Predictors of severe and recurrent adult anaphylaxis, and gaps in the cascade of care: a retrospective, single-centre study 2009-2018.

BACKGROUND: Anaphylaxis is a severe, potentially fatal, systemic allergic reaction. Understanding predictors of recurrent and severe anaphylaxis in adults, and identifying gaps in ongoing anaphylaxis care, is needed to minimise its impact. AIMS: To evaluate the risk factors in adults with severe and recurrent anaphylaxis presentations and to evaluate the management of patients in regard to the recommended cascade of care. METHODS: We completed a retrospective audit of adults with confirmed anaphylaxis who presented to an inner-city emergency department from 1 January 2009 through 31 December 2018. Data recorded included demographics, background history, medication use, severity, co-factors, triggers, management, discharge disposition and referral for follow-up. Data were managed in REDCap and analysed using Stata. Associations were assessed through odds ratios (ORs) and t tests. RESULTS: Six hundred sixteen individuals had 689 episodes of anaphylaxis over the audit period. Age over 65 (OR: 5.4 (95% confidence interval, CI: 2.3-13.2), P < 0.0001) and history of asthma (OR: 1.6 (95% CI: 1.03-2.5), P = 0.03) were independent risk factors for severe anaphylaxis. History of food allergy (P < 0.001) and food as the trigger were associated with recurrent presentations (OR: 2.1, 95% CI: 1.1-3.9, P = 0.01). Only 19% of patients met the recommended cascade of care, with post-adrenaline monitoring and recommending follow-up with an allergy specialist demonstrating the largest gaps. There were increased presentations with time but no difference in triggers or severity. CONCLUSIONS: Increased age and asthma were identified as risk factors for severe presentations. History of food allergy was a risk factor for recurrent presentations. Further research is needed on the gaps in care for adults with anaphylaxis to identify the reasons why, so we can better care for these patients.

Specific human leucocyte antigen-DQ risk epitope mismatches are associated with chronic lung allograft dysfunction after lung transplantation.

A high-risk epitope mismatch (REM) (found in DQA1∗05 + DQB1∗02/DQB1∗03:01) is associated with de novo donor specific antibodies after lung transplantation (LTx). Chronic lung allograft dysfunction (CLAD) remains a barrier to LTx survival. This study aimed to measure the association between DQ REM and the risk of CLAD and death after LTx. A retrospective analysis of LTx recipients at a single center was conducted between January 2014 and April 2019. Molecular typing at human leucocyte antigen-DQA/DQB identified DQ REM. Multivariable competing risk and Cox regression models were used to measure the association between DQ REM, time-to-CLAD, and time-to-death. DQ REM was detected in 96/268 (35.8%), and DQ REM de novo donor specific antibodies were detected in 34/96 (35.4%). CLAD occurred in 78 (29.1%), and 98 (36.6%) recipients died during follow-up. When analyzed as a baseline predictor, DQ REM status was associated with CLAD (subdistribution hazard ratio (SHR), 2.19; 95% confidence interval [CI], 1.40-3.43; P = .001). After adjustment for time-dependent variables, DQ REM dn-DSA (SHR, 2.43; 95% CI, 1.10-5.38; P = .029) and A-grade rejection score (SHR, 1.22; 95% CI, 1.11-1.35; P = <.001), DQ REM status was not independently associated with CLAD. DQ REM was not associated with death (hazard ratio, 1.18; 95% CI, 0.72-1.93; P = .51). Classification of DQ REM may identify patients at risk of poor outcomes and should be incorporated into clinical decision-making.

A Comparison of Gender-Affirming Chest Surgery in Nonbinary Versus Transmasculine Patients.

BACKGROUND: Increasingly more nonbinary patients are obtaining better access for gender-affirming chest surgery (top surgery), representing an important subset of patients who undergo such surgery. OBJECTIVE: We review our experience at gender-affirming chest surgery in nonbinary versus transmasculine patients in an integrated health care setting. METHODS: We performed a retrospective study of nonbinary and transmasculine patients who underwent gender-affirming chest surgery from May 1, 2012, to December 27, 2017. RESULTS: There were 111 nonbinary patients and 665 transmasculine patients included in the final analyses. Nonbinary patients were more likely to seek more than 1 surgical consultations than transmasculine patients (24.3% vs 1.7%, respectively, P < 0.0001). More nonbinary patients (17.3%) indicated nipple sensation to be important relative to their transmasculine counterparts (0.4%, P < 0.0001). Fewer nonbinary patients were on testosterone before surgery (33.64%) in comparison to transmasculine patients (86.14%, P < 0.0001). When only prior reduction mammaplasty or top surgery were considered, nonbinary patients (8.1%) were more likely than transmasculine patients (3.5%) to have had a prior chest surgery. When evaluating patients who did not have prior chest surgery before undergoing top surgery at our institution (n = 721), rates of major complications, minor complications, as well as revisions, were comparable between nonbinary and transmasculine patients. CONCLUSIONS: This study demonstrated that more nonbinary patients requested nonflat chests relative to their transmasculine counterparts. Both groups in our sample displayed comparable rates of complications after top surgery.

