Modeling human gastric cancers in immunocompetent mice

Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC 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.

Meningoencephalitis due to Listeria monocytogenes in a Young Immunocompetent Patient: Case Report with Literature Review

Meningoencephalitis secondary to Listeria monocytogenes (L. monocytogenes) mainly affects newborns, the elderly and immunocompromised people;there are extremely rare cases in which said infection occurs in immunocompetent individuals. We present the case of a young adult patient without immunocompromise, who developed meningoencephalitis due to L. monocytogenes;This case is exceptional, since it occurred in an individual outside the classic age group, in addition to not having risk factors, which is why it should be considered an atypical causal agent.

Varicella-Zoster Virus Encephalitis with Hyponatremia in an Immunocompetent Elderly Patient:A Case Report

As a common cause of viral encephalitis,varicella-zoster virus(VZV)may invade the central nervous system of immunosuppressed patients during reactivation.Herein,we report a rare case of an immunocompetent patient with VZV encephalitis who developed severe hyponatremia and was considered to have a suspected primary infection.The patient was diagnosed with the support of second-generation sequencing and had persistent hyponatremia after being cured.Although rare,this case suggests that VZV encephalitis may occur in unexpected patients and present with unusual clinical manifestations,requiring advanced detection methods and clinical expertise for resolution.

Disseminated tuberculosis presenting as meningitis and spondylodiscitis in an immunocompetent adult

Rationale:Disseminated tuberculosis involves the central nervous system in up to a third of cases.However,meningitis and spondylodiscitis due to miliary tuberculosis rarely occur together,particularly in the immuno-competent population.Patient concerns:A 37-year-old immunocompetent male presented with altered level of consciousness for one week and lower back pain with evening pyrexia for one month.Examination revealed spastic paraplegia and left hemiparesis.Diagnosis:Disseminated tuberculosis presenting with meningitis and spondylodiscitis.Interventions:Category I anti-tuberculous therapy with a tapering regimen of intravenous dexamethasone was administered.Outcomes:There was clinical improvement after nine months of treatment.Lessons:Tuberculosis may present with atypical clinical manifestations.Contrast enhanced computed tomography scan or magnetic resonance imaging combined with histopathological features,a high index of suspicion and clinical improvement with anti-tuberculous treatment can confirm the diagnosis in the absence of microbiological evidence,especially in extrapulmonary tuberculosis.

Coexisting cytomegalovirus colitis in an immunocompetent patient with Clostridioides difficile colitis:A case report

BACKGROUND Clostridioides difficile(C.difficile)colitis is one of the most common infections in hospitalized patients,characterized by fever and diarrhea.It usually improves after appropriate antibiotic treatment;if not,comorbidities should be considered.Cytomegalovirus(CMV)colitis is a possible co-existing diagnosis in patients with C.difficile infection with poor treatment response.However,compared with immunocompromised patients,CMV colitis in immunocompetent patients is not well studied.CASE SUMMARY We present an unusual case of co-existing CMV colitis in an immunocompetent patient with C.difficile infection.An 80-year-old female patient was referred to the infectious disease department due to diarrhea,abdominal discomfort,and fever for 1 wk during her hospitalization for surgery.C.difficile toxin B polymerase chain reaction on stool samples was positive.After C.difficile infection was diagnosed,oral vancomycin treatment was administered.Her symptoms including diarrhea,fever and abdominal discomfort improved for ten days.Unfortunately,the symptoms worsened again with bloody diarrhea and fever.Therefore,a sigmoidoscopy was performed for evaluation,showing a longitudinal ulcer on the sigmoid colon.Endoscopic biopsy confirmed CMV colitis,and the clinical symptoms improved after using ganciclovir.CONCLUSION Co-existing CMV colitis should be considered in patients with aggravated C.difficile infection on appropriate treatment,even in immunocompetent hosts.

