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Objectives: The primary objective was to compare the volume of distribution (Vd), clearance (CL), elimination rate (K e ), and half-life (t½) of amikacin in neonates with cyanotic defects, acyanotic defects, and controls, adjusted for gestational and postnatal age. Secondary objectives were to compare the incidence of acute kidney injury (AKI) between controls and the congenital heart disease (CHD) group and to identify potential risk factors., Methods: This retrospective cohort study included neonates receiving amikacin from January 1, 2013 to August 31, 2016. Patients were excluded if concentrations were not appropriately obtained or if AKI or renal anomalies were identified prior to amikacin initiation. Congenital heart disease was classified as acyanotic or cyanotic. Patients with CHD were matched 1:1 with non-CHD controls according to postmenstrual age. Bivariate analyses were performed using Wilcoxon-Mann-Whitney test, Pearson χ 2 tests, or Fisher exact as appropriate with a p value <0.05. Regression analyses included logistic and analysis of covariance., Results: Fifty-four patients with CHD were matched with 54 controls. Median (IQR) postnatal age (days) at amikacin initiation significantly differed between CHD and controls, 3.0 (1.0-16.0) versus 1.0 (1.0-3.0), p = 0.016. After adjusting for gestational and postnatal age, there was no difference in the mean (95% CI) Vd (L/kg) and CL (L/kg/hr) between CHD and controls, 0.47 (0.44-0.50) versus 0.46 (0.43-0.49), p = 0.548 and 0.05 (0.05-0.05) versus 0.05 (0.05-0.05), p = 0.481, respectively. There was no difference in K e or t½ between groups. There was no difference in AKI between the CHD and controls, 18.5% versus 9.3%, p = 0.16., Conclusions: Clinicians should consider using standard amikacin dosing for neonates with CHD and monitor renal function, since they may have greater AKI risk factors., Competing Interests: Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: mhelms@pediatricpharmacy.org 2021.)

Objective: The SENTINEL1 observational study characterized confirmed respiratory syncytial virus hospitalizations (RSVH) among U.S. preterm infants born at 29 to 35 weeks' gestational age (wGA) not receiving respiratory syncytial virus (RSV) immunoprophylaxis (IP) during the 2014 to 2015 and 2015 to 2016 RSV seasons., Study Design: All laboratory-confirmed RSVH at participating sites during the 2014 to 2015 and 2015 to 2016 RSV seasons (October 1-April 30) lasting ≥24 hours among preterm infants 29 to 35 wGA and aged <12 months who did not receive RSV IP within 35 days before onset of symptoms were identified and characterized., Results: Results were similar across the two seasons. Among infants with community-acquired RSVH ( N  = 1,378), 45% were admitted to the intensive care unit (ICU) and 19% required invasive mechanical ventilation (IMV). There were two deaths. Infants aged <6 months accounted for 78% of RSVH observed, 84% of ICU admissions, and 91% requiring IMV. Among infants who were discharged from their birth hospitalization during the RSV season, 82% of RSVH occurred within 60 days of birth hospitalization discharge., Conclusion: Among U.S. preterm infants 29 to 35 wGA not receiving RSV IP, RSVH are often severe with almost one-half requiring ICU admission and about one in five needing IMV., Competing Interests: E.J.A., J.P.D., E.A.F.S., L.R.K., M.L.F., P.S.P., C.M.E., R.C.W., L.I.W., R.Y., P.A.C., J.B.D., and N.H. are independent investigators who have received research support from AstraZeneca/MedImmune. J.P.D., E.A.F.S., L.R.K., and M.L.F. also received travel support from AstraZeneca/MedImmune to present the results of this or other research studies at scientific meetings. J.P.D., M.L.F., and P.S.P. have served on the speakers’ bureau for AstraZeneca/MedImmune. E.J.A., E.A.F.S., and J.P.D. have served as consultants to AbbVie; P.A.C. has received research support from AbbVie. S.J.M. is an independent statistical consultant to AstraZeneca. K.K.M. and C.S.A. are employees of AstraZeneca and hold stock. V.R.K. and C.P.R. were employees of AstraZeneca at the time this research was conducted. C.P.R. is a current employee of Sobi Inc., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Globally, human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children. There are no licensed vaccines despite the high worldwide disease burden. RSV fusion (F) glycoprotein vaccine is the most advanced candidate for maternal immunization. In this report, a baboon maternal immunization model was used to assess the immunogenicity and protection of infants against pulmonary challenge with human RSV/A. Vaccination in the third trimester produced high anti-RSV F IgG titers and virus-neutralizing antibodies. Infants born to immunized females had high levels of serum RSV antibodies that were comparable to maternal levels at birth and persisted for over 50 days with a half-life of 14-24 days. Furthermore, infants from immunized females and challenged with RSV/A were healthy, developed less severe disease, and had only mild pulmonary inflammatory changes whereas infants born to non-vaccinated females developed more severe disease with marked to moderate interstitial pneumonia, pulmonary edema, and bronchiolar obstruction. These results support the further development of the RSV F vaccine for maternal immunization., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Authors JHT, HL, MGX, DF, MJM, GG, LE, and GS are current or past employees of Novavax, Inc., a for-profit organization, and these authors own stock or hold stock options. These interests do no alter the authors’ adherence to policies on sharing data and materials. RCW, JP, AP, and VI declare no conflict of interest.]., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Ceftazidime use in the neonatal intensive care unit (NICU) has increased after a cefotaxime shortage. The impact of this change is unknown. The purpose was to assess the effect of increased ceftazidime use on susceptibilities of Gram-negative organisms in the NICU., Methods: Retrospective study of Gram-negative isolates identified in blood, urine, cerebrospinal fluid, tracheostomy, abdominal fluid and pleural fluid cultures from a single-center NICU over a 5-year period. Duplicate cultures that occurred within 90 days were noted. Pre- and postshortage periods were defined based on cessation of cefotaxime. Third- and fourth-generation cephalosporin susceptibility rates were compared between periods, as well as rates of extended-spectrum beta-lactamase (ESBL) Escherichia coli and Klebsiella species., Results: Analysis included 666 isolates. Twelve (1.8%) were duplicate isolates that occurred after a 90-day period. The preshortage period included 464 (69.7%) isolates, and the postshortage included 202 (30.3%). No significant differences in susceptibility rates were noted when excluding duplicates. No difference in ESBL rates for E. coli were noted between periods (3.8% vs. 4.9%, P =1.000). No ESBL-positive Klebsiella species were identified. A post-hoc analysis of duplicate isolates demonstrated significant lower susceptibility rates for Pseudomonas aeruginosa to ceftazidime (risk ratio 0.58; 95% CI: 0.43-0.79) and cefepime (risk ratio 0.66; 95% CI: 0.51-0.86)., Conclusions: Ceftazidime use did not appear to affect susceptibility rates for third- and fourth-generation cephalosporins for most Gram-negative organisms in the short-term of 1.5 years. However, susceptibility rates for P. aeruginosa decreased when evaluating duplicate isolates. Long-term monitoring is needed to assess the true impact.

