Citations

Background: The role of diet in multiple sclerosis (MS) is largely uncharacterized, particularly as it pertains to pediatric-onset disease. Objective: To determine the association between dietary factors and MS in children. Methods: Pediatric MS patients and controls were recruited from 16 US centers (MS or clinically isolated syndrome onset before age 18, <4 years from symptom onset and at least 2 silent lesions on magnetic resonance imaging). The validated Block Kids Food Screener questionnaire was administered 2011–2016. Chi-squared test compared categorical variables, Kruskal–Wallis test compared continuous variables, and multivariable logistic regression analysis was performed. Results: In total, 312 cases and 456 controls were included (mean ages 15.1 and 14.4 years). In unadjusted analyses, there was no difference in intake of fats, proteins, carbohydrates, sugars, fruits, or vegetables. Dietary iron was lower in cases ( p = 0.04), and cases were more likely to consume below recommended guidelines of iron (77.2% of cases vs 62.9% of controls, p < 0.001). In multivariable analysis, iron consumption below recommended guidelines was associated with MS (odds ratio = 1.80, p < 0.01). Conclusion: Pediatric MS cases may be less likely to consume sufficient iron compared to controls, and this warrants broader study to characterize a temporal relationship. No other significant difference in intake of most dietary factors was found.

OBJECTIVE During the Diabetes Control and Complications Trial (DCCT), intensive diabetes therapy achieving a mean HbA1c of ∼7% was associated with a threefold increase in the rate of severe hypoglycemia (defined as requiring assistance) compared with conventional diabetes therapy with a mean HbA1c of 9% (61.2 vs. 18.7 per 100 patient-years). After ∼30 years of follow-up, we investigated the rates of severe hypoglycemia in the DCCT/Epidemiology of Diabetes Inverventions and Complications (EDIC) cohort. RESEARCH DESIGN AND METHODS Rates of severe hypoglycemia were reported quarterly during DCCT and annually during EDIC (i.e., patient recall of episodes in the preceding 3 months). Risk factors influencing the rate of severe hypoglycemia over time were investigated. RESULTS One-half of the DCCT/EDIC cohort reported episodes of severe hypoglycemia. During EDIC, rates of severe hypoglycemia fell in the former DCCT intensive treatment group but rose in the former conventional treatment group, resulting in similar rates (40.8 vs. 36.6 episodes per 100 patient-years, respectively) with a relative risk of 1.12 (95% CI 0.91–1.37). A preceding episode of severe hypoglycemia was the most powerful predictor of subsequent episodes. Entry into the DCCT study as an adolescent was associated with an increased risk of severe hypoglycemia, whereas insulin pump use was associated with a lower risk. Severe hypoglycemia rates increased with lower HbA1c similarly among participants in both treatment groups. CONCLUSIONS Rates of severe hypoglycemia have equilibrated over time between the two DCCT/EDIC treatment groups in association with advancing duration of diabetes and similar HbA1c levels. Severe hypoglycemia persists and remains a challenge for patients with type 1 diabetes across their life span.

Rationale: Increasing evidence indicates that alterations of the cerebral microcirculation may play a role in Alzheimer disease, the leading cause of late-life dementia. The amyloid-β peptide (Aβ), a key pathogenic factor in Alzheimer disease, induces profound alterations in neurovascular regulation through the innate immunity receptor CD36 (cluster of differentiation 36), which, in turn, activates a Nox2-containing NADPH oxidase, leading to cerebrovascular oxidative stress. Brain perivascular macrophages (PVM) located in the perivascular space, a major site of brain Aβ collection and clearance, are juxtaposed to the wall of intracerebral resistance vessels and are a powerful source of reactive oxygen species. Objective: We tested the hypothesis that PVM are the main source of reactive oxygen species responsible for the cerebrovascular actions of Aβ and that CD36 and Nox2 in PVM are the molecular substrates of the effect. Methods and Results: Selective depletion of PVM using intracerebroventricular injection of clodronate abrogates the reactive oxygen species production and cerebrovascular dysfunction induced by Aβ applied directly to the cerebral cortex, administered intravascularly, or overproduced in the brain of transgenic mice expressing mutated forms of the amyloid precursor protein (Tg2576 mice). In addition, using bone marrow chimeras, we demonstrate that PVM are the cells expressing CD36 and Nox2 responsible for the dysfunction. Thus, deletion of CD36 or Nox2 from PVM abrogates the deleterious vascular effects of Aβ, whereas wild-type PVM reconstitute the vascular dysfunction in CD36-null mice. Conclusions: The data identify PVM as a previously unrecognized effector of the damaging neurovascular actions of Aβ and unveil a new mechanism by which brain-resident innate immune cells and their receptors may contribute to the pathobiology of Alzheimer disease.