Early Experiences With the Buttonhole Modification of the Double-Incision Technique for Gender-Affirming Mastectomies.

BACKGROUND: Little has been published about transmasculine and nonbinary gender-affirming mastectomies, particularly for patients with skin excess who desire reliable vascularity and sensation to the nipple-areolar complex. In this case series, we describe our experiences with the "buttonhole technique." METHODS: This was a retrospective case series of all consecutive patients who had a buttonhole mastectomy by a single surgeon. This technique maintains the nipple-areolar complex on a dermal pedicle rather than using a free nipple graft. RESULTS: Seventeen patients were included, with ages ranging from 21 to 49 years (median, 28 years). There were no major complications. Four patients had minor complications and/or required revision. CONCLUSIONS: The buttonhole technique should be considered for transmasculine and nonbinary patients with skin excess who are concerned about nipple vascularity and sensation.

Does Previous Breast Reduction Affect the Outcome of Gender-Affirming Subcutaneous Mastectomy?

INTRODUCTION: Despite the rising popularity of subcutaneous mastectomy (top surgery) in patients born female and identifying as male or nonbinary, there are limited studies on how prior breast surgeries affect subcutaneous mastectomy. This study evaluates if previous breast reduction affected subcutaneous mastectomy in this patient population. METHODS: The case series consists of 5 patients who, having had prior breast reductions, elected to have subcutaneous mastectomy. The data were collected retrospectively for mastectomy conducted from 2015 to 2016. Demographic data collected included age at surgery, body mass index, smoking status, medical comorbidity, and use of hormone medication. Outcome data included postoperative complications and need for operative revision. Postoperative follow-up was at 1 week and at 1, 3, 6, and 12 months. RESULTS: Patients' ages were between 29 and 46 years with body mass index from 24 to 33 kg/m. They underwent breast reduction approximately 9 to 26 months prior to subcutaneous mastectomy. All 5 patients successfully underwent subcutaneous mastectomy via double incision and free nipple grafts. Blood loss was estimated to be approximately 42 mL. All patients were discharged on the same day of surgery. The last follow-up averaged at 13 months after surgery and no major complication was reported. However, 1 patient required revision of the nipple graft and chest scars. CONCLUSIONS: This small case series suggests that subcutaneous mastectomy could be safely performed in transmasculine or nonbinary patients who had previous breast reduction.

Association of IMMP2L deletions with autism spectrum disorder: A trio family study and meta-analysis.

IMMP2L, the gene encoding the inner mitochondrial membrane peptidase subunit 2-like protein, has been reported as a candidate gene for Tourette syndrome, autism spectrum disorder (ASD) and additional neurodevelopmental disorders. Here we genotyped 100 trio families with an index proband with autism spectrum disorder in Han Chinese population and found three cases with rare exonic IMMP2L deletions. We have conducted a comprehensive meta-analysis to quantify the association of IMMP2L deletions with ASD using 5,568 cases and 10,279 controls. While the IMMP2L deletions carried non-recurrent breakpoints, in contrast to previous reports, our meta-analysis found no evidence of association (P > 0.05) between IMMP2L deletions and ASD. We also observed common exonic deletions impacting IMMP2L in a separate control (5,971 samples) cohort where subjects were screened for psychiatric conditions. This is the first systematic review and meta-analysis regarding the effect of IMMP2L deletions on ASD, but further investigations in different populations, especially Chinese population may be still needed to confirm our results.

Engineering Multifunctional RNAi Nanomedicine To Concurrently Target Cancer Hallmarks for Combinatorial Therapy.