Background: In various types of pulmonary research, pulmonary function testing (PFT) is performed to quantify the severity of lung disease. Induction of apnea and positive pressure ventilation are required for accurate PFT measurements in non-cooperative subjects. We compared two methods of apnea induction in infant olive baboons (Papio anubis)., Methods: Pulmonary function testing results were compared during apnea induced by hyperventilation (CO 2 washout) vs. intravenous propofol (1 dose 10 mg/kg). PFT was evaluated using a hot-wire pneumotachometer incorporated within an Avea ventilator in nine 1-month-old baboons., Results: Propofol induced apnea faster and more reliably. In both groups, PFT values passed the statistical equivalence test and were not significantly different (Student's t-test). There was a trend toward less data variability after propofol administration., Conclusions: Intravenous propofol was non-inferior to CO 2 washout for apnea induction in infant olive baboons. Propofol induced apnea faster and more reliably and yielded less variable PFT results., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: The primary aim was to compare attainment of goal serum amikacin concentrations using two dosage regimens in patients admitted to a neonatal intensive care unit. Secondary objectives included comparison of percentages of supratherapeutic trough concentrations, and subtherapeutic and supratherapeutic peak concentrations., Methods: This was an Institutional Review Board-approved, retrospective study of neonates receiving amikacin during January-December 2013 (group 1) and January-December 2014 (group 2). Group 1 received amikacin dosage consistent with published recommendations, whereas group 2 was dosed using a modified protocol that was based on postmenstrual and postnatal age. Goal serum amikacin peak concentration was defined as 20 to 35 mg/L; hence, subtherapeutic and supratherapeutic peak concentrations were defined as <20 mg/L and >35 mg/L, respectively. Supratherapeutic trough concentrations were >8 mg/L. Between-group analysis was performed using Wilcoxon-Mann-Whitney test, Student t -test or χ 2 , or Fisher exact analysis as appropriate with a p value <0.05., Results: A total of 278 neonates were included (group 1: n = 144; group 2: n = 134). Most patients were male (60%) and were admitted for prematurity or respiratory distress (77%). The median gestational age in group 1 was 34.4 weeks (range, 30.0-37.9 weeks) versus group 2 at 36.9 weeks (range, 31.4-38.9 weeks), whereas the postnatal age was similar between both groups at 4 days. There was a significant increase in attaining goal peak amikacin concentrations between groups 1 and 2, 34% versus 84%, p < 0.001, and decrease in supratherapeutic peak concentrations, 65% versus 12%, p < 0.001. There was no significant difference in subtherapeutic peak or supratherapeutic trough concentrations., Conclusions: A modified neonatal amikacin dosage protocol resulted in increased peak amikacin serum concentration compared with published dosage recommendations. Future research should focus on determination of the optimal dosage regimen in neonates.

Fusarium species are ubiquitous fungi causing a wide array of infections, including invasive disease in the immunosuppressed. We present a fusarium bone infection in a child with Pearson syndrome and review the literature. Ten cases of fusarium osteomyelitis were reported in the past 40 years, and we review the treatments.

Delayed ejaculation (DE) is an uncommon disorder that is difficult to treat because it is poorly understood. The aim was to evaluate the current opinion and clinical management of DE by practitioners in sexual medicine. Members of the Sexual Medicine Society of North America (SMSNA) were invited by email to participate in a web-based survey. The questionnaire consisted of eight questions pertaining to DE. Questions addressed patient volume, qualification of patient bother, ranking of etiologies, perceived success, treatments used, quantification of symptom resolution, and broad characterization of practitioner type. A total of 94 respondents completed the survey with 73% of those being urologists. Fifty-nine percent of the respondents saw ≤ 2 patients a month with DE and 89% of practitioners felt that DE was moderately or severely bothersome to the patients. Etiology was felt to be from medications and psychological factors primarily. Despite treatment modality, 'seldom' success was obtained for 49% of the time and 'never' for 11%. Carbergoline was the most common selected medication for DE. Academic and private urologists reported 'never' or 'seldom' success with sexual counseling compared to other practitioners, respectively (p = 0.008 and p = 0.001). Respondents who saw ≤ 2 patients per month often reported normalization of hypogonadism 'never' or 'seldom' corrected DE (p = 0.047). Delayed ejaculation is still a poorly understood disorder with inconsistent practice patterns seen among members of the SMSNA. A better understanding of this vexing disorder is needed with efforts placed on research and practitioner education., (© 2015 American Society of Andrology and European Academy of Andrology.)

