Citations

Purpose: To investigate the effects of a low- versus high-intensity aerobic training on biomarkers of inflammation and endothelial dysfunction in adolescents with obesity. Methods: Sixty-two adolescents with obesity [age = 15 (14) y, body mass index = 34.87 (4.22) kg·m−2] were randomized to receive either a high-intensity training (HIT, n = 31) or a low-intensity training (LIT, n = 31) for 24 weeks. All participants also received nutritional, psychological, and clinical counseling. Leptin, total and subtype leukocyte counts, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, soluble intercellular adhesion molecule-1, and soluble vascular cell adhesion molecule-1 were obtained at baseline and after 24 weeks. Results: HIT reduced neutrophils [from 4.4 (1.9) to 3.6 (1.3) µL−1 × 103; P = .01] and monocytes [from 7.2 (2.5) to 5.2 (1.8) µL−1 × 102; P < .01], but LIT increased neutrophils [from 4.5 (1.7) to 5.2 (3.3) µL−1 × 103; P = .01]. Although tumor necrosis factor-alpha increased in LIT [from 13.3 (7.5) to 17.7 (10.8) pg·mL−1; P = .01], it decreased in HIT [from 12.4 (7.5) to 11.3 (6.2) pg·mL−1; P = .01]. No changes in leukocyte counts, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and homeostasis assessment model for insulin resistance were observed. Conclusions: Both HIT and LIT improved the inflammatory profile. The study, however, indicated that the number of biomarkers and the magnitude of changes were higher in the HIT compared with LIT.

Abstract Background: PARP inhibitors (PARPis) are active in cancers with homologous recombination (HR) defects. Preclinical studies have shown that secondary mutations or alterations in gene expression (e.g., downregulation of 53BP1, Ku70, Ku80 or DNA-PKcs) restore HR and confer PARPi resistance. In addition, low PARP1 expression can diminish PARP trapping and cause PARPi resistance. ARIEL2 Part 1 is a phase 2 study of the PARPi rucaparib in platinum sensitive, relapsed high grade serous or endometrioid ovarian cancer (OC). Pretreatment OC biopsies were previously assayed for HR gene mutations and loss of heterozygosity (LOH), a genomic scar that reflects HR deficiency. Two tumor groups (BRCA wildtype [wt]/LOH high and BRCA1 or BRCA2 mutant) have objective response rates of 29.3% and 80%, respectively, as well as progression free survival (PFS) of 5.7 and 12.8 months, respectively, on rucaparib (E. Swisher et al., Lancet Oncol., in press). Common AEs included nausea (80%), asthenia/fatigue (78%), constipation (46%), and vomiting (44%). The present studies tested the hypotheses that i) lower PARP1 expression and/or ii) lower expression of NHEJ components 53BP1, DNA-PKcs, Ku80, Ku70, or LIG4, may correlate with diminished response rate as well as PFS in pts treated with rucaparib on ARIEL2. Methods: Immunohistochemical assays were developed for 53BP1, DNA-PKcs, Ku80, Ku70, LIG4, and PARP1 and validated in formalin fixed, paraffin embedded cell lines differing in analyte expression. Available pretreatment OC biopsies from ARIEL2 Part 1 were stained and scored for % of tumor nuclei that were negative (0), weak (1+), moderate (2+) or strong (3+). Modified H-scores were correlated with clinical characteristics and outcome measures. Results: Pretreatment biopsies from 62-68 pts were successfully stained for each repair protein. Across the samples, PARP1 H-scores varied from 0 to 300 (median 160). Focusing on the BRCA wt/LOH high group (n = 38), there was no significant difference in PFS of pts with low (&lt;100), intermediate (100-200) or high (&gt;200) PARP1 H-score (p = 0.57). Expression of DNA-PKcs, Ku70, Ku80, and LIG4 was generally lower (median H-scores 20-60) and did not individually correlate with response or PFS. In contrast, there was a trend toward improved PFS in BRCA wt/LOH high OC pts expressing intermediate or high 53BP1 (H-score ≥ 100, n = 10) compared to pts with low 53BP1 (H-score &lt;100, n = 25), with median PFS 20.7 vs. 5.5 months (p = 0.073), respectively. Staining of additional pretreatment biopsies is planned. Conclusions: In the BRCA wt/LOH high group, pretreatment PARP1 expression does not correlate with rucaparib response. In contrast, BRCA wt/LOH high OC pts with low 53BP1 have a trend toward shorter PFS with rucaparib, suggesting that 53BP1 downregulation might correlate with clinical PARPi resistance in BRCA wt/LOH high OC. Citation Format: Andrea E. Wahner Hendrickson, Kevin K. Lin, Daniel W. Visscher, Rachel M. Hurley, Mitch Raponi, Thomas C. Harding, Linda M. Murphy, Jill M. Wagner, Heidi Giordano, Iain McNeish, Elizabeth M. Swisher, Scott Kaufmann. DNA repair protein expression and response of homologous recombination deficient ovarian cancer to the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in the ARIEL2 Part 1 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4676. doi:10.1158/1538-7445.AM2017-4676

