Epstein-Barr Virus encephalitis associated hemophagocytic lymphohistiocytosis in childhood-onset systemic lupus erythematosus: a case-based review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation that results in an uncontrolled hyperinflammatory state. HLH is classified into two main categories: primary (familial) HLH and secondary (acquired) HLH. Secondary HLH can result from various underlying, including infection-associated hemophagocytic syndrome (IAHS) and macrophage activation syndrome (MAS) associated with rheumatologic disorders, among others. Epstein-Barr virus (EBV) often causes IAHS, but central nervous system (CNS) involvement is rare among systemic lupus erythematosus (SLE) patients. We report a case of EBV encephalitis associated with HLH in a patient with childhood-onset SLE. CASE PRESENTATION: A 12-year-old girl had received a diagnosis of SLE 2 months before presentation. After a period of inactive disease on treatment, fever and seizures, with altered mental status and hallucinations, developed over several weeks. A complete blood cell count (CBC) revealed pancytopenia, accompanied by elevated levels of inflammatory markers: 86 mm/hr erythrocyte sedimentation rate, 8.9 mg/dl c-reactive protein, and 3,966 ng/mL of ferritin. The differential diagnosis included active neuropsychiatric SLE, CNS infection and neurological manifestations in secondary HLH, which could have represented either IAHS or MAS. Meropenem and acyclovir were initially administered for clinical acute encephalitis, followed by pulse methylprednisolone; however, the fever persisted, and another CBC revealed progressive cytopenia. A bone marrow study showed hypocellularity and active hemophagocytic activity, and intravenous immunoglobulin was additionally given due to the diagnosis of HLH. Cerebrospinal fluid (CSF) analysis showed 60/mm3 white blood cells (N 55%, L 45%), 141 mg/dL glucose (0.7 blood-CSF glucose ratio), < 4 mg/dL protein; results of Gram stain and bacterial culture were negative. The viral encephalitis panel from the CSF confirmed EBV infection. Bone marrow immunohistochemistry examination revealed increasing levels of CD8 + T-cell and equivocal positive results for EBV-encoded RNA in situ hybridization; therefore, HLH potentially associated with EBV was diagnosed. After treatment with IVIg, cyclosporin A, and prednisolone, the patient's symptoms gradually improved and she was eventually able to return to school. CONCLUSIONS: Our case highlights the importance of a thorough differential diagnosis, including EBV encephalitis associated with HLH, in patients with childhood SLE, particularly in cases of clinical deterioration occurs after initial treatment.

Enhancing the differential diagnosis of small pulmonary nodules: a comprehensive model integrating plasma methylation, protein biomarkers, and LDCT imaging features.

BACKGROUND: Accurate differentiation between malignant and benign pulmonary nodules, especially those measuring 5-10 mm in diameter, continues to pose a significant diagnostic challenge. This study introduces a novel, precise approach by integrating circulating cell-free DNA (cfDNA) methylation patterns, protein profiling, and computed tomography (CT) imaging features to enhance the classification of pulmonary nodules. METHODS: Blood samples were collected from 419 participants diagnosed with pulmonary nodules ranging from 5 to 30 mm in size, before any disease-altering procedures such as treatment or surgical intervention. High-throughput bisulfite sequencing was used to conduct DNA methylation profiling, while protein profiling was performed utilizing the Olink proximity extension assay. The dataset was divided into a training set and an independent test set. The training set included 162 matched cases of benign and malignant nodules, balanced for sex and age. In contrast, the test set consisted of 46 benign and 49 malignant nodules. By effectively integrating both molecular (DNA methylation and protein profiling) and CT imaging parameters, a sophisticated deep learning-based classifier was developed to accurately distinguish between benign and malignant pulmonary nodules. RESULTS: Our results demonstrate that the integrated model is both accurate and robust in distinguishing between benign and malignant pulmonary nodules. It achieved an AUC score 0.925 (sensitivity = 83.7%, specificity = 82.6%) in classifying test set. The performance of the integrated model was significantly higher than that of individual methylation (AUC = 0.799, P = 0.004), protein (AUC = 0.846, P = 0.009), and imaging models (AUC = 0.866, P = 0.01). Importantly, the integrated model achieved a higher AUC of 0.951 (sensitivity = 83.9%, specificity = 89.7%) in 5-10 mm small nodules. These results collectively confirm the accuracy and robustness of our model in detecting malignant nodules from benign ones. CONCLUSIONS: Our study presents a promising noninvasive approach to distinguish the malignancy of pulmonary nodules using multiple molecular and imaging features, which has the potential to assist in clinical decision-making. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov on 01/01/2020 (NCT05432128). https://classic. CLINICALTRIALS: gov/ct2/show/NCT05432128 .

