Disseminated Cryptococcosis Post Eculizumab Therapy: A Case Report and Literature Review.

Eculizumab is a biologic medication used for the treatment of complement-related disorders including anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. It targets C5 complement, preventing its cleavage into active terminal components. Thus, vaccination against encapsulated organisms is advised before starting this treatment. C5 also has a critical role against Cryptococcus neoformans infection. Here, we present a case of a 34-year-old man with a history of myasthenia gravis who was treated with prednisone and azathioprine in addition to eculizumab that was added to his regimen about a year ago, and who came to the hospital with headache, and was found to have Cryptococcus meningitis with disseminated cryptococcosis. The patient was negative for human immunodeficiency virus. He was treated with antifungal medications, and his condition improved. Although rarely reported, it is important to have a low threshold for diagnosis of cryptococcosis in patients on eculizumab given its complement inhibition mechanism of action.

Unusual Presentation of Corynebacterium Endocarditis in a Patient Without Conventional Risk Factors: A Case Report.

Infective endocarditis (IE) is a widespread condition marked by the infection of native or prosthetic heart valves, the endocardial surface, or an indwelling cardiac device. While native-valve IE is uncommon, patients with IE represent a diverse spectrum. Some respond well to treatment with few complications, while others face severe complications and an increased risk of mortality. Various factors contribute to this outcome, including delayed diagnosis, underlying health conditions like immunocompromised status or chronic diseases, and intravenous drug use. The most prevalent causes of IE are typically streptococci and staphylococci. IE attributed to Corynebacterium species is an exceptionally rare phenomenon, especially in individuals lacking conventional risk factors. This report presents a distinctive case involving Corynebacterium endocarditis in a 63-year-old female with a medical history encompassing intracranial aneurysm, hypothyroidism, and alcoholic cirrhosis. The patient's initial symptoms included shortness of breath, neck pain, and generalized weakness. Despite an initial focus on mild flu-like symptoms and a suspected urinary tract infection, subsequent evaluation unveiled pancytopenia and positive blood cultures for Corynebacterium striatum, culminating in the diagnosis of mitral valve endocarditis. This intricate clinical scenario, replete with numerous complications, underscores the significance of considering unusual pathogens in atypical presentations of IE. It prompts further exploration into the underlying mechanisms contributing to such infrequent occurrences.

Incidence of bloodstream infections in patients with COVID-19: a retrospective cohort study of risk factors and outcomes.

Introduction: Prior evidence found that bloodstream infections (BSIs) are common in viral respiratory infections and can lead to heightened morbidity and mortality. We described the incidence, risk factors, and outcomes of BSIs in patients with COVID-19. Methods: This was a single-center retrospective cohort study of adults consecutively admitted from March to June 2020 for COVID-19 with BSIs. Data were collected by electronic medical record review. BSIs were defined as positive blood cultures (BCs) with a known pathogen in one or more BCs or the same commensal organism in two or more BCs. Results: We evaluated 290 patients with BCs done; 39 (13.4%) had a positive result. In univariable analysis, male sex, black/African American race, admission from a facility, hemiplegia, altered mental status, and a higher Charlson Comorbidity Index were positively associated with positive BCs, whereas obesity and systolic blood pressure (SBP) were negatively associated. Patients with positive BCs were more likely to have severe COVID-19, be admitted to the intensive care unit (ICU), require mechanical ventilation, have septic shock, and higher mortality. In multivariable logistic regression, factors that were independent predictors of positive BCs were male sex (OR=2.8, p=0.030), hypoalbuminemia (OR=3.3, p=0.013), ICU admission (OR=5.3, p<0.001), SBP<100 mmHg (OR=3.7, p=0.021) and having a procedure (OR=10.5, p=0.019). Patients with an abnormal chest X-ray on admission were less likely to have positive BCs (OR=0.3, p=0.007). Conclusions: We found that male sex, abnormal chest X-ray, low SBP, and hypoalbuminemia upon hospital admission, admission to ICU, and having a procedure during hospitalization were independent predictors of BSIs in patients with COVID-19.

Coexistence of Mucormycosis and Granulomatosis With Polyangiitis: A Diagnostic and Therapeutic Challenge.

Mucormycosis is a destructive, necrotizing, and potentially fatal fungal disease that usually affects immunocompromised or diabetic patients. Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis is a rare, aseptic necrotizing, granulomatous vasculitis affecting small- to medium-sized vessels, resulting in systemic manifestations. Here, we present a case of a 46-year-old gentleman with overlapping features of mucormycosis and GPA, that was successfully treated with isavuconazole monotherapy.

Inhibiting KDM6A Demethylase Represses Long Non-Coding RNA Hotairm1 Transcription in MDSC During Sepsis.

