The IL-6 hypothesis in COVID-19: A phase 2, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of free IL-6 sequestration by the monoclonal antibody sirukumab in severe and critical COVID-19.

Background: Upregulation of IL-6 has been associated with worse prognosis in COVID-19 patients. Impact on IL-6 signalling has mostly been limited to clinical outcomes in IL-6 receptor antagonist trials.

Methods: We performed a phase 2, randomised, double-blind, placebo-controlled trial (NCT04380961) of US-based hospitalised adults (<85 years) with laboratory-confirmed SARS-CoV-2 infection and severe (low levels of supplemental oxygen) or critical disease (high levels of oxygen supplementation).

Incidence and risk factors influencing the development of vancomycin nephrotoxicity in children.

Objective: To determine the incidence of vancomycin-associated nephrotoxicity in children and to examine potential risk factors for nephrotoxicity, including average serum trough concentrations ≥ 15 mg/L.

Study Design: Patients ≥ 1 week old to ≤ 19 years with normal baseline serum creatinine values who received vancomycin for ≥ 48 hours between December 2007 and April 2009 were retrospectively evaluated. Nephrotoxicity was defined as a serum creatinine increase of ≥ 0.

Two-dimensional 1H MR spectroscopy of the brain in human immunodeficiency virus (HIV)-infected children.

Purpose: To measure cerebral metabolites in brains of human immunodeficiency virus (HIV)-infected patients using two-dimensional (2D) proton ((1)H) magnetic resonance spectroscopy (MRS), which enables more sensitive detection of metabolites at lower concentrations and delineation of the components of the different choline (Ch) groups in the frequency domain when compared to one dimensional (1D) (1)H-MRS.

Materials And Methods: We examined metabolite/creatine (Cr) and metabolite/Ch ratios in the left frontal brain of 10 HIV-infected (mean age 13.7 +/- 4.

Cerebral metabolites in HIV-infected children followed for 10 months with 1H-MRS.

Background: Previous studies have shown that HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy (1H MRS), but the stability of these measurements over time has not been described in HIV-infected children. The authors recently reported a study of cerebral metabolites in 20 HIV-infected children (6 to 16 years of age); the current study followed 12 of these children (10.0 years +/- 3.

Altered neurometabolite development in HIV-infected children: correlation with neuropsychological tests.

Background: HIV-infected children have abnormal cerebral metabolites, measured by proton MR spectroscopy ((1)H-MRS), but how these abnormalities relate to brain function is unclear.

Methods: Metabolite concentrations in five brain regions of 20 HIV-infected and 13 control children were measured, and these findings were correlated with age, log(10) plasma viral load, CD4 count, and neuropsychological scores.

Results: Compared with control subjects, HIV patients had decreased choline concentration [Cho] in left frontal white matter (LFW) (-12%; p = 0.

Phase I/II trial of intravenous recombinant interleukin-2 in HIV-infected children.

Objectives: To define the tolerated dose of recombinant interleukin-2 (rIL-2) in HIV-infected children (part A), and to determine the safety and immunologic effects of the tolerated rIL-2 dose in a cohort of HIV-infected children (part B).

Design: Open-label, dose-escalation.

Setting: Multiple center study.

Effect of protease inhibitors combined with standard antiretroviral therapy on linear growth and weight gain in human immunodeficiency virus type 1-infected children.

Children with HIV-1 infection and poor growth have a significant increase in the risk of death. We studied the effects of protease inhibitors on the height and weight of 27 HIV-1-infected children and found that in our small pilot study, protease inhibitor therapy had a positive effect on the heights of HIV-1-infected children. Accelerated height velocity was sustained for at least 18 to 20 months.

Pneumococcal and influenza immunization and human immunodeficiency virus load in children.

Objective: HIV-infected children receiving influenza vaccine, pneumococcal vaccine and both vaccines concurrently were studied to examine the effect of immunization on plasma HIV viral load.

Methods: Thirteen children received immunizations: pneumococcal vaccine, 5; pneumococcal and influenza vaccines, 7; and influenza vaccine, 1. Most patients (12 of 13) were receiving combination reverse transcriptase inhibitor antiretroviral therapy without protease inhibitors at the time of immunization.

A "bloodless cesarean section" and perinatal transmission of the human immunodeficiency virus.

Objective: Perinatal transmission of the human immunodeficiency virus is the main pathway for children to become infected with this virus; however, the relative contribution and timing of this transmission, whether transplacental or by exposure through the birth process, have not yet been elucidated. An obvious question is whether the mode of delivery has an impact on this transmission rate. However, a routine cesarean section will primarily diminish the duration of exposure of maternal bodily fluids to the neonate but does not prevent the baby from being exposed to maternal blood coming from the uterine incision.

Early prognostic indicators in primary perinatal human immunodeficiency virus type 1 infection: importance of viral RNA and the timing of transmission on long-term outcome.

The time of perinatal human immunodeficiency virus type 1 (HIV-1) transmission and the pattern of early plasma viremia as predictors of disease progression were evaluated in infected infants followed from birth. Cox proportional hazards modeling demonstrated that a 1-log higher HIV-1 RNA copy number at birth was associated with a 40% increase in the relative hazard (RH) of developing CDC class A or B symptoms (P = .004), a 60% increase in developing AIDS (P = .

Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load.

Objective: To determine if there are levels of human immunodeficiency virus type 1 (HIV-1) associated with a high or low risk of perinatal transmission and to ascertain the mechanism by which zidovudine treatment reduces perinatal transmission.

Design: A nonrandomized prospective cohort study.

Setting: University medical center and two general hospital affiliates from May 1989 to September 1994.

Frequent recurrence and persistence of varicella-zoster virus infections in children infected with human immunodeficiency virus type 1.

Objective: To examine complications and treatment of varicella-zoster virus (VZV) infections in children infected with human immunodeficiency virus type 1 (HIV-1).

Methods: Cases of VZV infection were identified retrospectively by reports to the department of health services and review of medical charts. The CD4+ cell counts were correlated with severity and frequency of VZV episodes.

Correlation of clinical progression in human immunodeficiency virus-infected children with in vitro zidovudine resistance measured by a direct quantitative peripheral blood lymphocyte assay.

A rapid method for determination of zidovudine resistance was developed and results were correlated with clinical outcome in human immunodeficiency virus (HIV)-infected children. The zidovudine susceptibilities of HIV-1 isolates from 34 children were determined through a direct quantitative peripheral blood lymphocyte assay and compared with results of the AIDS Clinical Trials Group resistance assay. Patients' peripheral blood lymphocytes were 5-fold diluted and cocultured with donor lymphocytes and varying concentrations of zidovudine.

Rapid increases in load of human immunodeficiency virus correlate with early disease progression and loss of CD4 cells in vertically infected infants.

The relationship between viral burden, timing of transmission, and clinical progression was investigated in 110 children at risk for vertical human immunodeficiency virus (HIV) infection using quantitative polymerase chain reaction, coculture, and immune complex-dissociated p24 antigen assay. In a cross-sectional study, the mean HIV DNA copy number in 19 symptomatic children was significantly higher than in 31 infected, asymptomatic children (420 +/- 125 vs. 87 +/- 78; P < .

Factors predictive of maternal-fetal transmission of HIV-1. Preliminary analysis of zidovudine given during pregnancy and/or delivery.

Objective: To assess maternal risk factors potentially influencing vertical transmission of human immunodeficiency virus, type 1 (HIV-1), including maternal CD4 cell count; presence of immune complex dissociated (ICD) p24 antigen; maternal zidovudine therapy during pregnancy and/or delivery; complications of pregnancy, such as preterm labor and birth; and obstetric events during labor and delivery, such as duration of labor, mode of delivery, chorioamnionitis, and maternal blood exposure.

Design And Setting: A nonrandomized prospective cohort study at a university medical center and two general hospital affiliates.

Patients: Sixty-three HIV-1-seropositive pregnant women and their 68 infants.

Measles.

Measles has become epidemic over most of the world, with an important increase in the number of cases and associated morbidity and mortality in the United States since 1986. The two major factors responsible for this rise in the number of cases are, first, the increase in unvaccinated preschool-age children and, second, vaccine nonresponders (approximately 5%). The highest attack rate occurred in teenagers (15 to 19 years old) and in nine states (82% of cases).

Functional activities of human antibody induced by the capsular polysaccharide or polysaccharide-conjugate vaccines against Haemophilus influenzae type b.

To determine the in vitro and in vivo activity of human antibody induced by different Haemophilus influenzae type b (Hib) vaccines, pooled human antisera obtained from adults immunized with either polyribosyl ribitol phosphate (PRP) or PRP-conjugated with diphtheria toxoid (PRP-D) vaccines were evaluated for opsonic and protective activity against Hib. In vitro, opsonophagocytic studies revealed that PRP-D induced antisera were approximately 2.5-fold more effective than PRP-induced antisera in supporting neutrophil-mediated killing of an Hib strain.

Antimicrobial therapy of experimental group B streptococcal infection in mice.

Group B beta-hemolytic streptococci (GB-BHS) frequently cause severe infection in newborns. Previous in vitro studies showed accelerated killing of GB-BHS by ampicillin plus gentamicin as compared with ampicillin alone. To extend the in vitro observations, mice were infected experimentally with GB-BHS and treated with gentamicin plus ampicillin or ampicillin alone.

Alteration of lymphocyte subpopulations with cytomegalovirus infection in infancy.

The distribution of immunoglobulin bearing (Ig+), T, and null lymphocyte subpopulations and the lymphocyte response to phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) were determined in three infants with cytomegalovirus (CMV) infection. These infants had significantly decreased percentages of T cells (13%, 29% and 40%) compared to age-matched controls (61 +/- 2%). Compensatory increases in the percentages of Ig+ and null cells occurred.

Antibiotic-killing kinetics of group B streptococci.

Group B streptococci are uniformly susceptible to penicillin or ampicillin. Nevertheless, morbidity and mortality in newborn infants infected with group B streptococci is a major clinical problem. Bacteriologic determinants in the outcome of this infection were studied.