Primary anaplastic T-cell lymphoma of the omentum presenting as small bowel obstruction and complicated with Massilia timonae infection: a case report.

BACKGROUND: Anaplastic large-cell lymphoma primarily involving the omentum is an extremely rare entity with variable clinical presentation. Owing to its rarity and nonspecific clinical manifestation, omental T-cell lymphoma is often diagnosed at a later stage, riddled with complications. While imaging modalities such as computed tomography scan can help a physician reach a diagnosis, cases that present with complications may require a multidisciplinary approach that combines surgical exploration along with consultation from Oncology. CASE PRESENTATION: We hereby report a rare case of a 66-year-old African American male patient who presented to the emergency department with complaints of acute gastrointestinal obstruction. A computed tomography scan of the abdomen and pelvis revealed evidence of an internal hernia and surgical exploration revealed a hemorrhagic and infarcted omentum. Biopsies along with immunophenotypic studies confirmed the diagnosis of anaplastic T-cell lymphoma of the omentum complicated by Massilia timonae infection. CONCLUSION: The case highlights the significance of considering lymphoma, although rare, as a differential in a patient who presents with small bowel obstruction and the importance of investigating for malignancy for early diagnosis and treatment of primary omental lymphomas, before complications develop.

[Night sweats, a common symptom]. / Nachtzweten, een veelvoorkomend symptoom.

Night sweats are a common symptom. There is a lack of a uniform definition and a diagnostic guideline. In this article we propose a structural analysis for all levels of healthcare. First, we need to distinguish night sweats with or without fever. We will then discuss the main differential diagnoses (infection, malignancies, sleeping disorders and medication-related) and emphasize the role of diagnostic clues. A screening for infections, sleeping disorders and a medication review are a must for every patient. Furthermore we will explain the role of PET-CT and bone marrow examination.

[Growth factors PDGF-AA, PDGF-BB and BDNF as potential differentiating biomarkers of unipolar and bipolar depression]. / Faktory rosta PDGF-AA, PDGF-BB i BDNF kak potentsial'nye differentsiruyushchie biomarkery monopolyarnoi i bipolyarnoi depressii.

OBJECTIVE: To establish the differences and identify the prognostic value of biological markers - platelet growth factors PDGF-AA, PDGF-BB and brain-derived neurotrophic growth factor (BDNF) - for the differential diagnosis of patients with unipolar and bipolar depression using machine learning. MATERIAL AND METHODS: The study included 79 patients aged 48 [34; 57] years, including 35 people with bipolar depression (ICD-10. F31) and 44 people with unipolar depression (F32-33). Clinical assessment of the patients' condition was carried out using the Hamilton Depression Rating Scale (HDRS-17) and the Hamilton Anxiety Rating Scale (HARS). The concentration of growth factors in the blood serum of patients was determined using multiplex analyzers Magpix and Luminex 200 (Luminex, USA). To build a predictive model, the support vector machine was used. RESULTS: Patients with bipolar depression showed statistically significant higher concentrations of PDGF-AA and PDGF-BB, as well as lower concentrations of BDNF. When constructing a predictive model, it was possible to separate patients with unipolar and bipolar depression according to all three biomarkers; the sensitivity and specificity of the model were 0.96±0.06 and 0.95±0.05, respectively. CONCLUSIONS: The study of concentrations of BDNF and platelet-derived growth factors shows statistically significant differences in indicators in the case of unipolar and bipolar depression, which can potentially be used as prognostic biomarkers for differential diagnosis in appropriate clinical cases.

Constructing a predictive model based on peripheral blood signs to differentiate infectious mononucleosis from chronic active EBV infection.

