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To identify commonly used intravenous drugs that may produce endothelial damage.An experimental research study was performed using a sample of 62 intravenous drugs commonly used in emergency care, pH and osmolarity were measured. Subsequently, based on these values, the theoretical capacity to cause irritation or endovascular damage was determined and classified as high, moderate, and low.Samples from 19 drugs for fluid therapy, 21 antibiotics and 22 drugs for intravenous use were studied. Glucose solutions, sodium bicarbonate 1M and mannitol 10% showed a high capacity to cause venous irritation. Vancomycin, ciprofloxacin, amiodarone, haloperidol, and labetalol solution presented a high capacity for irritation based on their acidic pH. The antibiotics, dexketoprofen, diazepam, digoxin, etomidate, phenytoin, levetiracetam and metamizole also showed high osmotic values in their reconstituted or undiluted presentations. Moreover, osmolarity of diazepam, digoxin and phenytoin remained high despite being diluted in 100 ml of saline.Knowing the pH and osmolarity of intravenous drugs allows their capacity to cause endothelial damage to be assessed. The use of comprehensive tables based on the chemical properties of the drugs can be a useful tool to help prevent chemically-induced phlebitis.

Resumen Objetivos Analizar las caracteristicas fisicas, antropometricas y formativas de los reanimadores asociadas a la correcta compresion y reexpansion toracica durante la reanimacion cardiopulmonar. Metodologia Estudio observacional prospectivo. Profesionales y estudiantes sanitarios de urgencias y cuidados criticos realizaron 2 min de compresiones toracicas sobre un maniqui. Se evaluo la profundidad y la presion residual tras las compresiones, y se estudio su asociacion a diferentes variables (fisicas, antropometricas y formativas) mediante la creacion de modelos de regresion logistica. Resultados Participaron 238 voluntarios. Que el reanimador tuviese una experiencia previa en menos de 6 reanimaciones cardiopulmonares (OR: 3,03; IC 95%: 1,2-7,63) se asocio a una mayor probabilidad de no lograr una profundidad adecuada en las compresiones. Una mayor estatura (OR: 0,93; IC 95%: 0,87-0,99) y fuerza de aprehension (OR: 0,94; IC 95%: 0,89-0,99) fueron condiciones que actuaron como factores predisponentes a la ejecucion de una tecnica correcta. Ninguna caracteristica se asocio a la adecuacion de la reexpansion toracica. Conclusiones La experiencia previa del reanimador es el factor mas fuertemente asociado a la correcta ejecucion de las compresiones toracicas. En menor medida, tambien influye la estatura y la fuerza del tren superior del profesional. No se han identificado factores asociados a la adecuacion de la reexpansion toracica tras las compresiones.

Resumen Objetivos Identificar los medicamentos intravenosos de uso comun en el ambito hospitalario con capacidad de producir dano endotelial. Metodo Estudio experimental in vitro. La muestra estuvo formada por 62 medicamentos de uso comun en los servicios de urgencias y hospitalizacion. Las variables estudiadas fueron la osmolaridad y el pH. Posteriormente, en base a esos valores, se determino la capacidad teorica para provocar dano endotelial, clasificandola en alta, moderada y baja. Resultados Se analizaron 19 medicamentos para fluidoterapia, 21 antibioticos y 22 medicamentos intravenosos. Las soluciones de glucosa, el bicarbonato 1M y el manitol 10% presentaron una capacidad elevada para provocar irritacion venosa. Vancomicina, ciprofloxacino, amiodarona, haloperidol y labetalol mostraron una capacidad irritativa elevada derivada de su pH marcadamente acido. Los antibioticos, dexketoprofeno, diazepam, digoxina, etomidato, fenitoina, levetiracetam y metamizol presentaron valores extremos de osmolaridad en su presentacion reconstituida o sin diluir, y mantuvieron sus valores de tonicidad elevados despues de diluirlos en 100 ml de suero salino el diazepam, la digoxina y la fenitoina. Conclusiones Conocer el pH y la osmolaridad de los medicamentos intravenosos permite evaluar su capacidad para provocar dano endotelial. La creacion de tablas comprensivas en base a las propiedades quimicas de los medicamentos puede constituir una herramienta util que contribuya a prevenir la flebitis quimicamente inducida.