Myeloid-derived suppressor cells (MDSCs) prolong sepsis by promoting immunosuppression. We reported that sepsis MDSC development requires long non-coding RNA Hotairm1 interactions with S100A9. Using a mouse model that simulates the immunobiology of sepsis, we find that histone demethylase KDM6A promotes Hotairm1 transcription by demethylating transcription repression H3K27me3 histone mark. We show that chemical targeting of KDM6A by GSK-J4 represses Hotairm1 transcription, which coincides with decreases in transcription activation H3K4me3 histone mark and transcription factor PU.1 binding to the Hotairm1 promoter. We further show that immunosuppressive IL-10 cytokine promotes KDM6A binding at the Hotairm1 promoter. IL-10 knockdown repletes H3K27me3 and reduces Hotairm1 transcription. GSK-J4 treatment also relocalizes nuclear S100A9 protein to the cytosol. To support translation to human sepsis, we demonstrate that inhibiting H3K27me3 demethylation by KDM6A ex vivo in MDSCs from patients with protracted sepsis decreases Hotairm1 transcription. These findings suggest that epigenetic targeting of MDSCs in human sepsis might resolve post-sepsis immunosuppression and improve sepsis survival.

Native Valve Candida metapsilosis Endocarditis Following a Ruptured Appendix: A Case Report.

Candida parapsilosis complex has been further divided into C. parapsilosis, C. orthopsilosis, and C. metapsilosis. C. metapsilosis is considered to be the least virulent fungi of the complex. Candida endocarditis is uncommon but is associated with a very high mortality rate. Prosthetic or previously damaged valves act as common targets, but native, structurally normal valves are seldom affected.  We hereby present a case of Candida metapsilosis endocarditis involving a native aortic valve in an immunocompetent 55-year-old male who was successfully treated with surgical valve replacement and antifungal therapy.

A rare case of empyema due to Cutibacterium acnes in the setting of COVID-19.

Introduction: Cutibacterium acnes is a Gram-positive anaerobic rod that is part of the normal skin flora, as well as the oral cavity, genitourinary and gastrointestinal tracts. When detected, it is usually considered contaminant; but it is infrequently responsible for invasive infections, mainly neurosurgical and joint infections. It is rarely found as a pathogen responsible for lung infections or empyema. Case report: We present a unique case of C. acnes empyema following severe COVID-19, making this the first documented case of empyema due to this bacterium following COVID-19. The microorganism was identified by 16S rRNA gene sequencing. The patient was treated with a combination of antibiotics and surgical intervention. Conclusions: This case demonstrates the potential severity of C. acnes empyema. Further studies are needed to establish management guidance.

KDM6A Lysine Demethylase Directs Epigenetic Polarity of MDSCs during Murine Sepsis.

Sepsis-induced myeloid-derived suppressor cells (MDSCs) increase mortality risk. We previously identified that long non-coding RNA Hotairm1 supports myeloid precursor shifts to Gr1+CD11b+ MDSCs during mouse sepsis. A major unanswered question is what molecular processes control Hotairm1 expression. In this study, we found by a genetic deletion that a specific PU.1-binding site is indispensable in controlling Hotairm1 transcription. We then identified H3K4me3 and H3K27me3 at the PU.1 site on the Hotairm1 promoter. Controlling an epigenetic switch of Hotairm1 transcription by PU.1 was histone KDM6A demethylase for H3K27me3 that derepressed its transcription with possible contributions from Ezh2 methyltransferase for H3K27me3. KDM6A knockdown in MDSCs increased H3K27me3, decreased H3K4me3, and inhibited Hotairm1 transcription activation by PU.1. These results enlighten clinical translation research of PU.1 epigenetic regulation as a potential sepsis immune-checkpoint treatment site.

A Rare Case of Bacteremic Community-Acquired Pneumonia Due to Pasteurella Multocida Presenting With Hemoptysis.

Pasteurella multocida (PM) is a gram-negative bacterium known to cause soft tissue infections, especially after animal bites, with some human infections occurring after animal exposure, usually via inhalation of contaminated secretions. PM pneumonia mainly affects those who are immunocompromised and in individuals with comorbidities. The spectrum of pulmonary disease due to PM is wide, ranging from pneumonia to empyema. The clinical features are indistinguishable from other pathogens, however, hemoptysis seldom occurs as a consequence of PM infection. We present a case of PM pneumonia in an immunocompetent host who had a chief complaint of hemoptysis, making this the sixth documented case to ever-present with hemoptysis.

Clinical Features and Risk Factors for In-Hospital Mortality From COVID-19 Infection at a Tertiary Care Medical Center, at the Onset of the US COVID-19 Pandemic.

