Stem cell factor inhibition reduces Th2 inflammation and cellular infiltration in a mouse model of eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a T helper (Th)2-mediated inflammatory disorder characterized endoscopically by eosinophilic infiltration leading to fibrosis of the esophagus. Stem cell factor (SCF), a multifunctional cytokine, is upregulated in several allergic diseases, including in patients with EoE. Mast cells and eosinophils express c-kit, the cell surface receptor for SCF, and have been found to play an important role in EoE. Therefore, we investigated whether blocking SCF represents a potential therapeutic approach for EoE. Esophageal inflammation was induced in mice using peanut allergen. In mice with experimental EoE, we found that SCF was upregulated in the esophageal tissue. In EoE mice injected with a polyclonal antibody specific for SCF, we observed a decrease in both mast cells and eosinophils by histological and flow cytometric analysis. Furthermore, Th2 cytokines in the esophagus were decreased in anti-SCF treated mice, as were levels of Th2 cytokines from lung-draining and esophageal lymph nodes. Serum levels of peanut-specific immunoglobulin E were reduced following treatment with anti-SCF. In Kitlf/f-Col1-Cre-ERT mice, which have SCF deleted primarily in myofibroblasts that develop in EoE, we observed similar results as the anti-SCF treated animals for inflammatory cell accumulation, cytokines, and histopathology. These results indicate that therapeutic treatments targeting SCF can reduce allergic inflammation in EoE.

Evaluating a 10-Week Family-Focused E-Health Healthy Lifestyle Program for School-Aged Children with Overweight or Obesity: A Randomized Controlled Trial Study Protocol.

E-Health childhood obesity treatment interventions may serve as favorable alternatives to conventional face-to-face programs. More studies are needed to evaluate the effectiveness of such interventions beyond immediately post-program completion, including exploring program features impacting effectiveness. This randomized controlled trial with a qualitative component and waitlisted control group will evaluate the effectiveness of a 10-week family-focused e-Health program for school-aged children with overweight/obesity and explore the experience of families completing the program. The primary outcome is the change in BMI z-score and will be assessed from baseline to 10 weeks. Secondary outcomes include (the change in) waist circumference, dietary intake, physical activity, quality of life, and experiences, and will be assessed at baseline, post-10 weeks, and/or immediately, 3-, 6-, and/or 12-months post-program completion. Independent t-tests will be used to compare the differences in means and analyses of variances (ANOVAs) will be conducted to investigate the impact of the program or of being waitlisted and the effect size of the program on quantitative outcome measures. Reflexive thematic analysis will be used with qualitative data. Findings from this study are expected to provide learnings to upscale conventional childhood obesity treatment services, in the hopes of curbing the rising rate of childhood obesity.

Reducing Complications in Pilon Fracture Surgery: Surgical Time Matters.

OBJECTIVE: To correlate patient-specific and surgeon-specific factors with outcomes after operative management of distal intra-articular tibia fractures. DESIGN: Retrospective cohort study. SETTING: 3 Level 1 tertiary academic trauma centers. PATIENTS/PARTICIPANTS: The study included a consecutive series of 175 patients with OTA/AO 43-C pilon fractures. MAIN OUTCOME MEASUREMENTS: Primary outcomes included superficial and deep infection. Secondary outcomes included nonunion, loss of articular reduction, and implant removal. RESULTS: The following patient-specific factors correlated with poor surgical outcomes: increased age with superficial infection rate ( P < 0.05), smoking with rate of nonunion ( P < 0.05), and Charlson Comorbidity Index with loss of articular reduction ( P < 0.05). Each additional 10 minutes of operative time over 120 minutes was associated with increased odds of requiring I&D and any treatment for infection. The same linear effect was seen with the addition of each fibular plate. The number of approaches, type of approach, use of bone graft, and staging were not associated with infection outcomes. Each additional 10 minutes of operative time over 120 minutes was associated with an increased rate of implant removal, as did fibular plating. CONCLUSIONS: While many of the patient-specific factors that negatively affect surgical outcomes for pilon fractures may not be modifiable, surgeon-specific factors need to be carefully examined because these may be addressed. Pilon fracture fixation has evolved to increasingly use fragment-specific approaches applied with a staged approach. Although the number and type of approaches did not affect outcomes, longer operative time was associated with increased odds of infection, while additional fibular plate fixation was associated with higher odds of both infection and implant removal. Potential benefits of additional fixation should be weighed against operative time and associated risk of complications. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Geographic Access to Radiation Therapy Facilities in the United States.

