Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNFα-antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

Background: A feedforward pathological signaling loop generated by TNFα and IFN-γ synergy in the inflamed lung, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define the inflammatory biology of lethal COVID-19 respiratory failure.

Methods: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5 mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥50 compared to baseline and sustained for 48 h.

Rapid and sustained decline in CXCL-10 (IP-10) annotates clinical outcomes following TNF-α antagonist therapy in hospitalized patients with severe and critical COVID-19 respiratory failure.

Background: A feed-forward pathological signaling loop generated by TNFα and IFN-γ in inflamed lung tissue, driving CXCL-10 (IP-10) and CXCL-9 chemokine-mediated activated T-cell and monocyte/macrophage tissue recruitment, may define, sustain and amplify the inflammatory biology of lethal COVID-19 respiratory failure.

Methods: To assess TNFα-antagonist therapy, 18 hospitalized adults with hypoxic respiratory failure and COVID-19 pneumonia received single-dose infliximab-abda therapy 5mg/kg intravenously between April and December 2020. The primary endpoint was time to increase in oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) by ≥ 50 compared to baseline and sustained for 48 hours.

Late-afternoon communication and patient planning (CAPP) rounds: an intervention to allow early patient discharges.

Objective: Measure effect of late-afternoon communication and patient planning (CAPP) rounds to increase early electronic discharge orders (EDO).

Methods: We enrolled 4485 patients discharged from six subspecialty medical services. We implemented late-afternoon CAPP rounds to identify patients who could have morning discharge the subsequent day.

Prospective Observational Study Comparing Sepsis-2 and Sepsis-3 Definitions in Predicting Mortality in Critically Ill Patients.

Background: Sepsis definitions have evolved, but there is a lack of consensus over adoption of the most recent definition, Sepsis-3. We sought to compare Sepsis-2 and Sepsis-3 in the classification of patients with sepsis and mortality risk at 30 days.

Methods: We used the following definitions: Sepsis-2 (≥2 systemic inflammatory response syndrome criteria + infection), Sepsis-3 (prescreening by quick Sequential Organ Failure Assessment [qSOFA] of ≥2 of 3 criteria followed by the complete score change ≥2 + infection), and an amended Sepsis-3 definition, iqSOFA (qSOFA ≥2 + infection).

Selective method for identification and quantification of Bifidobacterium animalis subspecies lactis BB-12 (BB-12) from the gastrointestinal tract of healthy volunteers ingesting a combination probiotic of BB-12 and Lactobacillus rhamnosus GG.

Aim: To develop a novel validated method for the isolation of Bifidobacterium animalis ssp. lactis BB-12 (BB-12) from faecal specimens and apply it to studies of BB-12 and Lactobacillus rhamnosus GG (LGG) recovered from the healthy human gastrointestinal (GI) tract.

Methods And Results: A novel method for isolating and enumerating BB-12 was developed based on its morphologic features of growth on tetracycline-containing agar.

Characteristics and outcomes of neutropenia after orthotopic liver transplantation.

Neutropenia after orthotopic liver transplantation (LT) is relatively common, but the factors associated with its development remain elusive. We assessed possible predictors of neutropenia (absolute neutrophil count [ANC] ≤ 1000/mm(3) ) within the first year of LT in a cohort of 304 patients at a tertiary medical center between 1999 and 2009 using time-dependent survival analysis to identify risk factors for neutropenia. In addition, we analyzed neutropenia as a predictor of the clinical outcomes of death, bloodstream infection (BSI), invasive fungal infection, cytomegalovirus (CMV) disease, and graft rejection within the first year of LT.

No evidence of harms of probiotic Lactobacillus rhamnosus GG ATCC 53103 in healthy elderly-a phase I open label study to assess safety, tolerability and cytokine responses.

Background: Although Lactobacillus rhamnosus GG ATCC 53103 (LGG) has been consumed by 2 to 5 million people daily since the mid 1990s, there are few clinical trials describing potential harms of LGG, particularly in the elderly.

Objectives: The primary objective of this open label clinical trial is to assess the safety and tolerability of 1×1010 colony forming units (CFU) of LGG administered orally twice daily to elderly volunteers for 28 days. The secondary objectives were to evaluate the effects of LGG on the gastrointestinal microbiome, host immune response and plasma cytokines.

Pretransplant lymphopenia is a novel prognostic factor in cytomegalovirus and noncytomegalovirus invasive infections after liver transplantation.

Infection after liver transplantation (LT) remains a leading cause of morbidity and mortality. The risk of infection after LT is highest in those who are most immunosuppressed, but to date, no standard blood marker of one's degree of immunosuppression or risk index has been established. The purpose of this study was to determine whether pretransplant lymphopenia (absolute lymphocyte count < 500 cells/mm3 within 24 hours before LT) is a candidate marker of immunosuppression and could be useful in predicting the risk of cytomegalovirus (CMV) disease and non-CMV invasive infections after LT.

Blood stream infection (BSI) and acute GVHD after hematopoietic SCT (HSCT) are associated.

Blood stream infection (BSI) and acute GVHD (aGVHD) are serious complications of hematopoietic SCT (HSCT). We hypothesized that the two events were not independent of one another. We studied (1) associations between BSI and aGVHD; and (2) the impact of BSI and/or aGVHD on death within 100 days after HSCT, using a retrospective cohort analysis.

Risk factors for death after sepsis in patients immunosuppressed before the onset of sepsis.

