Diagnostic Challenge Research Articles

Tree-based classification model for Long-COVID infection prediction with age stratification using data from the national COVID cohort collaborative (N3C)

Abstract Objectives We propose and validate a domain knowledge-driven classification model for diagnosing Post-acute sequelae of SARS-CoV-2 infection (PASC), also known as Long COVID, using Electronic Health Records (EHR) data. Materials and Methods We developed a robust model that incorporates features strongly indicative of PASC or associated with the severity of COVID-19 symptoms as identified in our literature review. The XGBoost tree-based architecture was chosen for its ability to handle class-imbalanced data and its potential for high interpretability. Using the training data provided by the Long COVID Computation Challenge (L3C), which was a sample of the National COVID Collaborative (N3C), our models were fine-tuned and calibrated to optimize Area Under the Receiver Operating Characteristic curve (AUROC) and the F1 score, following best practices for the class-imbalanced N3C data. Results Our age-stratified classification model demonstrated strong performance with an average 5-fold cross-validated AUROC of 0.844 and F1 score of 0.539 across the young adult, mid-aged, and older-aged populations in the training data. In an independent testing dataset, which was made available after the challenge was over, we achieved an overall AUROC score of 0.814 and F1 score of 0.545. Discussion The results demonstrated the utility of knowledge-driven feature engineering in a sparse EHR data and demographic stratification in model development to diagnose a complex and heterogeneously presenting condition like PASC. The model's architecture, mirroring natural clinician decision-making processes, contributed to its robustness and interpretability, which are crucial for clinical translatability. Further, the model’s generalizability was evaluated over a new cross-sectional data as provided in the later stages of the L3C challenge. Conclusion The study proposed and validated the effectiveness of age-stratified, tree-based classification models to diagnose PASC. Our approach highlights the potential of machine learning in addressing the diagnostic challenges posed by the heterogeneity of Long COVID symptoms.

Degree of Airway Obstruction and Contributing Factors, Exploring Potential Mismatches and Pitfalls

BACKGROUND: The study investigates asthma, a chronic inflammatory respiratory condition that poses diagnostic challenges due to its variable symptoms, highlighting the importance of accurate documentation and interpretation. It aims to explore the demographic and clinical profiles of asthma patients, particularly focusing on the relationships among airway obstruction severity, spirometric measurements, atopic history, and family history to reveal the complex factors influencing asthma. AIMS: Employing a retrospective descriptive-analytic design, the research analyzes medical records of 107 patients treated at the Outpatient Installation of the Lung Polyclinic at Wlingi General Hospital in Blitar Regency from 2021 to 2022. The analysis incorporates descriptive statistics for demographic and clinical variables alongside Spearman correlation tests. METHOD: Results indicate a significant prevalence of smoking history among asthma patients, with 22.4% being active smokers and 52.3% passive smokers; however, no significant correlation with asthma control was found. Environmental risk factors such as dust and cold air were common but did not consistently correlate with asthma exacerbations. Spirometric analysis revealed a significant relationship between airway obstruction severity and parameters like FEV1, FVC, FEV1/FVC, PEF, FEF 25, FEF 50, and FEF 75, emphasizing the link between airflow obstruction and reduced lung function. Furthermore, no significant correlation was observed between stable asthma diagnosis and atopic or family history, suggesting that asthma control is influenced by various complex factors. CONCLUSION: Our research reveals critical pitfalls in the current understanding of asthma, advocating for a comprehensive evaluation of all contributing factors to enhance diagnostic accuracy and treatment efficacy. Recognizing these complexities is essential for improving asthma management and ensuring better health outcomes for patients.