Antiseptic agents, including chlorhexidine gluconate (CHG), are commonly utilized in the health care environment to reduce rates of health care-associated infections. A number of efflux pump genes, including smr and qacA/B , have been reported in Staphylococcus aureus isolates that are associated with higher MICs and minimum bactericidal concentrations (MBCs) to CHG.

In the late 1940s to 1950s, Staphylococcus aureus isolates first-gained resistance to penicillin. Recently, some centers have described an increase in the proportion of methicillin susceptible S. aureus (MSSA) which are also susceptible to penicillin (PSSA). There are little data on the frequency of PSSA infections in children. We investigated the prevalence of penicillin susceptibility among pediatric MSSA acute hematogenous osteoarticular infection (OAI) isolates. MSSA OAI isolates were obtained through surveillance studies at Texas Children’s and St. Louis Children’s Hospitals from January 2011 to December 2019. All isolates underwent PCR for blaZ β-lactamase, PVL genes and agr group. All blaZ negative isolates then underwent penicillin MIC determination. blaZ negative isolates with penicillin MIC ≤ 0.125 μg/mL were considered PSSA. Multilocus sequence typing (MLST) was conducted on a subset of isolates. A total of 329 unique isolates were included in the study. The median patient age was 9.2 years (IQR:5.1 to 12.2). Overall, 6.7% of isolates were penicillin susceptible. No PSSA were detected prior to 2015 but increased yearly thereafter. By the final study year, 20.4% of isolates were PSSA (P = 0.001). PSSA were similar to penicillin-resistant MSSA (PR-MSSA) isolates in terms agr group and PVL carriage as well as clinical presentation and outcomes. PSSA were of distinct sequence types compared to PR-MSSA. PSSA appears to be increasing among OAI in U.S. children. Overall, PSSA isolates are associated with a similar clinical presentation as penicillin-resistant isolates. The potential for use of penicillin treatment in PSSA OAI warrants further study.

Background Recent PIDS practice guidelines for acute hematogenous osteomyelitis (AHO) advocate for regular laboratory monitoring for adverse drug events. Data are limited however with respect to the frequency or clinical impact of antibiotic-related laboratory abnormalities (ARLA) in pediatric AHO. We reviewed the experience with ARLA in children undergoing treatment for S. aureus AHO. Methods Cases of S. aureus AHO in children were reviewed from 2011-2020. Eligible cases were those 1) discharged to complete therapy at home (IV or oral), 2) with baseline complete blood count (CBC), creatinine and AST/ALT obtained during the hospitalization and 3) at least one CBC, creatinine, and/or AST/ALT measurement in the outpatient setting while receiving AHO therapy. Neutropenia, thrombocytopenia and AST/ALT elevation were defined using the NIH DAIDS pediatric toxicity grading system; acute kidney injury (AKI) was defined using pRIFLE. Results 207 subjects met inclusion criteria. Outpatient CBC was obtained in 187 subjects, creatinine in 121 and AST/ALT in 63. Patients with and without ARLA were similar with respect to age and demographics. Neutropenia developed in 12 (6.4%) and thrombocytopenia in 5 (2.7%) at a median of 23 and 18 days of therapy, respectively (Figures 1). Outpatient hematologic abnormalities were more common among subjects with MRSA, history of inpatient ARLA and those receiving certain antibiotics, specifically vancomycin (Figures 2, 3). There was no clear relationship with hematologic abnormalities and vancomycin daily dose. Neutropenia prompted modification of therapy in 1 case. No infections or bleeding events were attributable to ARLA. Three cases of outpatient AKI occurred (2.1% [vancomycin, n=1; cefazolin, n=2]); one subject had therapy discontinued. Outpatient AST/ALT elevation occurred in six (9.5%), none of which were symptomatic. Patients with AST/ALT elevation were disproportionately treated with cefazolin (p=0.006). Panel A. The number of patients experiencing antibiotic-related laboratory abnormalities (ARLA). Panel B. Box plots depicting the timing of ARLA relative to initiation of antimicrobial therapy. Conclusion ARLAs, particularly neutropenia, are common in patients receiving outpatient therapy for AHO after 2-3 weeks of therapy. However, the majority of ARLA are mild and do not result in symptoms or modification of therapy. Further study is necessary to appreciate how these findings might be applicable to all cause osteomyelitis. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.

