Defining the window of opportunity and target populations to prevent peanut allergy.

BACKGROUND: Peanut allergy affects 1% to 2% of European children. Early introduction of peanut into the diet reduces allergy in high-risk infants. OBJECTIVE: We aimed to determine the optimal target populations and timing of introduction of peanut products to prevent peanut allergy in the general population. METHODS: Data from the Enquiring About Tolerance (EAT; n = 1303; normal risk; 3-year follow-up; ISRCTN14254740) and Learning Early About Peanut Allergy study (LEAP; n = 640; high risk; 5-year follow-up; NCT00329784) randomized controlled trials plus the Peanut Allergy Sensitization (PAS; n = 194; low and very high risk; 5-year follow-up) observational study were used to model the intervention in a general population. Peanut allergy was defined by blinded peanut challenge or diagnostic skin prick test result. RESULTS: Targeting only the highest-risk infants with severe eczema reduced the population disease burden by only 4.6%. Greatest reductions in peanut allergy were seen when the intervention was targeted only to the larger but lower-risk groups. A 77% reduction in peanut allergy was estimated when peanut was introduced to the diet of all infants, at 4 months with eczema, and at 6 months without eczema. The estimated reduction in peanut allergy diminished with every month of delayed introduction. If introduction was delayed to 12 months, peanut allergy was only reduced by 33%. CONCLUSIONS: The preventive benefit of early introduction of peanut products into the diet decreases as age at introduction increases. In countries where peanut allergy is a public health concern, health care professionals should help parents introduce peanut products into their infants' diet at 4 to 6 months of life.

Retrospective Evaluation of Splenic Artery Embolization Outcomes in the Management of Blunt Splenic Trauma: A Single Centre Experience at a Large Level 1 Trauma Centre.

PURPOSE: Retrospective review of splenic artery embolization (SAE) outcomes performed for blunt abdominal trauma. MATERIALS AND METHODS: 11-year retrospective review at a large level-1 Canadian trauma centre. All patients who underwent SAE after blunt trauma were included. Technical success was defined as angiographic occlusion of the target vessel and clinical success was defined as successful non-operative management and splenic salvage on follow-up. RESULTS: 138 patients were included of which 68.1% were male. The median age was 47 years (interquartile range (IQR) = 32.5 years). The most common mechanisms of injury were motor vehicle accidents (37.0%), mechanical falls (25.4%), and pedestrians hit by motor vehicles (10.9%). 70.3% of patients had American Association for the Surgery of Trauma (AAST) grade 4 injuries. Patients were treated with proximal SAE (n = 97), distal SAE (n = 23) or combined SAE (n = 18), and 68% were embolized with an Amplatzer plug. No significant differences were observed across all measures of hospitalization (Length of hospital stay: x2(2) = .358, P = .836; intensive care unit (ICU) stay: x2(2) = .390, P = .823; ICU stay post-procedure: x2(2) = 1.048, P = .592). Technical success and splenic salvage were achieved in 100% and 97.8% of patients, respectively. 7 patients (5%) had post-embolization complications and 7 patients (5%) died during hospital admission, but death was secondary to other injuries sustained in the trauma rather than complications related to splenic injury or its management. CONCLUSION: We report that SAE as an adjunct to non-operative management of blunt splenic trauma can be performed safely and effectively with a high rate of clinical success.

Characterising the age-dependent effects of risk factors on type 1 diabetes progression.

