Citations

OBJECTIVEThe long-term effects of surgical fusion on the growing subaxial cervical spine are largely unknown. Recent cross-sectional studies have demonstrated that there is continued growth of the cervical spine through the teenage years. The purpose of this multicenter study was to determine the effects of rigid instrumentation and fusion on the growing subaxial cervical spine by investigating vertical growth, cervical alignment, cervical curvature, and adjacent-segment instability over time.METHODSA total of 15 centers participated in this multi-institutional retrospective study. Cases involving children less than 16 years of age who underwent rigid instrumentation and fusion of the subaxial cervical spine (C-2 and T-1 inclusive) with at least 1 year of clinical and radiographic follow-up were investigated. Charts were reviewed for clinical data. Postoperative and most recent radiographs, CT, and MR images were used to measure vertical growth and assess alignment and stability.RESULTSEighty-one patients were included in the study, with a mean follow-up of 33 months. Ninety-five percent of patients had complete clinical resolution or significant improvement in symptoms. Postoperative cervical kyphosis was seen in only 4 patients (5%), and none developed a swan-neck deformity, unintended adjacent-level fusion, or instability. Of patients with at least 2 years of follow-up, 62% demonstrated growth across the fusion construct. On average, vertical growth was 79% (4-level constructs), 83% (3-level constructs), or 100% (2-level constructs) of expected growth. When comparing the group with continued vertical growth to the one without growth, there were no statistically significant differences in terms of age, sex, underlying etiology, surgical approach, or number of levels fused.CONCLUSIONSContinued vertical growth of the subaxial spine occurs in nearly two-thirds of children after rigid instrumentation and fusion of the subaxial spine. Failure of continued vertical growth is not associated with the patient’s age, sex, underlying etiology, number of levels fused, or surgical approach. Further studies are needed to understand this dichotomy and determine the long-term biomechanical effects of surgery on the growing pediatric cervical spine.

Abstract Purpose: Preplanned exploratory analyses were performed to identify biomarkers in circulating tumor cells (CTC) predictive of response to the topoisomerase 1 inhibitor etirinotecan pegol (EP). Experimental Design: The BEACON trial treated patients with metastatic breast cancer (MBC) with EP or treatment of physician's choice (TPC). Blood from 656 of 852 patients (77%) was processed with ApoStream to enrich for CTCs. A multiplex immunofluorescence assay measured expression of candidate response biomarkers [topoisomerase 1 (Top1), topoisomerase 2 (Top2), Ki67, RAD51, ABCG2, γH2AX, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL)] in CTCs. Patients were classified as Top1 low (Top1Lo) or Top1 high (Top1Hi) based on median CTC Top1 expression. Correlation of CTC biomarker expression at baseline, cycle 2 day 1 (C2D1), and cycle 4 day 1 with overall survival (OS) was investigated using Cox regression and Kaplan–Meier analyses. Results: Overall, 98% of samples were successfully processed, of which 97% had detectable CTCs (median, 47–63 CTCs/mL; range, 0–2,020 CTCs/mL). Top1, Top2, and TUNEL expression was detected in 52% to 90% of samples; no significant associations with OS were observed in pretreatment samples for either group. EP-treated patients with low C2D1Top1+ CTCs had improved OS compared with those with higher positivity (14.1 months vs. 11.0 months, respectively; HR, 0.7; P = 0.02); this difference was not seen in TPC-treated patients (HR, 1.12; P = 0.48). Patients whose CTCs decreased from Top1Hi to Top1Lo at C2D1 had the greatest OS benefit from EP (HR, 0.57; P = 0.01). Conclusions: CTC Top1 expression following EP treatment may identify patients with MBC most likely to have an OS benefit. Clin Cancer Res; 24(14); 3348–57. ©2018 AACR.

Purpose International health electives (IHEs) are widely available during residency and provide unique experiences for trainees. Theoretical models of professional identity formation and transformative learning may provide insight into residents’ experiences during IHEs. The purpose of this study was to explore transformative learning and professional identity formation during resident IHEs and characterize the relationship between transformative learning and professional identity formation. Method The authors used a constructivist grounded theory approach, with the sensitizing concepts of transformative learning and professional identity formation to analyze narrative reflective reports of residents’ IHEs. The Mayo International Health Program supports residents from all specialties across three Mayo Clinic sites. In 2015, the authors collected narrative reflective reports from 377 IHE participants dating from 2001 to 2014. Reflections were coded and themes were organized into a model for transformative learning during IHEs, focusing on professional identity. Results Five components of transformative learning were identified during IHEs: a disorienting experience; an emotional response; critical reflection; perspective change; and a commitment to future action. Within the component of critical reflection, three domains relating to professional identity were identified: making a difference; the doctor–patient relationship; and medicine in its “purest form.” Transformation was demonstrated through perspective change and a commitment to future action, including continued service, education, and development. Conclusions IHEs provide rich experiences for transformative learning and professional identity formation. Understanding the components of transformative learning may provide insight into the interaction between learner, experiences, and the influence of mentors in the process of professional identity formation.

Key Points Biomarker scores generated after 1 week of steroid treatment of GVHD are prognostic. Biomarkers reflect prognosis better than early clinical response to GVHD treatment.