Background The clinical presentation and management of acute hematogenous osteomyelitis (AHO) in children can vary significantly. Scores to predict acute complications utilize prolonged fever after antibiotics, bone abscess, suppurative arthritis, disseminated infection and delayed source control. By contrast, elevated CRP after 48-96 hours of therapy, disseminated disease and bone debridement are predictive of chronic complications. Such scoring systems have undergone limited validation. We examined factors associated with acute and chronic AHO complications at our center to identify other variables that may enhance published scores. Methods A retrospective chart review was conducted of all children 6 mo-18 years with AHO and with acute symptoms of < 14 days at Texas Children’s Hospital from January 2012 through December 2020. An acute complicated course was defined as treatment failure within 6 weeks of starting antibiotics, > 2 bone debridements, prolonged admission ( >14 days) and acute avascular necrosis. Chronic complications included growth arrest or limb leg discrepancy, pathologic fracture, avascular necrosis, chronic osteomyelitis or frozen joint. Statistical analysis was completed using STATA 17. Results 418 patients met the inclusion criteria. 106 (25.4%) had an acute complicated course. 51 (13.5%) of 377 followed had a chronic complication. Clinical factors associated with acute and chronic complications were very similar. Factors associated with either an acute complicated course (Figure 1) or chronic orthopedic complications (Figure 2) included: older age, tibia involvement, infection due to S. aureus/MRSA, presence of multifocal or disseminated infection, DVT, fever > 48 hours of antibiotic therapy, admission laboratory values including higher absolute neutrophil count (ANC) and higher CRP, ICU admission, associated suppurative arthritis, bacteremia, bone abscess, surgical debridement and delayed source control. Conclusion In children with AHO, risk factors for acute and chronic complications are highly similar. Older age, tibia involvement, MRSA, higher ANC and bacteremia were linked to complications in our population and will be assessed in current clinical scoring systems which may help guide management. Disclosures Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality: Grant/Research Support|Allergan: Provided reagents for unrelated research|Nabriva: Site investigator for multicenter clinical trial Kristina G. Hulten, PhD, Me-med: Grant/Research Support|Pfizer: Grant/Research Support Sheldon L. Kaplan, MD, MeMed: Grant/Research Support|Pfizer: Grant/Research Support.

Ceftaroline represents an attractive therapy option for methicillin-resistant Staphylococcus aureus (MRSA). Little data is available, however, regarding the frequency of reduced susceptibility (RS) to ceftaroline among pediatric MRSA infections. We screened invasive MRSA isolates at a tertiary children’s hospital for ceftaroline RS. Ceftaroline RS occurred in 2.9% of isolates and only among health care associated infections. Ceftaroline RS isolates were more often clindamycin-resistant. Sequencing data indicated the predominance of the CC5 lineage among ceftaroline RS isolates.

Rat bite fever is a systemic illness most commonly caused by Streptobacillus moniliformis that is classically characterized by fever, rash and migratory polyarthritis. Here, we highlight the highly variable clinical presentations of rat bite fever in children and the importance of maintaining a high degree of suspicion so appropriate treatment can be promptly initiated.

Background A higher rate of anxiety and depression is present in patients with inflammatory bowel disease (IBD). The COVID-19 pandemic has negatively impacted mental health in the general population. This study aims to compare the prevalence of depression and anxiety in patients with IBD during the pre-pandemic period and the pandemic period, and to explore trends in patients' specific IBD-related needs during the pandemic era. Methods Data was collected from subjects with IBD in two different timepoints: 2016 and 2021-2022. Self-administered questionnaires were given to adults with confirmed IBD attending an academic IBD Clinic. Data collected included demographic information, Patient Health Questionnaire-9 (PHQ-9) for major depressive disorder (MDD), General Anxiety Disorder-7 (GAD-7) questionnaire and subject’s need for referrals to other services such as nutrition, pain management, mental health services. Scores of 10 or more in the GAD-7 or PHQ-9 indicate need for professional evaluation. Statistical analysis was performed using R Studio v.4.2.1. This study is approved by the UPR MSC-IRB. Results Two hundred-fifty-two questionnaires were collected in 2016 and 196 during the 2021-22 pandemic period. The majority of subjects were male (54.6%) and had Crohn’s disease (69.9%). Mean ± SD age was 40.2 ± 14.6. In the PHQ-9, 33.7% (n=91) during 2016, and 16.33% (n=32) during 2021-22 screened positive for MDD. For the GAD-7, 30.7% (n=83) during 2016, and 12.76% (n=25) during 2021-22 screened positive for generalized anxiety disorder (GAD). Sex and age differences were not detected for MDD and GAD screening, with exception for age differences in MDD during 2021-2022. The most frequent needs for referrals during 2021-2022 were nutrition evaluation (n = 74), access to IBD education (n = 73), psychology services (n = 71) and participation in research for IBD studies (n = 66) Conclusion The frequency of depression and anxiety in Puerto Ricans with IBD during the pandemic period was lower than pre-pandemic. Possible factors related to this include active use of telemedicine providing regular follow-up, integrated psychological support as part of the regular clinic services, and access to information regarding COVID-19 and IBD.