BACKGROUND: Mortality from COVID-19 has been associated with older age, black race, and comorbidities including obesity, Understanding the clinical risk factors and laboratory biomarkers associated with severe and fatal COVID-19 will allow early interventions to help mitigate adverse outcomes. Our study identified risk factors for in-hospital mortality among patients with COVID-19 infection at a tertiary care center, in Detroit, Michigan. METHODS: We conducted a single-center, retrospective cohort study at a 776-bed tertiary care urban academic medical center. Adult inpatients with confirmed COVID-19 (nasopharyngeal swab testing positive by real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay) from March 8, 2020, to June 14, 2020, were included. Clinical information including the presence of comorbid conditions (according to the Charlson Weighted Index of Comorbidity (CWIC)), initial vital signs, admission laboratory markers and management data were collected. The primary outcome was in-hospital mortality. RESULTS: Among 565 hospitalized patients, 172 patients died for a case fatality rate of 30.4%. The mean (SD) age of the cohort was 64.4 (16.2) years, and 294 (52.0%) were male. The patients who died were significantly older (mean [SD] age, 70.4 [14.1] years vs 61.7 [16.1] years; P < 0.0001), more likely to have congestive heart failure (35 [20.3%] vs 47 [12.0%]; P = 0.009), dementia (47 [27.3%] vs 48 [12.2%]; P < 0.0001), hemiplegia (18 [10.5%] vs 18 [4.8%]; P = 0.01) and a diagnosis of malignancy (16 [9.3%] vs 18 [4.6%]; P = 0.03).From multivariable analysis, factors associated with an increased odds of death were age greater than 60 years (OR = 2.2, P = 0.003), CWIC score (OR = 1.1, P = 0.023), qSOFA (OR = 1.7, P < 0.0001), WBC counts (OR = 1.1, P = 0.002), lymphocytopenia (OR = 2.0, P = 0.003), thrombocytopenia (OR = 1.9, P = 0.019), albumin (OR = 0.6, P = 0.014), and AST levels (OR = 2.0, P = 0.004) on admission. CONCLUSIONS: This study identified risk factor for in-hospital mortality among patients admitted with COVID-19 in a tertiary care hospital at the onset of U.S. Covid-19 pandemic. After adjusting for age, CWIC score, and laboratory data, qSOFA remained an independent predictor of mortality. Knowing these risk factors may help identify patients who would benefit from close observations and early interventions.

A case of Gemella morbillorum native valve endocarditis and results of in vitro susceptibility testing.

We present a case of a 48 years old male with Gemella morbillorum native mitral valve endocarditis. Due to poor growth of the organism, antimicrobial susceptibility test (AST) could not be performed using the CLSI approved method. AST was determined using Etest© strips and the patient was successfully treated with mitral valve replacement and intravenous ceftriaxone.

Long Non-Coding RNA Hotairm1 Promotes S100A9 Support of MDSC Expansion during Sepsis.

Myeloid-derived suppressor cells (MDSCs) expand during mouse and human sepsis, but the mechanism responsible for this is unclear. We previously reported that nuclear transport of S100A9 protein programs Gr1+CD11b+ myeloid precursors into MDSCs in septic mice. Here, we show that long non-coding RNA Hotairm1 converts MDSCs from an activator to a repressor state. Mechanistically, increased Hotairm1 expression in MDSCs in mice converted S100A9 from a secreted proinflammatory mediator to an immune repressor by binding to and shuttling it from cytosol to nucleus during late sepsis. High Hotairm1 levels were detected in exosomes shed from MDSCs from late septic mice. These exosomes inhibited lipopolysaccharide-stimulated secretion of S100A9 from early sepsis Gr1+CD11b+ cells. Importantly, Hotairm1 knockdown in late sepsis Gr1+CD11b+ MDSCs prevented S100A9 cytosol to nuclear transfer and decreased repression of proimmune T cells. Notably, ectopic expression of Hotairm1 in early sepsis Gr1+CD11b+ cells shuttled S100A9 to the nucleus and promoted the MDSC repressor phenotype. In support of translating the mechanistic concept to human sepsis, we found that Hotairm1 binds S100A9 protein in CD33+CD11b+HLA-DR- MDSCs during established sepsis. Together, these data support that Hotairm1 is a plausible molecular target for treating late sepsis immune suppression in humans and its immune repressor mechanism may be cell autonomous.

HuR promotes miRNA-mediated upregulation of NFI-A protein expression in MDSCs during murine sepsis.

