Ca2+ signals in human umbilical endothelial cells derived from pregnancy with fetal growth restriction associated with hypertensive disorder.

Fetal growth restriction associated with hypertensive disorders of pregnancy (FGR-HDP) is a prevalent pathology with a higher risk of perinatal morbimortality. In this condition, placental insufficiency and endothelial dysfunction serve key roles. The present prospective cohort study monitored 11 patients with an FGR-HDP and 15 with full-term normotensive pregnancies and studied post-natal intracellular calcium concentration ([Ca2+]i) signals in human umbilical vein endothelial cells (HUVECs). Small fetuses with placental insufficiency were identified using fetal biometry with Doppler velocimetry. Mean gestational age and birth weight were 31.8±4.1 weeks and 1,260±646 g for FGR-HDP and 39.2±0.8 weeks and 3,320±336 g for normal births, respectively. Abnormal umbilical artery Doppler waveforms were found in 64% of neonates with FGR-HDP. A significant percentage (86%) of FGR newborns were admitted to the neonatal intensive care unit at Gustavo Fricke hospital, Viña del Mar, Chile, with one case of death after birth. [Ca2+]i signals were measured by microfluorimetry in Fluo-3-loaded HUVECs from primary cultures. Altered [Ca2+]i signals were observed in HUVECs from FGR-HDP, where the sustained phase of ATP-induced [Ca2+]i responses was significantly reduced compared with the normotensive group. Also, the [Ca2+]i signals induced with 10 mM Ca2+ after depletion of internal Ca2+ stores were significantly higher. The present study provides a better comprehension of the role of altered cytosolic Ca2+ dynamics in endothelial dysfunction and an in vitro model to assess novel therapeutic approaches for decreasing or preventing complications in FGR-HDP.

Mielopatía por déficit de cobre: serie de casos y revisión de la literatura / Myelopathy due to copper deficiency: A case series and review of the literature

El déficit de cobre puede presentarse como una mielopatía y manifestarse como una ataxia sensorial secundaria a una desmielinización de los cordones posteriores de la médula espinal. Puede acompañarse de citopenias, principalmente anemia y leucopenia. Se presenta una serie de casos de tres pacientes con mielopatía por déficit de cobre, diagnosticados y manejados desde el año 2020 al 2022 en un hospital universitario de alta complejidad en Colombia. Dos de los casos eran mujeres. El rango de edad fue entre 57 y 68 años. En los tres casos, los niveles séricos de cobre estaban disminuidos y en dos de ellos, se descartaron diferentes causas de mielopatía que afectan los cordones posteriores de la médula espinal como el déficit de vitamina B12, vitamina E y ácido fólico, tabes dorsal, mielopatía por virus de la inmunodeficiencia humana, esclerosis múltiple e infección por el virus linfotrópico humano de tipo I y II, entre otras. Sin embargo, un paciente tenía deficiencia de vitamina B12 asociada con de cobre en el momento del diagnóstico de la mielopatía. En los tres casos hubo ataxia sensitiva y en dos, la paraparesia fue el déficit motor inicial. Se deben incluir siempre la determinación de los niveles de cobre dentro del abordaje diagnóstico de todo paciente con enfermedad gastrointestinal crónica, con diarrea crónica, síndrome de mala absorción o reducción significativa de la ingestión en la dieta, y que desarrolle síntomas neurológicos sugestivos de compromiso de los cordones, ya que se ha reportado que el retraso en el diagnóstico de las mielopatías se asocia con pobres desenlaces neurológicos.

Copper deficiency can present as myelopathy by the manifestation of sensory ataxia, secondary to demyelination of the posterior cords of the spinal cord, accompanied by cytopenia, mainly anemia, and leukopenia. Case series study of three patients with myelopathy due to copper deficiency, diagnosed and managed from 2020 to 2022 in a highly complex university hospital in Colombia. Regarding gender, two cases were female patients. The age range was between 57 and 68 years. In all three cases serum copper levels were decreased, and in two of these, different causes of myelopathy affecting the posterior cords of the spinal cord were ruled out, such as vitamin B12, vitamin E and folic acid deficiency, tabes dorsalis, myelopathy due to human immunodeficiency virus, multiple sclerosis and infection by the human lymphotropic virus type I and II, among others. However, at the moment of the myelopathy diagnosis, one patient had vitamin B12 deficiency associated with copper insufficiency. All three cases presented sensory ataxia, and in two, paraparesis was the initial motor deficit. The diagnostic approach must include copper levels assessment in every case of patients with chronic gastrointestinal pathology, chronic diarrhea, malabsorption syndrome, or significant reduction in dietary intake; and the development of neurological symptoms that may suggest cord involvement. It has been reported that a delay in diagnosis can lead to poor neurological outcomes.