AIMS/HYPOTHESIS: Age is known to be one of the most important stratifiers of disease progression in type 1 diabetes. However, what drives the difference in rate of progression between adults and children is poorly understood. Evidence suggests that many type 1 diabetes disease predictors do not have the same effect across the age spectrum. Without a comprehensive analysis describing the varying risk profiles of predictors over the age continuum, researchers and clinicians are susceptible to inappropriate assessment of risk when examining populations of differing ages. We aimed to systematically assess and characterise how the effect of key type 1 diabetes risk predictors changes with age. METHODS: Using longitudinal data from single- and multiple-autoantibody-positive at-risk individuals recruited between the ages of 1 and 45 years in TrialNet's Pathway to Prevention Study, we assessed and visually characterised the age-varying effect of key demographic, immune and metabolic predictors of type 1 diabetes by employing a flexible spline model. Two progression outcomes were defined: participants with single autoantibodies (n=4893) were analysed for progression to multiple autoantibodies or type 1 diabetes, and participants with multiple autoantibodies were analysed (n=3856) for progression to type 1 diabetes. RESULTS: Several predictors exhibited significant age-varying effects on disease progression. Amongst single-autoantibody participants, HLA-DR3 (p=0.007), GAD65 autoantibody positivity (p=0.008), elevated BMI (p=0.007) and HOMA-IR (p=0.002) showed a significant increase in effect on disease progression with increasing age. Insulin autoantibody positivity had a diminishing effect with older age in single-autoantibody-positive participants (p<0.001). Amongst multiple-autoantibody-positive participants, male sex (p=0.002) was associated with an increase in risk for progression, and HLA DR3/4 (p=0.05) showed a decreased effect on disease progression with older age. In both single- and multiple-autoantibody-positive individuals, significant changes in HR with age were seen for multiple measures of islet function. Risk estimation using prediction risk score Index60 was found to be better at a younger age for both single- and multiple-autoantibody-positive individuals (p=0.007 and p<0.001, respectively). No age-varying effect was seen for prediction risk score DPTRS (p=0.861 and p=0.178, respectively). Multivariable analyses suggested that incorporating the age-varying effect of the individual components of these validated risk scores has the potential to enhance the risk estimate. CONCLUSIONS/INTERPRETATION: Analysing the age-varying effect of disease predictors improves understanding and prediction of type 1 diabetes disease progression, and should be leveraged to refine prediction models and guide mechanistic studies.

A simple strategy for sample annotation error detection in cytometry datasets.

Mislabeling samples or data with the wrong participant information can affect study integrity and lead investigators to draw inaccurate conclusions. Quality control to prevent these types of errors is commonly embedded into the analysis of genomic datasets, but a similar identification strategy is not standard for cytometric data. Here, we present a method for detecting sample identification errors in cytometric data using expression of human leukocyte antigen (HLA) class I alleles. We measured HLA-A*02 and HLA-B*07 expression in three longitudinal samples from 41 participants using a 33-marker CyTOF panel designed to identify major immune cell types. 3/123 samples (2.4%) showed HLA allele expression that did not match their longitudinal pairs. Furthermore, these same three samples' cytometric signature did not match qPCR HLA class I allele data, suggesting that they were accurately identified as mismatches. We conclude that this technique is useful for detecting sample-labeling errors in cytometric analyses of longitudinal data. This technique could also be used in conjunction with another method, like GWAS or PCR, to detect errors in cross-sectional data. We suggest widespread adoption of this or similar techniques will improve the quality of clinical studies that utilize cytometry.

Oral desensitization therapy for peanut allergy induces dynamic changes in peanut-specific immune responses.

BACKGROUND: The PALISADE study, an international, phase 3 trial of peanut oral immunotherapy (POIT) with AR101, resulted in desensitization in children and adolescents who were highly allergic to peanut. An improved understanding of the immune mechanism induced in response to food allergen immunotherapy would enable more informed and effective therapeutic strategies. Our main purpose was to examine the immunological changes in blood samples from a subset of peanut-allergic individuals undergoing oral desensitization immunotherapy with AR101. METHODS: Blood samples obtained as part of enrollment screening and at multiple time points during PALISADE study were used to assess basophil and CD4+ T-cell reactivity to peanut. RESULTS: The absence of clinical reactivity to the entry double-blinded placebo-controlled peanut challenge (DBPCFC) was accompanied by a significantly lower basophil sensitivity and T-cell reactivity to peanut compared with DBPCFC reactors. At baseline, peanut-reactive TH2A cells were observed in many but not all peanut-allergic patients and their level in peripheral blood correlates with T-cell reactivity to peanut and with serum peanut-specific IgE and IgG4 levels. POIT reshaped circulating peanut-reactive T-cell responses in a subset-dependent manner. Changes in basophil and T-cell responses to peanut closely paralleled clinical benefits to AR101 therapy and resemble responses in those with lower clinical sensitivity to peanut. However, no difference in peanut-reactive Treg cell frequency was observed between groups. CONCLUSION: Oral desensitization therapy with AR101 leads to decreased basophil sensitivity to peanut and reshapes peanut-reactive T effector cell responses supporting its potential as an immunomodulatory therapy.

Biomarkers of severity and threshold of allergic reactions during oral peanut challenges.

