Recurrent Salmonella bacteraemia and right internal iliac artery endarteritis in a splenectomised patient.

A man in his mid-70s with a complex medical history, including splenectomy, presented with fever and rigours. Workup revealed serotype bacteraemia and right internal iliac artery endarteritis. Two weeks following a 6-week course of antibiotics, he had a recurrence of Salmonella bacteraemia requiring an extended course of treatment.

Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI.

Introduction: Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI.

Objective, Design, And Patients: To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities.

Prevalence of Comorbid Factors in Patients With Recurrent Clostridioides difficile Infection in ECOSPOR III, a Randomized Trial of an Oral Microbiota-Based Therapeutic.

Background: Although comorbidities are risk factors for recurrent Clostridioides difficile infection (rCDI), many clinical trials exclude patients with medical conditions such as malignancy or immunosuppression. In a phase 3, double-blind, placebo-controlled, randomized trial (ECOSPOR III), fecal microbiota spores, live (VOWST, Seres Therapeutics; hereafter "VOS," formerly SER-109), an oral microbiota therapeutic, significantly reduced the risk of rCDI at week 8. We evaluated the efficacy of VOS compared with placebo in patients with comorbidities and other risk factors for rCDI.

Safety and Tolerability of SER-109 as an Investigational Microbiome Therapeutic in Adults With Recurrent Clostridioides difficile Infection: A Phase 3, Open-Label, Single-Arm Trial.

Importance: A safe and effective treatment for recurrent Clostridioides difficile infection (CDI) is urgently needed. Antibiotics kill toxin-producing bacteria but do not repair the disrupted microbiome, which promotes spore germination and infection recurrence.

Objectives: To evaluate the safety and rate of CDI recurrence after administration of investigational microbiome therapeutic SER-109 through 24 weeks.

Assessment of Quality of Life Among Patients With Recurrent Clostridioides difficile Infection Treated with Investigational Oral Microbiome Therapeutic SER-109: Secondary Analysis of a Randomized Clinical Trial.

Importance: Recurrent Clostridioides difficile infection (CDI) is a debilitating disease leading to poor health-related quality of life (HRQOL), loss of productivity, anxiety, and depression. The potential association of treatment with HRQOL has not been well evaluated.

Objectives: To explore the association of SER-109 compared with placebo on HRQOL in patients with recurrent CDI up to week 8.

Novel case of empyema necessitans caused by .

Poorly controlled long-standing empyema can dissect through soft tissues and skin resulting in empyema necessitans. We present the first reported case of empyema necessitans caused by which was treated successfully with antimycobacterial therapy. The case highlights the indolent nature of the pathogen and the importance of an accurate diagnosis.

BK virus associated with small cell carcinoma of bladder in a patient with renal transplant.

A man in his 70s with a complex medical history, including cadaveric renal transplant, presented with recurrent urinary tract infections. Investigation revealed recurrent urinary pathogens, including and persistent BK viruria. Cystoscopy revealed a pedunculated mass in the right posterior-lateral wall, inferior to the transplant urethral orifice, and biopsy of this mass showed invasive small cell carcinoma with a prominent adenocarcinoma component.

SER-109, an Oral Microbiome Therapy for Recurrent Infection.

Background: Current therapies for recurrent infection do not address the disrupted microbiome, which supports spore germination into toxin-producing bacteria. SER-109 is an investigational microbiome therapeutic composed of purified Firmicutes spores for the treatment of recurrent infection.

Methods: We conducted a phase 3, double-blind, randomized, placebo-controlled trial in which patients who had had three or more episodes of infection (inclusive of the qualifying acute episode) received SER-109 or placebo (four capsules daily for 3 days) after standard-of-care antibiotic treatment.

Compartmentalization of anti-oxidant and anti-inflammatory gene expression in current and former smokers with COPD.

Background: Patients with chronic obstructive pulmonary disease (COPD) have high oxidative stress associated with the severity of the disease. Nuclear factor erythroid-2 related factor 2 (Nrf2)-directed stress response plays a critical role in the protection of lung cells to oxidative stress by upregulating antioxidant genes in response to tobacco smoke. There is a critical gap in our knowledge about Nrf-2 regulated genes in active smokers and former-smokers with COPD in different cell types from of lungs and surrogate peripheral tissues.

Successful cure of daptomycin-non-susceptible, vancomycin-intermediate Staphylococcus aureus prosthetic aortic valve endocarditis directed by synergistic in vitro time-kill study.

Infectious complications following surgical valve replacements are extremely difficult to treat, often requiring prolonged antimicrobials therapy with or without surgery. Vancomycin-intermediate Staphylococcus aureus is an infrequent pathogen, with an estimated prevalence of less than 0.3%, but presents even greater challenges.

Professional learning and development of postdoctoral scholars: a scoping review protocol.

Background: A growing number of postdoctoral scholars are following diverse career paths that require broad skill sets to ensure success. Yet, most postdoctoral professional learning and development initiatives are intended for academic careers and seldom include professional skills needed to succeed in non-academic settings. Given that fewer than 20% of postdoctoral scholars will obtain tenure-track academic positions, there is a great need for postdoctoral scholars to prepare for a range of future careers.

Sialic Acid-Dependent Inhibition of T Cells by Exosomal Ganglioside GD3 in Ovarian Tumor Microenvironments.

The tumor microenvironment is rendered immunosuppressive by a variety of cellular and acellular factors that represent potential cancer therapeutic targets. Although exosomes isolated from ovarian tumor ascites fluids have been previously reported to induce a rapid and reversible T cell arrest, the factors present on or within exosomes that contribute to immunosuppression have not been fully defined. In this study, we establish that GD3, a ganglioside expressed on the surface of exosomes isolated from human ovarian tumor ascites fluids, is causally linked to the functional arrest of T cells activated through their TCR.