Purpose: Based on studies showing the circadian rhythmicity of testosterone the optimal time of day to draw total testosterone in men has classically been reported as between 8 and 11 a.m. However, further studies demonstrated that the testosterone circadian rhythmicity becomes blunted with age., Materials and Methods: We retrospectively reviewed the charts of 2,569 men who presented with erectile dysfunction for total testosterone and draw times. We compared the men by age group, including less than 40 years and 5-year groupings after age 40 years. Total testosterone was analyzed for variability during the most common draw time hours (7 a.m. to 2 p.m.)., Results: Mean total testosterone at 7 to 9 a.m. and 9 a.m. to 2 p.m. clinically and statistically differed only in men younger than 40 vs 40 to 44 years old (mean difference 207 ng/dl, 95% CI 98-315, p = 0.0004 vs 149 ng/dl, 95% CI 36-262, p = 0.01). No other group showed a clinically and statistically significant difference between those periods., Conclusions: Total testosterone in men with erectile dysfunction who are younger than 45 years should be drawn as close to 7 a.m. as possible because a statistically and clinically relevant decrease in testosterone will occur during the course of the day. Men older than 45 years with erectile dysfunction can have total testosterone drawn at any time before 2 p.m. without misleading results., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Biofilm formation on implanted medical devices is becoming more recognized as both a common finding and a potential problem. Although seen frequently in nature, these sequestered bacterial communities are proving to be an assiduous enemy as medical device technologies advance. The penile prosthesis has gone through many improvements, now with a more reliable mechanical function and a reduced infection rate. However, there remains a notable increase in infectious risk in revisions compared to novel cases, with many implants found to harbor a subclinical bacterial presence isolated in biofilms. This article focuses on recent updates in implant technology and surgical technique to combat infection, and reviews current research on biofilm prevention and treatment.

Introduction: Provoked and spontaneous nocturnal erections are thought to play a role in maintenance of male sexual health through oxygenation of the corpus cavernosa. Conversely, hypoxia is thought to be an etiological factor in the pathogenesis of cavernosal fibrosis and long-term erectile dysfunction. It has been hypothesized that the early penile hypoxia after radical prostatectomy (RP) may lead to fibrosis and consequently a decrease in stretched penile length and long-term erectile dysfunction., Aim: The aim of this study was to assess the changes in penile tissue oxygenation with vacuum erection device (VED) use., Methods: Twenty men between 2 and 24 months following RP were enrolled prospectively. Each man cycled a VED to achieve full erection 10 consecutive times over a period of approximately 2 minutes without constriction ring., Main Outcome Measures: Tissue oximetry was measured at baseline and immediately after VED using a tissue oximeter at five sites: right thigh, right corpora, glans, left corpora, and left thigh. Additional measurements were captured over the course of an hour., Results: Mean age and time from surgery was 58.2 years and 12.6 months, respectively, and the average Sexual Health Inventory for Men score was 7. Use of the VED significantly increased both glanular and corporal oximetry relative to the baseline values for the entire 60 minutes. An initial increase of 55% was seen in corporal oxygenation with VED use., Conclusions: This is the first study demonstrating that a single, brief application of the VED without a constriction ring results in significant improvement in penile oxygen saturation. The use of a VED has significant benefits for patients both with regard to cost and invasiveness when compared with other penile rehabilitation protocols., (© 2014 International Society for Sexual Medicine.)

Introduction. We present the case of a patient who received a two-piece Ambicor penile prosthesis for idiopathic recurrent "stuttering" priapism refractory to other treatment options. The patient returned unable to deflate the device due to an interesting anatomically induced mechanical failure. Aims. To describe the method and findings of this inflatable prosthesis failure. Results. Prosthesis failure occurred due to restrictive corporal diameter and the unique characteristics of fluid reservoir location in the two-piece inflatable prosthesis. The patient was successfully converted to a semirigid prosthesis with resolution of the pain that was due to his prosthesis autoinflation. Conclusion. Stuttering priapism remains a challenging clinical problem. Penile implantation is a reasonable long-term solution in a patient refractory to less invasive options. In patients with fibrotic corpora, a malleable device should be considered (at least temporarily) if unable to dilate comfortably to 13 mm.

Respiratory syncytial virus (RSV) infection of the lower respiratory tract is the leading cause of respiratory failure among infants in the United States of America and annually results in >300,000 deaths worldwide. Despite the importance of RSV, there is no licensed vaccine, and no specific form of therapy. This is largely due to the absence of an appropriate animal model for the evaluation of vaccines and therapeutic agents. We inoculated anesthetized infant (4 wk) baboons (Papio anubis) with a human strain of RSV intranasally or intratracheally. Baboons were monitored daily for clinical changes. Anesthetized baboons were intubated at various intervals, and bronchoalveolar lavage (BAL) was performed for viral culture and determination of leukocyte counts. Sham-infected baboons served as controls. Necropsies were performed on infected baboons on days 1, 3, 5, 8, or 13 after inoculation, with pathological analysis and immunohistochemical staining of lung tissues to detect RSV antigen. Infected baboons developed tachypnea and reduced oxygenation peaking from 4 to 8 days after infection and persisting for ≥14 days. Virus was recoverable in BAL fluid up to 8 days following infection. Necropsy revealed intense interstitial pneumonia, sloughing of the bronchiolar epithelium, and obstruction of the bronchiolar lumen with inflammatory cells and sloughed epithelial cells. RSV antigen was identified in bronchiolar and alveolar epithelium. We conclude that RSV-infected infant baboons develop clinical and pathological changes that parallel those observed in human infants with RSV infection. The infant baboon represents a much-needed model for studying the pathogenesis of RSV infection and evaluating antivirals and vaccines.

Urothelial carcinoma (UC) of the renal pelvis has been rarely shown to metastasize to the skin. Tumor seeding from iatrogenic procedures is a source of spreading of UC to the skin. We herein present a case of primary UC of the renal pelvis with spreading to the skin from a percutaneous nephrostomy tract.

