophy. We present a case of a 33-year-old male patient who exhibited concurrent muscle atrophy, muscle weakness, diarrhea, and mucopurulent bloody stools. Notably, the patient reported that his household or family members experienced similar symptoms of muscle weakness, without any apparent neurological or psychiatric manifestations. The patient’s intestinal symptoms were most consistent with ulcerative colitis, while the muscle weakness originated from dysferlinopathy following a comprehensive diagnostic work-up. The patient was initiated on vedolizumab therapy and L-carnitine therapy, and his symptoms improved after 1 month of follow-up. This case study underscores the necessity for clinicians to maintain a high level of suspicion for the presence of concomitant diseases when encountering IBD patients with muscle weakness. This approach is essential for achieving an early diagnosis and treatment.

An unexpected and tumultuous diagnosis of a left atrial mass.

This case presents a curious diagnosis in a young male presenting with chest pain. The first imaging tests suggested the presence of a hypovascular left atrial tumor. After cardiac magnetic resonance and the exclusion of extra-cardiac lesions, sarcoma emerged as the main diagnostic hypothesis. Unexpectedly, the histopathological study revealed the absence of malignancy, identifiable inflammatory and cardiac muscle tissue, and fibrosis. This pattern was compatible with inflammatory myofibroblastic tumor diagnosis, a rare entity with uncertain behavior but a known risk of recurrence and/or potentially fatal complications. This is a unique case of an unexpected finding at presentation, as well as a complex diagnostic work-up and a surprisingly unusual final diagnosis. It also highlights the increasing importance of the multimodality imaging approach, as well as the critical role of multidisciplinary discussion in optimizing patient management in such complex cases.

Medical Students' Observations of High Value and Potentially Wasteful Care Behaviors Modeled During Clinical Rotations.

Medical student exposure to role-modeling of high-value care (HVC) behaviors may shape professional identity formation and future HVC practices. To investigate the frequency and characteristics of HVC role-modeling witnessed by medical students during core clinical rotations. Cross-sectional survey study. Medical students on clinical rotations at 11 US medical schools. A validated 13-item survey was used to assess medical student perception of cost-conscious role-modeling behaviors or potentially wasteful role-modeling behaviors and modified to include whom demonstrated the behavior (attending vs resident/fellow) and during which clinical rotation the modeling occurred. Cost-conscious role-modeling behaviors were observed by medical students sometimes/often 52.9-70.5% (353/667-452/641) of the time across all clinical rotations, except for praising a student for ordering a cost-effective diagnostic work-up which was seen only 25.7% (143/556) of the time. Potentially wasteful role-modeling behaviors were observed sometimes/often 5-14.3% (26/537-87/609) of the time, except simultaneously ordering numerous tests before seeing results of initial screening tests 45.1% (273/605) and repeating tests rather than attempting to obtain recently performed test results 32.2% (194/602). HVC modeling was most often demonstrated by internal medicine attendings 67.7% (65/96) and least frequently by general surgery attendings 47.3% (17/36). Attendings were overall more likely to model HVC compared to residents/fellows. HVC role-modeling, as observed by medical students, is not consistently demonstrated across clinical rotations. Attendings generally model more HVC than residents and general surgery models less HVC compared to other specialties. Future studies should strive to identify factors which promote or inhibit HVC modeling.

Intense FAP Expression of Ovarian Metastatic Breast Cancer Detected by [68Ga]RTX-1363 PET/CT.

PET/CT targeting fibroblast activation protein α (FAP) in cancer-associated fibroblasts shows promise in theranostics. Here, we report the case of a 31-year-old woman with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer who presented with rising CA15-3 for further diagnostic workup. Whereas [18F]FDG PET/CT was unremarkable, novel [68Ga]RTX-1363 PET/CT revealed intense tracer accumulation in thoracoabdominal lymph nodes and both ovaries. Follow-up imaging confirmed tumor progression, and diagnostic laparoscopy verified metastatic disease in the ovaries with high FAP expression in the tumor stroma. This case underscores the superior sensitivity of [68Ga]RTX-1363 PET/CT over [18F]FDG PET/CT, enhancing breast cancer diagnostic and therapeutic strategies.

Diagnostic Accuracy of Shear Wave Elastography in Predicting Malignant Origins of Pleural Effusions in Emergency Departments.