Pharmacological Inhibition of p-21 Activated Kinase (PAK) Restores Impaired Neurite Outgrowth and Remodeling in a Cellular Model of Down Syndrome.

Down syndrome (DS) is characterized by the trisomy of chromosome 21 and by cognitive deficits that have been related to neuronal morphological alterations in humans, as well as in animal models. The gene encoding for amyloid precursor protein (APP) is present in autosome 21, and its overexpression in DS has been linked to neuronal dysfunction, cognitive deficit, and Alzheimer's disease-like dementia. In particular, the neuronal ability to extend processes and branching is affected. Current evidence suggests that APP could also regulate neurite growth through its role in the actin cytoskeleton, in part by influencing p21-activated kinase (PAK) activity. The latter effect is carried out by an increased abundance of the caspase cleavage-released carboxy-terminal C31 fragment. In this work, using a neuronal cell line named CTb, which derived from the cerebral cortex of a trisomy 16 mouse, an animal model of human DS, we observed an overexpression of APP, elevated caspase activity, augmented cleavage of the C-terminal fragment of APP, and increased PAK1 phosphorylation. Morphometric analyses showed that inhibition of PAK1 activity with FRAX486 increased the average length of the neurites, the number of crossings per Sholl ring, the formation of new processes, and stimulated the loss of processes. Considering our results, we propose that PAK hyperphosphorylation impairs neurite outgrowth and remodeling in the cellular model of DS, and therefore we suggest that PAK1 may be a potential pharmacological target.

Isolation and Purification of Chromaffin Granules from Adrenal Glands and Cultured Neuroendocrine Cells.

Chromaffin granules isolated from adrenal glands constitute a powerful experimental tool to the study of secretory vesicle components and their participation in fusion and docking processes, vesicle aggregation, and interactions with cytosolic components. Although it is possible to isolate and purify chromaffin granules from adrenal glands of different species, bovine adrenal glands are the most used tissue source due to its easy handling and the large amount of granules that can be obtained from this tissue. In this chapter, we describe an easy-to-use and short-term protocol for efficiently obtaining highly purified chromaffin granules from bovine adrenal medulla. We additionally include protocols to isolate granules from cultured bovine chromaffin cells and PC12 cells, as well as a section to obtain chromaffin granules from mouse adrenal glands.

Learning From Agility, Partnership and Innovation During the Covid-19 Pandemic: A Perspective From Industry.

Two years after the COVID-19 pandemic started, the world continues to adapt to the profound effects that Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has had on our lives. As the global crisis took hold, many looked to the medical technology/device industry for guidance and solutions. All while the industry itself, was disrupting its own processes and activities. In order to evolve and deliver accelerated innovation the industry had to be agile, resilient and collaborative with the broader healthcare community and technology partners. Now comes a time when we will start to see what changes were temporary and which ones will become part of the new process, but one thing is certain, we will not be going back to where we were pre-pandemic.

Detection of respiratory syncytial virus defective genomes in nasal secretions is associated with distinct clinical outcomes.

Respiratory syncytial virus (RSV) causes respiratory illness in children, immunosuppressed individuals and the elderly. However, the viral factors influencing the clinical outcome of RSV infections remain poorly defined. Defective viral genomes (DVGs) can suppress virus replication by competing for viral proteins and by stimulating antiviral immunity. We studied the association between detection of DVGs of the copy-back type and disease severity in three RSV A-confirmed cohorts. In hospitalized children, detection of DVGs in respiratory samples at or around the time of admission associated strongly with more severe disease, higher viral load and a stronger pro-inflammatory response. Interestingly, in experimentally infected adults, the presence of DVGs in respiratory secretions differentially associated with RSV disease severity depending on when DVGs were detected. Detection of DVGs early after infection associated with low viral loads and mild disease, whereas detection of DVGs late after infection, especially if DVGs were present for prolonged periods, associated with high viral loads and severe disease. Taken together, we demonstrate that the kinetics of DVG accumulation and duration could predict clinical outcome of RSV A infection in humans, and thus could be used as a prognostic tool to identify patients at risk of worse clinical disease.