Background: Influenza infection causes excess hospitalizations and deaths in younger patients, but susceptibility to severe disease is poorly understood. While mucosal antibodies can limit influenza-associated infection and disease, little is known about acute mucosal antibody responses to influenza infection., Objectives: These studies characterize mucosal antiviral antibody production in children during lower respiratory infection (LRI) with H1N1 influenza versus other viral LRI and examine the relationship between mucosal antiviral antibodies and protection against severe disease., Methods: B lymphocytes were assessed by immunohistochemistry in lung tissue from infants with fatal acute seasonal influenza infection. Nasopharyngeal secretions (NPS) were obtained at presentation from children with acute respiratory illness, including H1N1 (2009) influenza infection. Total and antiviral antibodies, and inflammatory and immune mediators, were quantified by ELISA. Neutralizing activity in NPS was detected using a pseudotyped virus assay. Viral burden was assessed by qPCR., Results and Conclusions: B lymphocytes were abundant in lung tissue of infants with fatal acute influenza LRI. Among surviving children with H1N1 infection, only a small subset (11%) demonstrated H1N1 neutralizing activity in NPS. H1N1 neutralizing activity coincided with high local levels of antiviral IgM, IgG and IgA, greater detection of inflammatory mediators, and higher viral burden (P = 0·016). Patients with mucosal antiviral antibody responses demonstrated more severe respiratory symptoms including greater hypoxia (P = 0·0018) and pneumonia (P = 0·038). These patients also trended toward younger age, longer duration of illness and longer hospital stays. Prophylaxis strategies that heighten neutralizing antibody production in the mucosa are likely to benefit both older and younger children., (© 2012 Blackwell Publishing Ltd.)

Background: The epidemic pattern of respiratory syncytial virus (RSV) in Croatia is biennial. In order to determine if the circulation of different RSV subtypes affects the outbreak cycle, the aim of the present study was to analyze the epidemic pattern of RSV in children in Croatia (Zagreb region) over a period of 3 consecutive years., Methods: The study group consisted of 696 inpatients, aged 0-5 years, who were hospitalized with acute respiratory tract infections caused by RSV, in Zagreb, in the period 1 January 2006-31 December 2008. The virus was identified in nasopharyngeal secretions using direct immunofluorescence. The virus subtype was determined on real-time polymerase chain reaction., Results: Of 696 RSV infections identified in children, subtype A virus caused 374 infections, and subtype B, 318. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by four epidemic waves of RSV infections: the first, smaller, in the spring of 2006; the second, larger, in December 2006/January 2007; the third in spring 2008, followed by a fourth outbreak beginning in November of 2008. The biennial virus cycles were persistent although the predominant RSV subtype in the first two epidemic waves was subtype B, and in the second two it was subtype A., Conclusion: Over a 3 year period of observation, the biennial RSV cycle in Croatia cannot be explained by a difference in the predominant circulating subtype of RSV. Other unknown factors account for the biennial cycle of RSV epidemics in Croatia., (© 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.)

Dendritic cells (DCs) are important cells of our innate immune system. Their role is critical in inducing adaptive immunity, tolerance, or allergic response in peripheral organs-lung and skin. The lung DCs are not developed prenatally before birth. The DCs develop after birth presumably during the first year of life; exposures to any foreign antigen or infectious organisms during this period can significantly affect DC developmental programming and generation of distinct DC phenotypes and functions. These changes can have both short-term and long-term health effects which may be very relevant in childhood asthma and predisposition for a persistent response in adulthood. An understanding of DC development at molecular and cellular levels can help in protecting neonates and infants against problematic environmental exposures and developmental immunotoxicity. This knowledge can eventually help in designing novel pharmacological modulators to skew the DC characteristics and immune responses to benefit the host across a lifetime.

Objectives: A systematic literature review and meta-analysis was performed to evaluate the impact of prophylaxis with palivizumab on mortality and morbidity associated with respiratory syncytial virus infection in infants at high risk (≤ 35 wks of gestational age, chronic lung disease, or congenital heart disease)., Data Sources: MEDLINE, EMBASE, and Current Contents were used. MEDLINE was searched from January 1, 1990 to May 16, 2007. The bibliographies of accepted studies and recent reviews and proceedings from the past 2 yrs were searched to identify additional relevant studies., Study Selection: Randomized controlled trials and prospective or retrospective cohort studies evaluating all-cause and respiratory syncytial virus-specific mortality, respiratory syncytial virus hospitalizations, and health care use in infants at high risk for respiratory syncytial virus infection receiving prophylaxis with palivizumab., Data Extraction: Data elements from each accepted study were extracted by one researcher and confirmed by a second researcher. Differences were resolved before data entry and analysis., Data Synthesis: A total of 2473 citations were screened and ten comparative studies of palivizumab prophylaxis evaluating >15,000 infants were included. Comparisons of mortality and hospitalization outcomes between infant groups using prophylaxis and not using prophylaxis were made using meta-analyses., Conclusions: Prophylaxis and nonprophylaxis infant groups appeared to be comparable at baseline. All-cause mortality during the respiratory syncytial virus season was 12 of 6380 (0.19%) for infants with prophylaxis vs. 33 of 8182 (0.53%) for infants without prophylaxis (Peto odds ratio, 0.30; 95% confidence interval, 0.17-0.55). Only five respiratory syncytial virus-specific deaths were reported, and the majority of the studies did not report respiratory syncytial virus-related deaths. The rate of respiratory syncytial virus hospitalization was significantly lower among preterm infants with prophylaxis compared with those without prophylaxis (4.1% vs. 10.4%; odds ratio, 0.35; 95% confidence interval, 0.25-0.47). Prophylaxis with palivizumab was associated with a reduction in all-cause mortality and respiratory syncytial virus hospitalization among preterm infants at high risk. Additional research on cause of death among infants at high risk is needed.