Although vaccination has reduced the incidence of Haemophilus influenzae type b, nontypeable H. influenzae and other encapsulated types remain a health threat. Little is known regarding the contemporary molecular epidemiology of these organisms. We conducted multilocus sequence typing on invasive H. influenzae during a period of increasing incidence.

Randomized simulation trial to analyze dispatcher-assisted cardiopulmonary resuscitation instructions provided from the emergency call center in an out-of-hospital heart arrest assisted by lay persons. An analysis of the telephone instructions was performed using a 14-item checklist by two external researchers. Simulations lasted nine minutes. Twenty-one volunteers were enrolled. All of them started resuscitation maneuvers. Telephone instructions were verbalized in very heterogeneous ways. Half of the indicators exceeded 90% compliance. Frequently the recommendation of push hard and fast on the patient’s chest was omitted and the dispatcher tended to mark a slower compression rate. The average time from the call to the start of the resuscitation was 3 min 33 s (SD: 1 min 7 s). The telephone instructions were verbalized in a very heterogeneous way. It is necessary to standardize and provide training in how to guide a dispatcher-assisted resuscitation.

Geminiviruses (viruses with circular, single-stranded DNA genomes) are one of the major groups of plant viruses causing severe economic problems for agriculture worldwide. The control of these pathogens has become a priority to maintain the production of important crops, including cotton, maize, cassava, and other vegetables. Obtaining resistant plants is the most powerful strategy and a key factor to stablish an effective integrated pest management for a robust control. In the last few decades, numerous studies have successfully approached that goal using diverse strategies based on plant variability or on the engineered expression of proteins/RNAs. The increasing knowledge of the mechanisms involved in the geminivirus-plant-vector interactions, in combination with the development of gene editing technology and nanoparticles, draw new and promising strategies for a durable control of these emerging pathogens.

Paranasal sinuses (PNS) infections are common in children. They may cause common and well-known complications, but also, unusual and potentially devastating complications. Diagnosing PNS infections and complications in children requires knowledge of the unique anatomy of the nasal cavity and the PNS. In fetal life, nasal mucosa evaginations into the lateral nasal walls initiate the development of the PNS. The PNS continue to develop after birth and complete their maturation and pneumatization at different ages during childhood which makes the pattern of PNS infections determined by patient age. Complications are caused by direct spread of the infection to the orbit, face, intracranial or osseous structures or hematogenous spread of the infection to the intracranial structures. Emergent imaging studies are often necessary in the evaluation of the complications in pediatric patients when the symptoms persist for 10 days and/or if there is evidence of intracranial or orbital complications. In addition, immunocompromised children are especially vulnerable to developing unusual complications. Computed tomography (CT) is excellent for determining whether there is intraorbital extension of PNS disease. However, when the infection approaches the orbital apex, a magnetic resonance imaging (MRI) study with contrast is necessary to assess spread into the cavernous sinus and the intracranial compartment. The goal of this manuscript is to review and characterize imaging findings of PNS infections using CT and MRI allowing determination of the extent of PNS infections and their common and unusual complications in children. In addition, a summary of the development of the normal PNS is provided.

