Project description:Background: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer diagnosed in the United States. The disease causes a decrease in hematopoiesis, so children often present with symptoms related to anemia, thrombocytopenia, and leukopenia. Symptoms for this malignancy may have significant overlap with other conditions such as osteomyelitis. Case Report: A 2-year-old male with no significant medical history presented with lower extremity pain and fever. Initial investigations, including imaging and complete blood count, led physicians to diagnose bilateral osteomyelitis. The patient was prescribed a course of antibiotics; however, his symptoms returned. Eventually, a bone marrow aspiration showed CD99 membrane-positive small round blue cell tumors. The patient was diagnosed with ALL. He was successfully treated with chemotherapy and is now in remission. Conclusion: This case demonstrates the importance of a broad differential diagnosis for a child presenting with leg pain and fever.
Project description:BackgroundContrastive learning is known to be effective in teaching medical students how to generate diagnostic hypotheses in clinical reasoning. However, there is no international consensus on lists of diagnostic considerations across different medical disciplines regarding the common signs and symptoms that should be learned as part of the undergraduate medical curriculum. In Japan, the national model core curriculum for undergraduate medical education was revised in 2016, and lists of potential diagnoses for 37 common signs, symptoms, and pathophysiology were introduced into the curriculum. This study aimed to validate the list of items based on expert consensus.MethodsThe authors used a modified Delphi method to develop consensus among a panel of 23 expert physician-teachers in clinical reasoning from across Japan. The panel evaluated the items on a 5-point Likert scale, based on whether a disease should be hypothesized by final-year medical students considering given signs, symptoms, or pathophysiology. They also added other diseases that should be hypothesized. A positive consensus was defined as both a 75% rate of panel agreement and a mean of 4 or higher with a standard deviation of less than 1 on the 5-point scale. The study was conducted between September 2017 and March 2018.ResultsThis modified Delphi study identified 275 basic and 67 essential other than basic items corresponding to the potential diagnoses for 37 common signs, symptoms, and pathophysiology that Japanese medical students should master before graduation.ConclusionsThe lists developed in the study can be useful for teaching and learning how to generate initial hypotheses by encouraging students' contrastive learning. Although they were focused on the Japanese educational context, the lists and process of validation are generalizable to other countries for building national consensus on the content of medical education curricula.
Project description:Health care providers are likely to encounter patients with recurrent unexplained abdominal pain. Because hereditary angioedema (HAE) is a rare disease, it may not be part of the differential diagnosis, especially for patients who do not have concurrent skin swelling in addition to abdominal symptoms. Abdominal pain is very common in patients with HAE, occurring in up to 93% of patients, with recurrent abdominal pain reported in up to 80% of patients. In 49% of HAE attacks with abdominal symptoms, isolated abdominal pain was the only symptom. Other abdominal symptoms that commonly present in patients with HAE include distension, cramping, nausea, vomiting, and diarrhea. The average time from onset of symptoms to diagnosis is 6 to 23 years. Under-recognition of HAE in patients presenting with predominant gastrointestinal symptoms is a key factor contributing to the delay in diagnosis, increasing the likelihood of unnecessary or exploratory surgeries or procedures and the potential risk of related complications. HAE should be considered in the differential diagnosis for patients with unexplained abdominal pain, nausea, vomiting, and/or diarrhea who have complete resolution of symptoms between episodes. As highly effective targeted therapies for HAE exist, recognition and diagnosis of HAE in patients presenting with isolated abdominal pain may significantly improve morbidity and mortality for these individuals.