BACKGROUND: Oral food challenge (OFC) is the criterion standard to assess peanut allergy (PA), but it involves a risk of allergic reactions of unpredictable severity. OBJECTIVE: Our aim was to identify biomarkers for risk of severe reactions or low dose threshold during OFC to peanut. METHODS: We assessed Learning Early about Peanut Allergy study, Persistance of Oral Tolerance to Peanut study, and Peanut Allergy Sensitization study participants by administering the basophil activation test (BAT) and the skin prick test (SPT) and measuring the levels of peanut-specific IgE, Arachis hypogaea 2-specific IgE, and peanut-specific IgG4, and we analyzed the utility of the different biomarkers in relation to PA status, severity, and threshold dose of allergic reactions to peanut during OFC. RESULTS: When a previously defined optimal cutoff was used, the BAT diagnosed PA with 98% specificity and 75% sensitivity. The BAT identified severe reactions with 97% specificity and 100% sensitivity. The SPT, level of Arachis hypogaea 2-specific IgE, level of peanut-specific IgE, and IgG4/IgE ratio also had 100% sensitivity but slightly lower specificity (92%, 93%, 90%, and 88%, respectively) to predict severity. Participants with lower thresholds of reactivity had higher basophil activation to peanut in vitro. The SPT and the BAT were the best individual predictors of threshold. Multivariate models were superior to individual biomarkers and were used to generate nomograms to calculate the probability of serious adverse events during OFC for individual patients. CONCLUSIONS: The BAT diagnosed PA with high specificity and identified severe reactors and low threshold with high specificity and high sensitivity. The BAT was the best biomarker for severity, surpassed only by the SPT in predicting threshold. Nomograms can help estimate the likelihood of severe reactions and reactions to a low dose of allergen in individual patients with PA.

IgE to epitopes of Ara h 2 enhance the diagnostic accuracy of Ara h 2-specific IgE.

BACKGROUND: Understanding the discrepancy between IgE sensitization and allergic reactions to peanut could facilitate diagnosis and lead to novel means of treating peanut allergy. OBJECTIVE: To identify differences in IgE and IgG4 binding to peanut peptides between peanut-allergic (PA) and peanut-sensitized but tolerant (PS) children. METHODS: PA (n = 56), PS (n = 42) and nonsensitized nonallergic (NA, n = 10) patients were studied. Synthetic overlapping 15-mer peptides of peanut allergens (Ara h 1-11) were spotted onto microarray slides, and patients' samples were tested for IgE and IgG4 binding using immunofluorescence. IgE and IgG4 levels to selected peptides were quantified using ImmunoCAP. Diagnostic model comparisons were performed using likelihood-ratio tests between each specified nominal logistic regression models. RESULTS: Seven peptides on Ara h 1, Ara h 2, and Ara h 3 were bound more by IgE of PA compared to PS patients on the microarray. IgE binding to one peptide on Ara h 5 and IgG4 binding to one Ara h 9 peptide were greater in PS than in PA patients. Using ImmunoCAP, IgE to the Ara h 2 peptides enhanced the diagnostic accuracy of Ara h 2-specific IgE. Ratios of IgG4/IgE to 4 out of the 7 peptides were higher in PS than in PA subjects. CONCLUSIONS: Ara h 2 peptide-specific IgE added diagnostic value to Ara h 2-specific IgE. Ability of peptide-specific IgG4 to surmount their IgE counterpart seems to be important in established peanut tolerance.

Clinical and Virologic Outcomes Following Initiation of Antiretroviral Therapy Among Seroconverters in the Microbicide Trials Network-020 Phase III Trial of the Dapivirine Vaginal Ring.