BACKGROUND AND PURPOSE: Bacterial meningitis most commonly affects young children and can result in critical adverse outcomes, including sensorineural hearing loss (SNHL). The purpose of this study is to determine the diagnostic accuracy of MR imaging for predicting the development of SNHL among infants with bacterial meningitis. MATERIALS AND METHODS: A retrospective review was performed among infants (age

Background The Streptococcus anginosus group (SAG, S. anginosus, S. intermedius and S. constellatus) are often associated with severe disease and abscess formation. In our institution, we observed an apparent increase in frequency of intraorbital and intracranial infections resulting from SAG at Texas Children's Hospital. We undertook a retrospective review to describe the frequency and clinical features of these infections. Methods We reviewed the database of the microbiology laboratory at Texas Children's Hospital from 2011 to 2018 for SAG-positive cultures. Cases included were those associated with (1) either otitis media or sinusitis and (2) Pott's puffy tumor, orbital abscesses, mastoiditis, epidural abscesses, subdural empyema, brain parenchymal abscesses or dural enhancement by imaging. The number of overall diagnoses were determined using diagnostic codes and used to estimate the proportion of disease caused by SAG. Results Ninety-five cases were identified meeting inclusion criteria. The median age of patients was 11.4 years, and 75.8% were previously healthy. S. intermedius was most commonly isolated (80%) followed by S. constellatus (12.6%) and S. anginosus (7.4%); 50.5% of cases were polymicrobial. Among polymicrobial cases, Staphylococcus aureus was most frequently isolated. All patients underwent surgical intervention. 8.4% of patients experienced persistent neurologic deficits. We observed a significant increase in disease incidence during the study period; in addition, the overall proportion of all intracranial infections caused by SAG increased. Conclusions Complications of otitis media and sinusitis caused by SAG are associated with substantial morbidity. These infections are becoming increasingly common at our center although the precise reason for this temporal trend is unclear.

The distribution of shape anisotropy constants in two colloids of iron oxide nanoparticles has been measured from the distribution of particle elongations within each system. The results are in good agreement with the values calculated from a temperature decay of remanence measurement. For a fluid with a saturation magnetisation of 420 emu/cc and an average particle elongation of ∼ 1.3, the distribution of energy barriers is controlled by both the distribution of particle sizes and particle elongations. For a fluid with a saturation magnetisation of 320 emu/cc and a wide distribution of particle sizes, the energy barrier to reversal can be assumed to be controlled by the distribution of particle volumes. These results highlight the need to take into account the distribution of anisotropy constants when making predictions of the heating properties of assemblies of magnetic nanoparticles for hyperthermia applications., The authors acknowledge fruitful discussions with Prof. Kevin O’Grady (emeritus) from the Department of Physics at the University of York and Liquids Research Ltd. Generous financial support from Liquids Research Ltd. is also greatly appreciated. The authors acknowledge TEM support from Prof. A. Hirohata from the Electronic Engineering department at the University of York. Funding is also acknowledged from EPSRC via their Impact Acceleration Account (EP/R51181X/1). The authors would like to acknowledge the use of Servicio General de Apoyo a la Investigación-SAI at Universidad de Zaragoza. These results/publication are part of the project PID2019-106947RB- C21 financed by MCIN/ AEI /10.13039/501100011033. CM also acknowledges financial support from the Regional Government of Aragón (DGA) for financial support through grant E28_20R.

Tuning of optical fiber laser emissions based on super-mode interference in a seven core fiber (SCF) is presented. This super-mode interference is generated by a super-mode Mach–Zehnder interferometer constructed with a few millimeters of SCF spliced between two single mode fibers (SMFs). In the SCF, two super-modes are exited via the fundamental mode of the SMF. Then, an interference pattern caused to the optical path difference between super-modes is generated at the final of the SCF, which is collected with the spliced SMF. This interference pattern induces and tunes laser line emissions by adjusting the laser cavity losses in an optical fiber laser. By bending the Mach–Zehnder interferometer, a wavelength shift of the interference pattern is induced, which in turn causes a wavelength shift of the laser cavity losses and, therefore, a displacement of the laser wavelength emission. Laser line emissions were tuned by linear factors of around 0.91 nm mm−1, and the switching of simultaneous emissions was also obtained. The stability and reliability of the laser emission on the proposed method are also discussed.

