Unmasking the Culprits: A Case of Epstein-Barr Virus-Associated Hemophagocytic Lymphohistiocytosis Presenting With Mouth Ulcers and Nosebleeds.

Hemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome of excessive immune activation. It usually occurs in children, mainly during the first year of life. Primary hemophagocytic lymphohistiocytosis is more common and usually occurs in immunocompromised patients. Secondary hemophagocytic lymphohistiocytosis, on the other hand, is less common, especially in immunocompetent patients. Here, we intend to present a case of a 55-year-old male patient who had no known immune deficiency, presented with epistaxis, and was found to have Epstein-Barr virus (EBV)-induced hemophagocytic lymphohistiocytosis.

Histoplasmosis in non-immunosuppressed patients from an endemic area in northeastern Brazil.

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: ten patients had acute pulmonary histoplasmosis (APH), one had chronic pulmonary histoplasmosis (CPH), two had progressive disseminated (PD) presentation, and six had the chronic disseminated (CD) form. The median age of our sample was 32.7 years old [IQR: 24 - 45]. Most of the patients were male (male-to-female ratio=15:4) and resided in the state capital (n=9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. The lung images of APH were characterized by nodules, enlarged hilar/mediastinal lymph nodes, and patches, and three patients were initially treated empirically for pulmonary tuberculosis; one death was registered. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the CD form were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heath patients.

This study aimed to describe the presentation of histoplasmosis outside the context of immunosuppression, including the diagnostic methods, epidemiology, and main radiological and clinical features. A better understanding of the various forms of this disease will help improve case management.

MORPHOLOGICAL DIFFERENCES BETWEEN THE LESSER AND THE GREATER OMENTA IN ALBINO RATS.

BACKGROUND: Publications report that all mammals have two omenta, namely, lesser omentum and greater omentum. Basically, these organs, which share the same name except for the adjective "lesser" or "greater," should not differ from each other. However, no clear description of the structure of the lesser omentum, as well as comparative morphological analysis between the lesser and greater omenta have been found in the literature, which necessitates a thorough investigation. Therefore, the aim of our study was to analyze the morphofunctional differences between the greater and lesser omenta in albino rats. METHOD: The experiment involved 20 mature male albino rats, weighing 298,28±7,36grams. The material for our study were preparations of lesser and greater omenta, fixed in 10% of neutral buffered formalin. Paraffin sections were stained with hematoxylin-eosin and Van Gieson stain. RESULTS: The findings of the study showed that the greater omentum in albino rats, unlike other derivatives of the omentum (ligaments and mesenteries), represents a free extension (mostly from the greater curvature of the stomach), in the form of an "apron," into a specific depth of the peritoneal cavity, duplicating the serous membrane. This duplication is characterized by the composition of two structurally interdependent formations. These include vascular-fatty arcades, associated with lymphoid nodules known as milky spots, and binding serous-reticular membranes. The findings of the study of the lesser omentum have established that in all cases it is located beneath the liver and becomes visualized only after hepatolifting. It is presented in the form of two ligaments: hepatoduodenal and hepatogastric, which contain two main structured formations, which we called vascular-fatty spurs, between these spurs, serous-reticular membranes are located. CONCLUSION: despite having similar names, the lesser omentum, a derivative of the peritoneum, is fundamentally different. As it is well known, the lesser omentum is represented by ligaments that extend from the liver hilus to the lesser curvature of the stomach and the duodenum. Due to this arrangement, the lesser omentum lacks the mobile activity characteristic of the greater omentum, which plays a crucial role in rapid response to damage in the gastrointestinal tract. Despite sharing the same names, both formations differ in shape, morphological structure, development and function.

Atypical cutaneous manifestations of methicillin resistant Staphylococcus aureus infections in two immunocompetent pediatric patients: Case reports and review of the literature.

Although many clinical variants of Staphylococcus aureus infection are well-recognized, atypical presentations may mimic other conditions. We describe two cases of atypical S. aureus infections in pediatric patients: a S. aureus infection presenting with a vesicopustular rash mimicking varicella zoster virus and a case of multifocal panniculitis. Both of these cases were specifically caused by methicillin-resistant S. aureus (MRSA). Additional cases of atypical S. aureus infections and presenting features from the current literature are also discussed.

Disseminated Nocardia cyriacigeorgica Infection Disguised as a Metastatic Adrenal Gland Malignancy in a Healthy Patient.

