Improving antibiotic prescribing in the emergency department for uncomplicated community-acquired pneumonia

BACKGROUND:The Pediatric Infectious Disease Society(PIDS)and Infectious Disease Society of America(IDSA)published an evidence-based guideline for the treatment of uncomplicated communityacquired pneumonia(CAP)in children,recommending aminopenicillins as the first-line therapy.Poor guideline compliance with 10%–50%of patients admitted to the hospital receiving narrow-spectrum antibiotics has been reported.A new clinical practice guideline(CPG)was implemented in our emergency department(ED)for uncomplicated CAP.The aim of this study was to examine baseline knowledge and ED provider prescribing patterns pre-and post-CPG implementation.METHODS:Prior to CPG-implementation,an anonymous case-based survey was distributed to evaluate knowledge of the current PIDS/IDSA guideline.A retrospective chart review of patients treated in the ED for CAP from January 2015 to February 2017 was performed to assess prescribing patterns for intravenous(IV)antibiotics in the ED at Children’s National Health System pre-and post-CPG implementation.RESULTS:ED providers were aware of the PIDS/IDSA guideline recommendations,with 86.4%of survey responders selecting ampicillin as the initial antibiotic of choice.However,only 41.2%of patients admitted to the hospital with uncomplicated CAP pre-CPG received ampicillin(P<0.01).There was no statistically signifi cant increase in ampicillin prescribing post-CPG(P=0.40).CONCLUSIONS:Providers in the ED are aware of the PIDS/IDSA guideline regarding the first-line therapy for uncomplicated CAP;however,this knowledge does not translate into clinical practice.Implementation of a CPG in isolation did not significantly change prescribing patterns for uncomplicated CAP.

Confidence level of pediatric trainees in management of shock states

AIM To assess overall confidence level of trainees in assessing and treating shock, we sought to improve awareness of recurrent biases in clinical decision-making to help address appropriate educational interventions.METHODS Pediatric trainees on a national listserv were offered the opportunity to complete an electronic survey anonymously. Four commonly occurring clinical scenarios were presented, and respondents were asked to choose whether or not they would give fluid, rank factors utilized in decision-making, and comment on confidence level in their decision. RESULTS Pediatric trainees have a very low confidence level for assessment and treatment of shock. Highest confidence level is for initial assessment and treatment of shock involving American College of Critical Care Medicine/Pediatric Advanced Life Support recommendations. Children with preexisting cardiac comorbidities are at high risk ofunder-resuscitation. CONCLUSION Pediatric trainees nationwide have low confidence in managing various shock states, and would benefit from guidance and teaching around certain common clinical situations.

The Fontan Circulation:Contemporary Review of Ongoing Challenges and Management Strategies

Since its original description,the Fontan operation has been widely used for the palliation of children with single ventricle physiology and has resulted in an increasing number of these patients surviving to adulthood.The Fontan operation is a unique approach to create a circulation in series without two distinct pumping chambers.Although the Fontan operation increased the survival rates of patients with single ventricle physiology,it carries an inevitable risk of long-term morbidities that impacts the outcomes and quality of life in these patients.In this review,we discuss the challenges resulting from the unique pathophysiology of Fontan circulation and propose management strategies.

Multisystem Inflammatory Disease with Respiratory Failure in a 7-Year-Old Boy

Relapsing polychondritis (RP) is a rare episodic and progressive inflammatory disease of presumed autoimmune etiology. The estimated incidence is 3.5 cases per million. Of these only 10% affect pediatric populations.

JASN:研究鉴定出可能让HIV感染肾细胞的受体

HIV－1相关肾病是一种能够在未合适地利用抗逆转录病毒疗法加以治疗的非洲裔HIV阳性患者体内产生的肾病。尽管经过多年的广泛研究。人们仍不清楚来自HIV阳性患者的并不表达主要的HIV-1CD4受体的肾上皮细胞是如何被HIV－1感染的。

New insights into molecules and pathways of cancer metabolism and therapeutic implications

Cancer cells are abnormal cells that can reproduce and regenerate rapidly.They are characterized by unlimited proliferation,transformation and migration,and can destroy normal cells.To meet the needs for cell proliferation and migration,tumor cells acquire molecular materials and energy through unusual metabolic pathways as their metabolism is more vigorous than that of normal cells.Multiple carcinogenic signaling pathways eventually converge to regulate three major metabolic pathways in tumor cells,including glucose,lipid,and amino acid metabolism.The distinct metabolic signatures of cancer cells reflect that metabolic changes are indispensable for the genesis and development of tumor cells.In this review,we report the unique metabolic alterations in tumor cells which occur through various signaling axes,and present various modalities available for cancer diagnosis and clinical therapy.We further provide suggestions for the development of anti-tumor therapeutic drugs.