Objective: The objective of this study was to test the hypothesis that enhanced ultraviolet germicidal irradiation (eUVGI) installed in our neonatal intensive care unit (NICU) heating ventilation and air conditioning system (HVAC) would decrease HVAC and NICU environment microbes, tracheal colonization and ventilator-associated pneumonia (VAP)., Study Design: The study was designed as a prospective interventional pre- and post-single-center study. University-affiliated Regional Perinatal Center NICU. Intubated patients in the NICU were evaluated for colonization, and a high-risk sub-population of infants <30 weeks gestation ventilated for ≥ 14 days was studied for VAP. eUVGI was installed in the NICU's remote HVACs. The HVACs, NICU environment and intubated patients' tracheas were cultured pre- and post-eUVGI for 12 months. The high-risk patients were studied for VAP (positive bacterial tracheal culture, increased ventilator support, worsening chest radiograph and ≥ 7 days of antibiotics)., Result: Pseudomonas, Klebsiella, Serratia, Acinetobacter, Staphylococcus aureus and Coagulase-negative Staphylococcus species were cultured from all sites. eUVGI significantly decreased HVAC organisms (baseline 500,000 CFU cm(-2); P=0.015) and NICU environmental microbes (P<0.0001). Tracheal microbial loads decreased 45% (P=0.004), and fewer patients became colonized. VAP in the high-risk cohort fell from 74% (n=31) to 39% (n=18), P=0.04. VAP episodes per patient decreased (Control: 1.2 to eUVGI: 0.4; P=0.004), and antibiotic usage was 62% less (P=0.013)., Conclusion: eUVGI decreased HVAC microbial colonization and was associated with reduced NICU environment and tracheal microbial colonization. Significant reductions in VAP and antibiotic use were also associated with eUVGI in this single-center study. Large randomized multicenter trials are needed.

Background: Influenza vaccine immunogenicity in premature infants is incompletely characterized., Objective: To assess the immunogenicity of trivalent, inactivated influenza vaccine (TIV) in extremely low-birth-weight (≤ 1000 g birth weight) premature (<30 weeks gestation) infants. We hypothesized that geometric mean titers of influenza antibody would be lower in premature than in full-term (FT) (≥ 37 week) infants., Design/methods: In this prospective multicenter study, former premature and FT infants who were 6 to 17 months of age received 2 doses of TIV during the 2006-2007 or 2007-2008 influenza seasons. Sera were drawn before dose 1, and 4 to 6 weeks after dose 2. Antibody was measured by hemagglutination inhibition., Results: Over 2 years, 41 premature and 42 FT infants were enrolled; 36 and 33 of these infants, respectively, had postvaccination titers available. Premature infants weighed less (mean, 1.3-1.8 kg difference) at the time of immunization than FT infants. Prevaccination titers did not differ between groups. Premature infants had higher postvaccination antibody geometric mean titers than FT infants to H1 (2006-2007, 1:513 vs. 1:91, P = 0.03; 2007-2008, 1:363 vs. 1:189, P = 0.02) and B/Victoria (2006-2007, 1:51 vs. 1:10, P = 0.02). More premature than FT infants had antibody titers ≥ 1:32 to B/Victoria (85% vs. 60%, P = 0.04) in 2007-2008. Two (5%) premature and 8 (19%) FT infants had adverse events, primarily fever, within 72 hours after vaccination. No child had medically diagnosed influenza., Conclusions: Former premature infants had antibody responses to 2 TIV doses higher than or equal to those of FT children. Two TIV doses are immunogenic and well tolerated in extremely low-birth-weight, premature infants 6 to 17 months old.

The androgen receptor (AR) is expressed in a subset of prostate stromal cells and functional stromal cell AR is required for normal prostate developmental and influences the growth of prostate tumors. Although we are broadly aware of the specifics of the genomic actions of AR in prostate cancer cells, relatively little is known regarding the gene targets of functional AR in prostate stromal cells. Here, we describe a novel human prostate stromal cell model that enabled us to study the effects of AR on gene expression in these cells. The model involves a genetically manipulated variant of immortalized human WPMY-1 prostate stromal cells that overexpresses wildtype AR (WPMY-AR) at a level comparable to LNCaP cells and is responsive to dihydrotestosterone (DHT) stimulation. Use of WPMY-AR cells for gene expression profiling showed that the presence of AR, even in the absence of DHT, significantly altered the gene expression pattern of the cells compared to control (WPMY-Vec) cells. Treatment of WPMY-AR cells, but not WPMY-Vec control cells, with DHT resulted in further changes that affected the expression of 141 genes by 2-fold or greater compared to vehicle treated WPMY-AR cells. Remarkably, DHT significantly downregulated more genes than were upregulated but many of these changes reversed the initial effects of AR overexpression alone on individual genes. The genes most highly effected by DHT treatment were categorized based upon their role in cancer pathways or in cell signaling pathways (transforming growth factor-β, Wnt, Hedgehog and MAP Kinase) thought to be involved in stromal-epithelial crosstalk during prostate or prostate cancer development. DHT treatment of WPMY-AR cells was also sufficient to alter their paracrine potential for prostate cancer cells as conditioned medium from DHT-treated WPMY-AR significantly increased growth of LNCaP cells compared to DHT-treated WPMY-Vec cell conditioned medium.

Objective: To review the fatalities among children hospitalized with respiratory syncytial virus (RSV) infection, and identify factors leading to a fatal outcome., Research Design and Methods: Review of literature identified from a structured search of PubMed (1966-2009) using the following Medical Subject Headings: respiratory syncytial virus infection; hospitalized; infants; and risk factors. Publications were restricted to: English language; full papers; inclusion of > or =10 subjects; children aged < or =18 years, hospitalization for RSV infection; and deaths reported. Case fatality rates were defined as number of deaths divided by number of children hospitalized for RSV and were calculated for each study., Results: Thirty-six studies met the inclusion and exclusion criteria. Case fatality rates among children hospitalized for RSV ranged from 0 to 33%. In general, studies showed that subgroups of high-risk children (chronic lung disease [CLD] 3.5-23%, congenital heart disease [CHD] 2-37%, and prematurity 0-6.1%) had higher fatality rates than older or otherwise healthy children (consistently <1%). Presence of severe underlying comorbidities such as neuromuscular disease, immunosuppression, and malignancies was associated with death among term and/or older (>1 year) children. Higher fatality rates were reported for infants receiving intensive unit care (1.1-8.6%), extracorporeal life support (33%) or for those who acquired nosocomial RSV infection (0-12.2%). The majority of studies did not report cause of death and clinical details of the fatal cases were often not provided. Other limitations of this review include our search limits, the possibility of inherent bias in our methodology that could result in an under or over estimation of case-fatality rates, and potential publication bias., Conclusions: Children at high risk for RSV (CLD, CHD and prematurity), those with severe underlying comorbidities, or those with nosocomial RSV appear to be at increased risk for death after RSV hospitalization. More data are needed on cause of death and how much is directly attributable to RSV.

