Citations

AbstractIntroductionMicrosurgical reconstruction of complex head and neck defects often requires reliable tissue in multiple spatial configurations to achieve good functional and aesthetic outcomes. In addition to robust perforators, flap inset and wound closure require great caution to minimize complications especially in the presence of trismus with limited space for inset. This report describes the technique and results of our staged approach to flap inset which increases the chance of total flap survival in complex head and neck reconstructions.MethodsFrom February 2010 to August 2016, a total of 53 patients were identified via a retrospective chart review. Patients who were suspected to have a high risk of vascular compromise and subsequently underwent complex head and neck reconstruction with staged inset of anterolateral thigh (ALT) flaps were included. The flap was inset only partially at the recipient site initially with fewer sutures. At a second stage, after neovascularization from surrounding tissue was established, the flap was partially elevated, divided and mobilized on its own pedicle for definitive inset.ResultsFifty‐one patients had complete survival of flaps and had uneventful postoperative course. Six cases required immediate re‐exploration to release wound tension or reposition the pedicle. Of these, 4 flaps were salvaged, 2 failed due to small perforators despite anastomosis revision. The flap survival rate was 96.2% and the average time between 2 stages was 24 days (range, 21–28).ConclusionStaged flap inset can improve free flap survival in complex head and neck reconstructions.

Abstract Background Unlike enterococcal native and prosthetic valve infective endocarditis (IE), enterococcal CIED infections are not well described. Methods Data from the Multicenter Electrophysiologic Device Infection Collaboration (MEDIC), a prospective, observational, multinational cohort study of CIED infections, were used to provide a descriptive analysis of adult patients with CIED infections due to enterococcal species. Results Of 433 patients, 21 (4.8%) were diagnosed with enterococcal CIED infection. Specific data on enterococcal species and antimicrobial susceptibilities were not recorded. The mean age was 70.8 years. No patient had previous CIED infection. Twelve patients (57%) had permanent pacemakers, 5 (24%) had implantable cardioverter defibrillators, and 4 (19%) had biventricular devices. Among the 21 infections, 3 (14%) were categorized as CIED-related bloodstream infections and 18 (86%) as IE; no patient had isolated pocket infection. Of the IE cases, four were valvular IE, eight were lead IE, and six were both. Fourteen cases of IE (78%) were definite by the modified Duke criteria. Median time from last device procedure to infection was 510 days (range 37–2,952 days). The most common presenting symptom was fever (48%); five patients (24%) exhibited local signs of pocket infection. All 21 patients underwent TEE with vegetations demonstrated in 17 (81%). Blood cultures grew enterococci from all patients. The most common antimicrobial regimen was a penicillin plus aminoglycoside (38%); two patients (9.5%) received ampicillin + ceftriaxone. Antibiotics were given for a median of 43 days. Only 14 patients (67%) had complete device removal; the seven patients retaining their device were judged to be at high risk for extraction. There was one death during the index hospital stay with four additional patients dying over the 6 months after therapy (overall mortality 24%); two of the seven patients retaining their CIED died. Conclusion Enterococci caused 4.8% of all CIED infections in our cohort. Most infections appeared to be hematogenous in origin with late onset. IE was the most common infectious syndrome. A penicillin plus aminoglycoside, given for 6 weeks, was the most frequent therapy. Only 67% of patients underwent device removal. At 6 months follow-up, no relapses had occurred but overall mortality was 24%. Disclosures J. E. Peacock Jr., Pfizer, Inc.: Shareholder, Owns common stock in Pfizer which was inherited and held in a trust. M. R. Sohail, TyRx Inc.: Investigator, Research support. Medtronic Inc.: Investigator, Research support. Medtronic Inc.: Consultant, Speaker honorarium. Spectranetics: Consultant, Speaker honorarium. Boston Scientific Corp: Consultant, Speaker honorarium. L. M. Baddour, UpToDate: Collaborator, Royalty payment. J. M. Miro, Abbvie: Consultant and Grant Investigator, Consulting honoraria and Research grant. Bristol-Myers Squibb: Consultant and Grant Investigator, Consulting honoraria and Research grant. Genentech: Consultant and Grant Investigator, Consulting honoraria and Research grant. Medtronic: Consultant and Grant Investigator, Consulting honoraria and Research grant. Novartis: Consultant and Grant Investigator, Consulting honoraria and Research grant. Gilead Sciences: Consultant and Grant Investigator, Consulting honoraria and Research grant. Pfizer: Consultant and Grant Investigator, Consulting honoraria and Research grant. ViiV Healthcare: Consultant and Grant Investigator, Consulting honoraria and Research grant. A. J. Greenspon, Medtronic: Consultant, Speaker honorarium. Boston Scientific: Consultant, Speaker honorarium. St. Jude: Consultant, Speaker honorarium. R. G. Carrillo, St. Jude Medical Group: Speaker’s Bureau, Research support. Spectranetics: Consultant, Speaker honorarium. Sorin Group: Speaker’s Bureau, None. Boston Scientific Corp: Speaker’s Bureau, None. D. Z. Uslan, Medtronic: Investigator, Research support. Boston Scientific: Consultant, Speaker honorarium.