Successful treatment of multidrug-resistant pubic symphysis osteomyelitis with ceftolozane/tazobactam.

New antibiotic options are needed for the treatment of multidrug-resistant (MDR) infections. We present a case of a man aged 64 years with a bladder fistula due to radiation, ultimately causing osteomyelitis of the pubic symphysis. Repeated antibiotic courses, without correcting the fistula, resulted in infection with MDR He was successfully treated for his osteomyelitis through cystectomy, aggressive debridement and a prolonged course of antimicrobials directed at the MDR isolate.

Correction: Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

[This corrects the article DOI: 10.1371/journal.pone.

Lack of Effect of Oral Sulforaphane Administration on Nrf2 Expression in COPD: A Randomized, Double-Blind, Placebo Controlled Trial.

Background: COPD patients have high pulmonary and systemic oxidative stress that correlates with severity of disease. Sulforaphane has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2).

Methods: This parallel, placebo-controlled, phase 2, randomized trial was conducted at three US academic medical centers.

Native valve Proteus mirabilis endocarditis: successful treatment of a rare entity formulated by in vitro synergy antibiotic testing.

Infective endocarditis caused by Proteus mirabilis is a rare and poorly reported disease, with no well-defined effective antibiotic regimen. Here, we present a case of P. mirabilis aortic valve endocarditis.

Burkholderia ginsengisoli bacteraemia: emergence of a novel pathogen.

Burkholderia ginsengisoli is a non-pathogenic Gram-negative bacterium that ordinarily serves as a plant endosymbiont. We report the first case of human infection with B. ginsengisoli presenting as bacteraemia in a young man with severe Crohn's disease.

The Impact of Exogenous Factors on Respiratory Pathogen-Induced Innate Alveolar Macrophage Responses in COPD.

Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have fundamentally impaired innate immune responses to toll-like receptor (TLR) ligands of nontypeable Haemophilus influenzae (NTHI). However, whether dysfunctional inflammatory responses in COPD extend to macrophage interactions with intact respiratory pathogens beyond NTHI has not been explored. Furthermore, the influences of exogenous factors, including active smoking and medications, on pathogen-induced innate immune responses have only begun to be investigated.

Impaired Innate COPD Alveolar Macrophage Responses and Toll-Like Receptor-9 Polymorphisms.

Background: Dysfunctional innate responses of alveolar macrophages to nontypeable Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae contribute to morbidity in chronic obstructive pulmonary disease (COPD). Our earlier studies discovered impaired COPD alveolar macrophage responses to Toll-like receptor (TLR) ligands of nontypeable H. influenzae and provide rationale for further evaluation of TLR signaling.

Extracellular Vesicles Present in Human Ovarian Tumor Microenvironments Induce a Phosphatidylserine-Dependent Arrest in the T-cell Signaling Cascade.

The identification of immunosuppressive factors within human tumor microenvironments, and the ability to block these factors, would be expected to enhance patients' antitumor immune responses. We previously established that an unidentified factor, or factors, present in ovarian tumor ascites fluids reversibly inhibited the activation of T cells by arresting the T-cell signaling cascade. Ultracentrifugation of the tumor ascites fluid has now revealed a pellet that contains small extracellular vesicles (EV) with an average diameter of 80 nm.

Impaired innate immune alveolar macrophage response and the predilection for COPD exacerbations.

Background: Alveolar macrophages (AM) in COPD have fundamentally impaired responsiveness to Toll-like receptor 2 (TLR2) and TLR4 ligands of non-typeable Haemophilus influenzae (NTHI). However, the contribution of innate immune dysfunction to exacerbations of COPD is unexplored. We hypothesised that impaired innate AM responses in COPD extend beyond NTHI to other pathogens and are linked with COPD exacerbations and severity.

Non-typeable Haemophilus influenzae infective endocarditis in a renal transplant recipient: compromised host or virulent strain?

Non-typeable Haemophilus influenzae (NTHI) rarely cause endocarditis. Of the limited reports of H influenzae endocarditis, most have been due to encapsulated organisms or have had limited bacterial characterisation. We encountered a transplant recipient with native valve NTHI endocarditis and were intrigued to find no previous descriptions of this entity.

Phagocytic dysfunction of human alveolar macrophages and severity of chronic obstructive pulmonary disease.

Background: Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have fundamental impairment of phagocytosis for nontypeable Haemophilus influenzae (NTHI). However, relative selectivity of dysfunctional phagocytosis among diverse respiratory pathogens: NTHI, Moraxella catarrhalis (MC), Streptococcus pneumoniae (SP), and nonbacterial particles, as well as the contribution of impaired phagocytosis to severity of COPD, has not been explored.

Methods: Alveolar macrophages, obtained from nonsmokers (n = 20), COPD ex-smokers (n = 32), and COPD active smokers (n = 64), were incubated with labeled NTHI, MC, SP, and fluorescent microspheres.

Pseudomonas aeruginosa intrapetrous internal carotid artery mycotic aneurysm--a complication of mastoiditis: first reported case.

Mycotic aneurysms of the intrapetrous carotid artery are a rare complication of adjacent middle ear infections that occur by direct invasion of arterial adventitia. We report the first case of a Pseudomonas aeruginosa mycotic intrapetrous carotid aneurysm arising from mastoiditis, confirmed with middle ear cultures, presenting with high-grade bacteraemia and otorrhagia in a diabetic man. Infection was related to elective myringotomy tube placement and was initially treated with empiric antibiotics.