The CD24-Siglec G axis protects mice against cuprizone-induced oligodendrocyte loss: targeting danger signal for neuroprotection

Oligodendrocytes play a critical role in neuroprotection by both remyelination-dependent and remyelination-independent mechanisms and confer protection in both inflammatory and degenerative diseases that involve the central nervous system,including multiple sclerosis,Alzheimer’s disease and potentially Parkinson’s disease.1,2,3,4 Although accumulating data have supported a major role for inflammation in the susceptibility of oligodendrocytes to cuprizone,the molecular pathways that regulate oligodendrocyte survival have not been well established.Here,we report that the targeted mutation of either Cd24 or Siglecg,which forms an axis that selectively regulates the innate inflammatory response to danger-associated molecular patterns(DAMPs),protects mice against cuprizone-induced oligodendrocyte loss.Moreover,the systemic administration of CD24Fc,which is known to stimulate Siglec G signaling and suppress the inflammatory response in vivo,protects oligodendrocytes against chronic exposure to cuprizone.Our data suggest that the host response to cellular injury actively participates in oligodendrocyte loss and provides a new approach to maintain oligodendrocytes under pathological conditions.

PLGA nanodepots co-encapsulating prostratin and anti-CD25 enhance primary natural killer cell antiviral and antitumor function

Natural killer(NK)cells are attractive effector cells of the innate immune system against human immunodeficiency virus(HIV)and cancer.However,NK cell therapies are limited by the fact that target cells evade NK cells,for example,in latent reservoirs(in HIV)or through upregulation of inhibitory signals(in cancer).To address this limitation,we describe a biodegradable nanoparticlebased“priming”approach to enhance the cytotoxic efficacy of peripheral blood mononuclear cell-derived NK cells.We present poly(lactic-co-glycolic acid)(PLGA)nanodepots(NDs)that co-encapsulate prostratin,a latency-reversing agent,and anti-CD25(aCD25),a cell surface binding antibody,to enhance primary NK cell function against HIV and cancer.We utilize a nanoemulsion synthesis scheme to encapsulate both prostratin and aCD25 within the PLGA NDs(termed Pro-aCD25-NDs).Physicochemical characterization studies of the NDs demonstrated that our synthesis scheme resulted in stable and monodisperse Pro-aCD25-NDs.The NDs successfully released both active prostratin and anti-CD25,and with controllable release kinetics.When Pro-aCD25-NDs were administered in an in vitro model of latent HIV and acute T cell leukemia using J-Lat 10.6 cells,the NDs were observed to prime J-Lat cells resulting in significantly increased NK cell-mediated cytotoxicity compared to free prostratin plus anti-CD25,and other controls.These findings demonstrate the feasibility of using our Pro-aCD25-NDs to prime target cells for enhancing the cytotoxicity of NK cells as antiviral or antitumor agents.

En masse discovery of anti-cancer human monoclonal antibodies by de novo assembly of immunoglobulin sequences from transcriptomes and genome sequences of cancer tissues

TO THE EDITOR:Characterization of the tumor-infiltrating B cell immunoglobulin(Ig)repertoire is critical to understanding B cell immunity in tumors and developing monoclonal antibody therapy.However,the generation of specific antibodies for cancer therapy1,2 is a major endeavor,involving a lengthy process of antigen identification,immunization,hybridoma production and,in most cases,antibody humanization.As a radical departure from the conventional approach,we hereby describe a rapid and potentially en masse identification of cancer-specific antibodies directly from human cancer tissues by de novo assembly from transcriptome and genome sequences.Our integrated computational framework was developed and successfully tested for antibody discovery by mining 1945 solid tumor RNA-sequencing-based samples for abundant Ig CDR3 sequences among the TCGA database of glioblastoma multiforme(GBM),lower grade glioma(LGG),lung adenocarcinoma(LUAD),lung squamous carcinoma(LUSC),pancreatic adenocarcinoma(PAAD),and skin cutaneous melanoma(SKCM).

A novel and promising addition to the treatment arsenal for post-intubation subglottic stenosis: Holmium laser ablation and cryotherapy via flexible bronchoscopy

Dr.Jiao et al1 from Beijing Children’s Hospital present an impressive report on the novel use of a holmium laser and subsequent cryotherapy delivered via a flexible bronchoscopy as a treatment modality for post-intubation acquired subglottic stenosis in children.Excellent outcomes were achieved in 16 consecutive patients with serial procedures,including clinical cure(defined as:resolution of respiratory symptoms,significant improvement in subglottic stenosis grade,and tracheotomy decannulation)in 15 of 16 patients.They had no serious complications.This novel approach with promising results adds to the toolbox of methods available to address the vexing problem of post-intubation subglottic stenosis.