•No mortality events were observed among infected patients.•SARS-CoV-2 infection was associated with pulmonary complications.•Symptomatic infection was not associated with adverse outcomes.
To ...understand whether perioperative SARS-CoV-2 infection increases risk of pulmonary complications in children.
A retrospective cohort study of children who underwent surgery with perioperative SARS-CoV-2 infection at a children's hospital from March 1, 2020, to June 30, 2021. Uninfected, age-matched control patients who underwent the same procedure as infected patients over the past ten years were included in the study in a 3:1 ratio to infected patients. Primary outcomes were 7- and 30-day mortality. Secondary outcomes were development of pulmonary complications, readmission, length of hospital or ICU stay, and oxygen administration in post-anesthesia care unit (PACU).
Our study included 73 patients who underwent surgery with perioperative diagnosis of SARS-CoV-2, and 218 control patient undergoing similar procedures. One total mortality event was observed within 7 days in an uninfected control patient, and none occurred in infected patients. Perioperative SARS-CoV-2 infection was associated with increased risk for pulmonary complications in univariate analysis. Infection was not associated with any of our other secondary outcomes. Symptomatic SARS-CoV-2 infection and timing of diagnosis was not associated with development of pulmonary complications among infected patients.
Children with perioperative SARS-CoV-2 infection may be at increased risk for development of pulmonary complications. Larger studies should be performed to confirm our results.
To evaluate the decision making processes of pediatricians regarding diagnosis and management of developmental dysplasia of the hip (DDH) by conducting a survey of pediatricians in the United States.
...An electronic survey was sent to multiple American Academy of Pediatrics state chapters and academic pediatrics groups, and responses were received from pediatricians in 10 states. The survey included demographics, guideline use, clinical scenarios, and referrals/imaging practices. The number of responses to each survey question and their relative frequencies were calculated.
We received 139 responses and included 126 in our analyses. Only 50% of the responding pediatricians (63 of 126) practiced in an institution that endorses a care pathway for DDH. Only 5.6% of the pediatricians (7 of 125) have referred patients at 12-18 months between diagnosis and management to a specialist for suspected DDH, and 9.5% (12 of 125) have referred patients between 6 and 9 months. Almost one-quarter of the pediatricians (23%; 29 of 126) cited “hip click” as an abnormality that would prompt them to refer a patient to a specialist, and 72.2% (91 of 126) indicated that family history of DDH warrants an ultrasound regardless of the physical examination findings. Moreover, 10.3% of the surveyed pediatricians (13 of 126) reported being only “somewhat” or “moderately” familiar with the Barlow and Ortolani maneuvers.
The results of this study indicate that there is an opportunity to better distribute and implement DDH guidelines. The large number of pediatrician respondents who would not refer patients to a specialist or order imaging studies appropriately represents an opportunity for education. The implementation of a care map with standard referral and imaging practices could improve the care of patients with DDH.
Developmental dysplasia of the hip (DDH) is a common condition, affecting 1% to 2% of full-term infants. The American Academy of Orthopaedic Surgeons (AAOS) and American Academy of Pediatrics have ...published guidelines detailing best practices for DDH screening and treatment. The purpose of this survey was to determine DDH treatment practices of pediatric orthopaedic surgeons in North America.
We queried orthopaedic surgeon members of the Pediatric Orthopaedic Society of North America (POSNA) about referral patterns, treatment practices, and use of DDH guidelines. The survey included demographics, clinical scenarios, referrals patterns, and ultrasound practices.
Of the 1392 members of POSNA, we received 432 total responses and included 353 in statistical analyses. Results show that 68% (233/342) of surgeons practice in an institution that does not endorse a standard care pathway for DDH. Of surgeons who personally use a DDH care pathway, the AAOS guidelines were most cited (143/353, 41%). The majority (94%, 316/337) of surgeons do not believe that universal ultrasound screening should be adopted in the United States. Responses regarding ultrasound screening for "high risk" infants as outlined by AAOS varied based on risk factor. Many (57%, 200/353) surgeons have performed initial evaluations for patients over 12 months of age. While 80% (260/327) of orthopaedic surgeons believe that primary care providers are referring patients appropriately, only 57% (183/323) believe that primary care providers are ordering imaging studies appropriately.