BACKGROUND: A vaginal ring containing dapivirine, a non-nucleoside human immunodeficiency virus (HIV)-1 reverse transcriptase inhibitor (NNRTI), was safe and effective in preventing HIV-1 infection in African women. We examined the impact of dapivirine ring use at the time of HIV-1 acquisition on subsequent HIV-1 disease progression and responses to NNRTI-containing antiretroviral therapy (ART). METHODS: HIV-1 disease progression and virologic failure following initiation of ART were assessed among women who acquired HIV-1 while participating in Microbicide Trials Network-020, a randomized, placebo-controlled trial of a monthly, dapivirine vaginal ring. RESULTS: Among the 158 participants who acquired HIV-1 (65 dapivirine, 93 placebo), no differences between dapivirine and placebo participants were observed in CD4+ cell counts or plasma HIV-1 RNA over the first year after infection (prior to ART). During follow-up, 100/158 (63%) participants initiated NNRTI-containing ART (dapivirine: 39/65; placebo: 61/93); the median time to HIV-1 RNA <200 copies/ml was approximately 90 days for both dapivirine and placebo ring recipients (log-rank P = .40). Among the 81 participants with at least 6 months of post-ART follow-up, 19 (24%) experienced virologic failure (dapivirine: 6/32, 19%; placebo: 13/39, 27%; P = .42). CONCLUSIONS: The acquisition of HIV-1 infection during dapivirine or placebo treatment in ASPIRE did not lead to differences in HIV-1 disease progression. After the initiation of NNRTI-containing ART, dapivirine and placebo participants had similar times to virologic suppression and risks of virologic failure. These results provide reassurance that NNRTI-based ART regimens are effective among women who acquired HIV-1 while receiving the dapivirine vaginal ring. CLINICAL TRIALS REGISTRATION: NCT016170096 and NCT00514098.

Impact of an embedded genetic counselor on breast cancer treatment.

BACKGROUND: We predicted that embedding a genetic counselor within our breast practice would improve identification of high-risk individuals, timeliness of care, and appropriateness of surgical decision making. The aim of this study is to compare cancer care between 2012 and 2014, prior to embedding a genetic counselor in the breast center and following the intervention, respectively. METHODS: A retrospective review of patients diagnosed with breast cancer in 2012 (n = 471) and 2014 (n = 440) was performed to assess patterns of medical genetics referral, compliance with referral, genetic testing findings, and impact on treatment. RESULTS: Between 2012 and 2014, patients were 49% more likely to be referred to genetics, 66% more likely to follow through with their genetic counseling appointment, experienced a 73% reduction in wait times to genetic counseling visits and 69% more likely to have genetic testing results prior to surgery. Notably, while the number of genetic mutations identified was in the expected range over both time periods (9% of those tested in 2012 vs. 6.6% of those tested in 2014), there was a 31% reduction in time to treatment in 2014 vs. 2012. CONCLUSION: Awareness of germline genetic mutations is critical in surgical decision making for newly diagnosed breast cancer patients. Having an experienced genetics specialist on site in a busy surgical breast clinic allows for timely access to genetic counseling and testing, and may have influenced time to treatment in our institution.

Can polyp detection rate be used prospectively as a marker of adenoma detection rate?

BACKGROUND: Adenoma detection rate (ADR) is a quality indicator for screening colonoscopy, but its calculation is time-consuming. Polyp detection rate (PDR) has been found to correlate with ADR; however, its use as a quality indicator has been criticized out of concern for endoscopists artificially inflating the PDR. We aim to evaluate whether active monitoring affects PDR. METHODS: In March 2015, 14 endoscopists were made aware that their personal PDRs would be tracked monthly as a quality improvement project. Endoscopists received a report of their individual monthly and cumulative PDR, departmental averages, and a benchmark PDR. Following the intervention, data were collected for consecutive patients undergoing average risk screening colonoscopy for six months. PDR, ADR, and adenoma to polyp detection ratio quotient (APDRQ) were compared to a six-month pre-intervention period. RESULTS: 2203 patients were included in the study. There was no statistically significant difference in PDR when comparing pre- and post-intervention (44 vs. 45%, OR 1.04; 95% CI 0.77-1.36). No statistically significant difference in ADR was observed when comparing pre- and post-intervention (29 vs. 30%, OR 1.03; 95% CI 0.64-1.52). There was no statistically significant difference in APDRQ when comparing pre- and post-intervention (0.67 vs. 0.66, OR 0.99; 95% CI 0.69-1.33). CONCLUSIONS: Monthly report cards did not result in a change in PDR or APDRQ. In some environments, PDR can be used as a surrogate marker of ADR, despite endoscopist awareness that PDR is being measured.

Determinants of short and long term outcomes in patients undergoing immediate breast reconstruction following neoadjuvant chemotherapy.