Respiratory syncytial virus is the most common cause of severe lower respiratory disease in infants and young children. Its importance as a pathogen in the elderly and in the immunocompromised is becoming more clearly understood. RSV infection in infancy may lead to chronic lung disease ion later life. Newer forms of therapy are needed. This review will discuss the status of many types of compounds that interfere with RSV infection, including antibodies, inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitors, fusion inhibitors, entry inhibitors, anti-sense RNA inhibitors, and nucleoprotein inhibitors., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Background: Respiratory syncytial virus (RSV) is the most important respiratory viral pathogen of infancy. The only unequivocally effective pharmacological compound for the management of RSV infection is palivizumab, a monoclonal antibody against the fusion protein of RSV. Recently, motavizumab, a similar but more potent monoclonal antibody, has been developed and tested against palivizumab., Objective: In this review, we summarize data comparing the safety and efficacy of the two monoclonal antibodies in prevention of RSV infection. Other therapeutic options also are discussed., Methods: We reviewed all published articles listing motavizumab or palivizumab in the title or keywords., Results/conclusion: In a large comparative clinical trial for which peer review is pending, motavizumab proved noninferior to palivizumab for prevention of RSV-related hospital admission in infants with underlying conditions placing them at high risk for hospitalization after RSV infection. In this trial, motavizumab in comparison to palivizumab significantly reduced the severity of illness among those infants hospitalized with RSV infection, as well as the number of outpatient lower respiratory infections caused by RSV. Safety profiles of each of the two compounds were excellent. Based on these data, motavizumab should eventually replace palivizumab in the prevention of RSV infection.

Background: The epidemic pattern of respiratory syncytial virus (RSV) is quite different in regions of Europe (biennial epidemics in alternating cycles of approximately 9 and 15 months) than in the Western Hemisphere (annual epidemics). In order to determine if these differences are accounted for by the circulation of different RSV subtypes, we studied the prevalence of RSV subtype A and B strains in Zagreb County from 1 January 2006 to 31 December 2007., Results: RSV was identified in the nasopharyngeal secretions of 368 inpatients using direct fluorescence assays and/or by virus isolation in cell culture. The subtype of recovered strains was determined by real-time PCR. Of 368 RSV infections identified in children during this interval, subtype A virus caused 94 infections, and subtype B 270. Four patients had a dual RSV infection (subtypes A and B). The period of study was characterized by two epidemic waves of RSV infections-one, smaller, in the spring of 2006 (peaking in March), the second, larger, in December 2006/January 2007 (peaking in January). The predominant subtype in both outbreaks was RSV subtype B. Not until November 2007 did RSV subtype A predominate, while initiating a new outbreak continuing into the following calendar year., Conclusion: Though only two calendar years were monitored, we believe that the biennial RSV cycle in Croatia occurs independently of the dominant viral subtype.

Antiviral antibody production during respiratory syncytial virus (RSV) infection in infants is poorly understood. To characterize local B lymphocyte responses, lung tissue and secretions from infants with RSV bronchiolitis were analyzed for innate B cell-stimulating factors and antiviral antibodies. In lung tissues of infants with fatal RSV bronchiolitis, CD20(+) lymphocytes and IgM-positive, IgG-positive, and IgA-positive plasma cells were prominent but CD4(+) T lymphocytes were not. Type I interferon-induced proteins and B cell tropic factors, including B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL), were colocalized in infected epithelium. In nasopharyngeal secretions from infants who survived RSV infection, class-switched antiviral and antinucleosomal antibodies were detected at presentation and correlated with BAFF and APRIL levels. Expression of APRIL and antiviral antibodies of IgA and IgM but not IgG isotype predicted better oxygen saturation. We conclude that B lymphocyte-stimulating factors derived from infected epithelium are primary determinants of the mucosal antibody response in infant RSV bronchiolitis.

Background: Respiratory syncytial virus (RSV) is the most common cause of severe lower respiratory tract infections (LRTI) in infants. The aim of the present study was to analyze the epidemiologic characteristics of RSV outbreaks in Croatian children., Methods: Over a period of 11 consecutive years (1994-2005), 3435 inpatients with acute respiratory infections (ARI) aged from birth to 10 years and were residing in Zagreb County were tested for infection with RSV and other respiratory viruses at the Virology Department, Croatian National Institute of Public Health. RSV was identified in nasopharyngeal secretions by isolation on cell culture and/or detection with monoclonal antibodies using a direct fluorescence assay., Results: RSV was the most common causative agent of ARI (42.2%; 658/1559) for the infants 0-6 months of age. It was also the etiologic agent of LRTI in 49% (495/1010) of infants of similar age. RSV was demonstrated in 56.5% (382/676) of infants with bronchiolitis, and in 36.5% (49/134) of those with pneumonia in this age group., Conclusion: The overall prevalence of RSV infection in Croatian children with acute respiratory illness, and its occurrence in various age groups, has remained stable over the past decade. RSV was found to be the most common cause of bronchiolitis occurring throughout childhood (52.7%; 482/913).

Although respiratory syncytial virus (RSV) infection is the most important cause of bronchiolitis in infants, the pathogenesis of RSV disease is poorly described. We studied histopathologic changes in a panel of lung tissue specimens obtained from infants with fatal cases of primary RSV infection. In these tissues, airway occlusion with accumulations of infected, apoptotic cellular debris and serum protein was consistently observed. Similar observations were found after RSV infection in New Zealand black (NZB) mice, which have constitutive deficiencies in macrophage function, but not in BALB/c mice. A deficiency in the number of alveolar macrophages in NZB mice appears to be central to enhanced disease, because depletion of alveolar macrophages in BALB/c mice before RSV exposure resulted in airway occlusion. In mice with insufficient numbers of macrophages, RSV infection yielded an increased viral load and enhanced expression of type I interferon-associated genes at the height of disease. Together, our data suggest that innate, rather than adaptive, immune responses are critical determinants of the severity of RSV bronchiolitis.