Few studies have focused on sepsis in patients with pre-existing immunosuppression. Since the numbers and the incidence of sepsis are increasing, sepsis in immunosuppressed patients will increase in importance. We studied the epidemiology of sepsis and risk factors for 28-d mortality in patients immunosuppressed prior to the onset of sepsis using data from the Academic Medical Center Consortium's (AMCC) prospective observational cohort study of sepsis.

Blood stream infection after hematopoietic stem cell transplantation is associated with increased mortality.

Blood stream infection (BSI) is a serious complication of hematopoietic stem cell transplantation (HSCT). The aim of this retrospective cohort analysis was to describe BSI after HSCT, and to assess the predictors and outcomes of BSI after HSCT using multivariable modeling. Of the 243 subjects transplanted, 56% received allogeneic HSCT and 106 (43.

Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients.

Objective: Vancomycin resistant enterococcal (VRE) blood stream infection (BSI) in neutropenic patients is associated with poor outcome. We report our experience in treating VRE BSI in febrile, neutropenic patients with daptomycin, a recently licensed lipopeptide with bactericidal activity against VRE.

Patients And Methods: Patients with fever, neutropenia and VRE BSI were treated with more than one dose of daptomycin (either 6 mg/kg/day or 4 mg/kg/day) in an open label, emergency-use trial.

The clinical impact of ganciclovir prophylaxis on the occurrence of bacteremia in orthotopic liver transplant recipients.

Background: Cytomegalovirus (CMV) infection or receipt of a CMV-seropositive donor liver has been shown to be an independent predictor of bacteremia in orthotopic liver transplant (OLT) recipients. However, prevention of CMV infection through use of intense CMV prophylaxis has not been examined to assess the impact on bacteremia in liver transplant recipients.

Methods: We analyzed the impact of CMV prophylaxis on rates of bacteremia by examining 192 consecutive OLT recipients during a 2-year follow-up period.

Late and atypical cytomegalovirus disease in solid-organ transplant recipients.

Posttransplantation cytomegalovirus (CMV) disease typically occurs 1-4 months after solid-organ transplantation. The case definition invariably includes unexplained fever for > or =3 days, often with leukopenia. Late and atypical presentation of CMV disease has been rarely reported.

Antimicrobial resistance in the chronically critically ill patient.

Infection caused by organisms resistant to conventional antimicrobial therapy is an emerging problem of global proportions. This article describes the epidemiology of infections caused by resistant organisms in chronically critically ill patients and explores factors and mechanisms that lead to the development of resistance. Specific organisms and strategies for the treatment and control of these resistance organisms are discussed.

Induction of circulating antagonists to IL-1 and TNF by IL-2 administration and their effects on IL-2 induced cytokine production in vitro.

The objectives of this study were to determine whether intensive immunotherapy with IL-2 results in detectable levels of circulating IL-1 and TNF antagonists and whether the levels achieved in vivo are sufficient to affect the generation of secondary proinflammatory cytokines such as IL-1 beta and TNF-alpha. We also sought to determine the extent to which endogenous TNF mediates the generation of an IL-1 antagonist by IL-2-activated PBMCs. In patients undergoing high dose IL-2 immunotherapy, plasma IL-1 receptor antagonist (IL-1ra) levels rose dramatically after the first IL-2 injection, reaching a plateau of 11.

Cross-linking of the beta-glucan receptor on human monocytes results in interleukin-1 receptor antagonist but not interleukin-1 production.

The beta-glucan receptor, found on monocytes and neutrophils, binds glucose polymers derived from fungi. Ligands for the receptor have various immunomodulatory effects, including increased microbicidal killing activity. We have investigated the effect of beta-glucans on the production of interleukin-1 (IL-1) and its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1Ra).

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans.

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin.

Measuring circulating cytokines.

Cytokines, i.e., regulatory proteins derived primarily (but not exclusively) from cells of the immune system, are receiving increasing attention for their influences on physiological processes.

Comparison of first use and reuse of cuprophan membranes on interleukin-1 receptor antagonist and interleukin-1 beta production by blood mononuclear cells.

The magnitude of the changes in a variety of blood constituents on exposure to the dialysis membrane has been used as an index of "biocompatibility," and dialyzer reuse has been postulated to improve biocompatibility by attenuating these changes. We studied the hemodialysis-induced changes in the in vitro production of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-1 beta (IL-1 beta) by peripheral blood mononuclear cells (PBMCs), and compared the effect of first use and reuse of cuprophan membranes on these changes. Studies were performed during dialysis with first use and third reuse of the same kidney.

Detection of tumor necrosis factor soluble receptor p55 in blood samples from healthy and endotoxemic humans.

The tumor necrosis factor (TNF) soluble receptor derived from the cell surface p55 TNF receptor (TNFsRp55) is a naturally occurring substance generated during infection and inflammation. TNFsRp55 inhibits biologic effects of TNF. An RIA was developed to quantitate TNFsRp55 in human blood.

In vitro production of interleukin-1 receptor antagonist in chronic renal failure, CAPD and HD.

Dialysis-related symptoms are believed to be mediated, at least in part, by monocyte/macrophage-derived pro-inflammatory cytokines including interleukin-1 (IL-1) and tumor necrosis factor (TNF). Measuring the production of interleukin-1 receptor antagonist (IL-Ra), a naturally occurring inhibitor of IL-1, opens avenues to study the balance between these two cytokines in patients. We studied the cell content and production of IL-1 beta and IL-Ra by unstimulated and endotoxin- or IgG-stimulated peripheral blood mononuclear cells (PBMC) in undialyzed patients with chronic renal failure (CRF), patients on continuous ambulatory peritoneal dialysis (CAPD) and patients on chronic hemodialysis with reuse cuprophan membranes (HD), and compared them to healthy controls.