Objective: Ultrasound is a valuable diagnostic tool in the diagnostic work-up of dyspnea and can identify even small pleural effusions. The incorporation of shear wave elastography (SWE) represents a possible tool in stratifying pleural effusions by the risk of underlying malignancy. No previous studies on ultrasound with the incorporation of SWE have been conducted in an emergency department (ED), where such stratification might have a clinical impact by hastening referrals for the diagnostic work-up of underlying malignancy. The objective of this study was to appraise the diagnostic accuracy of ultrasonographic findings associated with thoracic malignancy as well as to calculate the optimal cutoff values for SWE in this regard. Methods: Patients with a unilateral pleural effusion of unknown origin were included in the ED and subjected to a thoracic ultrasound (TUS) scan during their first 48 h after admittance. Two index tests were applied: (i) traditional B-mode TUS examination registering the presence of diaphragmatic nodules, pleural thickenings and other findings associated with malignancy and (ii) an SWE examination of different regions of interest. The reference test was defined as the subsequent diagnosis of malignant pleural effusion (MPE) in the three months following inclusion. Results: In total, 39 patients were included. The B-mode TUS index test yielded a sensitivity of 28.57% (95%CI 3.67-70.96%) and a specificity of 90.62% (95%CI 74.98-98.02%). The SWE max of the intercostal space yielded a sensitivity of 100% (95%CI 47.82-100%) and a specificity of 59.09% (95%CI 36.35-79.29%). Conclusions: A TUS with integrated SWE may aid in identifying MPEs and improving referrals for the diagnostic work-up of underlying malignancy. Larger, adequately powered studies are warranted.

β-Trace Protein as a Potential Biomarker for CSF-Venous Fistulas.

Accurately identifying patients with CSF-venous fistulas (CVF) causing spontaneous intracranial hypotension, is a diagnostic dilemma. This conundrum underscores the need for a CVF biomarker to help select who should undergo an invasive myelogram for further diagnostic work-up. β-trace protein (BTP) is the most abundant CNS-derived protein in the CSF and, therefore, is a potential venous biomarker for CVF detection. The purpose of our study was to measure venous BTP levels as a potential CVF biomarker. We prospectively enrolled 14 patients with CVFs and measured the BTP in venous blood samples from the paraspinal veins near the CVF and compared those levels with those in the peripheral blood. Myelograms used initially to identify the CVF were evaluated for technique, CVF laterality, CVF level, and the venous drainage pattern. Patient sex and age and symptom duration were also collected. Brain MR images were reviewed for Bern scores. We also measured the peripheral blood BTP levels in 20 healthy controls. In patients with CVF, the mean BTP level near the CVF was 54.5% higher (0.760 [SD, 0.673] mg/L versus 0.492 [SD, 0.095] mg/L; P = .069) compared with peripheral blood. Nine (64.3%) patients with CVFs had a higher paraspinal BTP level than peripheral BTP level. The 20 control patients had a higher mean peripheral BTP level of 0.720 (SD, 0.191) mg/L compared with patients with CVF (P < .001). We found that venous blood at the site of the CVF had higher BTP values compared with peripheral blood in most but not all patients with CVF. This finding may reflect the intermittent leaking nature of CVF. Additionally, we found that patients with CVF had a lower peripheral blood BTP level compared with healthy controls. BTP requires further evaluation as a potential CVF biomarker.

Performance of ChatGPT-4o in the diagnostic workup of fever among returning travelers requiring hospitalization: a validation study.

Febrile illness in returned travelers presents a diagnostic challenge in non-endemic settings. Chat generative pretrained transformer (ChatGPT) has the potential to assist in medical tasks, yet its diagnostic performance in clinical settings has rarely been evaluated. We conducted a preliminary validation assessment of ChatGPT-4o's performance in the workup of fever in returning travelers. We retrieved the medical records of returning travelers hospitalized with fever during 2009-2024. The clinical scenarios of these cases at time of presentation to the emergency department were prompted to ChatGPT-4o, using a detailed uniform format. The model was further prompted with four consistent questions concerning the differential diagnosis and recommended workup. To avoid training, we kept the model blinded to the final diagnosis. Our primary outcome was ChatGPT-4o's success rates in predicting the final diagnosis (gold standard) when requested to specify the top 3 differential diagnoses. Secondary outcomes were success rates when prompted to specify the single most likely diagnosis, and all necessary diagnostics. We also assessed ChatGPT-4o as a predicting tool for malaria and qualitatively evaluated its failures. ChatGPT-4o predicted the final diagnosis in 68% (95% CI 59-77%), 78% (95% CI 69-85%), and 83% (95% CI 74-89%) of the 114 cases, when prompted to specify the most likely diagnosis, top three diagnoses, and all possible diagnoses, respectively. ChatGPT-4o showed a sensitivity of 100% (95% CI 93-100%) and a specificity of 94% (95% CI 85-98%) for predicting malaria. The model failed to provide the final diagnosis in 18% (20/114) of cases, primarily by failing to predict globally endemic infections (16/21, 76%). ChatGPT-4o demonstrated high diagnostic accuracy when prompted with real-life scenarios of febrile returning travelers presenting to the emergency department, especially for malaria. Model training is expected to yield an improved performance and facilitate diagnostic decision-making in the field.

EXPLORING THE UTILITY OF CELLULAR INDICES IN THE DIAGNOSIS OF ULCERATIVE COLITIS.

