Infantile hemangioma presenting as colocolic intussusception in an infant case report with review of pathologic lead points

Infantile hemangioma (IH) is one of the most common vascular anomalies of early childhood and is usually recognized in the first few weeks to months of life as a solitary cutaneous lesion. This report documents our experience with a GLUT-1 positive IH presenting as the pathologic lead point in a colocolic intussusception in a 10-week-old infant who had no skin lesions. Literature suggests approximately 2% of all children presenting with an intussusception require surgical intervention; however, an IH as the pathologic lead point is unique

Demographic and clinical characteristics associated with the failure of nonoperative management of uncomplicated appendicitis in children: Secondary analysis of a nonrandomized clinical trial

Importance: The factors associated with the failure of nonoperative management of appendicitis and the differences in patient-reported outcomes between successful and unsuccessful nonoperative management remain unknown. Objectives: To investigate factors associated with the failure of nonoperative management of appendicitis and compare patient-reported outcomes between patients whose treatment succeeded and those whose treatment failed. Design, Setting, and Participants: This study was a planned subgroup secondary analysis conducted in 10 children\u27s hospitals that included 370 children aged 7 to 17 years with uncomplicated appendicitis enrolled in a prospective, nonrandomized clinical trial between May 1, 2015, and October 31, 2018, with 1-year follow-up comparing nonoperative management with antibiotics vs surgery for uncomplicated appendicitis. Statistical analysis was performed from November 1, 2019, to February 12, 2022. Interventions: Nonoperative management with antibiotics vs surgery. Main Outcomes and Measures: Failure of nonoperative management and patient-reported outcomes. The relative risk (RR) of failure based on sociodemographic and clinical characteristics was calculated. Patient-reported outcomes were compared based on the success or failure of nonoperative management. Results: Of 370 patients (34.6% of 1068 total patients; 229 boys [61.9%]; median age, 12.3 years [IQR, 10.0-14.6 years]) enrolled in the nonoperative group, treatment failure occurred for 125 patients (33.8%) at 1 year, with 53 patients (14.3%) undergoing appendectomy during initial hospitalization and 72 patients (19.5%) experiencing delayed treatment failure after hospital discharge. Higher patient-reported pain at presentation was associated with increased risk of in-hospital treatment failure (RR, 2.1 [95% CI, 1.0-4.4]) but not delayed treatment failure (RR, 1.3 [95% CI, 0.7-2.3]) or overall treatment failure at 1 year (RR, 1.5 [95% CI, 1.0-2.2]). Pain duration greater than 24 hours was associated with decreased risk of delayed treatment failure (RR, 0.3 [95% CI, 0.1-1.0]) but not in-hospital treatment failure (RR, 1.2 [95% CI, 0.5-2.7]) or treatment failure at 1 year (RR, 0.7 [95% CI, 0.4-1.2]). There was no increased risk of treatment failure associated with age, white blood cell count, sex, race, ethnicity, primary language, insurance status, transfer status, symptoms at presentation, or imaging results. Health care satisfaction at 30 days and patient-reported, health-related quality of life at 30 days and 1 year were not different. Satisfaction with the decision was higher with successful nonoperative management at 30 days (28.0 vs 27.0; difference, 1.0 [95% CI, 0.01-2.0]) and 1 year (28.1 vs 27.0; difference, 1.1 [95% CI, 0.2-2.0]). Conclusions and Relevance: This analysis suggests that a higher pain level at presentation was associated with a higher risk of initial failure of nonoperative management and that a longer duration of pain was associated with lower risk of delayed treatment failure. Although satisfaction was high in both groups, satisfaction with the treatment decision was higher among patients with successful nonoperative management at 1 year. Trial Registration: ClinicalTrials.gov Identifier: NCT02271932

Accuracy of chest computed tomography in distinguishing cystic pleuropulmonary blastoma from benign congenital lung malformations in children