Chronic pulmonary mucormycosis caused by rhizopus microsporus mimics lung carcinoma in an immunocompetent adult:A case report

BACKGROUND Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients.This disease usually develops acutely and progresses rapidly,often leading to a poor clinical prognosis.Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients.CASE SUMMARY A 43-year-old man,who was a house improvement worker with a long history of occupational dust exposure,presented with an irritating cough that had lasted for two months.The patient was previously in good health,without dysglycemia or any known immunodeficiencies.Chest computed tomography revealed a mass in the left lower lobe,measuring approximately 6 cm in diameter,which was suspected to be primary lung carcinoma complicated with obstructive pneumonia.Thoracoscopic-assisted left lower lobectomy was performed,and metagenomic next-generation sequencing detection,along with special pathological staining of surgical specimens,suggested Rhizopus microsporus infection.Postoperatively,the patient’s respiratory symptoms were relieved,and no signs of recurrence were found during the six-month follow-up.CONCLUSION This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency.The patient’s surgical outcome was excellent,reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.

Next-generation sequencing technology for the diagnosis of Pneumocystis pneumonia in an immunocompetent female:A case report

BACKGROUND Pneumocystis pneumonia(PCP)is a serious fungal infection usually seen in patients with human immunodeficiency virus,and it is more frequently found and has a high fatality rate in immunocompromised people.Surprisingly,it rarely occurs in immunocompetent patients.However,the clinical diagnosis of this pathogen is made more difficult by the difficulty of obtaining accurate microbiological evidence with routine tests.This case reports a PCP patient with normal immune function who was diagnosed through next-generation sequencing(NGS).CASE SUMMARY A 23-year-old female who had no special disease in the past was admitted to the hospital with a persistent fever and cough.Based on the initial examination results,the patient was diagnosed with bipulmonary pneumonia,and empirical broad-spectrum antibiotic therapy was administered.However,due to the undetermined etiology,the patient's condition continued to worsen.She was transferred to the intensive care unit because of acute respiratory failure.After the diagnosis of Pneumocystis jirovecii infection through NGS in bronchoalveolar lavage fluid and treatment with trimethoprim/sulfamethoxazole and caspofungin,the patient gradually recovered and had a good prognosis.CONCLUSION This case emphasizes that,for patients with normal immune function the possibility of PCP infection,although rare,cannot be ignored.NGS plays an important role in the diagnosis of refractory interstitial pneumonia and acute respiratory failure.

Esophagitis Due to Actinomycosis in an Immunocompetent Patient with a History of SARS-Cov-2 Infection: Case Report

We present an unusual case of esophageal actinomycosis that developed in a patient with normal immunity and a history of acute SARS-CoV-2 infection. We report a case of a 56-year-old female patient without chronic degenerative pathologies with a history of non-severe acute SARS-CoV-2 infection that occurred two months prior to her presentation, treated with prednisone and betamethasone orally and inhaled, respectively for 21 days. The pivotal symptom is dysphagia and definitive diagnosis requires a tissue culture of the affected organ or a biopsy that shows the classic sulfur granules. Currently, antibiotic treatment with beta-lactams, such as amoxicillin/clavulanic acid, is still effective, as it was in our patient.

Atypical Presentation of Ramsay Hunt Syndrome without Facial Palsy in an Immunocompetent Senegalese Adulte Patient

First described in 1907 by James Ramsay Hunt, Ramsay Hunt syndrome is a recurrence (reactivation) of varicella-zoster virus (VZV) affecting the geniculate ganglion, secondary to a decrease in cell-mediated immunity. The strict definition of Ramsay Hunt syndrome is peripheral facial nerve palsy accompanied by erythematous vesicular rash on the ear. We report a 57-year-old female immunocompetent patient complaining of otalgia, small vesicles on the Ramsey Hunt Zone. She does not complain fever, hearing loss, nausea, vomiting or dizziness. There was no peripheral facial nerve palsy, no reduction of taste sensation, no ataxia or nystagmus, Romberg sign was negative. Our patient targets two of the three criteria needed for the diagnosis of Ramsay Hunt syndrome. She began to take Acyclovir-Steroid (AS) therapy very early with good outcome. This suggests that prompt diagnosis and management improve outcome and prevent occurrence of nerve palsy in Ramsay Hunt syndrome.