Results from this survey of POSNA membership indicate an opportunity to better distribute and implement DDH guidelines. In addition, the implementation of a care map with a focus on standard referral and imaging practices could improve the care of patients with DDH by: (1) reducing the total cost of care, (2) increasing the use of appropriate imaging, (3) increasing timely referral for DDH care, and (4) reducing the presentation rate of walking age DDH patients.
The level of evidence rating for this survey-based study is level IV.
Background
We evaluated screening, referral and treatment practices for developmental dysplasia of the hip (DDH) in India by surveying Orthopaedic surgeons who treat patients with DDH. The survey ...assessed the timing of DDH presentation, resource availability, and current state of screening and diagnosis, which would help in the development of a DDH care pathway for India.
Methods
An online survey was distributed to Orthopaedic surgeons practicing in India via email and administered onsite to those attending the annual conference of the Pediatric Orthopaedic Society of India in 2019.
Results
173 completed surveys were received from surgeons practicing in a predominantly urban setting. 68.8% of respondents had performed initial evaluations on children with DDH aged over 1 year in the past 12 months, and 49.1% had assessed children with DDH aged > 2 years on initial presentation. There was no consistent use of established guidelines, with only 30% of respondents stating that a care pathway was in place at their institution. However, 91.9% would support the implementation of a care pathway developed in India, to decrease the incidence of delayed diagnosis and facilitate earlier intervention. 85% of respondents had ready access to ultrasound scans and 95.4% had access to X-rays.
Conclusions
In India, there is still a large number of late-presenting cases of DDH, which could be improved with effective screening. The development of a care pathway for DDH in India is well-supported by Orthopaedic surgeons and may help decrease the incidence of late presenting cases; potentially improving outcomes, decreasing morbidity, and upskilling local practitioners.
The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to ...characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10(-3) and 1.42 × 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.
Here, a set of experiments to assess the feasibility of using an invasive and widespread freshwater mussel (Dreissena rostrformis bugensis) as a sentinel species for nanoplastic detection is ...reported. Under laboratory experimental conditions, mussels ingest and retain fluorescent polystyrene (PS) beads with carboxylic acid (COOH) termination over a size range of 200–2000 nm. The number of beads the mussels ingested is quantified using fluorescence spectroscopy and the location of the beads in the mussels is imaged using fluorescence microscopy. PS beads of similar size (1000–2000 nm) to mussels' preferred food are trafficked in the ciliated food grooves of the gills. Beads of all sizes are observed in the mussels' digestive tracts, indicating that the mussels do not efficiently reject the beads as unwanted foreign material, regardless of size. Fluorescence microscopy shows all sizes of beads are concentrated in the siphons and are retained there for longer than one month postexposure. Combined atomic force microscopy–infrared spectroscopy and photothermal infrared spectroscopy are used to locate, image, and chemically identify the beads in the mussel siphons. In sum, these experiments demonstrate the potential for using mussels, specifically their siphons, to monitor environmental accumulation of aquatic nanoplastics.
Can quagga mussels (Dreissena rostriformis bugensis), a widespread and invasive freshwater species that alters local ecosystems, act as a sentinel species for detecting nanoplastics? In the laboratory, mussels ingest and retain 200–2000 nm fluorescent polystyrene beads, which are in the size range for the mussels' preferred food and are trafficked like food in the ciliated grooves of the gills.
Vorasidenib and ivosidenib inhibit mutant forms of isocitrate dehydrogenase (mIDH) and have shown preliminary clinical activity against mIDH glioma. We evaluated both agents in a perioperative phase ...1 trial to explore the mechanism of action in recurrent low-grade glioma (IGG) and select a molecule for phase 3 testing. Primary end-point was concentration of D-2-hydroxyglutarate (2-HG), the metabolic product of mIDH enzymes, measured in tumor tissue from 49 patients with mIDH1-R132H nonenhancing gliomas following randomized treatment with vorasidenib (50 mg or 10 mg once daily, q.d.), ivosidenib (500 mg q.d. or 250 mg twice daily) or no treatment before surgery. Tumor 2-HG concentrations were reduced by 92.6% (95% credible interval (CrI), 76.1-97.6) and 91.1% (95% CrI, 72.0-97.0) in patients treated with vorasidenib 50 mg q.d. and ivosidenib 500 mg q.d., respectively. Both agents were well tolerated and follow-up is ongoing. In exploratory analyses, 2-HG reduction was associated with increased DNA 5-hydroxymethylcytosine, reversal of 'proneural' and 'stemness' gene expression signatures, decreased tumor cell proliferation and immune cell activation. Vorasidenib, which showed brain penetrance and more consistent 2-HG suppression than ivosidenib, was advanced to phase 3 testing in patients with mIDH LGGs. Funded by Agios Pharmaceuticals, Inc. and Servier Pharmaceuticals LLC; ClinicalTrials.gov number NCT03343197.