Cardiac metastasis from carcinoma gall bladder - a rare case detected on autopsy

Metastasis to the heart is uncommon compared to other organs, posing notable diagnostic challenges. Incidence in autopsy studies typically ranges between 0.7% and 3.5%. Lung, breast, and hematologic cancers are the main sources of such metastases, leading to varied clinical presentations and severe complications. Postmortem viscera from a 47 year old male with a suspected history of jaundice. Only limited information was available. Gross examination showed a solid mass in the gall bladder with areas of hemorrhage and necrosis, while no other abnormalities were observed in other viscera received. Brain examination showed congested blood vessels, while heart sections exhibited atypical cell deposits in the pericardium and myocardium. Coronary arteries displayed pathological thickening. Lung and liver sections also displayed similar metastatic atypical cell deposits, infiltrating tissue and causing necrosis. Gall bladder examination revealed irregular glandular formations lined with polygonal tumor cells positive for cytokeratin. The final diagnosis based on histomorphological features and immunohistochemistry confirmed gall bladder adenocarcinoma metastasising to the heart, liver and lungs.

Diagnostic Approach to Mesenchymal and Spindle Cell Tumors of the Breast

Mesenchymal and spindle cell tumors of the breast represent a broad and heterogeneous group of lesions that may be sampled on core needle biopsy or surgical excision. Mesenchymal lesions unique to the breast are those that derive from the specialized breast myofibroblast, such as mammary myofibroblastoma and pseudoangiomatous stromal hyperplasia. However, any mesenchymal lesion arising in extramammary soft tissue may also arise in the breast, including fibroblastic, peripheral nerve sheath, adipocytic, and vascular lesions. The spindle cell lesions pose the greatest diagnostic challenge, due to the significant radiographic, morphologic, and immunophenotypic overlap within the category of mesenchymal lesions and more broadly with other nonmesenchymal breast lesions. The distinction is particularly challenging on the limited material of breast core needle biopsies, and caution should be taken before definitively classifying a breast spindle cell lesion on core needle biopsy to avoid unnecessary treatment if misdiagnosed. Consideration of a wide differential diagnosis, adequate sampling of a resection specimen, use of a targeted immunopanel, and selective use of molecular assays are essential steps for accurate classification of mesenchymal lesions in the breast. This review covers the clinical, histologic, and immunophenotypic features of mesenchymal tumors of the breast, with a special emphasis on the differential diagnoses unique to the breast and challenges encountered on breast core needle biopsy.

Proximity predicament: a rare case of hydatid cyst in the porta hepatis region

Hydatid cysts near the porta hepatis present notable medical challenges due to their intricate positioning and potential influence on crucial structures within the liver and its vicinity. While relatively rare, their presence can lead to intricate medical scenarios because of their proximity to vital liver and bile duct structures, but their occurrence can present complex medical situations due to their proximity to critical structures in the liver and bile ducts. We present an unusual case of a 33-year-old male with no known comorbidities presented to the outpatient department of general surgery with pain, insidious in onset and gradually progressive, in the right hypochondrial region for the past 3 months, along with mild fever, reduced appetite, and weight loss of 3 kg. Managing hepatic cysts, especially when near the porta hepatis, poses significant diagnostic challenges. Imaging scans revealed multiple hypodense lesions suggestive of hepatic cysts, with the largest one measuring 5 cm × 8 cm in segment VI. Native post-contrast lesions were also observed in the right lower lobe. Although hepatic duct dilation was not observed, the presence of a cyst near the porta hepatis an atypical site for hydatid cyst, complicated potential PAIR procedures (puncture, aspirate, injection, re-aspirate), raising concerns about the risk of damaging vital structures like the hepatic artery or major bile duct. A multidisciplinary approach engaged interventional radiology to evaluate PAIRS feasibility. PAIRS was performed successfully, except for the cyst near the porta hepatis to avoid complications. Despite this, the patient continued to experience abdominal discomfort post-operation, although liver function tests improved in the postop period. This case underscores the uncommon occurrence of hydatid cysts near the porta hepatis and highlights the need for additional research to comprehend its prevalence and causes. Further investigation is crucial to enhance our understanding of the epidemiology and optimal management strategies involving PAIRS in such challenging cases.