OBJECTIVE: To develop a prediction model based on peripheral blood signs to distinguish between infectious mononucleosis and chronic active EBV infection. METHODS: Retrospective data was collected for 60 patients with IM (IM group) and 20 patients with CAEBV infection (CAEBV group) who were hospitalized and diagnosed at the General Hospital of Tianjin Medical University between December 2018 and September 2022. The analyses used were univariate and LASSO (least absolute shrinkage and selection operator) logistic regression. RESULTS: Univariate analyses revealed that both IM and CAEBV-infected patients displayed overlapping and intersecting clinical manifestations, such as fever, sore throat, enlarged lymph nodes, and enlargement of the liver and spleen, and that in contrast to inflammatory responses in peripheral blood, CAEBV-infected patients had more severe inflammatory responses. Nine biomarkers-HGB, lymphocyte count, percentage of lymphocytes, ALB, fibrinogen, CRP, IFN-, IL-6, and EBV-DNA load-were subsequently selected by LASSO logistic regression modeling to serve as discriminatory models. CONCLUSIONS: Our investigation offers a solid foundation for diagnosing IM and CAEBV infection using the LASSO logistic regression model based on the significance and availability of peripheral blood indicators. Infected patients with CAEBV require early medical attention.

A 53-Year-Old Man with Persistent Epigastric Pain.

AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 53-year-old man who had epigastric pain that he described as a sensation of burning behind his sternum. It persisted for months despite treatment with proton pump inhibitors. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.

Pediatric Diffuse Lung Disease in Infants: Imaging Findings and Histopathologic Correlation.

Childhood interstitial lung disease (chILD) encompasses a diverse group of genetic, infectious, and inflammatory conditions affecting infants and children. The recognition and understanding of these entities have highlighted the necessity for more accurate classification. This group of rare heterogeneous diseases comprises more than 200 different conditions and has a combined estimated prevalence of less than one patient per 100 000 children. Hence, a systematic diagnostic approach is crucial. This article describes a diagnostic approach for pediatric diffuse lung diseases in infancy, including an analysis of clinical presentations and imaging and histologic features to effectively distinguish among various chILD entities. Although they often have overlapping and nonspecific radiologic features, some chILD entities may exhibit typical imaging findings, resulting in a CT diagnosis or aiding in narrowing the differential diagnosis, thus guiding the clinician to the appropriate genetic tests, potentially limiting unnecessary biopsies. This approach aims to enhance the understanding and diagnosis of chILD in infants, thereby facilitating improved patient care.

Primary axillary hydatid cyst: A case report.

BACKGROUND: Hydatid disease, also known as echinococcosis, is an endemic parasitic infection, most commonly caused by Echinococcus granulosus. It may affect any organ resulting in the formation of hydatid cysts, but most frequently involves liver and lungs. Hydatid cyst arising primarily from axilla is an extremely rare manifestation of this condition, with only a few cases reported in medical literature. CASE PRESENTATION: Here we present the case of a 32-year-old Indian male farmer, who presented with a painless, slow-growing mass in the left axillary region of 8 months duration. Preoperative imaging led us to the diagnosis of primary axillary hydatid cyst, with no other associated cysts or masses anywhere else in the body. Following antihelmintic therapy, the cyst was surgically excised without rupture. The diagnosis was further confirmed by macroscopic and histopathological examination. CONCLUSION: This case report highlights the importance of considering hydatid cyst in the differential diagnosis of palpable masses in the axillary region, especially in regions where the disease is endemic. Early recognition and accurate diagnosis are crucial for appropriate management and optimal patient outcomes.

Influence of sex and functional status on the value of serum steroid profiling in discriminating adrenocortical carcinoma from adrenocortical adenoma.

Background: It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. Methods: In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. Results: The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Conclusion: Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.

Beyond the Liver: Neurologic Manifestations of Alcohol Use.

Alcohol use, while commonly associated with liver damage, also has significant neurologic implications, which often mimic hepatic encephalopathy and complicate diagnosis and management. Alcohol mediates its acute central nervous system effects by altering neurotransmitter balance, notably between gamma-aminobutyric acid and glutamate. Its chronic neurotoxicity, compounded by thiamine deficiency, results in chronic neurologic complications. Clinically, alcohol-related neurologic disorders present a spectrum from acute intoxication and withdrawal to chronic conditions like Korsakoff syndrome, dementia, cerebellar degeneration, and peripheral neuropathy. This review underscores differentiating these conditions from hepatic encephalopathy and highlights the importance of history-taking and physical examination in clinical practice.