Cancer hallmarks allow the complexity and heterogeneity of tumor biology to be better understood, leading to the discovery of various promising targets for cancer therapy. An amorphous iron oxide nanoparticle (NP)-based RNAi strategy is developed to co-target two cancer hallmarks. The NP technology can modulate the glycolysis pathway by silencing MCT4 to induce tumor cell acidosis, and concurrently exacerbate oxidative stress in tumor cells via the Fenton-like reaction. This strategy has the following features for systemic siRNA delivery: 1) siRNA encapsulation within NPs for improving systemic stability; 2) effective endosomal escape through osmotic pressure and/or endosomal membrane oxidation; 3) small size for enhancing tumor tissue penetration; and 4) triple functions (RNAi, Fenton-like reaction, and MRI) for combinatorial therapy and in vivo tracking.

Tantalum Sulfide Nanosheets as a Theranostic Nanoplatform for Computed Tomography Imaging-Guided Combinatorial Chemo-Photothermal Therapy.

Near-infrared (NIR)-absorbing metal-based nanomaterials have shown tremendous potential for cancer therapy, given their facile and controllable synthesis, efficient photothermal conversion, capability of spatiotemporal-controlled drug delivery, and intrinsic imaging function. Tantalum (Ta) is among the most biocompatible metals and arouses negligible adverse biological responses in either oxidized or reduced forms, and thus Ta-derived nanomaterials represent promising candidates for biomedical applications. However, Ta-based nanomaterials by themselves have not been explored for NIR-mediated photothermal ablation therapy. In this work, we report an innovative Ta-based multifunctional nanoplatform composed of biocompatible tantalum sulfide (TaS2) nanosheets (NSs) for simultaneous NIR hyperthermia, drug delivery, and computed tomography (CT) imaging. The TaS2 NSs exhibit multiple unique features including (i) efficient NIR light-to-heat conversion with a high photothermal conversion efficiency of 39%. (ii) high drug loading (177% by weight), (iii) controlled drug release triggered by NIR light and moderate acidic pH, (iv) high tumor accumulation via heat-enhanced tumor vascular permeability, (v) complete tumor ablation and negligible side effects, and (vi) comparable CT imaging contrast efficiency to the widely clinically used agent iobitridol. We expect that this multifunctional NS platform can serve as a promising candidate for imaging-guided cancer therapy and selection of cancer patients with high tumor accumulation.

Atlantic salmon endothelial cells from the heart were more susceptible than fibroblasts from the bulbus arteriosus to four RNA viruses but protected from two viruses by dsRNA pretreatment.

Heart diseases caused by viruses are major causes of Atlantic salmon aquaculture loss. Two Atlantic salmon cardiovascular cell lines, an endothelial cell line (ASHe) from the heart and a fibroblast cell line (BAASf) from the bulbus arteriosus, were evaluated for their response to four fish viruses, CSV, IPNV, VHSV IVa and VHSV IVb, and the innate immune agonist, double-stranded RNA mimic poly IC. All four viruses caused cytopathic effects in ASHe and BAASf. However, ASHe was more susceptible to all four viruses than BAASf. When comparing between the viruses, ASHe cells were found to be moderately susceptible to CSV and VHSV IVb, but highly susceptible to IPNV and VHSV IVa induced cell death. All four viruses were capable of propagating in the ASHe cell line, leading to increases in virus titre over time. In BAASf, CSV and IPNV produced more than one log increase in titre from initial infection, but VHSV IVb and IVa did not. When looking at the antiviral response of both cell lines, Mx proteins were induced in ASHe and BAASf by poly IC. All four viruses induced Mx proteins in BAASf, while only CSV and VHSV IVb induced Mx proteins in ASHe. IPNV and VHSV IVa suppressed Mx proteins expression in ASHe. Pretreatment of ASHe with poly IC to allow for Mx proteins accumulation protected the culture from subsequent infections with IPNV and VHSV IVa, resulting in delayed cell death, reduced virus titres and reduced viral proteins expression. These data suggest that endothelial cells potentially can serve as points of infections for viruses in the heart and that two of the four viruses, IPNV and VHSV IVa, have mechanisms to avoid or downregulate antiviral responses in ASHe cells. Furthermore, the high susceptibility of the ASHe cell line to IPNV and VHSV IVa can make it a useful tool for studying antiviral compounds against these viruses and for general detection of fish viruses.

Microgeographic factors and patterns of aeroallergen sensitisation.