Background Proper soft tissue balance is paramount to maintaining stability and a functional arc of motion in shoulder arthroplasty but is impaired in patients with prior glenohumeral (GH) dislocations. The purpose of this study was to determine the clinical outcomes, revisions, and complications of reverse shoulder arthroplasty (RSA) in patients with a history of glenohumeral dislocation. Methods Twenty-four patients with a history of GH dislocations that developed arthropathy underwent primary RSA from 2007 to 2013 were retrospectively reviewed. Mean follow-up was 3.3 years (2–7 years). Mean age was 70 years. Eight patients (33%) and 7 patients (29%) had complete or partial subscapularis deficiency, respectively. Results Twenty-two patients (92%) had little to no pain at final follow-up. Mean shoulder elevation improved from 48° to 120° ( P < .001) and mean external rotation increased from 13.2° to 48° ( P < .001). There were trends toward less complete pain relief and poorer motion in those with complete subscapularis deficiency. None of the patients experienced a postoperative dislocation or evidence of glenoid loosening at final radiographic follow-up, but 1 patient (4.2%) underwent early revision to a hemiarthroplasty for glenoid loosening. Conclusion RSA provides patients with prior glenohumeral dislocations a stable, pain-free arc of motion. Postoperative instability was not identified as a major failure mode at short-term follow-up. Complete subscapularis deficiency is a risk factor for poorer clinical outcome.

Adrenal cortical hyperplasia manifests radiologically as a non-malignant growth, or enlargement, of the adrenal glands, specifically the cortex, although the cortex cannot be definitively identified by conventional imaging. Controlled by the pituitary gland, the adrenal cortex drives critical processes, such as the production of cortisol, mineralocorticoid and sex hormones. Any disruption in the multiple enzymes and hormones involved in these pathways may cause serious or life-threatening symptoms, often associated with anatomical changes in the adrenal glands. Diagnosis and treatment of adrenal cortical hyperplasia requires a thorough clinical evaluation. As imaging has become more robust so has its role in the diagnosis and treatment of adrenal conditions. CT has been the primary modality for adrenal imaging owing to reproducibility, temporal and spatial resolution and broad access. MRI serves a complimentary role in adrenal imaging and can be used to further evaluate indeterminate CT findings or serve as an adjunct tool without the use of ionizing radiation. Ultrasound and fluoroscopy (genitography) are most commonly used in children and foetuses to evaluate congenital adrenal hyperplasia. This article will discuss the clinical presentation, laboratory workup and imaging features of adrenal cortical hyperplasia, both congenital and acquired.

Background: Following resection of malignant tumors of the spine and pelvis, reconstructive surgeons often face large structural defects. Unlike reconstruction in the extremities, wherein a free vascularized fibular graft (FVFG) is a highly utilized option for segmental osseous reconstruction, there are limited data on the use of an FVFG in the spine and pelvis. The aim of this study was to review our institution’s experience with reconstruction with use of an FVFG following oncological resection in the spine and pelvis. Methods: We reviewed 24 cases involving the use of an FVFG in reconstruction of segmental osseous defects of the spine and pelvis following oncological resection from 2000 to 2015. The cohort consisted of 12 male and 12 female patients with a mean age of 37 years and a mean follow-up of 5 years. Fifty-four percent of the reconstructions were spinopelvic or sacropelvic. Results: The overall 2, 5, and 10-year rate of survival was 76%, 55%, and 37%, respectively. With regard to disease-free survival, the overall 2, 5, and 10-year rate was 81%, 72%, and 48%. The overall rate of union was 86%, with a mean time to union of 7 months. Complications were common, with 83% of the patients sustaining at least 1 postoperative complication. Following the procedure, the mean Musculoskeletal Tumor Society rating was 53%. Conclusions: An FVFG provides a durable means of reconstruction of osseous defects in the spine and pelvis. Although patient function was acceptable following these large reconstructions, the rate of postoperative complications was high. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