This randomized, open-label trial compared dacomitinib (PF-00299804), an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, with erlotinib, a reversible ...EGFR inhibitor, in patients with advanced non-small-cell lung cancer (NSCLC).
Patients with NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, no prior HER-directed therapy, and one/two prior chemotherapy regimens received dacomitinib 45 mg or erlotinib 150 mg once daily.
One hundred eighty-eight patients were randomly assigned. Treatment arms were balanced for most clinical and molecular characteristics. Median progression-free survival (PFS; primary end point) was 2.86 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (hazard ratio HR = 0.66; 95% CI, 0.47 to 0.91; two-sided P = .012); in patients with KRAS wild-type tumors, median PFS was 3.71 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (HR = 0.55; 95% CI, 0.35 to 0.85; two-sided P = .006); and in patients with KRAS wild-type/EGFR wild-type tumors, median PFS was 2.21 months for patients treated with dacomitinib and 1.84 months for patients treated with erlotinib (HR = 0.61; 95% CI, 0.37 to 0.99; two-sided P = .043). Median overall survival was 9.53 months for patients treated with dacomitinib and 7.44 months for patients treated with erlotinib (HR = 0.80; 95% CI, 0.56 to 1.13; two-sided P = .205). Adverse event-related discontinuations were uncommon in both arms. Common treatment-related adverse events were dermatologic and gastrointestinal, predominantly grade 1 to 2, and more frequent with dacomitinib.
Dacomitinib demonstrated significantly improved PFS versus erlotinib, with acceptable toxicity. PFS benefit was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants.
Background and Purpose
Over past decades, targeted therapies and immunotherapy have improved survival and reduced the morbidity of patients with BRAF‐mutated melanoma. However, drug resistance and ...relapse hinder overall success. Therefore, there is an urgent need for novel compounds with therapeutic efficacy against BRAF‐melanoma. This prompted us to investigate the antiproliferative profile of a tachykinin‐peptide from the Octopus kaurna, Octpep‐1 in melanoma.
Experimental Approach
We evaluated the cytotoxicity of Octpep‐1 by MTT assay. Mechanistic insights on viability and cellular damage caused by Octpep‐1 were gained via flow cytometry and bioenergetics. Structural and pharmacological characterization was conducted by molecular modelling, molecular biology, CRISPR/Cas9 technology, high‐throughput mRNA and calcium flux analysis. In vivo efficacy was validated in two independent xerograph animal models (mice and zebrafish).
Key Results
Octpep‐1 selectively reduced the proliferative capacity of human melanoma BRAFV600E‐mutated cells with minimal effects on fibroblasts. In melanoma‐treated cells, Octpep‐1 increased ROS with unaltered mitochondrial membrane potential and promoted non‐mitochondrial and mitochondrial respiration with inefficient ATP coupling. Molecular modelling revealed that the cytotoxicity of Octpep‐1 depends upon the α‐helix and polyproline conformation in the C‐terminal region of the peptide. A truncated form of the C‐terminal end of Octpep‐1 displayed enhanced potency and efficacy against melanoma. Octpep‐1 reduced the progression of tumours in xenograft melanoma mice and zebrafish.
Conclusion and Implications
We unravel the intrinsic anti‐tumoural properties of a tachykinin peptide. This peptide mediates the selective cytotoxicity in BRAF‐mutated melanoma in vitro and prevents tumour progression in vivo, providing a foundation for a therapy against melanoma.
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