Project description:BackgroundPseudohypoparathyroidism (PHP) is a rare disease whose phenotypic features are rather difficult to identify in some cases. Thus, although these patients may present with the Albright's hereditary osteodystrophy (AHO) phenotype, which is characterized by small stature, obesity with a rounded face, subcutaneous ossifications, mental retardation and brachydactyly, its manifestations are somewhat variable. Indeed, some of them present with a complete phenotype, whereas others show only subtle manifestations. In addition, the features of the AHO phenotype are not specific to it and a similar phenotype is also commonly observed in other syndromes. Brachydactyly type E (BDE) is the most specific and objective feature of the AHO phenotype, and several genes have been associated with syndromic BDE in the past few years. Moreover, these syndromes have a skeletal and endocrinological phenotype that overlaps with AHO/PHP. In light of the above, we have developed an algorithm to aid in genetic testing of patients with clinical features of AHO but with no causative molecular defect at the GNAS locus. Starting with the feature of brachydactyly, this algorithm allows the differential diagnosis to be broadened and, with the addition of other clinical features, can guide genetic testing.MethodsWe reviewed our series of patients (n = 23) with a clinical diagnosis of AHO and with brachydactyly type E or similar pattern, who were negative for GNAS anomalies, and classify them according to the diagnosis algorithm to finally propose and analyse the most probable gene(s) in each case.ResultsA review of the clinical data for our series of patients, and subsequent analysis of the candidate gene(s), allowed detection of the underlying molecular defect in 12 out of 23 patients: five patients harboured a mutation in PRKAR1A, one in PDE4D, four in TRPS1 and two in PTHLH.ConclusionsThis study confirmed that the screening of other genes implicated in syndromes with BDE and AHO or a similar phenotype is very helpful for establishing a correct genetic diagnosis for those patients who have been misdiagnosed with "AHO-like phenotype" with an unknown genetic cause, and also for better describing the characteristic and differential features of these less common syndromes.
Project description:The improved capacity to acquire quantitative data in a clinical setting has generally failed to improve outcomes in acutely ill patients, suggesting a need for advances in computer-supported data interpretation and decision making. In particular, the application of mathematical models of experimentally elucidated physiological mechanisms could augment the interpretation of quantitative, patient-specific information and help to better target therapy. Yet, such models are typically complex and nonlinear, a reality that often precludes the identification of unique parameters and states of the model that best represent available data. Hypothesizing that this non-uniqueness can convey useful information, we implemented a simplified simulation of a common differential diagnostic process (hypotension in an acute care setting), using a combination of a mathematical model of the cardiovascular system, a stochastic measurement model, and Bayesian inference techniques to quantify parameter and state uncertainty. The output of this procedure is a probability density function on the space of model parameters and initial conditions for a particular patient, based on prior population information together with patient-specific clinical observations. We show that multimodal posterior probability density functions arise naturally, even when unimodal and uninformative priors are used. The peaks of these densities correspond to clinically relevant differential diagnoses and can, in the simplified simulation setting, be constrained to a single diagnosis by assimilating additional observations from dynamical interventions (e.g., fluid challenge). We conclude that the ill-posedness of the inverse problem in quantitative physiology is not merely a technical obstacle, but rather reflects clinical reality and, when addressed adequately in the solution process, provides a novel link between mathematically described physiological knowledge and the clinical concept of differential diagnoses. We outline possible steps toward translating this computational approach to the bedside, to supplement today's evidence-based medicine with a quantitatively founded model-based medicine that integrates mechanistic knowledge with patient-specific information.
Project description:Abstract Background The differential diagnosis between gallbladder cancer (GBC) and xanthogranulomatous cholecystitis (XGC) remains quite challenging, and can possibly lead to improper surgery. This study aimed to distinguish between XGC and GBC by combining computed tomography (CT) images and deep learning (DL) to maximize the therapeutic success of surgery. Methods We collected a dataset, including preoperative CT images, from 28 cases of GBC and 21 XGC patients undergoing surgery at our facility. It was subdivided into training and validation (n = 40), and test (n = 9) datasets. We built a CT patch‐based discriminating model using a residual convolutional neural network and employed 5‐fold cross‐validation. The discriminating performance of the model was analyzed in the test dataset. Results Of the 40 patients in the training dataset, GBC and XGC were observed in 21 (52.5%), and 19 (47.5%) patients, respectively. A total of 61 126 patches were extracted from the 40 patients. In the validation dataset, the average sensitivity, specificity, and accuracy were 98.8%, 98.0%, and 98.5%, respectively. Furthermore, the area under the receiver operating characteristic curve (AUC) was 0.9985. In the test dataset, which included 11 738 patches, the discriminating accuracy for GBC patients after neoadjuvant chemotherapy (NAC) (n = 3) was insufficient (61.8%). However, the discriminating model demonstrated high accuracy (98.2%) and AUC (0.9893) for cases other than those receiving NAC. Conclusion Our CT‐based DL model exhibited high discriminating performance in patients with GBC and XGC. Our study proposes a novel concept for selecting the appropriate procedure and avoiding unnecessary invasive measures. The differential diagnosis between gallbladder cancer and xanthogranulomatous cholecystitis remains quite challenging, and can possibly lead to improper surgery. We have successfully developed a model combining CT images and deep learning that accurately makes the distinction.