Unusual presentation of PYGM gene mutation as late-onset McArdle disease with camptocormia: a case report.

BACKGROUND: Glycogen storage disease type 5 (McArdle disease) leads to a deficiency in the activity of myophosphorylase resulting in an impaired glucose utilization. The disease can be caused by a variety of mutations in the PYGM gene, and its typical clinical manifestation is muscles weakness within the first three decades of life. CASE PRESENTATION: In this case report we present the diagnostic work-up of a physically active 78-year-old Caucasian patient suffering from a 2-year history of progressive camptocormia including clinical, radiologic, histological, and genetic tests. There was no history of neuro-muscular diseases in the family. Serum CK levels were moderately increased while other blood/urine parameters were normal. Magnetic resonance imaging showed fatty remodeling of the muscles of the back. Histochemical examination of a muscle biopsy revealed the absence of myophosphorylase activity, while gene analysis identified a known early-onset McArdle mutation in the PYGM gene. CONCLUSION: This case highlights that the clinical spectrum of PYGM gene mutation typically manifest during adolescence, but it is also a differential diagnosis in late onset muscle disorders and emphases the investigation of the role of ACE inhibitors in this disease.

Colitis cystica profunda associated with diverticulosis and calcification mimicking colorectal carcinoma: a case report and a brief literature review.

Colitis cystica profunda (CCP) is a rare, uncommon and nonneoplastic condition that can occur anywhere in gastrointestinal tract, but its main occurrence is in the rectum and sigmoid colon. It is characterized by the presence of mucin filled cysts, lined by benign epithelium, beneath the muscularis mucosae, usually confined to the submucosa, and it can clinically and radiologically mimic a neoplasm. Here we report a rare case of CCP in a patient with a 2-months history of abdominal pain and severe anemia, associated with diverticulosis. The knowledge of this entity and its differential diagnosis, in particular with the intestinal mucinous adenocarcinoma, is necessary, as it can be a clinically and histological mimic of a malignant neoplasm.

[Amputation neuroma with a difficult differential diagnosis from perihilar cholangiocarcinoma:a case report].

Biliary amputation neuroma is a rare benign tumor that develops due to the peribiliary dissection of nerve fibers during cholecystectomy, a common bile duct surgery, or lymph node dissection performed in gastric cancer surgery. We report a case of amputation neuroma that presented a challenging differential diagnosis from perihilar cholangiocarcinoma. A 64-year-old man, who had undergone open cholecystectomy 30 years ago, was incidentally found to have a bile duct tumor during computed tomography (CT) following surgery for renal cell carcinoma. He had no specific symptoms, and blood test results showed only a slight elevation in alkaline phosphatase levels. Contrast-enhanced CT revealed a 10-mm solid tumor with contrast effect in the common bile duct. On cholangiography, the tumor appeared as a protruding lesion with a smooth surface unilaterally. Given the atypical findings suggestive of cholangiocarcinoma, three bile duct biopsies were performed. Pathological examination did not rule out adenocarcinoma. The patient opted for surgery;however, an intraoperative rapid histological examination confirmed a benign disease, thereby avoiding extensive surgery. Consequently, a minimally invasive bile duct resection was performed. Postoperative histopathological examination revealed the tumor to be an amputation neuroma. Biliary amputation neuromas are characterized as unilateral protruding lesions with contrast effect or benign strictures. If such findings are observed in a patient with a history of surgery around the bile duct, the possibility of an amputation neuroma should be considered. However, completely ruling out malignancy preoperatively, even when suspecting amputation neuroma, can be challenging;therefore, considering surgery to achieve a definitive diagnosis is reasonable. During surgery, a rapid intraoperative histological examination is useful to avoid extensive procedures. In conclusion, diagnosing an amputation neuroma before surgery can be difficult, as it can mimic malignant tumors such as bile duct cancers. In this case, although a preoperative diagnosis of amputation neuroma was not feasible, performing a rapid intraoperative pathological examination helped avoid extensive surgery.

Noninvasive Assessment in Takotsubo Syndrome: A Diagnostic Challenge.