Efficacy and safety of corticosteroids in immunocompetent patients with septic shock

BACKGROUND: The use of corticosteroids in septic shock has been studied for many decades but yielded conflicting results. We conducted a systematic review to evaluate the efficacy and the safety of corticosteroids in immunocompetent patients with septic shock.METHODS: Medline via Pub Med, Cochrane Central Register of Controlled Trials(CENTRAL) in the Cochrane Library, and EMBASE were searched from inception to March 2020. Two reviewers independently identified randomized controlled trials(RCTs) comparing corticosteroids with a control group for immunocompetent patients with septic shock. Data were abstracted and reported following the Cochrane Handbook for Systematic Review of Intervention and Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) statement. The efficacy outcome included mortality and shock reversal. The safety outcomes were infection, gastrointestinal bleeding, and hyperglycemia.RESULTS: Nine RCTs with a total of 1,298 patients were included. Compared with the control group, corticosteroid group did not lower the short-term(28 or 30 days) mortality(risk ratio [RR] 0.95, 95% confidence interval(CI) 0.85 to 1.06, inconsistency [I2]=0%, trial sequential analysis [TSA]-adjusted CI 0.83 to 1.09, moderate-certainty evidence). Corticosteroids significantly shortened the time to shock reversal compared with the control group(mean difference [MD] –21.56 hours;95% CI –32.95 to –10.16, I2=0%;TSA-adjusted CI –33.33 to –9.78, moderate-certainty evidence). The corticosteroid treatment was associated with an increased risk of hyperglycemia but not the infection or gastrointestinal bleeding.CONCLUSIONS: The corticosteroid treatment is not associated with lower short-or longterm mortality compared with placebo in immunocompetent patients with septic shock. However, corticosteroids significantly shorten the time to shock reversal without increasing the risk of infection. The patient's immune status should also be considered during clinical treatment and clinical trials in future.

Pulmonary nocardiosis due to Nocardia otitidiscaviarum in an immunocompetent host-A rare case report

Nocardiosis is a localized or disseminated infection caused by soil-borne aerobic actinomycetes. Pulmonary nocardiosis is a rare infection mostly occurring in immunocompromised patients.We reported a case of 36 year old immunocompetent non-smoker female patient with no premorbid illness who presented with fever,cough with scanty sputum,hemoptysis,left sided chest pain and exertional dyspnea for two weeks.There was no past history of tuberculosis,diabetes mellitus or steroid therapy.Chest X-ray showed homogenous peripherally based opacity in the left upper zone.Bronchoscopy was done and brushing sent for culture,which showed colonies with features of Nocardia species after 48 hours.Further phenotypic characterization revealed it to be Nocardia otitidiscaviarum.Patient was treated with cotrimaxazole for six months after which complete recovery was evidenced symptomatically and radiologically.We report this case to emphasize the fact that among the Nocardia species,Nocardia otitidiscaviarum as causative agent of pulmonary disease is rarely reported even in immunocompromised individuals.

Cytomegalovirus ileitis in an immunocompetent elderly adult

Cytomegalovirus enteritis is most usually associated with patients positive for human immunodeficiency virus or immunosuppressed transplant patients. The gastrointestinal tract may be affected anywhere from the esophagus to the colon, but the small bowel involvement is rare. We report a case of cytomegalovirus ileitis in an immunocompetent adult, which was confirmed by histopathologic findings through colonoscopic biopsy.

A rare case of community acquired Burkholderia cepacia infection presenting as pyopneumothorax in an immunocompetent individual

Burkholderia cepacia(6.cepacia)infection is rarely reported in an immunocompetent host.It is a well known occurence in patients with cystic fibrosis and chronic granulomatous disease where it increases both morbidity and mortality.It has also been included in the list of organisms causing nosocomial infections in an immunocompetent host,most of them transmitted from the immunocompromised patient in which this organism harbors.We report a rare case of isolation of B.cepacia from the bronchoalveolar lavage fluid of an immunocompetent agriculturist who presented with productive cough and fever associated with a pyopneumothorax.This is the first case of community acquired infection reported in an immunocompetent person in India.