Nocardia, typically recognized as an uncommon opportunistic pathogen affecting immunocompromised individuals, has also been documented in various case reports involving infections in immunocompetent hosts. Transmission occurs through inhalation or inoculation into compromised skin. Subsequently, it can lead to disseminated infection via hematogenous spread, affecting nearly any organ with a particular affinity for the central nervous system. Dissemination to the adrenal glands is extremely rare, with only a few cases reported. In this report, we present a rare case of disseminated Nocardia cyriacigeorgica, initially resembling a metastatic adrenal gland malignancy in an otherwise healthy individual. The patient presented with non-specific symptoms, had multiple sets of negative blood cultures, clinical findings suggestive of an underlying adrenal gland malignancy, and lacked identifiable risk factors for Nocardia, creating a significant diagnostic challenge. Additionally, we review the existing literature on nocardiosis involving the adrenal glands. This case marks the third reported instance of a Nocardia cyriacigeorgica adrenal gland abscess in the literature.

Neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst.

Neurobrucellosis is a rare complication of brucella infection which presents as meningitis, meningoencephalitis, subdural empyema, brain abscess, myelitis, and radiculo- neuritis. We report the first case of neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst in a young immunocompetent male who presented with fever and acute raised intracranial pressure. MRI brain showed an extra-axial mass in the right cerebellopontine angle cistern with peripheral rim enhancement and diffusion restriction. Emergency surgery unveiled a well-encapsulated lesion containing thick pus and keratinous material, confirming an infected epidermoid cyst. Intriguingly, the culture revealed Brucella infection, but the source of the infection remained unclear.

KR158 Spheres Harboring Slow-Cycling Cells Recapitulate High-Grade Glioma Features in an Immunocompetent System.

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

Mice fatal pneumonia model induced by less-virulent Streptococcus pneumoniae via intratracheal aerosolization.

Aim: Animal models of fatal pneumonia caused by Streptococcus pneumoniae (Spn) have not been reliably generated using many strains of less virulent serotypes. Materials & methods: Pulmonary infection of a less virulent Spn serotype1 strain in the immunocompetent mice was established via the intratracheal aerosolization (ITA) route. The survival, local and systemic bacterial spread, pathological changes and inflammatory responses of this model were compared with those of mice challenged via the intratracheal instillation, intranasal instillation and intraperitoneal injection routes. Results: ITA and intratracheal instillation both induced fatal pneumonia; however, ITA resulted in better lung bacterial deposition and distribution, pathological homogeneity and delivery efficiency. Conclusion: ITA is an optimal route for developing animal models of severe pulmonary infections.

What is this article about? Streptococcus pneumoniae (Spn), a type of bacteria, can cause serious illness and death in otherwise healthy people. One way that we study pneumonia is using animals. However, pneumonia in animals infected with Spn in the laboratory does not mimic that in humans very well. To study this illness, we need a new way to set up a proper animal model.What were the results? This study set up a method called intratracheal aerosolization (ITA). In ITA, bacteria can form small droplets called aerosols and reach the deepest parts of a mouse's lung. ITA can cause deadly illness in mice infected with Spn, even if the mice are healthy.What do the results of the study mean? The ITA method could be a useful tool to set up animal models of serious pneumonia with less virulent bacteria.

Nocardia brasiliensis Pyomyositis in an Immunocompetent Patient Following Gardening Activity.

Nocardia pyomyositis in immunocompetent patients is a rare occurrence. The diagnosis may be missed or delayed with the risk of progressive infection and suboptimal or inappropriate treatment. We present the case of a 48-year-old immunocompetent firefighter diagnosed with pyomyositis caused by Nocardia brasiliensis acquired by direct skin inoculation from gardening activity. The patient developed a painful swelling on his right forearm that rapidly progressed proximally and deeper into the underlying muscle layer. Ultrasound imaging of his right forearm showed a 7-mm subcutaneous fluid collection with surrounding edema. Microbiologic analysis of the draining pus was confirmed to be N brasiliensis by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) Mass Spectrometry. After incision and drainage deep to the muscle layer to evacuate the abscess and a few ineffective antibiotic options, the patient was treated with intravenous ceftriaxone and oral linezolid for 6 weeks. He was then de-escalated to oral moxifloxacin for an additional 4 months to complete a total antibiotic treatment duration of 6 months. The wound healed satisfactorily and was completely closed by the fourth month of antibiotic therapy. Six months after discontinuation of antibiotics, the patient continued to do well with complete resolution of the infection. In this article, we discussed the risk factors for Nocardia in immunocompetent settings, the occupational risks for Nocardia in our index patient, and the challenges encountered with diagnosis and treatment. Nocardia should be included in the differential diagnosis of cutaneous infections, particularly if there is no improvement of "cellulitis" with traditional antimicrobial regimens and the infection extends into the deeper muscle tissues.

Immune Boosting Effect of Limosilactobacillus Reuteri in Immunocompetent C57BL/6J Mice.