Takotsubo syndrome (TTS) is a clinical syndrome characterized by a transient left ventricular dysfunction whose diagnosis can be challenging due to its resemblance to acute myocardial infarction (AMI). Despite the growing recognition of TTS, acute complications and long-term mortality rates are comparable to those observed in AMI patients. In this context, a systematic diagnostic approach is imperative for an accurate patient assessment, with due consideration of the distinctive characteristics and optimal timing of each imaging modality. Coronary angiography with ventriculography may be reserved for cases presenting with ST-segment elevation, whereas in all other cases, the use of multimodality noninvasive imaging allows for a comprehensive evaluation of typical diagnostic features and detection of acute complications while also providing prognostic insights. The aim of this review is to evaluate the current research on non-invasive modalities and to propose a diagnostic algorithm that will facilitate the identification and management of TTS.

'Color Doppler stripes' make it difficult to diagnose the severity of valvular heart diseases: a report of two cases.

BACKGROUND: Echocardiography remains the reference-standard imaging technique for assessing valvular heart disease (VHD), but artifacts like the 'color Doppler stripe' can complicate diagnosis. This artifact is not widely recognized and can mimic severe VHD, leading to potential misdiagnoses. We present two cases where color Doppler stripes mimicked severe VHD, highlighting the need for awareness and accurate interpretation in echocardiographic assessments. CASE PRESENTATIONS: Case 1: An 85-year-old patient was referred for mitral valve surgery due to suspected severe mitral regurgitation (MR). Upon evaluation, transthoracic echocardiography (TTE) showed mitral valve prolapse (P3) and a high-echoic, vibrating structure attached to the mitral valve, indicative of chordal rupture. Color Doppler echocardiography revealed strong systolic signals in the left atrium, mimicking severe MR. Transesophageal echocardiography (TEE) also detected the vibrating structure and color Doppler stripes in the left atrium, left ventricle, and outside the cardiac chambers. The PISA method on TEE indicated moderate MR and left ventriculography showed Sellers grade II MR. The artifact was identified as color Doppler stripes caused by the vibrating high-echoic structure from the ruptured chorda. Case 2: A 64-year-old patient with severe aortic stenosis, end-stage kidney disease requiring hemodialysis, and a history of coronary bypass grafting presented for routine follow-up. B-mode echocardiography showed a severely calcified tricuspid aortic valve with a vibrating calcified nodule and restricted opening, corresponding to severe aortic stenosis. During systole, color Doppler signals were observed around the aortic, pulmonary, and tricuspid valves, mimicking significant pulmonary stenosis and tricuspid regurgitation. However, pulmonary stenosis was ruled out as the pulmonary valve opening was normal. Mild tricuspid regurgitation was confirmed in the apical view. CONCLUSIONS: These cases highlight the diagnostic challenges posed by color Doppler stripes. Recognizing and understanding this artifact are crucial for the accurate diagnosis and management of VHD, ensuring appropriate treatment and patient outcomes.

Assessing the Trajectory of Bipolar Disorder Effectively in Order to Treat Effectively.

Accurate diagnosis of mood disorders, particularly depression and bipolar disorder, is essential for effective treatment planning and patient management. This article emphasizes the need for systematic symptom assessment and longitudinal analysis in facilitating the precise diagnosis and planning appropriate treatment interventions. By meticulously evaluating the symptomatology and delineating the longitudinal trajectory of the illness, clinicians can distinguish between unipolar depression and bipolar disorder, and therefore optimise patient outcomes. The article describes the inherent complexities in diagnosing mood disorders. It describes the overlapping symptomatology and diagnostic challenges. Through a comprehensive review of literature and clinical insights, it argues for a structured approach to symptom assessment, focusing on both the current presentation and also retrospective evaluation of illness progression. By elucidating the longitudinal trajectory of the illness, including the presence of episodes of high mood suggestive of bipolar disorder, clinicians can differentiate between mood disorders accurately. The article discusses the implications of accurate diagnosis on treatment planning and patient prognosis. A precise diagnosis enables clinicians to plan treatment strategies to the specific needs of the individual, including pharmacotherapy, psychotherapy, or both. By addressing the underlying mechanisms and trajectory of the illness, clinicians can implement targeted interventions which reduce the risk of misdiagnosis and which optimize therapeutic outcomes.