Genetic conditions are individually rare but are common in aggregate, and they often present in the neonatal and early pediatric periods. These conditions are often severe, can be difficult to ...diagnose and manage, and may heavily affect patients, families, health care systems, and society. Because of recent technological advances, the availability and uptake of genetic and genomic testing are increasing rapidly. However, there is a dearth of trained geneticists and genetic counselors to help guide and explain these conditions and relevant tests. To help hospitalists, neonatologists, and related practitioners navigate this complex and evolving field, we have compiled a list of free (mostly Web-based) resources relevant to the diagnosis and management of genetic conditions and related disorders. These resources, which we describe individually, can be useful for nongeneticist clinicians, and some also include material that can be used to explain concepts and conditions to patients or families. The resources presented are divided into the following categories (which overlap): general information, databases of genetic conditions, resources that can help generate differential diagnoses, databases of genetic testing laboratories (to help with logistics of ordering tests), information on newborn screening, and other resources. We also include a separate list of helpful textbooks and manuals. We conclude with 2 examples describing how some of these resources would be used by a pediatric hospitalist or neonatologist during the inpatient management of a child with a suspected genetic condition.
We discovered a transient adhesion property in poly(ethylene glycol) dimethacrylate (PEG-DMA) hydrogels and employed it to develop a novel "stem cell bandage" model of cellular delivery. First, we ...cultured human mesenchymal stromal cells (MSCs) on the surface of PEG-DMA hydrogels with high amounts of arginine-glycine-aspartic acid (RGD) adhesive peptides (RGD++) or without RGD (RGD-). On day 1, MSCs underwent an initial adhesion to RGD- hydrogels that was not significantly different over 13 days (n = 6). In addition, cells appeared to be well spread by day 3. Significantly fewer cells were present on RGD- hydrogels on day 15 compared to day 9, suggesting that RGD- hydrogels allow for an initial cellular adhesion that is stable for multiple days, but transient over longer periods with a decrease by day 15. This initial adhesion is especially surprising considering that PEG-DMA does not contain any biological adhesion motifs and is almost chemically identical to poly(ethylene glycol) diacrylate (PEG-DA), which has been shown to be non-adhesive without RGD. We hypothesized that MSCs could be cultured on RGD- PEG-DMA hydrogels and then applied to a wound site to deliver cells in a novel approach that we refer to as a "stem cell bandage". RGD- donor hydrogels were successfully able to deliver MSCs to PEG-DMA acceptor hydrogels with high RGD content (RGD++) or low amounts of RGD (RGD+). Our novel "bandage" approach promoted cell delivery to these model surfaces while preventing cells from diffusing away. This stem cell delivery strategy may provide advantages over more common stem cell delivery approaches such as direct injections or encapsulation and thus may be valuable as an alternative tissue engineering approach.
Objective
To define those children who develop acute kidney injury (AKI) within 48 h of admission from the emergency department (ED) and ascertain patient-related factors in the ED associated with ...AKI.
Methods
Retrospective, cohort study of children, birth to 19 years, admitted to a tertiary pediatric hospital from the ED between January 2010 and December 2013 who had serum creatinine (SCr) drawn as part of clinical care. AKI was defined as a 50% increase in SCr above baseline, as measured within 48 h of hospital presentation. Multivariable logistic regression was performed to determine factors associated with AKI by comparing those with and without kidney injury on hospital presentation.
Results
Of all ED admissions, 13,827 subjects (27%) were included; 10% developed AKI. Of kids with AKI, 75% had a measured SCr consistent with AKI while in the ED, 36% were admitted to the intensive care unit, and 2% died (all significantly more than children without AKI). Young age, history of AKI or solid organ transplant, receipt of intravenous fluids or central venous access in the ED, and admission to intensive care were factors independently associated with AKI (AUC = 0.793, 95% CI 0.78–0.81).
Conclusions
One in 10 children who had SCr measured and were admitted to a tertiary pediatric hospital had AKI on or within 48 h of presentation. Inherent characteristics, identifiable in the ED, are associated with an increased risk of AKI. Future research should focus on improving AKI recognition in the ED by the development of a risk stratification tool.
To determine if differences in patient characteristics, treatments, and outcomes exist between children with sepsis who arrive by emergency medical services (EMS) versus their own mode of transport ...(self-transport).
Retrospective cohort study of patients who presented to the Emergency Department (ED) of two large children's hospitals and treated for sepsis from November 2013 to June 2017. Presentation, ED treatment, and outcomes, primarily time to first bolus and first parental antibiotic, were compared between those transported via EMS versus patients who were self-transported.