BACKGROUND: We evaluated oncologic outcomes and complications of skin-sparing mastectomy (SSM) and nipple-sparing mastectomy (NSM) with immediate reconstruction (IR) after neoadjuvant chemotherapy (NAC) in patients with early-stage and locally advanced breast cancer (BC). METHODS: BC patients from 2000 to 2014 treated with NAC followed by SSM/NSM and IR were reviewed. Patient demographics, tumor characteristics, NAC response, complications, and recurrence were analyzed. RESULTS: Two hundred sixty-nine patients with 280 BCs were treated with NAC followed by SSM (94%) or NSM (6%) with IR. Median age was 47 (26-72) years with a median follow-up of 45 months. Pathologic complete response (pCR) was noted in 49 (17.5%) cases. Overall 30-day complication rate was 13.2%. Variables associated with complications included BMI (P < 0.0001), tobacco use (P = 0.015), and adjuvant radiation (P = 0.025). Local-regional recurrence was 3.2% and metastatic recurrence was 13.2%. Variables predicting recurrence risk were pre-NAC tumor size (P < 0.001), residual tumor size (P = 0.002), Grade III (P = 0.002), HER-2 negative (P = 0.025), pre-NAC nodal disease (P = 0.05), and lack of pCR (P = 0.045). CONCLUSION: Following NAC, risk factors for complications in patients undergoing SSM/NSM with IR are high BMI, smoking, and adjuvant XRT. SSM/NSM following NAC is associated with excellent local control. These data support expanding the indications for NSM/SSM to include patients receiving NAC.

A New Scoring System to Predict the Risk for High-risk Adenoma and Comparison of Existing Risk Calculators.

BACKGROUND: Colorectal cancer (CRC) screening guidelines likely over-generalizes CRC risk, 35% of Americans are not up to date with screening, and there is growing incidence of CRC in younger patients. GOALS: We developed a practical prediction model for high-risk colon adenomas in an average-risk population, including an expanded definition of high-risk polyps (≥3 nonadvanced adenomas), exposing higher than average-risk patients. We also compared results with previously created calculators. STUDY: Patients aged 40 to 59 years, undergoing first-time average-risk screening or diagnostic colonoscopies were evaluated. Risk calculators for advanced adenomas and high-risk adenomas were created based on age, body mass index, sex, race, and smoking history. Previously established calculators with similar risk factors were selected for comparison of concordance statistic (c-statistic) and external validation. RESULTS: A total of 5063 patients were included. Advanced adenomas, and high-risk adenomas were seen in 5.7% and 7.4% of the patient population, respectively. The c-statistic for our calculator was 0.639 for the prediction of advanced adenomas, and 0.650 for high-risk adenomas. When applied to our population, all previous models had lower c-statistic results although one performed similarly. CONCLUSIONS: Our model compares favorably to previously established prediction models. Age and body mass index were used as continuous variables, likely improving the c-statistic. It also reports absolute predictive probabilities of advanced and high-risk polyps, allowing for more individualized risk assessment of CRC.

Laparoscopic versus open inguinal hernia repair in patients with obesity: an American College of Surgeons NSQIP clinical outcomes analysis.

INTRODUCTION: The laparoscopic approach to inguinal hernia repair (IHR) has proven beneficial in reducing postoperative pain and facilitating earlier return to normal activity. Except for indications such as recurrent or bilateral inguinal hernias, there remains a paucity of data that specifically identities patient populations that would benefit most from the laparoscopic approach to IHR. Nevertheless, previous experience has shown that obese patients have increased wound morbidity following open surgical procedures. The aim of this study was to investigate the effect of a laparoscopic versus open surgical approach to IHR on early postoperative morbidity and mortality in the obese population using the National Surgical Quality Improvement Program (NSQIP) database. METHODS: All IHRs were identified within the NSQIP database from 2005 to 2013. Obesity was defined as a body mass index ≥30 kg/m2. A propensity score matching technique between the laparoscopic and open approaches was used. Association of obesity with postoperative outcomes was investigated using an adjusted and unadjusted model based on clinically important preoperative variables identified by the propensity scoring system. RESULTS: A total of 7346 patients met inclusion criteria; 5573 patients underwent laparoscopic IHR, while 1773 patients underwent open IHR. On univariate analysis, obese patients who underwent laparoscopic IHR were less likely to experience a deep surgical site infection, wound dehiscence, or return to the operating room compared with those who underwent an open IHR. In both the adjusted and unadjusted propensity score models, there was no difference in outcomes between those who underwent laparoscopic versus open IHR. CONCLUSIONS: The laparoscopic approach to IHR in obese patients has similar outcomes as an open approach with regard to 30-day wound events. Preoperative risk stratification of obese patients is important to determining the appropriate surgical approach to IHR. Further studies are needed to investigate the long-term effects of the open and laparoscopic approaches to IHR in the obese population.