Facial cutaneous tuberculosis infected by non-tuberculous mycobacteria

BackgroundCutaneous infections caused by non-tuberculous mycobacteria (NTM) are extremely rare, particularly when they are localized to the facial area. This condition presents significant diagnostic challenges due to its unusual presentation and the need for precise microbiological identification.Case PresentationA two-year-old male patient presented with a progressively enlarging reddish-brown mass on the left side of his face. Despite the absence of systemic symptoms, the lesion’s growth warranted investigation due to its growth. Ultrasonography showed a hypoechoic mass in the dermis, indicating an underlying abscess. The subsequent aspiration resulted in pale yellow pus, which upon testing and culture, confirmed the presence of Mycobacterium avium complex infection, a species of NTM. This case exemplifies the synergy between imaging modalities and microbiological analysis, highlighting the crucial role of both in achieving favorable clinical outcomes in patients with suspected cutaneous NTM infections. Ultrasound can expedite diagnosis, improve treatment planning, and enhance patient care by enabling targeted interventions and monitoring response to therapy in these scenarios. However, it is the combination of pathogen-specific diagnostics that ensures accurate etiological attribution and appropriate antimicrobial stewardship.ConclusionAlthough rare, facial cutaneous infections caused by NTM still deserve thorough investigation to determine the exact cause. Ultrasound is used to identify cutaneous lesions, measure their extent, and guide surgical procedures. The ultimate diagnosis is based on microbiological confirmation.

The Diagnostic Challenge in the Atypical Presentation of a Patient with Neuro-Behçet Disease: A Case Report

The Diagnostic Challenge in the Atypical Presentation of a Patient with Neuro-Behçet Disease: A Case Report

Diagnostic Challenges in Atypical Rasmussen’s Encephalitis (RE) Presenting with Brainstem Involvement

Diagnostic Challenges in Atypical Rasmussen’s Encephalitis (RE) Presenting with Brainstem Involvement

Utility of smart watch in expediting diagnosis of cold drink-triggered atrial fibrillation: a case report

BackgroundPatients presenting to the emergency department with recent palpitations are a diagnostic challenge when the arrhythmia and its symptoms have resolved prior to arrival. Newer smart watch technology, adept at detecting atrial fibrillation, can assist in the diagnostic evaluation of transitory palpitations. We report a case of cold drink-triggered atrial fibrillation whose diagnosis would not have been possible without the assistance of the patient’s smart watch.Case presentationA middle-aged man without cardiac history developed sudden rapid, irregular palpitations with shortness of breath while drinking a glass of cold juice. He activated his smart watch with 1-lead electrocardiography technology which detected rapid atrial fibrillation. He sought medical care, but while waiting, his symptoms—then 90 min in duration—spontaneously resolved. His initial diagnostic evaluation documented only sinus rhythm, as did several follow-up evaluations with cardiology the next several weeks. Had it not been for his smart watch, the etiology of his transitory palpitations would have remained undiagnosed. His physicians encouraged trigger avoidance. In the following months, he avoided rapid ingestion of cold drink, taking instead small sips. The atrial fibrillation has not recurred.ConclusionsThe case illustrates the valuable contribution of smart watch technology in the diagnostic evaluation of patients with short-lived palpitations. The case also educates clinicians about cold drink and food as a trigger of paroxysmal atrial fibrillation. This trigger, like alcohol, can be modified. Cold drink trigger avoidance has been reported by patients to reduce atrial fibrillation recurrence and is a low-risk, cost-effective strategy that is often successful.

Diagnostic Challenges in Nevoid Melanoma: Does Depth Matter?

Diagnostic Challenges in Nevoid Melanoma: Does Depth Matter?