Of the 1813 children treated in the ED for sepsis, 1452 were self-transported and 361 were transported via EMS. The EMS group were more frequently male, of black race, and publicly insured than the self-transport group. The EMS group was more likely to have a critical triage category, receive initial care in the resuscitation suite (51.9 vs. 22%), have hypotension at ED presentation (14.4 vs. 5.4%), lactate >2.0 mmol/L (60.6 vs. 40.8%), vasoactive agents initiated in the ED (8.9 vs. 4.9%), and to be intubated in the ED (14.4 vs. 2.8%). The median time to first IV fluid bolus was faster in the EMS group (36 vs. 57 min). Using Cox LASSO to adjust for potential covariates, time to fluids remained faster for the EMS group (HR 1.26, 95% CI 1.12, 1.42). Time to antibiotics, ICU LOS, 3- or 30-day mortality rates did not differ, yet median hospital LOS was significantly longer in those transported by EMS versus self-transported (6.5 vs. 5.3 days).
Children with sepsis transported by EMS are a sicker population of children than those self-transported on arrival and had longer hospital stays. EMS transport was associated with earlier in-hospital fluid resuscitation but no difference in time to first antibiotic. Improved prehospital recognition and care is needed to promote adherence to both prehospital and hospital-based sepsis resuscitation benchmarks.
•Children with septic shock transported by EMS are a distinct vulnerable sick subset•They have longer hospital length of stay•Time to fluid administration, but not to antibiotics, was shorter in the EMS group.
Dual implants for distal femur periprosthetic fractures is a growing area of interest for these challenging fractures with dual plating (DP) emerging as a viable construct for these injuries. In the ...current study, an experience with DP constructs is described.
Retrospective case series with comparison group.
Level 1 academic trauma center.
Adults >50 years old sustaining comminuted OTA/AO 33-A2 or 33-A3 DFPF treated with either DP or a single distal femur locking plating (DFLP). Patients with simple 33-A1 fractures were excluded. Prior to 2018, patients underwent DFLP after which the treatment of choice became DP.
Reoperation rate, alignment, and complications.
34 patients treated with DFLP and 38 with DP met inclusion and follow up criteria. Average follow up was 18.2 ± 13.8 months in the DFLP group and 19.8 ± 16.1 months in the DP group ( P = 0.339). The average patient age in the DFLP group was 74.8 ± 7.3 years compared to 75.9 ± 11.3 years in the DP group. There were no statistical differences in demographics, fracture morphology, loss of reduction, or reoperation for any cause ( P >.05). DP patients were more likely to be weight bearing in the twelve-week postoperative period ( P <0.001) and return to their baseline ambulatory status ( P = 0.004) compared to DFLP patients.
Dual plating of distal femoral periprosthetic fractures maintained coronal alignment with a low reoperation rate even with immediate weight bearing and these patients regained baseline level of ambulation more reliably as compared to patients treated with a single distal femoral locking plate.
Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Abstract
Objectives
Management of colorectal cancer warrants mutational analysis of KRAS/NRAS when considering anti–epidermal growth factor receptor therapy and BRAF testing for prognostic ...stratification. In this multicenter study, we compared a fully integrated, cartridge-based system to standard-of-care assays used by participating laboratories.
Methods
Twenty laboratories enrolled 874 colorectal cancer cases between November 2017 and December 2018. Testing was performed on the Idylla automated system (Biocartis) using the KRAS and NRAS-BRAF cartridges (research use only) and results compared with in-house standard-of-care testing methods.
Results
There were sufficient data on 780 cases to measure turnaround time compared with standard assays. In-house polymerase chain reaction (PCR) had an average testing turnaround time of 5.6 days, send-out PCR of 22.5 days, in-house Sanger sequencing of 14.7 days, send-out Sanger of 17.8 days, in-house next-generation sequencing (NGS) of 12.5 days, and send-out NGS of 20.0 days. Standard testing had an average turnaround time of 11 days. Idylla average time to results was 4.9 days with a range of 0.4 to 13.5 days.
Conclusions
The described cartridge-based system offers rapid and reliable testing of clinically actionable mutation in colorectal cancer specimens directly from formalin-fixed, paraffin-embedded tissue sections. Its simplicity and ease of use compared with other molecular techniques make it suitable for routine clinical laboratory testing.
Since the onset of fisheries science, monitoring programs have been implemented to support stock assessments and fisheries management. Here, we take inventory of the monitoring programs of the U.S. ...Gulf of Mexico (GOM) surveying fish and invertebrates and conduct a gap analysis of these programs. We also compile a large monitoring database encompassing much of the monitoring data collected in the U.S. GOM using random sampling schemes and employ this database to fit statistical models to then map the spatial distributions of 61 fish and invertebrate functional groups, species and life stages of the U.S. GOM. Finally, we provide recommendations for improving current monitoring programs and designing new programs, and guidance for more comprehensive use and sharing of monitoring data, with the ultimate goal of enhancing the inputs provided to stock assessments and ecosystem-based fisheries management (EBFM) projects in the U.S. GOM. Our inventory revealed that 73 fisheries-independent and fisheries-dependent programs have been conducted in the U.S. GOM, most of which (85%) are still active. One distinctive feature of monitoring programs of the U.S. GOM is that they include many fisheries-independent surveys conducted almost year-round, contrasting with most other marine regions. A major sampling recommendation is the development of a coordinated strategy for collecting diet information by existing U.S. GOM monitoring programs for advancing EBFM.