Purpose: Recent data indicate a decline in the urological education of third and fourth year medical students. To determine if this decline has an impact on the treatment of patients we performed a survey to evaluate the general level of knowledge, attitudes and practices with regard to common urological issues seen in a general medical practice among medical students and faculty involved in primary care at an academic institution., Materials and Methods: A confidential questionnaire was distributed to attendings, residents and fellows, and the clinical medical students at our academic institution to ascertain how they evaluate and treat patients with common urological complaints. All responses were entered into SPSS statistical software., Results: A total of 300 surveys were distributed, 150 of which were returned with complete information for data analysis. Knowledge with regard to various conditions including hematuria, recognition of an age specific abnormality in serum prostate specific antigen and overactive bladder was low for all groups. Furthermore, respondents demonstrated a low likelihood of requesting formal urological evaluation for these conditions. Exposure to a urology elective in medical school had a positive impact on some areas of urological evaluation., Conclusions: General urological knowledge with regard to the primary care setting is insufficient. The potential for impact on patient care is enormous. These data highlight the need for a definitive urological curriculum in medical school as well as continued education at the resident and faculty level with regard to evaluation, management and recognition of when to request formal urological evaluation in the primary care setting.

Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more severe illness. We analyzed lung tissue from fatal cases of RSV and influenza LRTI to determine the types of inflammatory cells present. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza, rather than RSV, infection. Lung tissues from fatal RSV and influenza LRTI cases demonstrated extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication and apoptotic crisis.

The immune response to respiratory syncytial virus (RSV) infection has fascinated and frustrated investigators for decades. After adverse responses to early attempts at vaccination, it became popularly held that disease following infection was related to overly aggressive immune responses. However, recent data illustrate that severe forms of disease are related to inadequate, rather than hyperresponsive, adaptive immune reactions. Thus, recovery from primary (and perhaps later) RSV infection is dependent on the quality of innate immune responses. These findings should have enormous significance to the development of vaccines and antiviral compounds.

The paper analyses the epidemic pattern of respiratory syncytial virus (RSV) outbreaks in children in Croatia. Over a period of 11 consecutive winter seasons (1994-2005) 3,435 inpatients from Zagreb County aged from infancy to 10 years who were hospitalised with acute respiratory tract infections were tested for RSV-infection. RSV was identified in nasopharyngeal secretions of patients by virus isolation in cell culture and by detection of viral antigen with monoclonal antibodies. In the Zagreb area, RSV outbreaks were proven to vary in a two-year cycle, which was repeated every 23-25 months. This biennial cycle comprised one larger and one smaller season. Climate factors correlated significantly with the number of RSV cases identified only in the large seasons, which suggests that the biennial cycle is likely to continue regardless of meteorological conditions. Knowledge of this biennial pattern should be useful in predicting the onset of RSV outbreaks in Croatia, and would facilitate planning for the prevention and control of RSV infections in the region.

During the neonatal period, the mammalian host is exposed through mucosal surfaces for the first time to a plethora of environmental macromolecules and microbial agents. The neonatal mucosa is endowed with all major elements of innate and adaptive immunologic repertoire. Rudimentary Peyer's patches and mucosal lymphoid follicles expressing HLA-DR+ and CD4+ cells can be observed as early as 10-11 weeks of gestation. CD5+ and IgA+ B cells can be detected in Peyer's patches by 16-18 weeks. CD7+ CD3+ T lymphocytes have been observed in fetal Peyer's patches, epithelial surfaces as well as in the lamina propria. Interestingly, however, the early neonatal period is also characterized by a relative deficiency in antigen-presenting cell functions, altered cell-mediated immune responses, and a relative increase in apoptosis and eosinophilic responses. After birth, each human being may be colonized by over 100 trillion bacteria, representing over 500 bacterial species. The ratio of bacterial to human cells in a normal adult may exceed 10:1. The nature and the species of microflora acquired in the first few months of life is determined by many factors including, external environmental microflora, introduction of cow's milk, use of antibiotics and immunomodulatory agents, and use of breastfeeding. Recent Investigations have shown that the nature of mucosal microflora acquired in early infancy determines the outcome of mucosal inflammation and the subsequent development of mucosal disease, autoimmunity and allergic disorders later in life. It appears that altered mucosal microflora in early childhood alters signaling reactions which determine T cell differentiation and/or the induction of tolerance. Reduced Th1 and increased Th2 cytokine expression in the respiratory tract associated with increased allergic disease has been correlated with reduced exposure to microbial agents associated with Th1 responses. In contrast, reduced exposure to helminthes in the gut associated with reduced Th2 expression appears to correlate well with dominant Th1 cytokine expression and inflammatory bowel disease. These observations suggest that the nature of interaction between the external environment and the mucosal tissues in the early neonatal period and infancy may be critical in directing and controlling the expression of disease-specific responses in later life.

To obtain knowledge of how meteorological conditions affect community epidemics of respiratory syncytial virus (RSV) infection, RSV activity was recorded year-round in 9 cities that differ markedly in geographic location and climate. Local weather conditions were correlated with weekly or monthly RSV cases. Similar reports from other areas varying in climate were also reviewed. Results demonstrated that for all sites combined, weekly RSV activity was related to temperature in a bimodal fashion, with peaks of activity at temperatures more than 24-30 degrees C and at 2-6 degrees C. RSV activity also was greatest at 45-65% relative humidity. RSV activity was inversely related to ultraviolet B (UVB) radiance at 3 sites where this could be analyzed; the fourth site had minimal amounts of annual UVB radiance. At sites with persistently warm temperatures and high humidity, RSV activity was continuous throughout the year, peaking in summer and early autumn. In temperate climates, RSV activity was maximal during winter, correlating with lower temperatures. In areas where temperatures remained cold throughout the year, RSV activity again became nearly continuous. These data led us to conclude that community activity of RSV is substantial when both ambient temperatures and absolute humidity are very high, perhaps reflecting greater stability of RSV in aerosols; transmission of RSV in cooler climates is inversely related to temperature, possibly as a result of increased stability of the virus in secretions in the colder environment; and UVB radiation may inactivate the virus in the environment or influence susceptibility to RSV by altering host resistance.