Safety of Large-Volume, Same-Day Oral Bowel Preparations During Deep Sedation: A Prospective Observational Study.

BACKGROUND: Colonoscopy quality is directly related to the bowel preparation. It is well established that bowel preparations are improved when at least part of the laxative is ingested on the day of the procedure. However, there is concern that this can result in higher gastric residual volumes (GRV) and increase the risk of pulmonary aspiration. The aim of this study is to evaluate GRV and gastric pH in patients who received day-before bowel preparation versus those ingesting their laxative on the day of colonoscopy under anesthesiologist-directed propofol deep sedation. METHODS: This is a prospective observational study for patients undergoing same-day upper endoscopy and colonoscopy. All included patients had large-volume polyethylene glycol lavage preparation and received propofol sedation. Gastric fluid was collected during the upper endoscopy for volume and pH measurement. RESULTS: The study included 428 patients with 56% receiving same-day laxative preparation and the remainder evening-before preparation. Mean ± SD GRV was 18.1 ± 10.2 mL, 16.3 ± 16.5 mL in each of these preparation groups, respectively (P = .69). GRV ≥ 25 mL or higher than expected GRV adjusted by weight (0.4 mL/kg) were also not different among the study groups (P = .90 and P = .87, respectively). Evaluating GRV based on time since last ingestion of preparation (3-5, 5-7, >7 hours) did not result in any differences (P = .56). Gastric pH was also similar between the bowel preparation groups (P = .23), with mean ± SD of 2.5 ± 1.4 for evening-before and 2.5 ± 1.3 for the same-day preparation. There were more inadequate bowel preparations in day before bowel preparations (P = .001). CONCLUSIONS: A large-volume bowel preparation regimen finished on the day of colonoscopy as close as 3 hours before the procedure results in no increase in GRV or decrease in gastric pH.

Mid-Term Results and Predictors of Patient-Reported Outcomes of Birmingham Hip Resurfacing.

BACKGROUND: Birmingham hip resurfacing (BHR) is the only Food and Drug Administration approved resurfacing option currently available in the United States. While adequate BHR outcomes are established, there is a paucity of US-based literature demonstrating factors critical to improve patient reported outcomes (PROs). This study answers: (1) What is the implant survivorship in a large US cohort? (2) Which preoperative factors result in higher PRO scores over 5 years postoperatively? METHODS: A retrospective 541 hip single-surgeon cohort with mean of 6.2 years follow-up (range 5-8.1) was collected. Preoperative patient/implant variables, including postoperative radiographic acetabular inclination and femoral component position, clinical outcomes, and follow-up PRO questionnaire information were collected. Validated PROs included the Hip Disability and Osteoarthritis Outcome Score (HOOS), Veterans Rand-12, and University of California Los Angeles (UCLA) activity. PROs were modeled with ordinary least squares then used to create nomograms. RESULTS: Average patient age was 53 years with 391 (72%) males. Seven hips were revised, resulting in an overall survival of 98.8% at 5 years. Predictive modeling identified preoperative variables (sex, body mass index, smoking, and comorbidity) that had statistically significant associations with HOOS pain (P = .049), HOOS activities of daily living (P = .017), UCLA activity (P < .001), and Veterans Rand-12 physical (P < .001) PROs at latest follow-up. Nomograms predicted follow-up PROs using preoperative patient-specific variables. CONCLUSION: This study documents excellent survival of the largest reported single-center cohort of BHRs in the United States with a mean 6.2 years follow-up. Multivariate modeling shows male nonsmokers with low body mass index, and no comorbidities will have less hip pain, better function in daily life, higher activity, and better general physical health after BHR arthroplasty.

Role of donor hemodynamic trajectory in determining graft survival in liver transplantation from donation after circulatory death donors.