Project description:The difficulty in developing a diagnostic assay for Creutzfeldt - Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs) stems in part from the fact that the infectious agent is an aberrantly folded form of an endogenous cellular protein. This precludes the use of the powerful gene based technologies currently applied to the direct detection of other infectious agents. To circumvent this problem our research objective has been to identify a set of proteins exhibiting characteristic differential abundance in response to TSE infection. The objective of the present study was to assess the disease specificity of differentially abundant urine proteins able to identify scrapie infected mice. Two-dimensional differential gel electrophoresis was used to analyze longitudinal collections of urine samples from both prion-infected mice and a transgenic mouse model of Alzheimer's disease. The introduction of fluorescent dyes, that allow multiple samples to be co-resolved and visualized on one two dimensional gel, have increased the accuracy of this methodology for the discovery of robust protein biomarkers for disease. The accuracy of a small panel of differentially abundant proteins to correctly classify an independent naïve sample set was determined. The results demonstrated that at the time of clinical presentation the differential abundance of urine proteins were capable of identifying the prion infected mice with 87% sensitivity and 93% specificity. The identity of the diagnostic differentially abundant proteins was investigated by mass spectrometry.
Project description:Psychotic disorders are common and disabling mental conditions. The relative importance of immune-related mechanisms in psychotic disorders remains subject of debate. Here, we present a large-scale retrospective study of blood and cerebrospinal fluid (CSF) immune cell profiles of psychosis spectrum patients. We performed basic CSF analysis and multi-dimensional flow cytometry of CSF and blood cells from 59 patients with primary psychotic disorders (F20, F22, F23, and F25) in comparison to inflammatory (49 RRMS and 16 NMDARE patients) and non-inflammatory controls (52 IIH patients). We replicated the known expansion of monocytes in the blood of psychosis spectrum patients, that we identified to preferentially affect classical monocytes. In the CSF, we found a relative shift from lymphocytes to monocytes, increased protein levels, and evidence of blood-brain barrier disruption in psychosis. In fact, these CSF features confidently distinguished autoimmune encephalitis from psychosis despite similar (initial) clinical features. We then constructed machine learning models incorporating blood and CSF parameters and demonstrated their superior ability to differentiate psychosis from non-inflammatory controls compared to individual parameters. Multi-dimensional and multi-compartment immune cell signatures can thus support the diagnosis of psychosis spectrum disorders with the potential to accelerate diagnosis and initiation of therapy.
Project description:Glycosylated ferritin (GF) has been reported as a good diagnostic biomarker for adult-onset Still’s disease (AOSD), but only a few studies have validated its performance. We performed a retrospective study of all adult patients with at least one GF measurement over a 2-year period in one hospital laboratory. The diagnosis of AOSD was based on the expert opinion of the treating physician and validated by two independent investigators. Patients’ characteristics, disease activity, and outcome were recorded and compared. Twenty-eight AOSD and 203 controls were identified. Compared to controls, the mean GF was significantly lower (22.3% vs. 39.3, p < 0.001) in AOSD patients. GF had a high diagnostic accuracy for AOSD, independent of disease activity or total serum ferritin (AUC: 0.674 to 0.915). The GF optimal cut-off value for AOSD diagnosis was 16%, yielding a specificity of 89% and a sensitivity of 63%. We propose a modified diagnostic score for AOSD, based on Fautrel’s criteria but with a GF threshold of 16% that provides greater specificity and increases the positive predictive value by nearly 5 points. GF is useful for ruling out differential diagnoses and as an appropriate classification criterion for use in AOSD clinical trials.