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE ( n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

ABSTRACT Background The Accreditation Council for Graduate Medical Education (ACGME) Clinical Learning Environment Review (CLER) is an innovative element of the ACGME's new accreditation system. To date, little information has been collected regarding the value of CLER. Objective The purpose of this study is to collect information on designated institutional officials' (DIOs') perspectives about the initial CLER visits conducted at their institutions. Methods The authors created and distributed a survey to DIOs about their initial CLER visits. Demographic data were compared across survey responses with Spearman's rank correlation and the Kruskal-Wallis test. Results The authors received responses from 63% of DIOs (186 of 297) at institutions that participated in the initial CLER visits, with 88% (164 of 186) having served as DIO during the visit. Seventy-two percent (114 of 158) reported institutional changes to address CLER focus areas prior to the visit, yet only 32% (51 of 157) reported that additional resources were allocated to these areas after the site visit. Sixty-five percent (102 of 156) reported institutional executive leadership was positive about participating in CLER; 85% (134 of 158) reported that ACGME conducted the visits efficiently; 84% (133 of 158) reported that the site visit accurately assessed the institution's performance in the CLER focus areas; and 60% (93 of 156) reported CLER provided high-value information. Conclusion Survey results from DIOs suggest that CLER is an effective mechanism to improve the learning environment. Common concerns included limited advance notice for the site visit and disruptions of clinical practice.

AbstractPurposeLocal control for Ewing sarcoma (ES) has improved in modern studies. However, it is unclear if these gains have also been achieved for pelvis tumors. The purpose of this study is to evaluate local control and survival in pelvis ES patients treated in the modern era.MethodsAll pelvis ES patients diagnosed from 1990 to 2012 and seen at Mayo Clinic were identified. Factors relevant to survival and local control were analyzed.ResultsThe cohort consisted of 48 patients. Fifty‐two percent had metastatic disease at diagnosis. The 5‐year overall survival and event‐free survival was 73% and 65%, respectively, for localized disease. The 5‐year cumulative incidence of local recurrence was 19%, with a 26% incidence for radiation, 13% for surgery, and 0% for surgery + radiation (P = 0.54). All local failures occurred in‐field. Sacral involvement by tumor trended toward a higher incidence of local recurrence (hazard ratio 3.06, P = 0.09). Patients treated with definitive radiation doses ≥5,600 cGy had a lower incidence of local recurrence (17% vs. 28%, P = 0.61).ConclusionsOur study demonstrates excellent survival for localized tumors in the modern era. Anatomical localization within the pelvis likely correlates with outcomes. Local control remains problematic, especially for patients treated with definitive radiation. Though statistically not significant, surgery + radiation and definitive radiation dose ≥5,600 cGy were associated with the lowest incidence of local failure, suggesting treatment intensification may improve local control for pelvis ES.

Background: Reliable acetabular fixation in total hip arthroplasty following periacetabular resections is challenging. Tantalum components have been successfully implemented for difficult revision arthroplasties, but, to our knowledge, have not been reported for acetabular reconstruction following oncologic periacetabular resection. The primary purpose of the current study was to determine the early clinical outcomes, complications, and radiographic findings for acetabular reconstruction after oncologic periacetabular resection. In addition, a novel classification scheme for primary periacetabular resections and reconstructions is presented. Methods: We reviewed 10 consecutive patients treated with tantalum acetabular reconstruction following periacetabular resection. All patients had a primary acetabular malignancy including chondrosarcoma (n = 7) and osteosarcoma (n = 3). The cohort included 6 males (60%). The mean age was 54 years (range, 30 to 73 years). The mean follow-up was 59 months (range, 8 to 113 months). Results: At the most recent follow-up, 9 patients were alive and 1 had died of the respective disease. All patients obtained full ambulatory status with the use of gait aids. Postoperative complications included dislocation (n = 3), wound-healing disturbance (n = 1), and deep venous thrombosis (n = 1). Two patients underwent reoperations for recurrent dislocations. The mean postoperative Harris hip score was 75 points (range, 49 to 92 points). Conclusions: Preliminary results of tantalum reconstruction following periacetabular resections provide reasonable improvement in early clinical outcomes and stable fixation in situations with massive bone loss and compromised bone quality. As expected due to the lack of a functioning abductor mechanism from the wide oncologic resection, early dislocations remain a concern. As such, we now consider the primary use of increasing constraint, but it must be balanced with the often compromised host bone. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.