When to perform urine cultures in respiratory syncytial virus-positive febrile older infants?

BACKGROUND: Respiratory syncytial virus (RSV) infections are associated with clinically significant rate of urinary tract infections (UTIs) in young infants. Previous research investigating RSV infections and UTIs has been performed mainly in infants younger than 2 to 3 months and has not focused on the risk of UTI in infants 3 to 12 months. OBJECTIVE: This study aimed to assess the rate of UTIs in febrile RSV-positive older infants admitted as inpatients and identify predictors of UTI in febrile RSV-positive older infants. METHODS: This is a retrospective comparative study of febrile RSV-positive infants 0 to 12 months of age admitted to the inpatient pediatric unit of Lincoln Medical and Mental Health Center, Bronx, from September through April 2006 to 2012. Infants 3 to 12 months were considered the cases, and infants 0 to 3 months were the comparative group. The rate of UTIs between the 2 groups was compared. Univariate tests and multiple logistic regression were used to identify demographic/clinical factors associated with UTI in febrile RSV-positive older infants. RESULTS: A total of 414 RSV-positive febrile infants were enrolled including 297 infants 3 to 12 months of age. The rate of UTI in older infants was 6.1% compared with 6.8% in infants younger than 3 months. Positive urinalysis finding was an independent predictor of UTI (P = 0.003) in older infants. All 11 boys with UTI were uncircumcised, and none of the 51 circumcised boys had UTI. Demographic (race, sex, and age) and clinical factors (temperature, white blood cell count, and absolute neutrophil count) were not associated with UTI. CONCLUSIONS: Febrile older infants who are RSV positive have a clinically significant rate of UTIs. It seems prudent to examine the urine of these older infants. Positive urinalysis finding was a predictive factor of UTI. Circumcised boys are at a decreased risk of UTI, compared with uncircumcised boys.

Fragile X Syndrome: A Review for General Pediatricians.

Fragile X syndrome is the most commonly inherited form of intellectual disability. Identifying fragile X syndrome at a young age can be quite challenging because the classical physical features usually present in late childhood or early adolescence; therefore, it is important to consider genetic testing for all males with unexplained developmental delays, intellectual disability, and autism, females with developmental delays, intellectual disability or autism, and a family history of fragile X gene disorders. There is no specific treatment to manage fragile X syndrome. Still, a prompt referral for early intervention is essential to help maximize the child's learning potential, as well as a referral to child psychology if any behavioral concerns are present. It is of paramount importance for families with a history of fragile X syndrome to have access to genetic counseling as it can aid in future reproductive decisions and the risk of future recurrences of this condition. [Pediatr Ann. 2024;53(7):e269-e271.].

Diagnosing Transient Erythroblastopenia of Childhood: A Review for Pediatricians.

Transient erythroblastopenia of childhood is a rare, benign, self-limited condition seen in infants and young children. Laboratory studies will show moderate or severe normochromic normocytic anemia accompanied by absent or low reticulocytes, neutropenia, and mild thrombocytosis or thrombocytopenia. The etiology is unclear, but it has been associated with clinical or laboratory evidence of a recent viral syndrome. Initial diagnostic studies should be aimed at identifying potential causes of anemia, but a confirmed diagnosis is usually obtained once the hemoglobin level has normalized spontaneously. Differentiation from Diamond-Blackfan anemia is critical, especially in infants. Once the diagnosis is established, treatment is supportive, but red blood cell transfusion is indicated in severe cases. High clinical suspicion is imperative to avoid needless diagnostic and therapeutic measures. [Pediatr Ann. 2024;53(1):e34-e36.].

Slipped Capital Femoral Epiphysis: A Review for Pediatricians.

Slipped capital femoral epiphysis (SCFE) is one of the most common hip pathologies that occurs during adolescence, and its incidence has been increasing over the past decades. For this reason, pediatricians should be aware of this entity to ensure an early diagnosis and intervene in a timely manner. The typical patient with SCFE is an adolescent who is obese presenting with hip pain, but it can also occur in children who are not obese; therefore, SCFE should be part of the differential diagnosis in any skeletally immature patient presenting with hip or knee pain. This article provides an overview for the clinician of relevant aspects of this disease that can lead to serious long-term consequences if not diagnosed and treated appropriately. [Pediatr Ann. 2018;47(9):e377-e380.].

Comparison of urinary tract infection rates among 2- to 12-month-old febrile infants with RSV infections using 1999 and 2011 AAP diagnostic criteria.