Development of a Machine‐Learning Model for Diagnosis of Pancreatic Cancer from Serum Samples Analyzed by Thermal Liquid Biopsy

Pancreatic ductal adenocarcinoma (PDAC) poses a considerable diagnostic and therapeutic challenge due to the lack of specific biomarkers and late diagnosis. Early detection is crucial for improving prognosis, but current techniques are insufficient. An innovative approach based on differential scanning calorimetry (DSC) of blood serum samples, thermal liquid biopsy (TLB), combined with machine‐learning (ML) analysis, may offer a more efficient method for diagnosing PDAC. Serum samples from a cohort of 212 PDAC patients and 184 healthy controls are studied. DSC thermograms are analyzed using ML models. The generated models are built applying algorithms based on penalized regression, resampling, categorization, cross validation, and variable selection. The ML‐based model demonstrates outstanding ability to discriminate between PDAC patients and control subjects, with a sensitivity of 90% and an area under the ROC receiver operating characteristic curve of 0.83 in the training and test groups. Application of the model to an independent validation cohort of 113 PDAC patients confirms its robustness and utility as a diagnosis tool. The application of ML to serum TLB data emerges as a promising methodology for early diagnosis, representing a significant advance for detecting and managing PDAC, envisaging a minimally invasive and more efficient methodology for identifying biomarkers.

Characterization of neurologic disease-associated Streptococcus suis strains within the United States swine herd and use of diagnostic tools.

Streptococcus suis negatively impacts swine health, posing diagnostic and preventative challenges. S. suis can induce disease and also quietly reside on mucosal surfaces. The limited use of diagnostic tools to identify disease-associated strains and rule out differential diagnoses, alongside the complex ecology of S. suis, poses significant challenges in comprehending this important pathogen and defining pathotypes. This study evaluated 2,379 S. suis central nervous system (CNS) isolates from diagnostic submissions between 2015 and 2019. Isolates originating from submissions with histologic evidence of CNS infection (n = 1,032) were further characterized by standard and advanced diagnostic techniques. We identified 29 S. suis serotypes and 4 reclassified serotypes as putative causes of CNS disease. Among these, serotypes 1 and 7 emerged as the predominant putative causes of CNS infection (32% of submissions). Furthermore, 51 sequence types (STs), of which 15 were novel, were detected with ST1 predominating. Through whole-genome sequencing of 145 isolates, we observed that five commonly used virulence-associated genes (VAGs; epf, mrp, sly, ofs, and srtF) were not present in most disease-associated isolates, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) yielded false-positive results in 7% of isolates. These data indicate that (i) clinical signs and site of isolation alone are insufficient for defining a pathotype, (ii) S. suis serotypes and STs associated with CNS infection are more diverse than previously reported, (iii) MALDI-TOF MS may need to be supplemented with additional diagnostic tools for precise S. suis identification, and (iv) VAGs remain an unreliable means for identifying isolates associated with CNS disease.IMPORTANCEStreptococcus suis is an important and complex systemic bacterial pathogen of swine. Characterization of S. suis strains originating from pigs with histologic confirmation of neurologic disease is limited. Review of swine diagnostic submissions revealed that fewer than half of cases from which S. suis was isolated from the brain had histologic evidence of neurologic disease. This finding demonstrates that clinical signs and site of isolation alone are not sufficient for identifying a neurologic disease-associated strain. Characterization of strains originating from cases with evidence of disease using classic and advanced diagnostic techniques revealed that neurologic disease-associated strains are diverse and commonly lack genes previously associated with virulence.

Narratives of resilience: Understanding Iranian breast cancer survivors through health belief model and stress-coping theory for enhanced interventions

Breast cancer poses a significant global health challenge, with Iran experiencing particularly high incidence and mortality rates. Understanding the adaptation process of Iranian breast cancer survivors’ post-treatment is crucial. This study explores the health perceptions, barriers, and coping mechanisms of Iranian survivors by integrating Stress-Coping Theory (SCT) and the Health Belief Model (HBM). Semi-structured interviews were conducted with 17 survivors, and a grounded theory approach guided the deductive content analysis of the data. The findings reveal key themes, including perceived susceptibility, benefits, barriers to care, cues to action, self-efficacy, and appraisal of action. Perceived susceptibility highlights diagnostic challenges stemming from practitioner errors and symptom misconceptions. Perceived benefits underscore the importance of early detection and support from healthcare providers and families. Barriers include cultural and financial obstacles, while cues to action reflect the influence of media, family, and personal experiences on healthcare-seeking behavior. The study also examines coping strategies, such as problem-focused and emotion-focused approaches, along with family support and external stressors. To address these barriers and enhance support systems, the study suggests specific strategies for healthcare providers, including targeted training to improve diagnostic accuracy and patient communication. Culturally sensitive awareness campaigns can correct symptom misconceptions, while financial counseling can mitigate economic barriers. Establishing community-based support groups and involving family members in care plans can enhance emotional and psychological support. These strategies aim to overcome the identified barriers and improve support systems for Iranian breast cancer survivors, ultimately fostering better recovery outcomes.