Lesser degrees of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini/TDLU, are associated with elevated breast cancer risk. In rodent models, the insulin‐like growth factor (IGF) system regulates involution of the mammary gland. We examined associations of circulating IGF measures with TDLU involution in normal breast tissues among women without precancerous lesions. Among 715 Caucasian and 283 African American (AA) women who donated normal breast tissue samples to the Komen Tissue Bank between 2009 and 2012 (75% premenopausal), serum concentrations of IGF‐I and binding protein (IGFBP)‐3 were quantified using enzyme‐linked immunosorbent assay. Hematoxilyn and eosin‐stained tissue sections were assessed for numbers of TDLUs (“TDLU count”). Zero‐inflated Poisson regression models with a robust variance estimator were used to estimate relative risks (RRs) for association of IGF measures (tertiles) with TDLU count by race and menopausal status, adjusting for potential confounders. AA (vs. Caucasian) women had higher age‐adjusted mean levels of serum IGF‐I (137 vs. 131 ng/mL, p = 0.07) and lower levels of IGFBP‐3 (4165 vs. 4684 ng/mL, p < 0.0001). Postmenopausal IGFBP‐3 was inversely associated with TDLU count among AA (RRT3vs.T1 = 0.49, 95% CI = 0.28–0.84, p‐trend = 0.04) and Caucasian (RRT3vs.T1=0.64, 95% CI = 0.42–0.98, p‐trend = 0.04) women. In premenopausal women, higher IGF‐I:IGFBP‐3 ratios were associated with higher TDLU count in Caucasian (RRT3vs.T1=1.33, 95% CI = 1.02–1.75, p‐trend = 0.04), but not in AA (RRT3vs.T1=0.65, 95% CI = 0.42–1.00, p‐trend = 0.05), women. Our data suggest a role of the IGF system, particularly IGFBP‐3, in TDLU involution of the normal breast, a breast cancer risk factor, among Caucasian and AA women.

There are no evidence-based guidelines for antithrombotic therapy in left ventricular assist device patients. We evaluated the efficacy of a multi-agent, test-guided protocol, which remained consistent throughout our use of the Heartware HVAD. Thrombelastography and platelet function analyzer (PFA)-100 guide antiplatelet titration. Goals are normal kaolin thrombelastography maximum amplitude and prolonged PFA-100. We analyzed incidence and rates of nonprocedural bleeding, stroke, and pump thrombosis for all 81 primary Heartware left ventricular assist devices implanted since 2011. For each event, we examined whether each test was within goal range. We also compared medication burden and dosage between patients with and without events. Pump thrombosis and hemorrhagic stroke each occurred in two patients (2.5%; 0.03 events/patient-year [EPPY]), and ischemic stroke in six (7.4%; 0.10 EPPY). Nonprocedural bleeding occurred 75 times in 34 patients (42%; 1.24 EPPY), primarily gastrointestinal (28%; 0.66 EPPY). Subtherapeutic international normalized ratio (INR) was the most common at thrombotic events; supratherapeutic partial thromboplastin time, international normalized ratio (INR), and PFA-adenosine diphosphate (ADP) were common at bleeding events. Medication burden and dosage were lower in patients with events than in stable patients. Protocol-guided antithrombotic therapy resulted in low rates of pump thrombosis and hemorrhagic stroke. Ischemic stroke and gastrointestinal bleeding rates were higher than in a comparable HVAD population. Optimization of our protocol to decrease its complexity and to reduce bleeding is underway.

Abstract Rationale By minimizing tidal lung strain and maintaining alveolar recruitment, high-frequency oscillatory ventilation (HFOV) may protect against ventilator-induced lung injury. Objectives To summarize the current evidence in support of the use of HFOV in adult patients with acute respiratory distress syndrome. Methods We conducted a systematic review and meta-analysis of randomized trials comparing mortality rates with the use of HFOV versus conventional mechanical ventilation for adult patients with acute respiratory distress syndrome. Eligible trials were identified from previously published systematic reviews and an updated literature search. Data on 28-day mortality, oxygenation, adverse events, and use of rescue therapies were collected; effects were pooled using random effects models weighted by inverse variance. Strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. Results Six trials were eligible for inclusion (total n = 1,715 patients). Four trials mandated lung-protective ventilation in the control group and one trial applied a higher positive end-expiratory pressure (PEEP) ventilation strategy in the control group. None of the trials were judged to be at high risk of bias, though all were unblinded. In trials that did not systematically employ any cointerventions with HFOV and that targeted low tidal volumes in the patients randomized to conventional ventilation (primary analysis), HFOV had no significant effect on mortality (three trials; risk ratio [RR], 1.14; 95% confidence interval [CI], 0.88 to 1.48; evidence grade = high). Pooled analysis of all six trials also did not suggest a significant mortality reduction (RR, 0.94; 95% CI, 0.71 to 1.24; evidence grade = low). The single trial that employed a conventional ventilation strategy with both lower tidal volumes and higher PEEP as control reported higher mortality in patients receiving HFOV (RR, 1.41; 95% CI, 1.12 to 1.79). HFOV was not associated with improved oxygenation after 24 hours (five trials; mean increase of 10 mm Hg; 95% CI, −16 to 37 mm Hg). Rates of barotrauma were not different between HFOV and conventional ventilation, although significant benefit or harm could not be excluded (RR, 1.15; 95% CI, 0.61 to 2.17). Conclusions Published randomized trials suggest that HFOV is not associated with a mortality benefit, and may even be harmful in comparison to ventilation with low tidal volumes and higher levels of PEEP.