Objectives The aim of this study was to evaluate if a high-resolution photon-counting detector computed tomography (PCD-CT) system with a 1024×1024 matrix reconstruction can improve the visualization of fine structures in the lungs compared with conventional high-resolution CT (HRCT). Materials and Methods Twenty-two adult patients referred for clinical chest HRCT (mean CTDI vol, 13.58 mGy) underwent additional dose-matched PCD-CT (mean volume CT dose index, 13.37 mGy) after written informed consent. Computed tomography images were reconstructed at a slice thickness of 1.5 mm and an image increment of 1 mm with our routine HRCT reconstruction kernels (B46 and Bv49) at 512 and 1024 matrix sizes for conventional energy-integrating detector (EID) CT scans. For PCD-CT, routine B46 kernel and an additional sharp kernel (Q65, unavailable for EID) images were reconstructed at 1024 matrix size. Two thoracic radiologists compared images from EID and PCD-CT noting the highest level bronchus clearly identified in each lobe of the right lung, and rating bronchial wall conspicuity of third- and fourth-order bronchi. Lung nodules were also compared with the B46/EID/512 images using a 5-point Likert scale. Statistical analysis was performed using a Wilcoxon signed rank test with a P < 0.05 considered significant. Results Compared with B46/EID/512, readers detected higher-order bronchi using B46/PCD/1024 and Q65/PCD/1024 images for every lung lobe (P < 0.0015), but in only the right middle lobe for B46/EID/1024 (P = 0.007). Readers were able to better identify bronchial walls of the third- and fourth-order bronchi better using the Q65/PCD/1024 images (mean Likert scores of 1.1 and 1.5), which was significantly higher compared with B46/EID/1024 or B46/PCD/1024 images (mean difference, 0.8; P < 0.0001). The Q65/PCD/1024 images had a mean nodule score of 1 ± 1.3 for reader 1, and −0.1 (0.9) for reader 2, with one reader having improved nodule evaluation scores for both PCD kernels (P < 0.001), and the other reader not identifying any increased advantage over B46/EID/1024 (P = 1.0). Conclusions High-resolution lung PCD-CT with 1024 image matrix reconstruction increased radiologists' ability to visualize higher-order bronchi and bronchial walls without compromising nodule evaluation compared with current chest CT, creating an opportunity for radiologists to better evaluate airway pathology.

Abstract Context Previous epidemiological studies had inconsistent results regarding the relationship between blood lead level (BLL) and adiposity. Objective We aimed to investigate the associations of BLL with body mass index (BMI) particularly using Mendelian randomization analyses and examine the interaction between obesity-predisposing genes and BLL on the associations. Design and Setting A total of 3922 participants were enrolled from 16 sites in East China in 2014 from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (ChiCTR-ECS-14005052, www.chictr.org.cn). We calculated the weighted BMI genetic risk score (GRS) based on 29 variants that were identified and validated in East Asians. BLL was measured by atomic absorption spectrometry. Main Outcome Measure BMI was calculated, and BMI ≥25 kg/m2 was defined as overweight. Results Multivariable logistic regression analysis demonstrated significant associations between BMI with each unit increase in lnBLL (β = 0.24; 95% CI, 0.08 to 0.40; P &lt; 0.001) and each 1-point increase in BMI-GRS (β = 0.08; 95% CI, 0.05 to 0.11; P &lt; 0.001). The causal regression coefficients of genetically determined BMI for lnBLL were −0.003 (95% CI, −0.075 to 0.070), which showed no significance. The GRS modified the association of BLL with BMI and overweight (BMI ≥25 kg/m2; P for interaction = 0.031 and 0.001, respectively). Each unit of lnBLL was associated with 63% higher odds of overweight (OR 1.63; 95% CI, 1.30 to 2.05) in the highest quartile of GRS, but no significant associations were found in the lower three quartiles. Conclusions The associations of BLL with BMI and overweight (BMI ≥25 kg/m2) were significantly modulated by BMI genetic susceptibility.