SummaryMany patients with epilepsy caused by hypothalamic hamartomas (HHs) have cognitive impairments during the course of the disease or following neurosurgical treatment. The purpose of this study was to assess cognitive function in these patients, as well as factors influencing preoperative cognitive performance and cognitive outcome after neurosurgical treatment. Using the two largest and most detailed neuropsychology datasets on HH and epilepsy from two centers, we retrospectively report on cognitive functions in 48 patients with structural epilepsy due to HH (mean age ± standard deviation [SD] 20 ± 12 years, range 5–53 years, median 16 years; disease duration mean 17 ± 11 years). Intelligence, verbal learning and recall, and speed and executive functions (processing speed and cognitive flexibility) were assessed before and on average 19 (±11) months after surgery (interstitial radiosurgery: N = 22; neurosurgical resection/disconnection: N = 26). Prior to neurosurgical treatment, 52% of patients showed impaired executive and 62% showed reduced verbal memory functions. A trend for a detrimental effect of higher drug load on cognitive functioning was found. After neurosurgical treatment, intellectual functions for the entire cohort tended to increase. This correlated with improved seizure frequency and decreased number of antiepileptic drugs (AEDs). However, postoperative outcomes for individual patients were highly variable, with significant deteriorations in 17% (processing speed) to 34% (cognitive flexibility and verbal learning), and performance increases in 17% (intellectual functioning) up to 39% (processing speed) of the patients. Higher levels of presurgical performance were significant predictors of cognitive decline after surgery. These results are highly relevant for patient consultation and may help with therapeutic decisions.

Background: Although obesity is associated with increased complication rates after lower-extremity arthroplasty, there is a relative paucity of studies examining the effect of body mass index (BMI) on shoulder arthroplasty. The purpose of this investigation was to evaluate the effect of BMI on implant survival and the rate of complications after shoulder arthroplasty. Methods: Using an institutional total joint registry, 4,567 consecutive shoulder arthroplasty cases from 1970 to 2013 were studied. The mean BMI was 29.7 kg/m 2 (range, 14 to 66 kg/m 2 ), with 1,622 patients (36%) with a BMI of 30 to 40 kg/m 2 and 297 patients (7%) with a BMI of >40 kg/m 2 . There were 2,493 female patients (55%). BMI was dichotomized after examination of the smoothing spline curve. The associations of factors and complications were assessed using Cox proportional hazard regression analysis. Results: Increasing BMI was associated with an increased risk of a revision surgical procedure, reoperation, revision for mechanical failure, and superficial infection, and it was negatively associated with risk of a periprosthetic fracture. The risk of a revision surgical procedure increased in a linear fashion with increasing BMI (hazard ratio [HR], 1.05, or a 5% increased risk per 1 unit of BMI; p = 0.03). Increased BMI was also associated with an increased risk of revision for mechanical failure (HR, 1.05; p = 0.004). In a multivariate model, the association of BMI and risk of a revision for any reason, revision for mechanical failure, and reoperation maintained significance (p ≤ 0.02). The most marked association between increasing BMI and any complication in shoulder arthroplasty was its association with superficial wound infection (HR, 1.09; p = 0.03). Conclusions: Increasing BMI is strongly associated with increased rates of revision surgical procedures and postoperative complications after shoulder arthroplasty. It is important to consider these findings when counseling patients, estimating risks, and estimating complication risks in policy decisions. Level of Evidence: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

AbstractAfter decades on the margins of primary health care, surgical and anaesthesia care is gaining increasing priority within the global development arena. The 2015 publications of the Disease Control Priorities third edition on Essential Surgery and the Lancet Commission on Global Surgery created a compelling evidenced‐based argument for the fundamental role of surgery and anaesthesia within cost‐effective health systems strengthening global strategy. The launch of the Global Alliance for Surgical, Obstetric, Trauma, and Anaesthesia Care in 2015 has further coordinated efforts to build priority for surgical care and anaesthesia. These combined efforts culminated in the approval of a World Health Assembly resolution recognizing the role of surgical care and anaesthesia as part of universal health coverage. Momentum gained from these milestones highlights the need to identify consensus goals, targets and indicators to guide policy implementation and track progress at the national level. Through an open consultative process that incorporated input from stakeholders from around the globe, a global target calling for safe surgical and anaesthesia care for 80% of the world by 2030 was proposed. In order to achieve this target, we also propose 15 consensus indicators that build on existing surgical systems metrics and expand the ability to prioritize surgical systems strengthening around the world.