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The recent trial Pediatric Neuro-Oncology Consortium 003 (PNOC003) utilized a molecular tumor board to recommend personalized treatment regimens based on tumor sequencing results in children with DIPG. We separately developed the Central Nervous System Targeted Agent Prediction (CNS-TAP) tool, which numerically scores targeted anticancer agents using preclinical, clinical, and patient-specific data. We hypothesized that highly scored agents from CNS-TAP would overlap with the PNOC003 tumor board’s recommendations. For each of the 28 participants, actionable genetic alterations were derived from PNOC003 genomic reports and input to CNS-TAP to identify the highest scoring agents. These agents were then compared with PNOC003 recommendations, with a resultant concordance percentage calculated. Overall, 38% of the total agents recommended by the tumor board were also selected by CNS-TAP, with higher concordance (63%) in a subanalysis including only targeted anticancer agents. Furthermore, nearly all patients (93%) had at least 1 drug chosen by both methods. We demonstrate overlap between agents recommended by CNS-TAP and PNOC003 tumor board, though this does not appear to improve survival. We do observe some discordance, highlighting strengths and limitations of each method. We propose that a combination of expert opinion and data-driven tools may improve targeted treatment recommendations for children with DIPG.

•This is the first report of Staphylococcus equorumcarrying two distinct cfr-bearing plasmids, both structurally different from previously identified cfr-containing plasmids.•Besides the cfrgene, these plasmids also genes for arsenic, copper and cadmium resistance, along with the lincosamide-pleuromutilin-streptogramin a resistance gene lsa(B). The co-occurrence of both antimicrobial and heavy metal resistance genes increases the potential for co-selection of these plasmids.•This study emphasizes the critical need for ongoing surveillance to prevent the spread of multi-drug resistance from food-producing animals, underlining its importance for food safety and public health.

It was to verify the association between the definition of sex of rearing and, clinical and cytogenetic features among patients with genital ambiguity referred without a sex assignment.

•We studied the presence of mastitis-associated bovine Staphylococcus aureusin Rwanda.•Two clonal lineages, CC3666 and CC3591, have an important role in cattle health and dairy production in Rwanda.•The dominance of CC97 underlines the widespread global distribution of this cattle-adapted clonal lineage.•The occurrence of human-associated CC152 suggests interspecies transmission.

There is insufficient evidence to guide the initial evaluation of hypothermic infants. We aimed to evaluate risk factors for serious bacterial infections (SBI) among hypothermic infants presenting to the emergency department (ED).We conducted a multicenter case-control study among hypothermic (rectal temperature <36.5°C) infants ≤90 days presenting to the ED who had a blood culture collected. Our outcome was SBI (bacteremia, bacterial meningitis, and/or urinary tract infection). We performed 1:2 matching. Historical, physical examination and laboratory covariables were determined based on the literature review from febrile and hypothermic infants and used logistic regression to identify candidate risk factors.Among 934 included infants, 57 (6.1%) had an SBI. In univariable analyses, the following were associated with SBI: age > 21 days, fever at home or in the ED, leukocytosis, elevated absolute neutrophil count, thrombocytosis, and abnormal urinalysis. Prematurity, respiratory distress, and hypothermia at home were negatively associated with SBI. The full multivariable model exhibited a c-index of 0.91 (95% confidence interval: 0.88–0.94). One variable (abnormal urinalysis) was selected for a reduced model, which had a c-index of 0.82 (95% confidence interval: 0.75–0.89). In a sensitivity analysis among hypothermic infants without fever (n = 22 with SBI among 116 infants), leukocytosis, absolute neutrophil count, and abnormal urinalysis were associated with SBI.Historical, examination, and laboratory data show potential as variables for risk stratification of hypothermic infants with concern for SBI. Larger studies are needed to definitively risk stratify this cohort, particularly for invasive bacterial infections.

Extensively drug-resistant (XDR) strains of Salmonella entericaserotype Typhi have emerged in Pakistan and Iraq. We report 13 children with enteric fever in Southeast Texas seen over 3.5 years, of whom 23.1% had XDR isolates.

BRAFgenomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n= 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system–penetrant, type II RAF inhibitor tovorafenib (420 mg m−2once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n= 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n= 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485.