Restraint of Human Skin Fibroblast Motility, Migration, and Cell Surface Actin Dynamics, by Pannexin 1 and P2X7 Receptor Signaling.

Wound healing is a dynamic process required to maintain skin integrity and which relies on the precise migration of different cell types. A key molecule that regulates this process is ATP. However, the mechanisms involved in extracellular ATP management are poorly understood, particularly in the human dermis. Here, we explore the role, in human fibroblast migration during wound healing, of Pannexin 1 channels and their relationship with purinergic signals and in vivo cell surface filamentous actin dynamics. Using siRNA against Panx isoforms and different Panx1 channel inhibitors, we demonstrate in cultured human dermal fibroblasts that the absence or inhibition of Panx1 channels accelerates cell migration, increases single-cell motility, and promotes actin redistribution. These changes occur through a mechanism that involves the release of ATP to the extracellular space through a Panx1-dependent mechanism and the activation of the purinergic receptor P2X7. Together, these findings point to a pivotal role of Panx1 channels in skin fibroblast migration and suggest that these channels could be a useful pharmacological target to promote damaged skin healing.

Evaluation of the FecalSwab for Stool Specimen Storage and Molecular Detection of Enteropathogens on the BD Max System.

The FecalSwab system (Copan Italia, Brescia, Italy) is a convenient alternative to bulk stool for the diagnosis of enteric pathogens. Although the U.S. Food and Drug Administration (FDA) approved for transport and culture of enteric bacterial pathogens, the FecalSwab has not been well assessed for its suitability with molecular platforms. In this study, we evaluated the FecalSwab as a specimen type for the BD Max system using the viral and bacterial enteric panels (BD Diagnostics, Baltimore, MD, USA). A total of 186 unpreserved stool specimens were collected and used to prepare matched bulk stool and FecalSwab samples. Performance was equivalent (P > 0.48) to bulk stool for all targets when 50 µl of FecalSwab specimen was loaded onto the BD Max assays. As stool specimens are often collected off-site from the clinical microbiology laboratory and require transport, we assessed the stability of stool specimens stored for up to 14 days at 4°C, 22°C, or 35°C to account for varying transportation conditions. Molecular detection for the majority of viral targets (excluding astrovirus) was unaffected (change in cycle threshold [ΔCT ] ≤ 1) by sample storage temperature over the 2-week period; however, detection of enteric bacteria was variable if specimens were not refrigerated (22°C or 35°C). By demonstrating equivalent performance to matched bulk stool and maintaining molecular detection sensitivity when stored at 4°C, we suggest that the FecalSwab is a suitable specimen type for enteropathogen diagnostics on the BD Max system.

Routine HIV Test Results in 6 US Clinical Laboratories Using the Recommended Laboratory HIV Testing Algorithm With Geenius HIV 1/2 Supplemental Assay.

BACKGROUND: Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. METHODS: We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. RESULTS: Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. CONCLUSIONS: Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

Evaluation of the automated aptima HIV-1 quant Dx assay for both qualitative and quantitative testing in pediatric patients.

BACKGROUND: There are currently no FDA-cleared assays with a dual-claim for both diagnosis and monitoring of HIV-1. The Aptima HIV-1 Quant Dx Assay on the Panther platform (Panther) is the first commercially available test that is CE-marked for both HIV-1 diagnosis and monitoring, but only FDA-cleared for HIV-1 monitoring. OBJECTIVE: To evaluate the Panther assay for use as a qualitative and quantitative HIV-1 assay in a pediatric population, including patients younger than 24 months old, and review its effect on laboratory efficiency and hands-on-time following its implementation. STUDY DESIGN: 100 patient specimens previously tested on the Abbott m2000 RealTime HIV-1 assay (RealTime) and 185 patient specimens previously tested on the Aptima HIV-1 RNA Qualitative Assay (RNA Qual) were tested on the Panther. Verification panels were used to establish precision and linearity. In addition, 268 samples from 134 patients under 24 months of age were also evaluated on the Panther. RESULTS: Overall agreement between the Panther and RealTime assays was 83 %. The mean difference between the two methods was 0.10 Log copies/mL. All Panther measurements were linear across the dynamic range (R2 = 0.999). The Panther and RNA Qual assays showed 100 % agreement. Implementation of the assay opened 600 sq. ft. of space, saved 0.4 FTE and reduced hands-on-time by 70 %. CONCLUSIONS: The Panther assay is an excellent option for HIV-1 qualitative detection and quantitative testing in pediatric patients, including those under 24 months of age. HIV testing on one platform has opened up space in the clinical laboratory and reduced hands on testing time.