Encephalitis with convulsive status in an immunocompetent pediatric patient caused by Bartonella henselae

Cat scratch's disease caused by Bartonella henselae, is known to be a self-limited benign process in immunocompetent children. The association with neurologic manifestations is very uncommon especially in patient with no immunologic defects and in cases without specific treatment. A 7 years old male patient, without any immunocromised defect, presented an atypic presentation of the cat scratch disease. The patient came to the hospital in two opportunities in a status epilepticus, in both cases the diagnosis was encephalitis by Bartonella henselae and the evolution with treatment was monitored with PCR(polymerase chain reaction) in cerebrospinal fluid and blood, as well as IFI(IgM, IgG) serology(indirect immunofluorescence). The patient had a favorable clinical and laboratory evolution for 6 months showing no recurrence of the disease.

Cytomegalovirus-associated colitis causing diarrhea in an immunocompetent patient

Cytomegalovirus （CMV） colitis rarely occurs in immunocompetent patients. We report a case of disabling and life threatening diarrhea in an immunocompetent elderly woman due to CMV colitis. The diagnosis of CMV was based on histological examination of tissues biopsied at colonoscopy, positive CMV antigen and high CMV-lgM titer in peripheral blood samples and a good response to systemic gancyclovir treatment. We conclude that CMV should be considered in the differential diagnosis of colitis in elderly immunocompetent patients.

Cytomegalovirus ileo-pancolitis presenting as toxic megacolon in an immunocompetent patient: A case report

BACKGROUND Cytomegalovirus(CMV) enterocolitis presenting in the form of pancolitis or involving the small and large intestines in an immunocompetent patient is rarely encountered, and CMV enterocolitis presenting with a serious complication, such as toxic megacolon, in an immunocompetent adult has only been reported on a few occasions.CASE SUMMARY We describe the case of a 70-year-old male with no history of inflammatory bowel disease or immunodeficiency who presented with toxic megacolon and subsequently developed massive hemorrhage as a complication of CMV ileopancolitis. The patient was referred to our institute for abdominal pain and distension. Abdominal X-ray showed marked dilatation of ileum and whole colon without air-fluid level, and sigmoidoscopy with biopsy failed to reveal any specific finding. After 7 d of conservative treatment, massive hematochezia developed, and he was diagnosed to have CMV enterocolitis by colonoscopy with biopsy. Although the diagnosis of CMV enterocolitis was delayed, the patient was treated successfully by repeat colonoscopic decompression and antiviral therapy with intravenous ganciclovir.CONCLUSION This report cautions that CMV-induced colitis should be considered as a possible differential diagnosis in a patient with intractable symptoms of enterocolitis or megacolon of unknown cause, even when the patient is nonimmunocompromised.

Pleural effusion in an immunocompetent host with cryptococcal pneumonia:A case report

BACKGROUND Pulmonary cryptococcosis is an opportunistic infection that mainly occurs among immunocompromised patients although it can sometimes occur in immunocompetent individuals.However,the imaging findings of pulmonary cryptococcosis in immunocompetent hosts differ from those in immunosuppressed patients.In addition,the most common imaging findings of isolated pulmonary cryptococcosis are single or multiple nodules.Cavities and the halo sign are,however,prevalent in immunosuppressed patients.In immunocompetent patients,lung consolidation,pleural effusion or cavities are scarce.CASE SUMMARY A 29-year-old Asian male was admitted to our hospital with complaints of cough and fever that had persisted for a month.As a chest computed tomography scan showed consolidation in his left lower lobe,he was initially diagnosed with pneumonia and received antibiotic treatment.A second review of the chest computed tomography image revealed multiple cavities and pleural effusion.Flexible fiberoptic bronchoscopy was subsequently performed,bronchoalveolar lavage fluid and serum cryptococcal antigen tests were positive.Cryptococcus capsules were observed in bronchoalveolar lavage fluid ink stain.Histopathological examination of a percutaneous lung biopsy from the left lower lobe further revealed granulomatous inflammation,and periodic acid-Schiff staining showed red-colored yeast walls,signifying pulmonary cryptococcosis.The patient was then treated with a daily dose of fluconazole(0.4 g),but the cough and fever still persisted.We therefore changed treatment to voriconazole(0.2 g,twice a day),and the patient’s clinical outcome was satisfactory.CONCLUSION Although rare,clinicians should not disregard the possibility of cavities and pleural effusion occurring in immunocompetent hosts without underlying diseases.