ObjectiveThe lack of evidence-based criteria to guide chest radiograph (CXR) use in young febrile infants results in variation in its use with resultant suboptimal quality of care. We sought to describe the features associated with radiographic pneumonias in young febrile infants.Study designSecondary analysis of a prospective cohort study in 18 emergency departments (EDs) in the Pediatric Emergency Care Applied Research Network from 2016 to 2019. Febrile (≥38°C) infants aged ≤60 days who received CXRs were included. CXR reports were categorised as ‘no’, ‘possible’ or ‘definite’ pneumonia. We compared demographics, clinical signs and laboratory tests among infants with and without pneumonias.ResultsOf 2612 infants, 568 (21.7%) had CXRs performed; 19 (3.3%) had definite and 34 (6%) had possible pneumonias. Patients with definite (4/19, 21.1%) or possible (11/34, 32.4%) pneumonias more frequently presented with respiratory distress compared with those without (77/515, 15.0%) pneumonias (adjusted OR 2.17; 95% CI 1.04 to 4.51). There were no differences in temperature or HR in infants with and without radiographic pneumonias. The median serum procalcitonin (PCT) level was higher in the definite (0.7 ng/mL (IQR 0.1, 1.5)) vs no pneumonia (0.1 ng/mL (IQR 0.1, 0.3)) groups, as was the median absolute neutrophil count (ANC) (definite, 5.8 K/mcL (IQR 3.9, 6.9) vs no pneumonia, 3.1 K/mcL (IQR 1.9, 5.3)). No infants with pneumonia had bacteraemia. Viral detection was frequent (no pneumonia (309/422, 73.2%), definite pneumonia (11/16, 68.8%), possible pneumonia (25/29, 86.2%)). Respiratory syncytial virus was the predominant pathogen in the pneumonia groups and rhinovirus in infants without pneumonias.ConclusionsRadiographic pneumonias were uncommon in febrile infants. Viral detection was common. Pneumonia was associated with respiratory distress, but few other factors. Although ANC and PCT levels were elevated in infants with definite pneumonias, further work is necessary to evaluate the role of blood biomarkers in infant pneumonias.

•CS585 is a novel prostacyclin receptor agonist that effectively inhibits integrin activation, granule secretion, and aggregation.•CS585 is a highly potent and selective compound available both orally and IV and prevents thrombosis between 24 and 48 hours.

Rapid population growth, global conflict, and the COVID-19 pandemic are all contributing to the surge in global food insecurity.Nanoparticles (NPs) show promise toward alleviating food insecurity as several NPs used in greenhouse and field studies are outperforming conventional agrochemicals.NP characteristics determine their uptake and translocation into plants.Literature precedent demonstrates that it is possible to tune critical NP properties such as size, surface charge, shape, surface modifications, and transformations to impact the NP’s performance within the plant.While studies done to date are promising, more systematic studies with the most promising NPs are needed to achieve the full potential benefit of NP-enabled agriculture.

Coronavirus-associated coagulopathy (CAC) is a morbid and lethal sequela of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CAC results from a perturbed balance between coagulation and fibrinolysis and occurs in conjunction with exaggerated activation of monocytes/macrophages (MO/Mφs), and the mechanisms that collectively govern this phenotype seen in CAC remain unclear. Here, using experimental models that use the murine betacoronavirus MHVA59, a well-established model of SARS-CoV-2 infection, we identify that the histone methyltransferase mixed lineage leukemia 1 (MLL1/KMT2A) is an important regulator of MO/Mφ expression of procoagulant and profibrinolytic factors such as tissue factor (F3; TF), urokinase (PLAU), and urokinase receptor (PLAUR) (herein, “coagulopathy-related factors”) in noninfected and infected cells. We show that MLL1 concurrently promotes the expression of the proinflammatory cytokines while suppressing the expression of interferon alfa (IFN-α), a well-known inducer of TF and PLAUR. Using in vitro models, we identify MLL1-dependent NF-κB/RelA–mediated transcription of these coagulation-related factors and identify a context-dependent, MLL1-independent role for RelA in the expression of these factors in vivo. As functional correlates for these findings, we demonstrate that the inflammatory, procoagulant, and profibrinolytic phenotypes seen in vivo after coronavirus infection were MLL1-dependent despite blunted Ifna induction in MO/Mφs. Finally, in an analysis of SARS-CoV-2 positive human samples, we identify differential upregulation of MLL1 and coagulopathy-related factor expression and activity in CD14+ MO/Mφs relative to noninfected and healthy controls. We also observed elevated plasma PLAU and TF activity in COVID-positive samples. Collectively, these findings highlight an important role for MO/Mφ MLL1 in promoting CAC and inflammation.

Phlebectomy of large voluminous varicose veins comes with a risk of substantial blood loss. The purpose of the present study was to investigate the outcomes associated with the use of an adjunct tourniquet during varicose vein surgery of complex and large truncular varicosities.

External iliac artery endofibrosis (EIAE) classically presents in cyclists with intimal thickening of the affected arteries. We investigated possible anatomical predisposing factors including psoas muscle hypertrophy, arterial tortuosity, inguinal ligament compression, and arterial kinking via a case-control comparison of symptomatic and contralateral limbs.