PURPOSE: The current distribution of radiation therapy (RT) facilities in the United States is not well established. A comprehensive inventory of U.S. RT facilities was last assessed in 2005, based on data from state regulatory agencies and dosimetric quality assurance bodies. We updated this database to characterize population-level measures of geographic access to RT and analyze changes over the past 15 years. METHODS AND MATERIALS: We compiled data from regulatory and accrediting organizations to identify U.S. facilities with linear accelerators used to treat humans in 2018 to 2020. Addresses were geocoded and analyzed with Geographic Information Services software. Geographic access was characterized by assessing the Euclidian distance between ZIP code tabulation areas/county centroids and RT facilities. Populations were assigned to each county to estimate the effect of facility changes at the population level. Logistic regressions were performed to identify features associated with increased distance to RT and associated with regions that gained an RT facility between the 2 time points studied. RESULTS: In 2020, a total of 2313 U.S. RT facilities were reported, compared with 1987 in 2005, representing a 16.4% growth in facilities over nearly 15 years. Based on population attribution to the centroids of ZIP Code Tabulation Areas, 77.9% of the U.S. population lives within 12.5 miles of an RT facility, and 1.8% of the U.S. population lives more than 50 miles from an RT facility. We found that increased distance to RT was associated with nonmetro status, less insurance, older median age, and less populated regions. Between 2005 and 2020, the population living within 12.5 miles from an RT facility increased by 2.1 percentage points, whereas the population living furthest from RT facilities decreased 0.6 percentage points. Regions with improved geographic RT access are more likely to be higher income and better insured. CONCLUSIONS: The percentage of the U.S. population with limited geographic access to RT is 1.8%. We found that people benefiting from improved access to RT facilities are more economically advantaged, suggesting disparities in geographic access may not improve without intervention.

Is Psychiatric Illness Associated With Worse Outcomes Following Pilon Fracture?

Background: Patients with psychiatric comorbidities represent a significant subset of those sustaining pilon fractures. The purpose of this study is to examine the association of psychiatric comorbidities (PC) in patients with pilon fractures and clinical outcomes. Methods: A multi-institution, retrospective review was conducted. Inclusion/exclusion criteria were skeletally mature patients with a tibia pilon fracture (OTA Type 43B/C) who underwent definitive fracture fixation utilizing open reduction internal fixation (ORIF) with a minimum of 24 weeks of follow-up. Patients were stratified into two groups for comparison: PC group and no PC group. Results: There were 103 patients with pilon fractures that met the inclusion/exclusion criteria of this study. Of these patients, 22 (21.4%) had at least one psychiatric comorbidity (PC) and 81 (78.6%) did not have psychiatric comorbidities (no PC). There was a higher percentage of female patients (PC: 59.1% vs no PC: 25.9%, p=0.0.005), smokers (PC: 40.9% vs no PC: 16.0%, p=0.02), and drug users (PC: 22.7% vs no PC: 8.6%, p=0.08) amongst PC patients. Fracture comminution (PC: 54.5% vs no PC: 32.1%, p=0.05) occurred more frequently in PC patients. The PC group had a higher incidence of weightbearing noncompliance (22.7% vs 7.5%, p=0.04) and reoperation (PC: 54.5% vs no PC: 29.6%, p=0.03). Conclusion: Patients with psychiatric comorbidities represent a significant percentage of pilon fracture patients and appear to be at higher risk for postoperative complication. Risk factors that may predispose patients in the PC group include smoking/substance use, weightbearing noncompliance, and fracture comminution. Level of Evidence: III.

Do Resident Surgical Volumes and Level of Training Correlate with Improved Performance on Psychomotor Skills Tasks: Construct Validity Testing of an ASSH Training Platform (STEP)?

The Surgical Training and Educational Platform (STEP) was developed by the American Society for Surgery of the Hand (ASSH) as a cost-effective set of surgical simulation modules designed to assess critical skills in hand surgery. Previous study demonstrated that STEP can differentiate between novice trainees and board-certified, certificate of added qualification hand surgeons. The purpose of this study was to assess construct validity of STEP by testing its ability to differentiate psychomotor skill level among intermediate trainees. METHODS: We evaluated 30 residents from 2 orthopaedic residency programs on 8 modules: (1) lag screw fixation, (2) depth of plunge during bicortical drilling, (3) flexor tendon repair, (4) phalangeal fracture pinning, (5) central axis scaphoid fixation, (6) full-thickness skin graft harvest, (7) microsurgery, and (8) wrist arthroscopy. Spearman correlation was used to correlate total and task-specific scores to case log numbers, months in training, and number of hand surgery rotations. RESULTS: Senior residents had significantly higher mean number of total cases in their total case log (mean difference 96.2, 95% confidence interval [CI] 67.5-124.8, p < 0.01) and number of task-specific cases. Moderate correlation was observed between case log numbers and scaphoid fixation score (rs = 0.423, 95% CI 0.07-0.69) and total score (rs = 0.584, 95% CI 0.25-0.79). Moderate correlation was observed between months in training with: scaphoid fixation (rs = 0.377, 95% CI 0.01-0.66) and microsurgery (rs = 0.483, 95% CI 0.13-0.73); strong correlation was seen with total score (rs = 0.656, 95% CI 0.35-0.83). Moderate correlation with number of hand surgery rotations was observed with tendon repair (rs = 0.362, 95% CI -0.01 to 0.65), skin graft (rs = 0.385, 95% CI 0.01-0.66), wrist arthroscopy (rs = 0.391, 95% CI 0.02-0.67), microsurgery (rs = 0.461, 95% CI 0.10-0.71), and scaphoid fixation (rs = 0.578, 95% CI 0.25-0.79); and strong correlation was seen with total score (rs = 0.670, 95% CI 0.37-0.84). DISCUSSION/CONCLUSION: The STEP is a validated ASSH education tool that provides a cost-effective simulation for the assessment of fundamental psychomotor skills in hand surgery. Total STEP score correlated with total task-related case volumes as well as months in training and number of hand rotations. Scoring could be modified to improve the fidelity of assessing surgical performance. And, while both time and human resource consuming to perform, administer, and score, this study demonstrates construct validity of STEP in assessing the progression of surgical skill through residency.