To describe the usefulness of cellular indices in the diagnosis of ulcerative colitis (UC). Diagnostic study of patients under 15 years of age undergoing colonoscopy ± esophagogastroduodenoscopy for suspected inflammatory bowel disease between 2015-2022 in a pediatric hospital. Patients with normal biopsy and anatomopathological diagnosis of UC were included. Using the area under the ROC curve, the values of platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR), calculated by dividing the number of platelets, neutrophils, and monocytes by the number of lymphocytes, respectively, were compared to establish the sensitivity, specificity, predictive values and Odds Ratio of each parameter in the diagnosis of UC. Twenty-six patients were included: 14 with normal biopsy and 12 with UC. PLR and MLR values were significantly higher in patients with UC (p <0.05). The sensitivity, specificity, and negative predictive value of PLR, NLR and MLR for diagnosing UC were 58%, 83% and 91%; 85%, 35% and 50%; 70%, 71% and 87%, respectively. The biomarker with the highest diagnostic performance was MLR with a cutoff point of 0.235, area under the curve of 0.735 and Odds Ratio of 11 (95%CI 1.1-109.6; p= 0.041). MLR has a high sensitivity, negative predictive value, and Odds Ratio in the pre-endoscopic diagnosis of ulcerative colitis. These findings, although exploratory, suggest that MLR could be useful in clinical practice in the initial diagnostic workup of UC, and perhaps in the future in the prioritization of endoscopic studies according to MLR values.

Ischemia with Non-Obstructive Coronary Arteries (INOCA) in the 2024 European Society of Cardiology (ESC) Guidelines for the management of chronic coronary syndromes.

Chronic coronary syndromes (CCS) occur commonly in the absence of flow-limiting epicardial coronary stenoses. Ischemia or angina with no obstructive coronary arteries (INOCA/ANOCA) may be caused by coronary microvascular disease, coronary artery spasm, myocardial bridging, diffuse atherosclerosis, or a combination of disorders. We highlight the new recommendations in the 2024 European Society of Cardiology (ESC) guidelines on CCS relevant to the diagnosis and management of INOCA/ANOCA. The guidelines place a new emphasis on consideration of INOCA/ANOCA early during cardiovascular risk stratification and the initial diagnostic workup for chest pain. There is a new class I recommendation for the availability of invasive coronary function testing (CFT) at the time of initial coronary angiography, when mechanisms of chest pain are uncertain after non-invasive testing, and in patients with established INOCA/ANOCA who have persistent symptoms and poor quality of life despite medical therapy. Once underlying disorders have been identified based on the results of invasive CFT, the ESC guidelines emphasize a patient-centered, mechanism-based approach to medical treatment of INOCA/ANOCA to improve symptoms and quality of life. The 2024 ESC CCS guidelines provide a new vision for the diagnosis and management of ANOCA/INOCA, with an expanded role for invasive CFT and targeted medical therapy to improve symptoms and quality of life in patients with angina.

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Proteomics accelerates diagnosis and research of muscular diseases by enabling the robust analysis of proteins relevant for the manifestation of neuromuscular diseases in the following aspects: (i) evaluation of the effect of genetic variants on the corresponding protein, (ii) prediction of the underlying genetic defect based on the proteomic signature of muscle biopsies, (iii) analysis of pathophysiologies underlying different entities of muscular diseases, key for the definition of new intervention concepts, and (iv) patient stratification according to biochemical fingerprints as well as (v) monitoring the success of therapeutic interventions. This review presents-also through exemplary case studies-the various advantages of mass proteomics in the investigation of genetic muscle diseases, discusses technical limitations, and provides an outlook on possible future application concepts. Hence, proteomics is an excellent large-scale analytical tool for the diagnostic workup of (hereditary) muscle diseases and warrants systematic profiling of underlying pathophysiological processes. The steady development may allow to overcome existing limitations including a quenched dynamic range and quantification of different protein isoforms. Future directions may include targeted proteomics in diagnostic settings using not only muscle biopsies but also liquid biopsies to address the need for minimally invasive procedures.

Cerebral vasculitis related to neurosarcoidosis: a case series and systematic literature review

Cerebral vasculitis is a rare but severe manifestation of neurosarcoidosis (NS) that has received little attention. The aim of the present study was to characterize clinical and diagnostic features as well as potential treatment strategies of cerebral vasculitis related to NS. We assessed 29 patients with cerebral vasculitis related to NS (15 female, mean age at time of diagnosis 45 years, SD = 11.85) among these were four new cases from our hospital records and 25 previously published cases from a systematic literature review. The demographic, clinical, and diagnostic features of those 29 patients with cerebral vasculitis related to NS were compared with a group of 73 NS patients without vasculitic involvement (37 female, mean age at time of diagnosis 47 years, SD = 14.79). Neurologic deficits and MRI abnormalities were significantly more frequent in cerebral vasculitis related to NS than in NS without vasculitic involvement. Patients with cerebral vasculitis related to NS significantly more often presented with headache, motor symptoms, and cognitive and/or behavioral changes. Non-neurologic manifestations of sarcoidosis did not significantly differ in character or frequency between both groups. Glucocorticoids in combination with methotrexate, cyclophosphamide, or infliximab were the most frequently used treatment strategies in cerebral vasculitis related to NS. Within the complex diagnostic work-up that is required in cerebral vasculitis related to NS sufficient angiographic imaging as digital subtraction angiography or MRI vessel wall imaging and tissue biopsy are of particular significance as they can detect vascular changes caused by inflammatory processes.