Lymphocytic meningoradiculitis (Bannwarth syndrome) is a rare manifestation of Lyme neuroborreliosis in children. It is the most common clinical manifestation of early Lyme neuroborreliosis in adults in European countries where the disease is endemic but is rare in children. We report an imported case of Bannwarth syndrome in a pediatric patient and review the literature for other pediatric cases reported.

Lymphocytic meningoradiculitis (Bannwarth syndrome) is a rare manifestation of Lyme neuroborreliosis in children. It is the most common clinical manifestation of early Lyme neuroborreliosis in adults in European countries where the disease is endemic but is rare in children. We report an imported case of Bannwarth syndrome in a pediatric patient and review the literature for other pediatric cases reported.

Although vaccination has reduced the incidence of Haemophilus influenzae type b, nontypeable H. influenzae and other encapsulated types remain a health threat. Little is known regarding the contemporary molecular epidemiology of these organisms. We conducted multilocus sequence typing on invasive H. influenzae during a period of increasing incidence.

BACKGROUND AND PURPOSE: Group B Streptococcus and Escherichia coli (E coli) are the 2 most common causes of bacterial meningitis in neonates. The purpose of this study was to determine whether CSF and/or MR imaging findings differ between infants with group B streptococcal or E coli meningitis. MATERIALS AND METHODS: A retrospective review was performed among neonates (younger than 28 days) and infants (younger than 120 days) with proved group B streptococcal (n = 57) or E coli meningitis (n = 50). A CSF or blood culture positive for Streptococcus or E coli and an elevated CSF white blood cell count were used as the criterion standard. Independent, blinded review of brain MRIs obtained within 21 days of presentation were performed by 2 board-certified neuroradiologists. CSF laboratory values and MR imaging findings were compared between the groups. RESULTS: There was no statistically significant difference between the mean age at presentation for patients with group B streptococcal (40 days; range, 2–111 days) versus patients with E coli meningitis (31 days; range, 12–115 days) (P = .18). There was no statistically significant difference in the CSF white blood cell count, glucose, or protein. There was a significant difference between group B streptococcal and E coli meningitis in the frequency of hydrocephalus (0% versus 22%, P = .001) and infarct (40% versus 14%; P = .038), respectively. There was no statistically significant difference in leptomeningeal enhancement, cerebritis, ventriculitis, abscess/granuloma, subdural effusion, extra-axial purulent material, intraventricular purulent material, hemorrhage, and sinus thrombosis. CONCLUSIONS: Although neonates and infants with group B streptococcal or E coli meningitis had similar age and CSF laboratory values, patients with group B streptococcal meningitis more frequently demonstrated infarcts, while those with E coli meningitis more frequently had early onset of hydrocephalus.

Resumen Objetivo Determinar el riesgo de contaminacion microbiologica de los humidificadores de burbujeo para oxigenoterapia de alto o bajo flujo de uso hospitalario. Metodos Revision sistematica de la literatura a traves de 6 bases de datos bibliograficas. Se seleccionaron estudios observacionales o experimentales publicados entre 1990 y 2016, en ingles o espanol, que analizaban la contaminacion microbiana de los humidificadores de burbujeo de los dispositivos de oxigenoterapia hospitalaria de alto y bajo flujo. Resultados Se incluyeron 12 articulos: 4 analizaron el agua de humidificadores reutilizables, 4 de desechables y otros 4 compararon muestras procedentes de ambos modelos. Se observo la presencia de contaminacion microbiana en todos los estudios que evaluaron humidificadores reutilizables (generalmente bacterias habituales de la flora cutanea). En 2 de ellos se notificaron aislamientos de especies potencialmente patogenicas. No se aislo contaminacion microbiana en las muestras procedentes de modelos desechables, independientemente de si fueron utilizados por un unico paciente o por varios de forma consecutiva a lo largo del tiempo. Conclusion Parece existir bajo riesgo de contaminacion en humidificadores desechables durante las primeras semanas de uso, pudiendo reutilizarse entre pacientes distintos sin riesgo de contaminacion cruzada. Por otro lado, cabe destacar que la manipulacion de los humidificadores reutilizables de forma no aseptica puede aumentar la probabilidad de contaminacion, por lo que la sustitucion de humidificadores reutilizables por modelos desechables podria ser la opcion mas segura.