Importance: The ability of computed tomography (CT) to distinguish between benign congenital lung malformations and malignant cystic pleuropulmonary blastomas (PPBs) is unclear. Objective: To assess whether chest CT can detect malignant tumors among postnatally detected lung lesions in children. Design, Setting, and Participants: This retrospective multicenter case-control study used a consortium database of 521 pathologically confirmed primary lung lesions from January 1, 2009, through December 31, 2015, to assess diagnostic accuracy. Preoperative CT scans of children with cystic PPB (cases) were selected and age-matched with CT scans from patients with postnatally detected congenital lung malformations (controls). Statistical analysis was performed from January 18 to September 6, 2020. Preoperative CT scans were interpreted independently by 9 experienced pediatric radiologists in a blinded fashion and analyzed from January 24, 2019, to September 6, 2020. Main Outcomes and Measures: Accuracy, sensitivity, and specificity of CT in correctly identifying children with malignant tumors. Results: Among 477 CT scans identified (282 boys [59%]; median age at CT, 3.6 months [IQR, 1.2-7.2 months]; median age at resection, 6.9 months [IQR, 4.2-12.8 months]), 40 cases were extensively reviewed; 9 cases (23%) had pathologically confirmed cystic PPB. The median age at CT was 7.3 months (IQR, 2.9-22.4 months), and median age at resection was 8.7 months (IQR, 5.0-24.4 months). The sensitivity of CT for detecting PPB was 58%, and the specificity was 83%. High suspicion for malignancy correlated with PPB pathology (odds ratio, 13.5; 95% CI, 2.7-67.3; P = .002). There was poor interrater reliability (κ = 0.36 [range, 0.06-0.64]; P \u3c .001) and no significant difference in specific imaging characteristics between PPB and benign cystic lesions. The overall accuracy rate for distinguishing benign vs malignant lesions was 81%. Conclusions and Relevance: This study suggests that chest CT, the current criterion standard imaging modality to assess the lung parenchyma, may not accurately and reliably distinguish PPB from benign congenital lung malformations in children. In any cystic lung lesion without a prenatal diagnosis, operative management to confirm pathologic diagnosis is warranted

A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure-activity relationships

a b s t r a c t A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior

A multi-decade record of high quality fCO2 data in version 3 of the Surface Ocean CO2 Atlas (SOCAT)

The Surface Ocean CO2 Atlas (SOCAT) is a synthesis of quality-controlled fCO2 (fugacity of carbon dioxide) values for the global surface oceans and coastal seas with regular updates. Version 3 of SOCAT has 14.7 million fCO2 values from 3646 data sets covering the years 1957 to 2014. This latest version has an additional 4.6 million fCO2 values relative to version 2 and extends the record from 2011 to 2014. Version 3 also significantly increases the data availability for 2005 to 2013. SOCAT has an average of approximately 1.2 million surface water fCO2 values per year for the years 2006 to 2012. Quality and documentation of the data has improved. A new feature is the data set quality control (QC) flag of E for data from alternative sensors and platforms. The accuracy of surface water fCO2 has been defined for all data set QC flags. Automated range checking has been carried out for all data sets during their upload into SOCAT. The upgrade of the interactive Data Set Viewer (previously known as the Cruise Data Viewer) allows better interrogation of the SOCAT data collection and rapid creation of high-quality figures for scientific presentations. Automated data upload has been launched for version 4 and will enable more frequent SOCAT releases in the future. High-profile scientific applications of SOCAT include quantification of the ocean sink for atmospheric carbon dioxide and its long-term variation, detection of ocean acidification, as well as evaluation of coupled-climate and ocean-only biogeochemical models. Users of SOCAT data products are urged to acknowledge the contribution of data providers, as stated in the SOCAT Fair Data Use Statement. This ESSD (Earth System Science Data) “living data” publication documents the methods and data sets used for the assembly of this new version of the SOCAT data collection and compares these with those used for earlier versions of the data collection (Pfeil et al., 2013; Sabine et al., 2013; Bakker et al., 2014). Individual data set files, included in the synthesis product, can be downloaded here: doi:10.1594/PANGAEA.849770. The gridded products are available here: doi:10.3334/CDIAC/OTG.SOCAT_V3_GRID

The 3′ Untranslated Regions of Influenza Genomic Sequences Are 5′PPP-Independent Ligands for RIG-I