11534 Background: To date, there are no validated blood-based biomarkers of predicting response to PD-1 blockade. We previously reported that Bim is a downstream signaling molecule of the PD-1 pathway, and that measurement of Bim levels in circulating T-cells may predict and monitor responses to anti–PD-1 therapy in melanoma. We have identified the existence of sPD-L1 in cancer patients and showed that the sPD-L1 is biologically active and capable of triggering apoptosis in activated T-cells. Here we evaluated T cell Bim and sPD-L1 in the peripheral blood (PB) as biomarkers of response in a cohort of patients with metastatic melanoma and lung cancer undergoing anti-PD1 therapy. Methods: 60 pts treated with anti-PD-1 had PB collected at baseline and at radiographic tumor evaluation. Frequencies of Bim+ T cells and Bim median fluorescence intensity (MFI) were measured by flow cytometry in gated tumor-reactive CD11ahighPD1+ CD8+ T cells. We also measured levels of sPD-L1 at baseline and serially during treatment with sPD-L1 ELISA. Baseline Bim and sPD-L1 levels and percent change in Bim levels in patients (pts) who had a radiographic response (CR/PR) were compared to those who had progressive disease (PD) at 12 wks. Results: Similarly to previously reported preliminary data, pts with objective response (CR/PR, 15/60) after 4 cycles of anti-PD1 therapy had higher frequency of Bim T cells at baseline compared to pts with PD (16/60) (mean 43% vs. 30%, P = 0.0484). The frequencies of Bim+ T cells decreased significantly after the first 3 months of treatment in responders compared with progressors (mean -16% vs. + 40% P = 0.0111). High baseline sPD-L1 were associated with progression on anti-PD1 therapy (mean 2.8 ng/mL vs. 0.7 ng/mL, p = 0.07, n = 13) and the levels increased by the first tumor assessment in patients resistant to anti-PD-1. Conclusions: Measurements of Bim and sPD-L1 levels may help to select patients who are likely to benefit from anti-PD1 monotherapy versus combinatorial strategies, and provide a new non-invasive way to monitor response to anti-PD-1 blockade. A larger validation study is underway.

10528 Background: Clinical risk factors associated with outcome in children with either localized or metastatic RMS were identified by Meza et al. (2006) and Oberlin et al. (2008). We re-examined risk stratification by adding FOXO1 to traditional clinical prognostic factors in children with localized or metastatic RMS in a large cohort from COG frontline clinical trials. Methods: Data from six COG clinical trials (D9602, D9802, D9803, ARST0331, ARTS0431, ARST0531) accruing previously untreated patients with RMS from 1997 to 2013 yielded 1,853 eligible patients (two studies each for low, intermediate and high risk patients). Survival tree regression for event-free survival (EFS) and overall survival (OS) was conducted to determine prognostic impact of risk factors. Recursively, the factor most strongly associated with outcome was selected for branching and split using a goodness of fit measure. Factors included were age, FOXO1, group, histology, nodal status, number of metastatic sites, primary site, sex, tumor size, and presence of metastases in bone/bone marrow, soft tissue, effusions, lung, distant lymph nodes, and other sites. Results: 5-year overall EFS and OS was 0.67 (SE, 0.01) and 0.77 (SE, 0.01), respectively. Survival trees for EFS and OS found localized versus metastatic at the first split and included FOXO1 as a significant risk factor. Conclusions: FOXO1 improves risk stratification of patients with localized RMS, although histology and pattern of metastases are more predictive for patients with metastatic RMS. Our findings support incorporation of FOXO1 in risk stratified clinical trials. [Table: see text]

AbstractIntroductionReconstruction of abdominal wall defects with enterocutaneous fistulas (ECF) remains challenging. The purpose of this report is to describe a single‐stage approach using combined microscopic enterolysis, pedicle seromuscular bowel flaps, mesh, fasciocutaneous, and myocutaneous flaps.MethodsBetween 1990 and 2016 a retrospective review identified a total of 18 patients with an average age of 39 years (ranging 26–59 years). Thirteen cases were associated with trauma, four were complication of previous mesh repair, and one was after an aortic dissection. Average diameter of defect size was 22 cm (ranging 20–24 cm). Surgical technique involved enterolysis using microscope magnification, a pedicle seromuscular bowel flap to reinforce the bowel anastomosis, mesh, musculocutaneous, and fasciocutaneous flaps to reconstruct the abdominal wall.ResultsFifteen patients required rotational flaps with an average skin paddle area of 442.7 cm2 (ranging 440 cm2–260 cm2) and 10 patients required a serosal patch with an average length of 5 cm (ranging 4–6 cm). Complications included three wound dehiscence and one abdominal wall bulging. Flap survival was 100%. The majority of patients (12 out of 18) were able to resume normal activities, and the remaining (n = 6) were able to resume most activities. Functional outcome as assessed by 36‐Item Short Form Survey (SF‐36) physical function component questionnaire at 18–24 months follow up was 67.8% (ranging from 59 to 72%). Mean length of hospital stay was 2.2 weeks (ranging 1.4–2.7 weeks). Mean follow‐up was 24 months (ranging 22–26 months) with clinical examination.ConclusionMicroscopically assisted intra‐abdominal dissection with resection of diseased bowel, replacement with well‐vascularized tissue at the anastomosis site in, and reinforcement with mesh combined with pedicle musculocutaneous and fasciocutaneous flaps may be an alternative when other local reconstructive options have failed.