Probiotics are well-known to be directly or indirectly involved in the host immune system. In this study, we analyzed the immune-boosting effects of lactic acid bacteria, including Limosilactobacillus and Lactococcus, in immunocompetent C57BL/6J mice. Three different lactic acid bacteria strains were orally administered to C57BL/6J mice for 8 weeks. Then, liver, spleen, and whole blood were harvested after sacrificing the animals. There were no significant changes in whole-body weight, weight of organs, or complete blood cell count by oral administration of lactic acid bacteria. The frequencies of CD3+, CD4+, and CD8+ T cells were significantly increased in the Limosilactobacillus reuteri MG5462 group compared to control. The frequency of NK1.1+ cells was significantly increased in the Lactococcus lactis MG5474 group compared to control. On the other hand, splenocyte proliferations and natural killer cytotoxicity did not differ between groups. In addition, the MG5462 group had a significant increase in the production of TNF-α compared to the control, which is consistent with the upregulation of T cells in the MG5462 group. Therefore, Limosilactobacillus reuteri could be a functional food additive to boost immunity by positively affecting T cell populations.

Modeling human gastric cancers in immunocompetent mice.

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. This cancer is determined by multiple (epi)genetic and environmental factors; can occur at distinct anatomic positions of the stomach; and displays high heterogeneity, with different cellular origins and diverse histological and molecular features. This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics. In the past decade, great progress has been made in the study of GC, particularly in molecular subtyping, investigation of the immune microenvironment, and defining the evolutionary path and dynamics. Preclinical mouse models, particularly immunocompetent models that mimic the cellular and molecular features of human GC, in combination with organoid culture and clinical studies, have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion, and the development of novel therapeutic strategies. Herein, we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models, emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

Trained Immunity and Trained Tolerance: The Case of Helicobacter pylori Infection.

Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. Helicobacter pylori, a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to H. pylori can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent H. pylori infections. However, interactions between H. pylori and trained immunity are intricate and produce both beneficial and detrimental effects. H. pylori infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and H. pylori and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.

Unravelling lung adenocarcinoma in an immunocompetent patient with endobronchial aspergilloma: A case report.

Inhalation of Aspergillus spp. can cause a wide spectrum of lung diseases. Endobronchial aspergilloma is an uncommon clinical entity that occurs because of Aspergillus spp. overgrowth in the airway lumen. We present a 73-year-old gentleman with a rare dual pathology of endobronchial aspergilloma and endobronchial adenocarcinoma. He initially presented with prolonged cough, dyspnoea, and haemoptysis. Bronchoscopy revealed an obstructed right main bronchus by a necrotic mass whereby histological examination showed evidence of Aspergillus spp. infection. The lesion however persisted despite treatment with anti-fungal agents. Repeated bronchoscopy and biopsy eventually unravelled an underlying endobronchial adenocarcinoma. He received chemotherapy but ultimately passed away 3 months later.

Metagenome next-generation sequencing plays a key role in the diagnosis and selection of effective antibiotics on the treatment of Nocardia pneumonia: a case report.

Nocardia disease is an opportunistic infection, the occurrence is rare and mostly occurs in patients with immune deficiency. Even if the patient is immunocompetent, it can still be life-threatening. This case report describes a previously healthy 78-year-old male farmer with lung lesions discovered on a computerized tomography scan. Combined with the patient's history of fever and the results of elevated laboratory markers associated with inflammation, the patient was diagnosed with a lung infection. After escalating empirical broad-spectrum antibiotics, antiviral and antifungal therapy, the patient continued to deteriorate to septic shock. In the meanwhile, the patient's sputum was cultured repeatedly, and no obvious positive pathogenic bacteria were found. Considering the patient was elderly and that these lesions were solid with burr signs, as well as the progression after antimicrobial therapy cancer was considered in the differential diagnosis. Artificial intelligence (YITU, Hangzhou Yitu Medical Technology Limited Company) was also applied, and it also calculated that these lesions were cancerous. The patient received a puncture biopsy of the largest lung lesion. During the puncture pus was withdrawn from largest lung lesion. Culture and metagenome next-generation sequencing (mNGS) detection performed on pus indicated Nocardia otitidiscaviarum. The test report of the mNGS is also attached with a susceptibility report of commonly used clinical antibiotics to this Nocardia spp. Using this result, the patient's disease was quickly controlled after selecting the targeted drug compound sulfamethoxazole and intravenous meropenem for treatment. In view of the high misdiagnosis rate and poor sensitivity of culture for Nocardia spp., this case emphasized mNGS playing a key role in the diagnosis and selection of effective antibiotics for the treatment of Nocardia spp. lung infections.

Challenging Diagnosis of Streptococcus intermedius-Associated Empyema in an Immunocompetent Adult: A Case Report and Literature Review.