Myeloid-derived suppressor cells (MDSCs) contribute to high mortality rates during sepsis, but how sepsis induces MDSCs is unclear. Previously we reported that microRNA (miR)-21 and miR-181b reprogram MDSCs in septic mice by increasing levels of DNA binding transcription factor, nuclear factor 1 (NFI-A). Here, we provide evidence that miR-21 and miR-181b stabilize NFI-A mRNA and increase NFI-A protein levels by recruiting RNA-binding proteins HuR and Ago1 to its 3' untranslated region (3'UTR). We also find that the NFI-A GU-rich element (GRE)-binding protein CUGBP1 counters miR-21 and miR-181b dependent NFI-A mRNA stabilization and decreases protein production by replacing 3'UTR bound Ago1 with Ago2. We confirmed the miR-21 and miR-181b dependent reprogramming pathway in MDSCs transfected with a luciferase reporter construct containing an NFI-A 3'UTR fragment with point mutations in the miRNA binding sites. These results suggest that targeting NFI-A in MDSCs during sepsis may enhance resistance to uncontrolled infection.

Doctor YouTube's opinion on seasonal influenza: A critical appraisal of the information available to patients.

BACKGROUND: Seasonal influenza is a respiratory illness caused by the influenza virus. During the 2017-2018 flu season, the Centers for Disease Control and Prevention noted approximately 959,000 hospitalizations and 79,400 deaths from influenza. We sought to evaluate the educational quality of informational videos pertaining to seasonal influenza on the popular social media forum, YouTube. METHODS: Using the keywords "seasonal influenza," all videos from 28 January to 5 February 2017 were included and analyzed for characteristics, source, and content. The source was further classified as healthcare provider, alternative-medicine provider, the patient and/or their parents, company, media, or professional society. Videos about other categories of influenza (e.g. swine or Spanish) or in foreign languages were excluded. A total of 10 blinded reviewers scored each video independently. RESULTS: Overall, 300 videos were analyzed, with a median of 341.50 views, 1.00 likes, 0 dislikes, and 0 comments. Based on the average scores of videos by source, there was statistically significant difference in the average score among videos by video source (p < 0.01). Healthcare provider videos had the highest mean scores whereas alternative medicine provider videos had the lowest. CONCLUSIONS: Although the aforementioned video sources scored higher than others, these videos did not fulfill our criteria as far as educating patients thoroughly. Our data also suggest alternative medicine and patient source videos were misleading for patients.Clinical implications: Although videos by healthcare providers were a better source of information, videos on seasonal influenza were shown to be poor sources of valid healthcare information. This study reiterates the need for higher-quality educational videos on seasonal influenza by the medical community.

Continuous Infusion Ampicillin for the Outpatient Management of Enterococcal Endocarditis: A Case Report and Literature Review.

Treatment of enterococcal endocarditis requires up to 6 weeks of intravenous (IV) antimicrobial therapy. When susceptible, an ampicillin-based regimen is preferred. Studies evaluating ampicillin stability utilizing high-pressure liquid chromatography have indicated enhanced stability (greater than 24 hours at room temperature), supporting outpatient administration. Thus, we report the successful treatment of a 30-year-old male with tricuspid valve enterococcal endocarditis in an outpatient setting using continuous infusion ampicillin via an ambulatory infusion pump. The patient received daily gentamicin at an outpatient infusion center with the ampicillin dose to be infused over the next 24 hours. Outpatient ambulatory infusion pumps allow for delivery of ampicillin via continuous infusion or pump-programmed pulse dosing. Preparation and administration in an outpatient infusion center may be a viable option to circumvent stability and delivery issues. Furthermore, 81% (34/42) of treatment days were completed outpatient, supporting that this approach may increase access to treatment and help reduce the economic burden to health care.

A case report of eustachian valve endocarditis due to Salmonella typhimurium in an AIDS patient.

INTRODUCTION: The eustachian valve is a normal remnant of the right valve of the sinus venosus, which directs blood in the embryo life from the inferior vena cava into the left atrium through the foramen ovale. CASE REPORT: We report a case of eustachian valve endocarditis (EVE) secondary to Salmonella typhimurium in a patient with acquired immunodeficiency syndrome (AIDS). The patient also had concomitant Pneumocystis pneumonia. DISCUSSION: Salmonella bacteremia is one of the AIDS-defining illnesses, and many patients will have recurrent episodes. Salmonella endocarditis on the other hand is rare, but when present, it has a significant morbidity and mortality. EVE rarely requires surgical intervention, and the appropriate antibiotics are the treatment of choice. CONCLUSIONS: We recommend clinicians to consider obtaining an echocardiography in AIDS patients with Salmonella bacteremia to search for possible endocarditis, as it does change the treatment plan.