Background: Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI., Methods: We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3., Results: Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis., Conclusions: Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis.

Respiratory syncytial (RSV) and parainfluenza (PIV) viruses are primary causes of acute bronchiolitis and wheezing illnesses in infants and young children. To further understand inflammation in the airways following infection, we tested for the presence of matrix metalloproteinases (MMP) and natural tissue inhibitors of MMP (TIMP) in primary and established human cell lines, and in the nasopharyngeal secretions (NPS) of human infants infected with RSV or PIV. Using ELISA and multiplex-based assays, MMP-9 and TIMP-1 proteins were, respectively, detected in 66/67 and 67/67 NPS. During PIV or RSV infection TIMP-1 concentrations were associated with hypoxic bronchiolitis. TIMP-1 amounts were also negatively correlated with O2 saturation, and positively correlated with IL-6, MIP-1alpha, and G-CSF amounts following RSV infection. IL-6, MIP-1alpha, and G-CSF were negatively correlated with O2 saturation during RSV infection. Acute respiratory tract disease was not associated with MMP-9 protein/protease activity. Additional studies using real-time quantitative PCR suggested that MMP-9 mRNA copy numbers were elevated in normal human bronchial epithelial (NHBE) cells infected with RSV, while TIMP-1 and TIMP-2 were not increased. However, ELISA did not reveal MMP-9 protein in the NHBE cell culture supernatants. Hence, the data implied that airway epithelial cells were not the primary source of MMP or TIMP following paramyxovirus infection. Taken together, the data suggested that paramyxovirus infection perturbs MMP-9/TIMP-1 homeostasis that in turn may contribute to the severity of respiratory tract disease., ((c) 2007 Wiley-Liss, Inc.)

Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children worldwide and is responsible for over 120 000 annual hospitalizations in infants in the US alone. RSV is also recognized as a major respiratory viral pathogen in the elderly and other high-risk populations. Bronchiolitis, pneumonia, apnea, respiratory failure, and death are well known manifestations of severe acute RSV disease. RSV infection has also been associated with recurrent wheezing in children, but the mechanisms involved in this association are not completely understood. The host immune response plays a significant role in controlling the infection but is likely also involved in augmenting the disease through pathways that have not been completely identified. The treatment options for RSV infection are very limited. Ribavirin, corticosteroids, and bronchodilators are not used routinely because they have not proven to be sufficiently effective. Education of caregivers, strict handwashing, and avoidance of exposure to environmental factors associated with severe forms of RSV infection are among the most effective preventive means. Passive immunization with monoclonal antibodies provides protection against severe RSV disease in high-risk children. Clinical trials to evaluate the safety and efficacy of a second-generation monoclonal antibody are underway. Efforts to develop a safe and effective RSV vaccine have continued despite the poor outcomes observed following the administration of formalin-inactivated formulations in the 1960s. In the last decade, live attenuated vaccines (including those developed by recombinant techniques) and purified subunit vaccines have all been evaluated in humans. Results of clinical trials have been encouraging, but the availability of a safe and effective RSV vaccine is not a reality yet. Better prevention strategies will have an impact, not only on acute morbidity caused by RSV, but will also likely have an effect on ameliorating the chronic consequences of this disease.

We studied epidemiologic and immunologic factors in infants with bronchiolitis caused by influenza virus. The proportion of these infants who were male and who had an immediate family member with a history of asthma was similar to that of a control group of infants with respiratory syncytial virus (RSV) bronchiolitis. In subjects with influenza virus infection, concentrations of the beta chemokine macrophage inflammatory protein-1alpha (MIP-1alpha), but not other beta chemokines, in nasopharyngeal secretions (NPS) were greater among infants with more severe, hypoxic bronchiolitis than in subjects with mild, nonhypoxic bronchiolitis, or upper respiratory tract infection alone. Quantities of MIP-1alpha were also correlated with lower values of oxygen saturation. These findings point out epidemiologic and immunologic similarities between bronchiolitis caused by influenza and RSV, and suggest that host factors are more important than the nature of the infecting virus in the development of severe forms of bronchiolitis caused by influenza and RSV.

In order to understand early events in the immune response to respiratory syncytial virus (RSV) infection, we studied the presence of various chemokines and cytokines in respiratory secretions of human infants with RSV infection. Interferon gamma (IFNgamma) was present in 30/39 (76.9%) subjects tested, but the IFNgamma-inducing cytokines interleukin (IL)12 and IL18 were detectable in 6/40 (15%) and 11/38 (28.9%) subjects, respectively. Quantities of IL12 and IL18 did not correlate with those of IFNgamma. IL18, but neither IFNgamma nor IL12 was found in significantly greater concentrations in subjects with mild, nonhypoxic forms of bronchiolitis than in those with upper respiratory illness alone or hypoxic bronchiolitis. The findings suggest that IFNgamma may be induced independently of the activities of IL12 and IL18 during RSV infection. Immune responses characterized by relatively greater release of IL18 may be associated with milder forms of bronchiolitis., (Copyright 2004 Wiley-Liss, Inc.)

Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of early life. Studies of the immune response in general (and the innate response in particular) to this agent are of interest for a number of reasons. First, severe forms of illness may be a result of enhanced immunologic responsiveness to viral constituents at the time of infection. Secondly, the immune response to RSV may consist principally of innate immune responses at the time of maximum severity of illness. Third, RSV infection in infancy may be linked via immune mechanisms to the development of childhood wheezing. Finally there are no meaningfully effective forms of therapy for RSV infection, and elucidation of the immune response may suggest new therapeutic approaches. This review will summarize our current knowledge of innate immune responses to RSV infection. Specifically we will review early interactions of the virus with surfactant proteins and Toll-like receptors, chemokine release from infected cells, cytokine release from activated inflammatory cells, activation of neuroimmune pathways, generation of dendritic cells, the release of soluble mediators of airway obstruction, and genetic polymorphisms associated with RSV-related illness., (Copyright Mary Ann Liebert, Inc.)