The significance of Streptococcus intermedius in infectious diseases, especially pleural infections, is gaining recognition. While traditional risk factors like dental procedures and immunosuppression remain pivotal in differential diagnosis, there is an emerging recognition of unconventional clinical presentations and risk factors linked to infections by S. intermedius. This shift compels medical professionals to broaden their diagnostic and therapeutic strategies, underscoring the intricate and evolving nature of managing infections associated with this opportunistic bacterium. We describe the case of a 48-year-old immunocompetent woman with untreated hypertension who experienced a 15-day episode of right-sided chest pain, which worsened with a sudden onset of dyspnea, yet her daily activities remained unaffected. Physical examination suggested a pleuropulmonary syndrome due to significant pleural effusion, with a computed tomography (CT) scan of the lungs revealing about 50% effusion on the right side. Laboratory tests indicated elevated inflammatory markers. Ultrasound-guided thoracentesis extracted purulent fluid compatible with empyema, necessitating the placement of a pleural drain and multiple pleural cavity lavages using alteplase, which led to the removal of substantial infected fluid. Culture of the pleural fluid identified S. intermedius, which was pansusceptible. Treatment with intravenous ceftriaxone was administered, resulting in a favorable clinical outcome. This case highlights the critical nature of recognizing atypical clinical presentations and managing complex bacterial infections in the pleural space.

Disseminated Cutaneous Histoplasmosis and Its Recurrence in an Apparently Immunocompetent Patient.

Histoplasmosis is a fungal infection caused by the fungus Histoplasma capsulatum. It can manifest in various ways, ranging from pulmonary to disseminated presentations. Most of the disseminated cases are seen in immunocompromised patients; here, we present an unusual case of an 81-year-old Mexican male with a history of cave exposure in his childhood, with 75 years of incubation period of the disease, who developed disseminated cutaneous histoplasmosis with no evident immunocompromising conditions. We considered the hypotheses of transient immunosuppression, CD4+ T lymphocytopenia, and immune senescence as the cause of this manifestation. The present case is also notable for its recurrence following therapy. This report underscores the challenges in diagnosing histoplasmosis in immunocompetent individuals and highlights the importance of long-term treatment and follow-up.

Cryptococcal Pleuritis in an Immunocompetent Patient: A Case Report and Literature Review.

Cryptococcosis, primarily an opportunistic infection, often occurs in immunocompromised patients but can also affect immunocompetent individuals. Cryptococcosis typically manifests in the lungs, but pleurisy is rare, particularly in immunocompetent patients. This report details a case of cryptococcal pleuritis in a 74-year-old immunocompetent male with a history of heart failure, presenting initially with pleural effusion. Diagnostic challenges arose due to the initial absence of intrapulmonary lesions. The diagnosis was eventually established through a surgical biopsy and tissue culture, revealing Cryptococcus neoformans. This case underscores the complexity of diagnosing cryptococcal infections, particularly in immunocompetent patients, and highlights the need for considering cryptococcosis in differential diagnoses of lymphocyte-predominant exudative pleural effusions.

First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province.

Nocardiosis is an infectious disease caused by Nocardia spp., mainly affecting immunocompromised hosts. Nocardia infection is not common; especially Nocardia wallacei infection is even rarer. The patient, female, 61 years old, farmer, has been working in the field for a long time and has normal immune function. Her main clinical manifestation was persistent back pain. Chest-enhanced computed tomography showed pulmonary inflammation. Rare pathogen Nocardia wallacei was detected in alveolar lavage fluid using matrix-assisted laser destructive ionization time-of-flight mass spectrometry. She received treatment with linezolid and was discharged after her condition improved.

A Case of Vaping-Associated Candida and Herpes Simplex Virus (HSV) Co-infection Causing Esophagitis in an Immunocompetent Patient.

Electronic cigarettes (e-cigarettes) and vaping have gained popularity in the last two to five years as an alternative way of consuming nicotine, as well as tetrahydrocannabinol (THC), particularly in the younger population. Vaping/e-cigarettes heat nicotine/THC and other chemical components to create the vapor to be inhaled, which increases the risk of mucosal infection and esophagitis. Although tobacco smoking has been extensively studied and known to affect the oral cavity and esophagus, the effect of vaping is yet to be well-studied. We report a case of odynophagia secondary to esophageal candidiasis, herpes simplex virus (HSV) esophagitis, and reflux esophagitis associated with vaping.

Herpes Zoster in a 13-Year-Old Male Without Prior Varicella Infection.

Herpes zoster (HZ) typically presents following reactivation of latent varicella-zoster virus (VZV) in adult and geriatric patients with a history of prior varicella infection. Primary VZV infection in patients compliant with vaccine schedules and without any immunocompromising condition is rare, with reactivation leading to HZ being even rarer. This case report details one such example involving a 13-year-old immunocompetent and fully immunized male with HZ despite no history of VZV infection, as well as possible explanatory mechanisms for this uncommon presentation. This case report contributes to a growing body of literature on atypical HZ presentations in pediatric populations without any history of prior VZV infection or exposure.