Reactivation Viremia in Pediatric Sepsis.

OBJECTIVES: Reactivation viremia is associated with adverse clinical outcomes and immune dysfunction in adults with sepsis. We determined the incidence of viremia and its association with clinical outcomes and immune paralysis phenotype in children with severe sepsis. DESIGN: Prospective cohort study. SETTING: Single academic PICU from September 2016 to March 2018. PATIENTS: Fifty-nine patients 2-17 years old treated for severe sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We performed real-time polymerase chain reaction assays on whole blood specimens to determine the incidence of cytomegalovirus. Cytomegalovirus was detected in three patients (5%). All patients with cytomegalovirus viremia were seropositive, with an incidence of 13% in this subset. We additionally performed Epstein-Barr virus and human herpesvirus-6 polymerase chain reaction assays on last available specimens and detected Epstein-Barr virus in 4% and human herpesvirus-6 in 30% of the study population. Overall, viremia was not associated with clinical outcomes or immune function in univariable analyses. However, viremia was associated with lower odds of complicated course (defined as death within 28 d or ≥ 2 organ dysfunctions at 7 d) after controlling for age, Pediatric Risk of Mortality III score, and blood transfusion (adjusted odds ratio, 0.08; 95% CI, 0.01-0.84; p = 0.04). CONCLUSIONS: Children with severe sepsis had low rates of detectable viremia, which limited analyses of its association with clinical outcomes or immune paralysis phenotype. Given the rare occurrence of cytomegalovirus viremia, in particular, our study does not support a role for viremia as a biomarker of illness severity or as a modifiable risk factor of clinical outcomes for most patients. Future studies on the role of viremia in pediatric sepsis will need to consider the challenges posed by low rates of viremia in this population.

Análisis bibliométrico y de mapeo de la educación en cirugía laparoscópica y robótica en urología / Bibliometric Analysis of Education in Laparoscopic and Robotic Surgery in Urology

Objetivo Se realizó un análisis bibliométrico para conocer la situación actual de la educación en cirugía laparoscópica y robótica en urología. Métodos La búsqueda fue realizada en la base de datos MEDLINE y EMBASE en marzo de 2020, a través del facilitador de búsqueda: FABUMED y PUBMED-PUBREMINER, utilizando los siguientes criterios (Laparoscopy OR robotics) AND (education urology) AND (1988:2019[dp])) y establecer los artículos disponibles respecto a educación en cirugía laparoscópica en urología. Adicionalmente se realizó un análisis de mapeo bibliométrico así como mapas de redes de colaboración. Resultados Se obtuvieron 1383 revisiones en la literatura publicadas en 172 revistas. Las revistas con más publicaciones fueron: Journal of Endourology (167) y factor de impacto (FI) 2.26, BJU International (101, FI 4.52) Urology (90, FI 1.86) y Journal of Urology (71, FI 5.6). La producción total se dio en 49 países, los países con mayor número de publicaciones fueron Estados Unidos con 362 (26.1%) y Reino Unido 152 (10.9%), Latinoamérica estuvo encabezada por Brasil con 17 publicaciones. Conclusiones El mayor número de publicaciones se observó a partir del 2006 years durante la última década ha estado liderado por Estados Unidos. En Colombia la investigación de educación en cirugía laparoscópica y robótica es mínima, posiblemente por carecer de programas de entrenamiento en los programas de residencia. Este análisis bibliométrico permite mostrar que la producción bibliográfica en esta área puede depender de que existan programas formales de entrenamiento que a futuro beneficien a toda la comunidad urológica.

Objective A bibliomeric analysis was performed to know the current situation of education in laparoscopic and robotic surgery in Urology. Methods The literature search was made using MEDLINE and EMBASE database on March 2020, we used de search facilitators FABUMED and PUBMED-PUBREMINER, we used the following criteria por the search (Laparoscopy OR robotics) AND (education urology) AND (1988: 2019 [dp])) and we obtained the articles available regarding education in laparoscopic surgery in urology. Additionally, a bibliometric mapping analysis was performed as well as collaboration network maps. Results We found 1383 reviews in the literature published in 172 journals. The journals with most publications were: Journal of Endourology (167) and impact factor (FI) 2.26, BJU International (101, FI 4.52) Urology (90, FI 1.86) and Journal of Urology (71, FI 5.6). Overall production was in 49 countries, the countries with the highest number of publications were the United States with 362 (26.1%) and the United Kingdom 152 (10.9%), Latin America was led by Brazil with 17 publications. Conclusions Most of publications was observed from 2006 and during the last decade it has been led by the United States. In Colombia, educational research in laparoscopic and robotic surgery is minimal, possibly due to the lack of training programs in residency programs. This bibliometric analysis shows that bibliographic production in this area may depend on the existence of formal training programs that will benefit the entire urological community in the future.