We investigated the microbiology, management, and orthopedic outcomes of osteoarticular infections in infants age ≤1 year at our institution. Among 87 patients, Staphylococcus aureus was the most common pathogen (44.8%), followed by group B Streptococcus. Twenty-nine patients (33%), with a median age of 9.2 months, were transitioned to oral antibiotic therapy after ≤14 days of parenteral therapy; orthopedic outcomes were similar to those with prolonged parenteral therapy.

Background & Aims Besides their physiological role in bile formation and fat digestion, bile acids (BAs) synthesised from cholesterol in hepatocytes act as signalling molecules that modulate hepatocellular carcinoma (HCC). Trafficking of cholesterol to mitochondria through steroidogenic acute regulatory protein 1 (STARD1) is the rate-limiting step in the alternative pathway of BA generation, the physiological relevance of which is not well understood. Moreover, the specific contribution of the STARD1-dependent BA synthesis pathway to HCC has not been previously explored. Methods STARD1 expression was analyzed in a cohort of human non-alcoholic steatohepatitis (NASH)-derived HCC specimens. Experimental NASH-driven HCC models included MUP-uPA mice fed a high-fat high-cholesterol (HFHC) diet and diethylnitrosamine (DEN) treatment in wild-type (WT) mice fed a HFHC diet. Molecular species of BAs and oxysterols were analyzed by mass spectrometry. Effects of NASH-derived BA profiles were investigated in tumour-initiated stem-like cells (TICs) and primary mouse hepatocytes (PMHs). Results Patients with NASH-associated HCC exhibited increased hepatic expression of STARD1 and an enhanced BA pool. Using NASH-driven HCC models, STARD1 overexpression in WT mice increased liver tumour multiplicity, whereas hepatocyte-specific STARD1 deletion (Stard1ΔHep) in WT or MUP-uPA mice reduced tumour burden. These findings mirrored the levels of unconjugated primary BAs, β-muricholic acid and cholic acid, and their tauroconjugates in STARD1-overexpressing and Stard1ΔHep mice. Incubation of TICs or PMHs with a mix of BAs mimicking this profile stimulated expression of genes involved in pluripotency, stemness and inflammation. Conclusions The study reveals a previously unrecognised role of STARD1 in HCC pathogenesis, wherein it promotes the synthesis of primary BAs through the mitochondrial pathway, the products of which act in TICs to stimulate self-renewal, stemness and inflammation. Lay summary Effective therapy for hepatocellular carcinoma (HCC) is limited because of our incomplete understanding of its pathogenesis. The contribution of the alternative pathway of bile acid (BA) synthesis to HCC development is unknown. We uncover a key role for steroidogenic acute regulatory protein 1 (STARD1) in non-alcoholic steatohepatitis-driven HCC, wherein it stimulates the generation of BAs in the mitochondrial acidic pathway, the products of which stimulate hepatocyte pluripotency and self-renewal, as well as inflammation., We acknowledge support from grants PID2019-111669RB-100, SAF2017-85877R and SAF2015-73579-JIN from Plan Nacional de I+D funded by the Agencia Estatal de Investigación (AEI), the Fondo Europeo de Desarrollo Regional (FEDER) and CIBEREHD; the center grant P50AA011999 Southern California Research Center for ALPD and Cirrhosis funded by NIAAA / NIH; as well as support from AGAUR of the Generalitat de Catalunya SGR-2017-1112, European Cooperation in Science & Technology (COST) ACTION CA17112 Prospective European Drug-Induced Liver Injury Network, the ‘ER stress-mitochondrial cholesterol axis in obesity-associated insulin resistance and comorbidities’-Ayudas FUNDACION BBVA and the Red Nacional 2018-102799-T de Enfermedades Metabólicas y Cáncer, and Project 201916/31 "Contribution of mitochondrial oxysterol and bile acid metabolism to liver carcinogenesis" 2019 by Fundació Marato TV3. We also acknowledge the support from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Spain (PI16/00598, co-funded by European Regional Development Fund / European Social Fund, ‘Investing in your future’) and Centro Internacional sobre el Envejecimiento (OLD-HEPAMARKER, 0348_CIE_6_E), Spain. We also acknowledge support from R01 CA2344128 and U01 AA022614 grants to M.K.