Drivers of Medicare Spending: A 15-Year Review of Radiation Oncology Charges Allowed by the Medicare Physician/Supplier Fee-for-Service Program Compared With Other Specialties.

PURPOSE: In 2019, the Centers for Medicare and Medicaid Services proposed a new radiation oncology alternative payment model aimed at reducing expenditures. We examined changes in aggregate physician Medicare charges allowed per specialty to provide contemporary context to proposed changes and hypothesize that radiation oncology charges remained stable through 2017. METHODS AND MATERIALS: Medicare physician/supplier utilization, program payments, and balance billing for original Medicare beneficiaries, by physician specialty, were analyzed from 2002 to 2017. Total allowed charges under the physician/supplier fee-for-service program, inflation-adjusted charges, and percent of total charges billed per specialty were examined. We adjusted for inflation using the consumer price index for medical care from the US Bureau of Labor Statistics. RESULTS: Total allowed charges increased from $83 billion in 2002 to $138 billion in 2017. The specialties accounting for the most charges billed to Medicare were internal medicine and ophthalmology. Radiation oncology charges accounted for 1.2%, 1.6%, and 1.4% of total charges allowed by Medicare in 2002, 2012, and 2017, respectively. Radiation oncology charges allowed increased 44% from 2002 to 2012 ($987.6 million to $1.42 billion) but decreased by 19% from 2012 to 2017 ($1.15 billion), adjusted for inflation. Total charges allowed by internal medicine decreased 2% from 2002 to 2012 ($8.53 to $8.36 billion), adjusted for inflation, and decreased 16% from 2012 to 2017 ($7.05 billion). When adjusting for inflation, ophthalmology charges increased 18% from 2002 to 2012 ($4.53 to $5.36 billion) and increased 3% from 2012 to 2017 ($5.5 billion). CONCLUSIONS: Radiation oncology physician charges represent a small fraction of total Medicare expenses and are not a driver for Medicare spending. Aggregate inflation-adjusted charges by radiation oncology have dramatically declined in the past 5 years and represent a stable fraction of total Medicare charges. The need to target radiation oncology with cost-cutting measures may be overstated.

Maternal gut microbiome regulates immunity to RSV infection in offspring.

Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.

Attenuation of Robust Glial Scar Formation Facilitates Functional Recovery in Animal Models of Chronic Nerve Compression Injury.

BACKGROUND: Late surgery for chronic nerve compression injuries usually improves sensation but rarely reverses motor atrophy. We hypothesized that a persistent glial scar after chronic nerve compression injury might account for poor motor recovery and that degradation of the glial scar as an adjunct to surgical decompression would improve functional recovery. METHODS: A previously described model of chronic nerve compression injury was created in C57BL/6 mice and Sprague-Dawley rats, and the nerves were harvested early or late after electrophysiological confirmation of the injury. Western blot, polymerase chain reaction, and quantitative immunohistochemical analyses were performed to determine levels of chondroitin sulfate proteoglycans and extracellular matrix molecules. Subsets of mice were treated either with surgical decompression alone or with decompression coupled with intraepineurial injection of a low dose (0.1 µgµL) or a high dose (0.2 µg/µL) of chondroitinase ABC at 6 weeks after injury. RESULTS: Aggrecan showed the greatest change in mRNA and protein levels at the early and late time points following creation of the chronic nerve compression injury. Quantitative immunohistochemical analysis revealed early aggrecan upregulation localized primarily to the endoneurium and late upregulation localized to the perineurium and epineurium (p < 0.0105). Quantitative immunohistochemical analysis for collagen IV, laminin-α2, and fibronectin also showed early upregulation with perineurial scarring. Quantitative immunohistochemical analysis and Western blot analysis for aggrecan demonstrated a marked increase in the endoneurium at the early time points and upregulation of expression in the epineurium and perineurium at the late time points. Decompression along with intraepineurial injection of high-dose chondroitinase ABC at 6 weeks after creation of the compression injury resulted in marked attenuation of decorin and aggrecan expression with functional improvement in nerve conduction velocity. CONCLUSIONS: Significant upregulation of chondroitin sulfate proteoglycans and other extracellular matrix components contributes to the pathogenesis of compression neuropathies in murine models. The administration of chondroitinase ABC degrades these chondroitin sulfate proteoglycans and improves functional recovery after chronic nerve compression injury; thus, it can be considered as a possible therapeutic adjunct.