BACKGROUND: Infants with RSV infections have been found to have a clinically significant rate of urinary tract infections (UTIs). The American Academy of Pediatrics (AAP) published a revised Clinical Practice Guideline on UTIs in 2011, which includes major changes in diagnostic criteria for UTIs. Past research has been done using previous diagnostic criteria. The objective of the study is to assess the rate of UTIs in febrile infants with respiratory syncytial virus (RSV) infections according to the 2011 revised AAP Diagnostic Criteria and compare the rate of UTIs against the 1999 AAP Diagnostic Criteria. METHODS: A retrospective comparative study of febrile infants (2-12 months) with RSV infections admitted to the Inpatient Pediatric unit of Lincoln Medical and Mental Center, Bronx, NY, from September through April 2006 to 2012. We applied the AAP's 1999 and 2011 diagnostic criteria for UTIs separately to assess the rates of UTIs. RESULTS: A total of 359 RSV-positive febrile patients who were investigated for UTIs were enrolled. Pyuria was found in 11.1% (40/359), positive urine culture 10 000 to 50 000 was found in 1.4% (5/359) and ≥50 000 in 4.7% (17/359). The rate of UTIs using AAP's 1999 criteria was 6.1% (22/359), and using the 2011 criteria the rate was 1.1% (4/359). The rate of UTIs was significantly different between the 2 groups (odds ratio [confidence interval] = 0.17 [0.05, 0.5], P = .001). CONCLUSIONS: The rate of UTIs in RSV-positive febrile infants is very low (1.1%) with the 2011 AAP diagnostic criteria. Previously described increased risk of UTIs may represent asymptomatic bacteriuria or contaminated specimens.

NIH consensus development statement on hydroxyurea treatment for sickle cell disease.

National Institutes of Health consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of (1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ), (2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, (3) questions and statements from conference attendees during open discussion periods that are part of the public session, and (4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the U.S. Government.The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.

Structure-function engineering of interferon-beta-1b for improving stability, solubility, potency, immunogenicity, and pharmacokinetic properties by site-selective mono-PEGylation.

Recombinant interferon-beta-1b (IFN-beta-1b) is used clinically in the treatment of multiple sclerosis. In common with many biological ligands, IFN-beta-1b exhibits a relatively short serum half-life, and bioavailability may be further diminished by neutralizing antibodies. While PEGylation is an approach commonly employed to increase the blood residency time of protein therapeutics, there is a further requisite for molecular engineering approaches to also address the stability, solubility, aggregation, immunogenicity and in vivo exposure of therapeutic proteins. We investigated these five parameters of recombinant human IFN-beta-1b in over 20 site-selective mono-PEGylated or multi-PEGylated IFN-beta-1b bioconjugates. Primary amines were modified by single or multiple attachments of poly(ethylene glycol), either site-specifically at the N-terminus, or randomly on the 11 lysines. In two alternate approaches, site-directed mutagenesis was independently employed in the construction of designed IFN-beta-1b variants containing either a single free cysteine or lysine for site-specific PEGylation. Optimization of conjugate preparation with 12 kDa, 20 kDa, 30 kDa, and 40 kDa amine-selective PEG polymers was achieved, and a comparison of the structural and functional properties of the IFN-beta-1b proteins and their PEGylated counterparts was conducted. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the attachment sites of the PEG polymer. Independent biochemical and bioactivity analyses, including antiviral and antiproliferation bioassays, circular dichroism, capillary electrophoresis, flow cytometric profiling, reversed phase and size exclusion HPLC, and immunoassays demonstrated that the functional activities of the designed IFN-beta-1b conjugates were maintained, while the formation of soluble or insoluble aggregates of IFN-beta-1b was ameliorated. Immunogenicity and pharmacokinetic studies of selected PEGylated IFN-beta-1b compounds in mice and rats demonstrated both diminished IgG responses, and over 100-fold expanded AUC exposure relative to the unmodified protein. The results demonstrate the capacity of this macromolecular engineering strategy to address both pharmacological and formulation challenges for a highly hydrophobic, aggregation-prone protein. The properties of a lead mono-PEGylated candidate, 40 kDa PEG2-IFN-beta-1b, were further investigated in formulation optimization and biological studies.

Tailoring structure-function and pharmacokinetic properties of single-chain Fv proteins by site-specific PEGylation.

The utility of single-chain Fv proteins as therapeutic agents would be realized if the circulating lives of these minimal antigen-binding polypeptides could be both prolonged and adjustable. We have developed a general strategy for creating tailored monoPEGylated single-chain antibodies. Free cysteine residues were engineered in an anti-TNF-alpha scFv at the C-terminus or within the linker segments of both scFv orientations, V(L)-linker-V(H) and V(H)-linker-V(L). High-level expression of 10 designed variant scFv proteins in Pichia pastoris allowed rapid purification. Optimization of site-specific conjugate preparation with 5, 20 and 40 kDa maleimide-PEG polymers was achieved and a comparison of the structural and functional properties of the scFv proteins and their PEGylated counterparts was performed. Peptide mapping and MALDI-TOF mass spectrometric analysis confirmed the unique attachment site for each PEG polymer. Independent biochemical and bioactivity analyses, including binding affinities and kinetics, antigenicity, flow cytometric profiling and cell cytotoxicity rescue, demonstrated that the functional activities of the 10 designed scFv conjugates are maintained, while scFv activity variations between these alternative assays can be correlated with conjugate and analytical designs. Pharmacokinetic studies of the PEGylated scFv in mice demonstrated up to 100-fold prolongation of circulating lives, in a range comparable to clinical antibodies.