Background While the majority of pediatric osteomyelitis cases are acute in nature, a significant subset present with prolonged symptoms often associated with substantial morbidity. Little data exist to guide clinicians in the management of these infections. We sought to describe the epidemiology, clinical features and management of chronic osteomyelitis (CO) in children. Methods We reviewed hospital admissions for CO from 2011 to 2018 at Texas Children's Hospital. Cases were included if symptoms lasted ≥28 days on presentation. Cases were classified as those associated with: (1) a contiguous focus of infection; (2) penetrating trauma; (3) orthopedic hardware; (4) postacute CO (PACO, those occurring after ≥28 days of therapy for acute osteomyelitis); and (5) primary hematogenous CO. Results One hundred fourteen cases met inclusion criteria. The median patient age was 11.8 years and 35.9% had comorbidities. 70.2% of patients underwent ≥1 surgical procedure. A microbiologic etiology was identified in 72.8% of cases and Staphylococcus aureus was most common (39.4%). Contiguous focus of infection was more often associated with polymicrobial disease with or without Pseudomonas. Postacute CO was caused by S. aureus in 95%. The median duration of total therapy was 210 days. 26.3% of patients experienced treatment failure of which 46% underwent repeat hospital admission/surgery. There was no association between duration of intravenous therapy for CO and treatment failure. Conclusions Children with CO represent a diverse group both in terms of pathogenesis and microbiology. Pathogenesis and clinical presentation can provide clues to microbiologic etiology. Prolonged intravenous therapy does not appear to improve outcomes in CO.

Background Acute hematogenous osteomyelitis (AHO) is a serious infection in children. ESPID guidelines recommend empiric therapy with antistaphylococcal β-lactams in regions with a low methicillin-resistant S. aureus (MRSA) prevalence. In areas with a moderate-high prevalence of MRSA, selection of empiric therapy can be more challenging. We sought to examine factors present at the time of admission which may predict etiology and guide treatment in pediatric AHO in a region with endemic MRSA. Methods We reviewed admissions with ICD9/10 codes for AHO from 2011-2020 in otherwise healthy children. Patients with chronic infection, open or penetrating trauma, orthopedic hardware in situ, or disease secondary to a contiguous focus were excluded. Medical records were reviewed for clinical and laboratory parameters present on the day of admission. Results 586 cases were included. An etiology was identified in 76.8% of cases and S. aureus was most commonly identified (66.2%, 19% MRSA, Figure 1). Infection due to Kingella kingae (0.7%) occurred in younger children (p=0.01). Significant differences in presenting features were noted across pathogens, although S. aureus dominated in all sub-groups (Figure 2). Among children with respiratory symptoms at presentation, Group A Streptococcus (GAS, 10.7%), and S. pneumoniae (2.6%, p=0.01) were identified twice as frequently. Among children with reptiles exposure, Salmonella was identified in 10.8% (p=0.04). Multifocal infections and those requiring ICU admission were due to S. aureus in 88% and 97% of cases, respectively; these cases were disproportionately MRSA (36.4%, p=0.01 and 54%, p< 0.001). Both ESR and CRP were higher among MRSA compared to any other pathogen (Figure 3, p< 0.01). A CRP at presentation > 7 mg/dl had a 79.6% sensitivity for MRSA infection with a negative predictive value of 91.5%. Among those with either an ESR > 50 mm/hr or a CRP > 7 mg/dl, an organism was identified in 83.2% Depiction of the relative frequency of major pathogens among a cohort of 586 cases of acute hematogenous osteomyelitis in children Depiction of the relative frequency of different organisms in children with AHO with various history, exam and laboratory findings Scatterplot depicting ESR and CRP levels across major hematogenous osteomyelitis pathogens Conclusion Subtle differences in symptoms, history and laboratory parameters can provide clues to etiology in pediatric AHO. A CRP > 7 mg/dl at time of presentation is suggestive of MRSA AHO, and this should be considered when planning empiric therapy. Likewise, the absence of extreme elevation of CRP may serve an antibiotic stewardship role in MRSA endemic regions. Disclosures Sheldon L. Kaplan, MD, Pfizer (Research Grant or Support) Jonathon C. McNeil, MD, Agency for Healthcare Research and Quality (Research Grant or Support)Allergan (Grant/Research Support)Nabriva (Grant/Research Support, Other Financial or Material Support, Site PI for a multicenter trial)