Outcomes of human adenovirus infection and disease in a retrospective cohort of pediatric solid organ transplant recipients.

Information about HAdV infection in SOT recipients is limited. We aimed to describe HAdV infection epidemiology and outcomes in a single-center retrospective cohort during the era of PCR availability. SOT recipients transplanted at the CHOP 2004-2013 were followed up for 180 days post-transplant. HAdV infection was defined as a positive HAdV PCR from a clinical specimen. HAdV disease was defined by organ-specific radiologic and/or laboratory abnormalities. No HAdV surveillance protocols were employed during the study period; testing was solely per clinician discretion. Progression of HAdV infection was defined as HAdV disease or ≥1-log viral load increase since a corresponding site's first positive specimen. Of the assembled 425 SOT recipients, 227 (52.6%) had ≥1 HAdV PCR. Twenty-four (10.6%) had ≥1 HAdV-positive PCR. HAdV-positive subjects were younger than uninfected subjects (2.0 years vs 6.5, P = 0.001). Infection incidence rates were highest in liver recipients (15.3%), followed by heart (8.6%), kidney (8.3%), and lung (4.2%). Four subjects (16.7%) met HAdV disease criteria at virus detection. Five subjects (20.8%) had progression of HAdV infection. All-cause mortality rates in positive and negative subjects were 0% and 3.9%, respectively. HAdV infection was infrequently detected in SOT recipients. Over one-third of HAdV-positive patients met disease criteria at detection or had infection progression, but none died. This low all-cause mortality raises questions about benefits of HAdV surveillance. Larger multicenter studies are needed to assess incidence variance by center and comparative effectiveness of therapeutic interventions.

Extragenital Screening Is Essential for Comprehensive Detection of Chlamydia trachomatis and Neisseria gonorrhoeae in the Pediatric Population.

Chlamydia trachomatis and Neisseria gonorrhoeae are the two most common causes of sexually transmitted disease in the United States. Studies in adults, mostly in men who have sex with men, have shown that the prevalence of C. trachomatis and N. gonorrhoeae infections is much higher in extragenital sources compared to urogenital sources. A similar large sample of data on the burden of C. trachomatis and N. gonorrhoeae infections by anatomic site is lacking in children. We retrospectively analyzed data from 655 patients tested for C. trachomatis (887 specimens) and N. gonorrhoeae (890 specimens) at the Children's Hospital of Philadelphia. We restricted the analysis to include patients between 2 and 17 years of age that had all three sources (urine, oropharynx, and rectum) collected at the same visit. The final data set included specimens from all three sources from 148 and 154 patients for C. trachomatis and N. gonorrhoeae, respectively. Specimens were tested for C. trachomatis and N. gonorrhoeae using a Gen-Probe Aptima Combo 2 assay. The burden of C. trachomatis and N. gonorrhoeae infection was significantly higher in the 14- to 17-year age group (24.7%, P = 0.041; 25.8%; P = 0.001) compared to the 10- to 13-year (5.9%; 5.6%), 6- to 9-year (4.6%; 4.6%), and 2- to 5-year (8.3%; 0%) age groups, respectively. The positivity rate for C. trachomatis was highest for rectal (16.2%), followed by urine (5.4%) and oropharyngeal (0.7%) sites. The positivity rate for N. gonorrhoeae was highest for rectal sites (10.4%), followed by oropharyngeal (9.7%) and urine (1.9%) sites. The source with highest diagnostic yield is rectum for C. trachomatis and rectum and oropharynx for N. gonorrhoeae Hence, extragenital screening is critical for the comprehensive detection of C. trachomatis and N. gonorrhoeae in the pediatric population.

Interpretation and management of positive anti-hepatitis B core antibody tests in immunocompromised pediatric patients.