The fibronectin (FN) isoform including the extradomain B (EDB) segment (EDB + FN) is a promising tumor target and is highly expressed in some tumor types, such as breast, head, and neck cancer. To date, mostly immunohistochemistry (IHC) and Western blot have been used for the analysis of EDB + FN. However, complete quantitative measurements of EDB + FN expression in a tumor and circulation are important for the development of anti-EDB therapeutics. To this end, a method using protein enrichment followed by online antipeptide antibody enrichment coupled with a nanoflow LC-MS/MS was developed to quantify EDB + FN in human and cynomolgus plasma, patient-derived xenograft (PDX) tumors, and PDX formalin-fixed paraffin-embedded (FFPE) samples. Mouse plasma EDB + FN was analyzed using a protein immunoaffinity method followed by nanoflow LC-MS/MS. EDB + FN concentrations were 63.1 pmol/g in PDX breast cancer tumor and 49.6 pmol/g in PDX head and neck tumor. Mean plasma concentration was 1.1 nM (pmol/mL, 47.4 ng/mL) in normal healthy humans and 0.35 nM (15.1 ng/mL) in naive cynomolgus. The assay sensitivity was 0.018 nM based on calibration with recombinant human EDB + FN (rhEDB + FN).

Laparoscopic cholecystectomy is frequently performed for acute cholecystitis and symptomatic cholelithiasis. Considerable variation in the execution of key steps of the operation remains. We conducted a systematic review of evidence regarding best practices for critical intraoperative steps for laparoscopic cholecystectomy.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.annemergmed.2005.10.019 Byline: Andrea T. Cruz (a), Andreea C. Cazacu (a), Latresha J. McBride (a), Jewel M. Greer (b), Gail J. Demmler (a)(b) Abstract: We evaluate the performance of a rapid assay (Binax NOW) for the detection of influenza A virus in children. Author Affiliation: (a) Department of Pediatrics, Baylor College of Medicine, Houston, TX (b) Diagnostic Virology Laboratory, Texas Children's Hospital, Houston, TX Article History: Received 7 July 2005; Revised 17 August 2005; Revised 16 September 2005; Revised 29 September 2005; Accepted 13 November 2005 Article Note: (footnote) Supervising editor: Steven M. Green, MD Author contributions: ATC and LJM were responsible for database creation. ATC, ACC, and GJD conducted data analysis. ATC and ACC were responsible for manuscript creation. JMG conducted database maintenance, performance of rapid assays, and viral cultures. GJD conducted manuscript review. ATC takes responsibility for the paper as a whole. Funding and support: This work was partially supported by grant D43 TW01036 from the National Institutes of Health-Fogarty International Center (ACC) and by the National Institutes of Health-Society for Pediatric Research Summer Student Research Program (LJM). Neither Binax nor any other pharmaceutical or corporate sponsor supported the study or any of the authors in any way.

The study is conducted to complete an evaluation of nevirapine (NVP) toxicity in a cohort of HIV+ pregnant women. It is found that NVP toxicities occurred in a very small fraction of patients and were not associated with fatalities.

PID usually is a mild disease, but it's associated with serious morbidity. These specialists in adolescent medicine show you how to evaluate your sexually active female patients for PID and [...]

Objective: This study reported pregnancy complications and neonatal outcomes for 49 live births in a group of women with eating disorders who were prospectively followed. Method: Subjects were recruited from 246 women participating in a longitudinal study of anorexia nervosa and bulimia nervosa, now in its 12th year. Subjects were interviewed by trained assistants and completed a brief self-report instrument that assessed both birth statistics and birth-related complications. Medical records and/or self-report data describing the neonates' birth status were obtained. Results: The majority of the women with eating disorders had normal pregnancies, resulting in healthy babies. Across the group, the mean length of pregnancy was 38.7 weeks, the mean birth weight was 7.6 lb, and mean Apgar scores at 1 and 5 minutes after birth were 8.2 and 9.0, respectively. Most outcomes were positive; however, three babies (6.1%) had birth defects, and 17 (34.7%) of the women experienced postpartum depression. The mean number of obstetric complications in the group was 1.3, and 13 (26.5%) of the women delivered by cesarean section. Women who showed symptoms of either anorexia nervosa or bulimia nervosa during pregnancy had a higher frequency of birth by cesarean section and postpartum depression than did nonsymptomatic women. Conclusions: Pregnant women with active eating disorders appear to be at greater risk for delivery by cesarean section and for postpartum depression. Pregnant women with past or current eating disorders should be viewed as being at high risk and monitored closely both during and after pregnancy to optimize maternal and fetal outcomes. (Am J Psychiatry 2001; 158:1461-1466)

The aim of this article is to report the usefulness of the plasma rich in growth factors for persistent macular hole closure. At the end of follow-up, complete macular hole closure was achieved in both cases. The use of plasma rich in growth factors may be an effective and safe surgical technique for persistent macular hole.