Acute mesenteric ischemia secondary to complete AV block and acute systolic heart failure: a case report

BackgroundAcute mesenteric ischemia (AMI) usually presents with abrupt and severe abdominal pain associated with nausea and vomiting. This case is notable due to the occurrence of AMI secondary to acute systolic heart failure caused by new onset complete heart block.Case PresentationA 65-year-old male presented with sudden onset epigastric pain. ECG showed complete AV block and acute ischemia, and a subsequent CTA revealed complete occlusion of the mid superior mesenteric artery. His emergent left heart catheterization showed non-occlusive coronary artery disease. The patient underwent emergent laparotomy and SMA thrombectomy. Postoperative complications included worsening congestive heart failure and persistent bradycardia, requiring a permanent pacemaker. The patient was discharged to a skilled nursing facility in stable condition.ConclusionsThis case highlights the diagnostic challenges of AMI in the setting of acute heart failure and new onset AV block mimicking acute cardiac events and emphasizes the importance of a multidisciplinary approach in managing such complex cases.

Diagnostic Challenge of Lupus with Overlap Syndrome in an Adolescent: A Case Report

Lupus with overlap syndrome is an uncommon autoimmune disease that typically affects teenage females. It can present as various symptoms affecting multiple organs. Delay in the diagnosis of lupus will lead to deleterious effects on the implicated adolescents’ health. The case report aims to describe the diagnostic challenge of a refractory skin disease leading to a delay in diagnosis and highlight its psychosocial impact. Here, we describe a case of a teenager who presented with poorly controlled chronic dermatitis. The chronic dermatitis was refractory to the first-line therapy of topical steroids and emollients. She was finally diagnosed with lupus and overlap syndrome, confirmed by a skin biopsy. In conclusion, any chronic refractory skin diseases warrant further referral and investigation at the tertiary centre. Assessment of psychosocial in managing chronic skin disease in adolescent is essential as it could implicate their mental health further.

Emergence of IGH::CCND1 rearrangement and mutations in TP53, BTK, and BCL2 associated with therapy resistance in chronic lymphocytic leukemia

AbstractChronic lymphocytic leukemia (CLL) is an indolent low‐grade B‐cell neoplasm that generally responds well to treatment. Rarely, CLL cases exhibit an IGH::CCND1 rearrangement, presenting a diagnostic challenge in distinguishing between clonal evolution within CLL and an independent mantle cell lymphoma. We report a case of CLL with the emergence of an IGH::CCND1 rearrangement and mutations associated with treatment resistance, including TP53, BTK, and BCL2, during disease progression. Immunophenotypic, cytogenetic, and molecular analyses support that these alterations are secondary events within the CLL clone. This case demonstrates dynamic clonal selection and expansion in response to treatments, which, in turn, contributes to treatment resistance.

A Literature-Based Study of Tardive Dyskinesia- From Pathogenesis to Treatment

: Tardive dyskinesia (TD) is induced by antipsychotic drugs that have dopamineantagonising properties. It frequently causes physical and mental anguish in individuals, lowering their quality of life. Recent research on the aetiology and pathogenesis of TD indicates that genetic predisposition, treatment options, age, sex, and lifestyle factors are among the key risk factors contributing to the development of TD. Various genetic polymorphisms along with severe oxidative stress and other diseased conditions help to precipitate TD while on antipsychotic medications or other dopamine receptor blockers. Individuals diagnosed with schizophrenia are at a higher likelihood of developing TD. The current piece of literature aims to review the probable underlying mechanisms of TD, explore its pathophysiology, address the diagnostic challenges, and present the available treatment options. This comprehensive analysis draws from a range of published peerreviewed publications, presenting the information in a clear and accessible manner.

Managing macrophage activation syndrome SLE: Clinical and therapeutic insights

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with frequent hematologic complications, including leukopenia, thrombocytopenia, autoimmune hemolytic anemia, and, in rare cases, macrophage activation syndrome (MAS). MAS, a severe hyperinflammatory condition, presents diagnostic challenges due to its overlap with SLE flares, infections, and drug-related adverse effects. This case report presents a 22-year-old female with SLE who experienced clinical deterioration following methotrexate initiation, manifesting as fever, pancytopenia, and transaminitis. Differential diagnoses were considered, including MAS, infection, and methotrexate toxicity. Prompt recognition and management with corticosteroids and immunoglobulins led to clinical improvement, underscoring the complexity of diagnosing and treating MAS in SLE patients.

Return-to-Play Post-Myocarditis for Athletes: To Play or Not to Play?

Myocarditis is a condition marked by inflammation of the heart muscle, which can lead to serious outcomes such as sudden cardiac death (SCD) and life-threatening arrhythmias. While myocarditis can affect any population, athletes, especially those engaged in high-intensity training, are at increased risk due to factors such as reduced immunity and increased exposure to pathogens. This review examines the clinical presentation, current guidelines, diagnostic challenges, and the significance of cardiac magnetic resonance imaging (CMR) in detecting myocardial inflammation and scarring. Current guidelines recommend a period of exercise restriction followed by thorough reassessment before athletes can return-to-play (RTP). However, there are several knowledge gaps, including the implications of persistent late gadolinium enhancement (LGE) on CMR and the optimal duration of exercise restriction. Additionally, the psychological impact of myocarditis on athletes highlights the importance of incorporating mental health support in the recovery process. A shared decision-making approach should be encouraged in RTP, considering the athlete's overall health, personal preferences, and the potential risks of resuming competitive sports. We have proposed an algorithm for RTP in athletes following myocarditis, incorporating CMR. Future research is warranted to refine RTP protocols and improve risk stratification, particularly through longitudinal studies that examine recovery and outcomes in athletes.

Planned and Unplanned Sarcoma Resections: Comparative Analysis of Local Recurrence, Metastasis, and Mortality

Background: Sarcomas, a diverse group of malignant tumors arising from mesenchymal tissues, pose significant diagnostic and therapeutic challenges. This study compares the outcomes of planned resections (PEs) and unplanned resections (UEs) to inform better clinical practices. Methods: Data were analyzed from the Swiss Sarcoma Network (SSN), including patients with soft tissue and bone sarcomas treated at two major hospitals. This study utilized logistic regression and Cox regression models to examine the odds of UEs and their impact on local recurrence-free survival. Results: Among 429 patients registered by SSN members, 323 (75%) underwent PEs and 106 (25%) experienced UEs. PEs were associated with significantly larger tumors (94 mm vs. 47 mm, p < 0.001) and higher-grade tumors (Grade 3: 50.5% vs. 37.4%, p = 0.03). Despite achieving superior resection margins (R0: 78.8% vs. 12.6%, p < 0.001), PEs showed higher metastasis rates at follow-up (31.0% vs. 10.4%, p < 0.001) and greater cancer-specific mortality (16.7% vs. 6.6%, p = 0.01). UEs, while linked to higher local recurrence, did not significantly affect metastasis-free survival (MFS) or overall survival (OS). Conclusions: PEs achieve superior immediate surgical outcomes but are linked to higher metastasis and cancer-specific mortality due to the advanced stage of tumors. UEs, while associated with higher local recurrence rates, do not significantly impact MFS or OS. Early detection, comprehensive diagnostics, and timely referrals to specialized sarcoma hubs are essential to avoid UEs and reduce metastatic risk. Future research should focus on developing diagnostic tools using individual tumor and patient characteristics to improve sarcoma management.