Intravenous immunoglobulin (IVIg) therapy is increasingly used in the pediatric population, in particular among children with immune-compromising conditions. Pooled immunoglobulin products are routinely tested for hepatitis B surface antigen (HBsAg) and nucleic acid; however, screening for hepatitis B core antibody (anti-HBc) is not commonly performed. Thus, the administration of IVIg containing anti-HBc to children with immune-compromising conditions may complicate the interpretation of hepatitis B serologic testing in that a positive anti-HBc test may represent passive transfer of antibody from IVIg or may indicate resolved or chronic hepatitis B infection. Due to the risk of hepatitis B reactivation in immunocompromised patients, a positive anti-HBc test must be carefully considered. As part of a quality improvement initiative, we identified and reviewed the records of all pediatric patients at our institution who tested positive for anti-HBc over an 18-month period. Of 44 total patients with positive anti-HBc tests, we found that 22 (50%) had previously received IVIg in the preceding 4 months. All but one of these, 21/22 (95%), went on to receive immunosuppressive therapy (IS). Among the patients who received IS, 19 (86%) had not undergone hepatitis B serologic testing prior to IVIg administration and 16 (73%) did not have subsequent testing to distinguish between passive acquisition of anti-HBc from IVIg and chronic hepatitis B infection. Our single-center experience reveals that a high proportion of positive anti-HBc tests in children are presumed to be because of the passive antibody transfer from IVIg. However, a low proportion of patients undergo confirmatory testing, despite the risk of hepatitis B reactivation during IS. We thus propose a risk-based algorithm for interpretation and monitoring of hepatitis B testing in immunocompromised children.

Outcomes of Human Adenovirus Infection and Disease in a Retrospective Cohort of Pediatric Hematopoietic Cell Transplant Recipients.

BACKGROUND: Human adenoviruses (HAdVs) are associated with significant morbidity and death after hematopoietic cell transplantation (HCT). In this study, we sought to determine the incidence of HAdV infection among pediatric HCT recipients in the polymerase chain reaction (PCR) testing era, identify risk factors for viremia among patients undergoing HAdV surveillance, and assess the effectiveness of preemptive cidofovir. METHODS: A single-center retrospective cohort of patients who underwent a transplant within a 10-year period was assembled. The incidence of and outcomes of patients with HAdV infection and disease were determined by PCR results and chart review. A Cox regression model was used for surveilled allogeneic HCT recipients to identify factors associated with viremia. We also used a discrete-time failure model with inverse probability treatment weights to assess the effectiveness of preemptive cidofovir for infection. RESULTS: Among 572 HCT recipients, 76 (13.3%) had ≥1 sample that was HAdV PCR positive (3.5% of autologous HCT recipients and 19.7% of allogeneic HCT recipients). Among 191 allogeneic HCT recipients under surveillance, 58 (30.4%) had HAdV detected from any source, and 50 (26.2%) specifically had viremia. The mortality rate was higher in allogeneic HCT recipients with HAdV infection versus those without infection (25.9% vs 11.3%; P = .01). Factors associated with infection included an age of 6 to 12 years, an absolute lymphocyte count of <200 cells/µL, recent prednisone exposure, and recent bacteremia. Preemptive cidofovir was not associated with a reduced risk of infection progression (odds ratio, 0.96 [95% confidence interval, 0.30-3.05]). CONCLUSIONS: HAdV infection is common and associated with an increased rate of death after allogeneic HCT. Using prediction models that incorporate factors associated with HAdV might help target surveillance. Preemptive cidofovir therapy was not protective in a subset of HAdV-positive patients. Larger observational or randomized investigations are necessary, because the utility of surveillance requires effective preemptive therapies.

Implementation of a rapid influenza A/B and RSV direct molecular assay improves emergency department oseltamivir use in paediatric patients.

PURPOSE: Influenza A virus (FluA), influenza B virus (FluB) and respiratory syncytial virus (RSV) illnesses increase hospitalizations during seasonal epidemics. METHODOLOGY: To determine the utility of the Simplexa FluA/B & RSV Direct Assay (Direct Flu/RSV) and its impact on oseltamivir use, we offered this assay to emergency department (ED) patients with influenza-like illness. RESULTS: Utilization of the Direct Flu/RSV provided a turnaround time (TAT) of 2 hours. Compared to the flu season prior to implementation of the Direct Flu/RSV, clinicians were more likely to prescribe 5 days of oseltamivir therapy for Direct Flu/RSV-positive patients in comparison to those with a negative test. CONCLUSIONS: Use of Direct Flu/RSV provides results rapidly, which leads to more appropriate use of oseltamivir. The ease of use of this assay and quick TAT allows for prompt decision-making, which is essential for patient care and effective disease control during the influenza season.