Cryptococcus infection with asymptomatic diffuse pulmonary disease in an immunocompetent patient:A case report

BACKGROUND Cryptococcus presenting as an opportunistic pathogen mainly affects immunocompromised patients,but the disseminated form of infection is rare among immunocompetent populations.The partial radiographic characteristics of pulmonary cryptococcosis mimic lung carcinoma,leading to unnecessary open chest exploratory surgery,and the lack of a gold-standard noninvasive diagnostic increases the risk of misdiagnosis.Positron emission tomography/computed tomography(PET/CT),a sensitive method for distinguishing malignant tumors,coupled with cryptococcal latex agglutination test showing a high positive rate may overcome these issues.CASE A 36-year-old man presented for general examination,without health complaints.Routine CT showed multiple pulmonary nodules and a mass with high maximum standardized uptake value.Initially,we suspected primary malignancy with hematogenous metastasis.Although his routine fungal analysis had been negative,subsequent CT-guided percutaneous core needle biopsy and histopathology examination indicated a diagnosis of pulmonary cryptococcosis.Fluconazole(200 mg/d)antifungal drug treatment was initiated,and 1 mo later the pulmonary mass had reduced in size markedly(on chest CT scan)without any complications.CONCLUSION Serologic and PET/CT examinations may not rule out cryptococcosis,and percutaneous lung puncture is critical under all circumstances.

Nonalcoholic fatty liver disease as a risk factor for cytomegalovirus hepatitis in an immunocompetent patient:A case report

BACKGROUND Almost 80 percent of adults in the United States have had cytomegalovirus(CMV)infection by age 40.The number of symptomatic CMV hepatitis cases has been increasing along with non-alcoholic fatty liver disease(NAFLD)cases in the United States that is estimated to be 25 percent of the population.In this paper,we try to link these two entities together.CASE SUMMARY In this case report,we describe a young female who presented with fever,nausea,and vomiting who was found to have NAFLD and CMV hepatitis that was treated supportively.CONCLUSION In this case report,we describe NAFLD as a risk factor for CMV hepatitis and discuss the possible impact on clinical practice.We believe,it is essential to consider NAFLD and it’s disease mechanisms’localized immu-nosuppression,as a risk factor of CMV hepatitis and severe coronavirus disease 2019 infection.

Cryptoccocal Neuromeningitis in Immunocompetent Infant in Bonassama District Hospital, Douala: A Case Report

Cryptococcosis is rare in children. We report a case of cryptococcal meningitis in an infant whose mother works as a poultry farmer (chicken farm). The infant was received in the context of fever with convulsions. We performed a lumbar puncture and started antibiotic treatment. Cerebrospinal fluid (CSF) analysis was performed including Indian ink staining. CSF results showed the presence of yeast and we replaced antibiotics with fluconazol-based treatment. After the loss of sight and the appearance of a motor deficit, a brain scan was performed showing cerebral edema. Several lumbar punctures were performed for 02 weeks until partial recovery of visual acuity and motor deficit. This case highlights the importance of taking into account the patient’s history when making the diagnosis. In our case, the working conditions and the employment of the mother guided the realization of the Indian ink coloring of the CSF. Treatment with fluconazol continued for 22 weeks with a completely regained visual acuity and gradual improvement in motor deficit despite limited resources.