Donation after circulatory death (DCD) donors show heterogeneous hemodynamic trajectories following withdrawal of life support. Impact of hemodynamics in DCD liver transplant is unclear, and objective measures of graft viability would ease transplant surgeon decision making and inform safe expansion of the donor organ pool. This retrospective study tested whether hemodynamic trajectories were associated with transplant outcomes in DCD liver transplantation (n = 87). Using longitudinal clustering statistical techniques, we phenotyped DCD donors based on hemodynamic trajectory for both mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2 ) following withdrawal of life support. Donors were categorized into 3 clusters: those who gradually decline after withdrawal of life support (cluster 1), those who maintain stable hemodynamics followed by rapid decline (cluster 2), and those who decline rapidly (cluster 3). Clustering outputs were used to compare characteristics and transplant outcomes. Cox proportional hazards modeling revealed hepatocellular carcinoma (hazard ratio [HR] = 2.53; P = 0.047), cold ischemia time (HR = 1.50 per hour; P = 0.027), and MAP cluster 1 were associated with increased risk of graft loss (HR = 3.13; P = 0.021), but not SpO2 cluster (P = 0.172) or donor warm ischemia time (DWIT; P = 0.154). Despite longer DWIT, MAP and SpO2 clusters 2 showed similar graft survival to MAP and SpO2 clusters 3, respectively. In conclusion, despite heterogeneity in hemodynamic trajectories, DCD donors can be categorized into 3 clinically meaningful subgroups that help predict graft prognosis. Further studies should confirm the utility of liver grafts from cluster 2. Liver Transplantation 22 1469-1481 2016 AASLD.

Immediate Reconstruction in Inflammatory Breast Cancer: Challenging Current Care.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive disease that is treated with trimodality therapy consisting of neoadjuvant chemotherapy, surgery, and post-mastectomy radiation therapy (PMRT). Traditionally, modified radical mastectomy without reconstruction has been the operation of choice for patients with IBC due to fears of high rates of margin positivity, risk of local recurrence, and the need for PMRT. METHODS: A retrospective review was performed to evaluate women with IBC at our institution from 2006 to 2014 who completed trimodality therapy. Patients were identified as undergoing reconstruction or no reconstruction (NR), with reconstruction being further classified as immediate (IR) if reconstruction occurred at the initial surgery, or delayed (DR) if initial reconstruction occurred after PMRT. RESULTS: Sixty women with IBC were identified using inclusion criteria. The median follow-up was 2.3 years (range 1.4-4.6). Patients with IR had a statistically significant increased risk (p = 0.006) in postoperative complication rates compared with DR (0 %) and NR (2.6 %). Two patients had positive skin margins on final pathology (one IR, one NR), with both eventually having recurrence. Time to PMRT was delayed 10 days in patients with IR compared with those without IR. No statistically significant difference in recurrence rates was observed (p = 0.86) when comparing patients with IR and those with NR, and no difference in survival was observed between patients who had reconstruction and those without (p = 0.91). CONCLUSION: Performing IR with mastectomy for IBC is associated with increased complications, but is not associated with decreased survival or increased recurrence in selected patients. IR in selected IBC patients can facilitate successful breast reconstruction.

Fertility in Women of Reproductive Age After Breast Cancer Treatment: Practice Patterns and Outcomes.

BACKGROUND: Breast cancer is the most frequently occurring cancer in women of reproductive age, and systemic treatments may adversely affect childbearing plans. Use of assisted reproductive technologies and therapies for ovarian protection improve fertility prospects. We evaluated whether patients had a documented fertility discussion (FD) with their oncology physician prior to therapy, what options were chosen, and if pregnancy was achieved. METHODS: A retrospective chart review from 2006 to 2014 was performed to evaluate women aged 40 years and younger who were diagnosed with breast cancer and treated with chemotherapy and/or antihormonal therapy. Patient demographics, treatment regimens, presence or absence of FD, in vitro fertilization (IVF) consultation, gonadotropin-releasing hormone (GnRH) agonist use, and subsequent successful pregnancy were analyzed. RESULTS: Among 303 patients meeting the inclusion criteria, 80 (26 %) had an FD with their physician documented; 71 of these 80 women (89 %) sought further fertility consultation and options. Sixteen (20 %) women were prescribed a GnRH agonist only for ovarian protection during chemotherapy, 50 (63 %) underwent IVF consultation only, and 5 (6 %) had both a GnRH agonist prescribed and an IVF consultation. The overall pregnancy rate was 7 % at a mean of 3 years post breast cancer treatment. Pregnancy after treatment was more common among those pursuing IVF consultation or prescribed a GnRH agonist. CONCLUSIONS: In treating young breast cancer patients, it is important to assess fertility desire, discuss treatment risks relating to fertility, and discuss preservation options. Although not every woman in this group desired pregnancy, 71/80 (89 %) women having a documented FD sought further fertility consultation and options.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.