Retinoic acid inducible gene-I (RIG-I) is a key regulator of antiviral immunity. RIG-I is generally thought to be activated by ssRNA species containing a 5′-triphosphate (PPP) group or by unphosphorylated dsRNA up to ∼300 bp in length. However, it is not yet clear how changes in the length, nucleotide sequence, secondary structure, and 5′ end modification affect the abilities of these ligands to bind and activate RIG-I. To further investigate these parameters in the context of naturally occurring ligands, we examined RNA sequences derived from the 5′ and 3′ untranslated regions (UTR) of the influenza virus NS1 gene segment. As expected, RIG-I-dependent interferon-β (IFN-β) induction by sequences from the 5′ UTR of the influenza cRNA or its complement (26 nt in length) required the presence of a 5′PPP group. In contrast, activation of RIG-I by the 3′ UTR cRNA sequence or its complement (172 nt) exhibited only a partial 5′PPP-dependence, as capping the 5′ end or treatment with CIP showed a modest reduction in RIG-I activation. Furthermore, induction of IFN-β by a smaller, U/A-rich region within the 3′ UTR was completely 5′PPP-independent. Our findings demonstrated that RNA sequence, length, and secondary structure all contributed to whether or not the 5′PPP moiety is needed for interferon induction by RIG-I

Infants with esophageal atresia and right aortic arch: Characteristics and outcomes from the Midwest Pediatric Surgery Consortium

Purpose Right sided aortic arch (RAA) is a rare anatomic finding in infants with esophageal atresia with or without tracheoesophageal fistula (EA/TEF). In the presence of RAA, significant controversy exists regarding optimal side for thoracotomy in repair of the EA/TEF. The purpose of this study was to characterize the incidence, demographics, surgical approach, and outcomes of patients with RAA and EA/TEF. Methods A multi-institutional, IRB approved, retrospective cohort study of infants with EA/TEF treated at 11 children's hospitals in the United States over a 5-year period (2009 to 2014) was performed. All patients had a minimum of one-year follow-up. Results In a cohort of 396 infants with esophageal atresia, 20 (5%) had RAA, with 18 having EA with a distal TEF and 2 with pure EA. Compared to infants with left sided arch (LAA), RAA infants had a lower median birth weight, (1.96 kg (IQR 1.54–2.65) vs. 2.57 kg (2.00–3.03), p = 0.01), earlier gestational age (34.5 weeks (IQR 32–37) vs. 37 weeks (35–39), p = 0.01), and a higher incidence of congenital heart disease (90% vs. 32%, p  0.29). Conclusion RAA in infants with EA/TEF is rare with an incidence of 5%. Compared to infants with EA/TEF and LAA, infants with EA/TEF and RAA are more severely ill with lower birth weight and higher rates of prematurity and complex congenital heart disease. In neonates with RAA, surgical repair of the EA/TEF is technically feasible via thoracotomy from either chest. A higher incidence of anastomotic strictures may occur with a right-sided approach

Identification and Evolution of Drug Efflux Pump in Clinical Enterobacter aerogenes Strains Isolated in 1995 and 2003

BACKGROUND: The high mortality impact of infectious diseases will increase due to accelerated evolution of antibiotic resistance in important human pathogens. Development of antibiotic resistance is a evolutionary process inducing the erosion of the effectiveness of our arsenal of antibiotics. Resistance is not necessarily limited to a single class of antibacterial agents but may affect many unrelated compounds; this is termed 'multidrug resistance' (MDR). The major mechanism of MDR is the active expulsion of drugs by bacterial pumps; the treatment of gram negative bacterial infections is compromised due to resistance mechanisms including the expression of efflux pumps that actively expel various usual antibiotics (beta-lactams, quinolones, ...). METHODOLOGY/PRINCIPAL FINDINGS: Enterobacter aerogenes has emerged among Enterobacteriaceae associated hospital infections during the last twenty years due to its faculty of adaptation to antibiotic stresses. Clinical isolates of E. aerogenes belonging to two strain collections isolated in 1995 and 2003 respectively, were screened to assess the involvement of efflux pumps in antibiotic resistance. Drug susceptibility assays were performed on all bacterial isolates and an efflux pump inhibitor (PAbetaN) previously characterized allowed to decipher the role of efflux in the resistance. Accumulation of labelled chloramphenicol was monitored in the presence of an energy poison to determine the involvement of active efflux on the antibiotic intracellular concentrations. The presence of the PAbetaN-susceptible efflux system was also identified in resistant E. aerogenes strains. CONCLUSIONS/SIGNIFICANCE: For the first time a noticeable increase in clinical isolates containing an efflux mechanism susceptible to pump inhibitor is report within an 8 year period. After the emergence of extended spectrum beta-lactamases in E. aerogenes and the recent characterisation of porin mutations in clinical isolates, this study describing an increase in inhibitor-susceptible efflux throws light on a new step in the evolution of mechanism in E. aerogenes

Marginal increase of sunitinib exposure by grapefruit juice

Clinical Oncolog

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis