Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the ...COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.
A prospective, observational cohort study.
Children with sepsis and organ failure in nine pediatric intensive care units in the United States.
Two hundred and fifty-five children were enrolled. Five distinct clinical multi-trajectory groups were identified. Plasma CRP (mg/dL), ferritin (ng/mL), and 31 cytokine levels were measured at two timepoints during sepsis (median Day 2 and Day 5). Group-based multi-trajectory models (GBMTM) identified groups of children with distinct patterns of CRP and ferritin.
Group 1 had normal CRP and ferritin levels ( n = 8; 0% mortality); Group 2 had high CRP levels that became normal, with normal ferritin levels throughout ( n = 80; 5% mortality); Group 3 had high ferritin levels alone ( n = 16; 6% mortality); Group 4 had very high CRP levels, and high ferritin levels ( n = 121; 11% mortality); and Group 5 had very high CRP and very high ferritin levels ( n = 30; 40% mortality). Cytokine responses differed across the five groups, with ferritin levels correlated with macrophage inflammatory protein 1α levels and CRP levels reflective of many cytokines.
Bedside CRP and ferritin levels can be used together to distinguish groups of children with sepsis who have different systemic inflammation cytokine responses and mortality risks. These data suggest future potential value in personalized clinical trials with specific targets for anti-inflammatory therapies.
Blunt trauma is a leading cause of morbidity and mortality in children. Despite the potential for malignancy, increased cost, limited small bowel injury detection sensitivity, and the low incidence ...of injury requiring operative intervention, the use of computed tomographic (CT) scan in pediatric blunt trauma evaluation remains common. Previous studies suggest that a clinical model using examination and laboratory data may help predict intra-abdominal injuries (IAIs) and potentially limit unnecessary CT scans in children.
A retrospective chart review of all blunt "trauma alerts" for patients younger than 16 years during an 18-month period was performed at a Level I trauma center. Clinical factors, which might predict blunt IAI (hemodynamics, abdominal examination, serology, and plain radiographs), and potential limitations to performing a reliable abdominal examination (altered mental status, young age) were reviewed. A previously defined clinical prediction model based on six high-risk clinical variables for blunt IAI (hypotension, abnormal abdominal examination, elevated aspartate aminotransferase, elevated amylase, low hematocrit, and heme-positive urinalysis) was applied to each patient.
Of the 125 "trauma alert" patients who sustained blunt trauma during the study period, 97 underwent abdominal CT scan, with only 15 identified as IAI. Our prediction rule would have identified 16 of 17 patients with IAI (SE, 94%) as high-risk and missed only 1 patient (grade I spleen laceration, which did not require operation) (negative predictive value, 99%). Of the 83 patients with no risk factors for IAI based on the prediction rule, 54 underwent a negative abdominal CT scan. Of these 54 patients, only 22 had a potential limitation to a reliable abdominal examination. Application of our prediction rule could have prevented unnecessary CT scan in at least 32 patients (33%) during an 18-month period.
Use of a prediction model based on high-risk variables for IAI may decrease cost and radiation exposure by reducing the number of abdominal CT scans in children being evaluated for blunt abdominal trauma.
Centers for Medicare and Medicaid Services (CMS) has requested hospitals collect and report patient-reported outcomes (PROs) beginning in 2024 including the Hip Disability and Osteoarthritis Outcome ...Score Joint Replacement (HOOS-JR). However, scale structural validity of the HOOS-JR has minimally been assessed. The purpose of this study was to assess internal consistency, structural validity, and multi-group invariance properties of the HOOS-JR in a large sample of patients who underwent a total hip arthroplasty (THA).
A cross-sectional study using the Surgical Outcomes System was retrospectively queried for patients who underwent a THA. Internal consistency was assessed using Cronbach's alpha and McDonald's Omega. A confirmatory factor analysis (CFA) was performed on the HOOS-JR using a priori cut-off values. Multi-group invariance testing was also performed on the sample of patients across sex and age groups.
Internal consistency was acceptable for 6-item (alpha = 0.88; omega = 0.88) and 5-item (alpha = 0.86; omega = 0.86) HOOS-JR. The one-factor, 6-item CFA did not meet the recommended fit indices. The one-factor, 5-item CFA had acceptable fit for the sample data. Invariance testing criteria were met between the age groups; however, scalar invariance was not met for sex.
The 6-item HOOS-JR did not meet contemporary model fit indices indicating that scale refinement is warranted. The 5-item met most goodness-of-fit indices and invariance criteria. However, further scale refinement may be warranted as localized fit issues were identified.
Metallo prodrugs that take advantage of the inherent acidity surrounding cancer cells have yet to be developed. We report a new class of pH-activated metallo prodrugs (pHAMPs) that are activated by ...light- and pH-triggered ligand dissociation. These ruthenium complexes take advantage of a key characteristic of cancer cells and hypoxic solid tumors (acidity) that can be exploited to lessen the side effects of chemotherapy. Five ruthenium complexes of the type (N,N)2Ru(PL)2+ were synthesized, fully characterized, and tested for cytotoxicity in cell culture (1 A : N,N = 2,2′-bipyridine (bipy) and PL, the photolabile ligand, = 6,6′-dihydroxybipyridine (6,6′-dhbp); 2 A : N,N = 1,10-phenanthroline (phen) and PL = 6,6′-dhbp; 3 A : N,N = 2,3-dihydro-1,4dioxino2,3-f1,10phenanthroline (dop) and PL = 6,6′-dhbp; 4 A : N,N = bipy and PL = 4,4′-dimethyl-6,6′-dihydroxybipyridine (dmdhbp); 5 A : N,N = 1,10-phenanthroline (phen) and PL = 4,4′-dihydroxybipyridine (4,4′-dhbp). The thermodynamic acidity of these complexes was measured in terms of two pK a values for conversion from the acidic form (X A ) to the basic form (X B ) by removal of two protons. Single-crystal X-ray diffraction data is discussed for 2 A , 2 B , 3 A , 4 B , and 5 A . All complexes except 5 A showed measurable photodissociation with blue light (λ = 450 nm). For complexes 1 A –4 A and their deprotonated analogues (1 B –4 B ), the protonated form (at pH 5) consistently gave faster rates of photodissociation and larger quantum yields for the photoproduct, (N,N)2Ru(H2O)22+. This shows that low pH can lead to greater rates of photodissociation. Cytotoxicity studies with 1 A –5 A showed that complex 3 A is the most cytotoxic complex of this series with IC50 values as low as 4 μM (with blue light) versus two breast cancer cell lines. Complex 3 A is also selectively cytotoxic, with sevenfold higher toxicity toward cancerous versus normal breast cells. Phototoxicity indices with 3 A were as high as 120, which shows that dark toxicity is avoided. The key difference between complex 3 A and the other complexes tested appears to be higher uptake of the complex as measured by inductively coupled plasma mass spectrometry, and a more hydrophobic complex as compared to 1 A , which may enhance uptake. These complexes demonstrate proof of concept for dual activation by both low pH and blue light, thus establishing that a pHAMP approach can be used for selective targeting of cancer cells.
Knowledge of spatial patterns of dengue virus (DENV) infection is important for understanding transmission dynamics and guiding effective disease prevention strategies. Because movement of infected ...humans and mosquito vectors plays a role in the spread and persistence of virus, spatial dimensions of transmission can range from small household foci to large community clusters. Current understanding is limited because past analyses emphasized clinically apparent illness and did not account for the potentially large proportion of inapparent infections. In this study we analyzed both clinically apparent and overall infections to determine the extent of clustering among human DENV infections.
We conducted spatial analyses at global and local scales, using acute case and seroconversion data from a prospective longitudinal cohort in Iquitos, Peru, from 1999-2003. Our study began during a period of interepidemic DENV-1 and DENV-2 transmission and transitioned to epidemic DENV-3 transmission. Infection status was determined by seroconversion based on plaque neutralization testing of sequential blood samples taken at approximately six-month intervals, with date of infection assigned as the middate between paired samples. Each year was divided into three distinct seasonal periods of DENV transmission. Spatial heterogeneity was detected in baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence calculated by trimester from 2001-2003 was spatially similar to preexisting DENV-1 and DENV-2 seroprevalence. Global clustering (case-control Ripley's K statistic) appeared at radii of ∼200-800 m. Local analyses (Kuldorf spatial scan statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999-2003. The number of seroconversions per cluster ranged from 3-34 with radii from zero (a single household) to 750 m; 65% of clusters had radii >100 m. No clustering was detected among clinically apparent infections.
Seroprevalence of previously circulating DENV serotypes can be a predictor of transmission risk for a different invading serotype and, thus, identify targets for strategically placed surveillance and intervention. Seroprevalence of a specific serotype is also important, but does not preclude other contributing factors, such as mosquito density, in determining where transmission of that virus will occur. Regardless of the epidemiological context or virus serotype, human movement appears to be an important factor in defining the spatial dimensions of DENV transmission and, thus, should be considered in the design and evaluation of surveillance and intervention strategies.
Mechanical percussion devices have become popular among sports medicine professionals. These devices provide a similar effect as manual percussion or tapotement used in therapeutic massage. To date, ...there are few published studies or evidence-based guidelines for these devices. There is a need to understand what professionals believe about this technology and how they use these devices in clinical practice.
To survey and document the knowledge, clinical application methods, and use of mechanical percussion devices among healthcare professionals in the United States.
Cross-sectional survey study.
A 25 question online survey was emailed to members of the National Athletic Trainers Association, Academy of Orthopedic Physical Therapy, and American Academy of Sports Physical Therapy.
Four hundred twenty-five professionals completed the survey. Most professionals (92%, n=391) used devices from two manufacturers: Hyperice® and Theragun®. Seventy-seven percent directed clients to manufacturer and generic websites (n=329) to purchase devices. Most respondents used a medium and low device speed setting for pre- and post-exercise (62%, n=185), pain modulation (59%, n=253), and myofascial mobility (52%, n=222). A large proportion of respondents preferred a total treatment time between 30 seconds and three minutes (36-48%, n=153-204) or three to five minutes (18-22%, n=76-93). Most respondents (54-69%, n=229-293) believed that mechanical percussion increases local blood flow, modulates pain, enhances myofascial mobility, and reduces myofascial restrictions. Most respondents (72%, n=305) were influenced by other colleagues to use these devices. Sixty-six percent used patient reported outcomes (n=280) to document treatment efficacy. Live instruction was the most common mode of education (79%, n=334).
These results are a starting point for future research and provide insight into how professionals use mechanical percussion devices. This survey also highlights the existing gap between research and practice. Future research should examine the efficacy of this technology and determine consensus-based guidelines.
3.
Mutations affecting the activity of the Wnt co-receptors LRP5 and LRP6 that cause alterations in skeletal biology confirmed the involvement of Wnt signaling in bone formation. We evaluated the ...potential role of Dkk1, an inhibitor of LRP5/6 activity, in bone formation by examining the normal expression pattern of Dkk1 in normal young mice and by assessing the consequences of osteoblast overexpression of Dkk1 in transgenic mice. Endogenous Dkk1 expression was detected primarily in osteoblasts and osteocytes. Transgenic over-expression of Dkk1 using two different rat collagen 1A1 promoters resulted in distinct bone phenotypes. More widespread Dkk1 expression (driven by the Col1A1 3.6 kb promoter) yielded osteopenia with forelimb deformities and hairlessness, while expression restricted to osteoblasts (driven by the Col1A1 2.3 kb promoter) induced severe osteopenia without limb defects or alopecia. The decrease in bone mass in vivo resulted from a significant 49% reduction in osteoblast numbers and was reflected in a 45% reduction in serum osteocalcin concentration; an in vitro study revealed that Dkk1 caused a dose-dependent suppression of osteoblast matrix mineralization. These data indicate that Dkk1 may directly influence bone formation and suggest that osteopenia develops in mice over-expressing Dkk1 at least in part due to diminished bone formation resulting from reduced osteoblast numbers.
Abstract
Purpose In this proof-of-concept pilot study, we aimed to increase nurse practitioner (NP) student knowledge of ophthalmology to prepare NPs for encounters in primary care settings. The ...Association of University Professors of Ophthalmology (AUPO) and the American Academy of Ophthalmology (AAO) endorse core knowledge that medical students should achieve. We assess the effectiveness of an innovative ophthalmologist-led curriculum based on these competencies tailored to issues NPs encounter in primary care.
Methods Johns Hopkins University NP students enrolled in a pre–post-cohort study and educational intervention. The didactic program was developed according to AUPO and AAO core ophthalmology content for medical students and was taught in-person by an ophthalmologist. Pre–post-assessments evaluated students' perceived readiness to encounter ophthalmic issues in the clinic and baseline knowledge of core competencies of ophthalmology.
Results A total of 42 NP students were included in the analysis. NP students improved in core knowledge and readiness to encounter ophthalmology issues. After the educational event, there was a statistically significant improvement in students' ratings of preparedness to obtain a focused history, exam, perform initial management and decide the urgency of a referral for acute painless vision loss (p < 0.001), chronic vision loss (p < 0.001), or a patient with a red/painful eye (p < 0.001). Students showed a statistically significant improvement in postdidactic event core ophthalmology knowledge assessment scores (p = 0.002).
Conclusion Primary care NPs are increasingly the initial point of contact for patients with ophthalmic complaints, and thus, high-quality and thorough education regarding ophthalmology triage and referral for NPs is necessary. NP student comfort with and knowledge of ophthalmic complaints and triage may be improved by a brief educational intervention taught by an ophthalmologist early in the NP curriculum.
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