Objective: To inform the future development of a pediatric prehospital sepsis tool, we sought to 1) describe the characteristics, emergent care, and outcomes for children with septic shock who are ...transported by emergency medicine services (EMS) and compare them to those self-transported; and 2) determine the EMS capture rate of common sepsis screening parameters and the concordance between the parameters documented in the EMS record and in the emergency department (ED) record. Methods: This is a retrospective cohort study of children ages 0 through 21 years who presented to a pediatric ED with septic shock between 11/2013 and 06/2016. Data, collected by electronic and manual chart review of EMS and ED records, included demographics, initial vital signs in both EMS and ED records, ED triage level, site of initial ED care, ED disposition, ED therapeutic interventions, outcomes, and times associated with processes. Potential screening parameters were dichotomized as normal vs. abnormal based on age-dependent normative data. Results: Of the children with septic shock treated in our ED, 19.3% arrived via EMS. These children as compared to those self-transported were more likely (i.e., p < 0.05) to be male, have public insurance, receive initial care in the ED resuscitation suite, be hypotensive on arrival, receive their first ED fluid bolus sooner (33 vs. 58 minutes), receive vasoactive agents, be mechanically ventilated in the first 24 hours, and have slightly longer length of hospital stays. Both groups had similar times to antibiotics. While poor outcomes were rare, the 3- and 30-day mortalities were similar for both groups. EMS capture rates were highest for heart rate and respiratory rate and lowest for temperature, glucose, and blood pressure. Interrater reliability was highest for heart rate. Conclusions: Children presenting to the ED with septic shock transported by EMS represent a critically ill subset of modest proportions. Realization of a sepsis screening tool for this vulnerable population will require both creation of a tool containing a limited subset of objective parameters along with processes to ensure capture.
Pediatric sepsis definitions have evolved, and some have proposed using the measure used in adults to quantify organ dysfunction, a Sequential Organ Failure Assessment (SOFA) score of 2 or more in ...the setting of suspected infection. A pediatric adaptation of SOFA (pSOFA) showed excellent discrimination for mortality in critically ill children but has not been evaluated in an emergency department (ED) population.
To delineate test characteristics of the pSOFA score for predicting in-hospital mortality among (1) all patients and (2) patients with suspected infection treated in pediatric EDs.
This retrospective cohort study took place from January 1, 2012, to January 31, 2020 in 9 US children's hospitals included in the Pediatric Emergency Care Applied Research Network (PECARN) Registry. The data was analyzed from February 1, 2020, to April 18, 2022. All ED visits for patients younger than 18 years were included.
ED pSOFA score was assigned by summing maximum pSOFA organ dysfunction components during ED stay (each 0-4 points). In the subset with suspected infection, visit meeting criteria for sepsis (suspected infection with a pSOFA score of 2 or more) and septic shock (suspected infection with vasoactive infusion and serum lactate level >18.0 mg/dL) were identified.
Test characteristics of pSOFA scores of 2 or more during the ED stay for hospital mortality.
A total of 3 999 528 (female, 47.3%) ED visits were included. pSOFA scores ranged from 0 to 16, with 126 250 visits (3.2%) having a pSOFA score of 2 or more. pSOFA scores of 2 or more had sensitivity of 0.65 (95% CI, 0.62-0.67) and specificity of 0.97 (95% CI, 0.97-0.97), with negative predictive value of 1.0 (95% CI, 1.00-1.00) in predicting hospital mortality. Of 642 868 patients with suspected infection (16.1%), 42 992 (6.7%) met criteria for sepsis, and 374 (0.1%) met criteria for septic shock. Hospital mortality rates for suspected infection (599 502), sepsis (42 992), and septic shock (374) were 0.0%, 0.9%, and 8.0%, respectively. The pSOFA score had similar discrimination for hospital mortality in all ED visits (area under receiver operating characteristic curve, 0.81; 95% CI, 0.79-0.82) and the subset with suspected infection (area under receiver operating characteristic curve, 0.82; 95% CI, 0.80-0.84).
In a large, multicenter study of pediatric ED visits, a pSOFA score of 2 or more was uncommon and associated with increased hospital mortality yet had poor sensitivity as a screening tool for hospital mortality. Conversely, children with a pSOFA score of 2 or less were at very low risk of death, with high specificity and negative predictive value. Among patients with suspected infection, patients with pSOFA-defined septic shock demonstrated the highest mortality.
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