OBJECTIVE: To examine patterns of airborne allergen (aeroallergen) sensitisation in the Greater Sydney area (Sydney), and their relationships with climate, coastal proximity and environment (urban v regional). DESIGN, SETTING, PARTICIPANTS: Retrospective cross-sectional study of patients who underwent aeroallergen skin prick testing at three Sydney allergy clinics, January 2001 - October 2014. MAIN OUTCOME MEASUREMENTS: Proportions of patients sensitised to specific aeroallergen types; relationships between sensitisation patterns and climate and geography. RESULTS: Of 1421 patients who met the selection criteria (mean age, 28.3 years [SD, 21.3]; 53.3% were female), 1092 (76.8%) were sensitised to at least one aeroallergen. Those living less than 15 km from the coast were less commonly sensitised to cockroach (< 15 km, 15.1%; 15-30 km, 40.0%; > 30 km, 39.7%; P < 0.001) and grass aeroallergens (< 15 km, 36.5%; 15-30 km, 52.2%; > 30 km, 58.1%; P < 0.001) than patients further inland; the same applied to mould, weed and tree aeroallergens. Subtropical grass sensitisation was more common in temperate/warm summer climates (about 50%) than in temperate/hot summer (27.1%) or subtropical climates (15%) (P < 0.001), and less common in urban (36.7%) than in regional areas (54%; P = 0.014). 72.4% of grass-sensitised patients were co-sensitised to both temperate and subtropical grasses. A selected ten-aeroallergen skin prick test panel identified 98.5% of atopic patients in this Sydney sample. CONCLUSIONS: Environmental and geographic factors are associated with different patterns of allergic sensitisation in Sydney. Extensive co-sensitisation to subtropical and temperate grasses has implications for immunotherapy in Australia, where most currently available therapies are based on formulations directed at temperate grasses only.

Human papillomavirus 16-specific T-cell responses and spontaneous regression of anal high-grade squamous intraepithelial lesions.

BACKGROUND: Most anal cancers are attributable to persistent human papillomavirus type 16 (HPV-16) infection. The anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), frequently regresses spontaneously. We hypothesized that T-cell responses are associated with HSIL regression. METHODS: In men who have sex with men undergoing anal cytology and high-resolution anoscopy, we measured responses to HPV-16 oncogenic proteins E6 and E7, using the CD25/CD134 assay for CD4(+) antigen-specific T cells and intracellular cytokine staining for CD4(+) and CD8(+) antigen-specific T cells. RESULTS: Of 134 participants (mean [SD] age, 51 [9.3] years; 31 [23.1%] infected with human immunodeficiency virus), 51 (38.1%) had HSIL. E6- and E7-specific CD4(+) T-cell responses were detected in 80 (59.7%) and 40 (29.9%) of the participants, respectively, and E6- and E7-specific CD8(+) T-cell responses were each detected in 25 (18.7%). HSIL was significantly associated with E7-specific CD8(+) T-cell responses (odds ratio, 4.09 [95% confidence interval, 1.55-10.77], P = .004), but not with any CD4(+) T-cell response (P ≥ .09). Twenty-six participants had HSIL a mean of 1 year before measurement of T-cell responses, and 6 (23%) of them were regressors. Five regressors (83%) had E6-specific CD4(+) T-cell responses vs 7 of 20 (35%) nonregressors (Pexact = .065). CONCLUSIONS: Systemic HPV-16 E6- and E7-specific T-cell responses were common in men who have sex with men. E6-specific CD4(+) T-cell responses may be associated with recent HSIL regression. CLINICAL TRIALS REGISTRATION: NCT02007421.

Molecular Diagnostic Yield of Chromosomal Microarray Analysis and Whole-Exome Sequencing in Children With Autism Spectrum Disorder.

IMPORTANCE: The use of genome-wide tests to provide molecular diagnosis for individuals with autism spectrum disorder (ASD) requires more study. OBJECTIVE: To perform chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in a heterogeneous group of children with ASD to determine the molecular diagnostic yield of these tests in a sample typical of a developmental pediatric clinic. DESIGN, SETTING, AND PARTICIPANTS: The sample consisted of 258 consecutively ascertained unrelated children with ASD who underwent detailed assessments to define morphology scores based on the presence of major congenital abnormalities and minor physical anomalies. The children were recruited between 2008 and 2013 in Newfoundland and Labrador, Canada. The probands were stratified into 3 groups of increasing morphological severity: essential, equivocal, and complex (scores of 0-3, 4-5, and ≥6). EXPOSURES: All probands underwent CMA, with WES performed for 95 proband-parent trios. MAIN OUTCOMES AND MEASURES: The overall molecular diagnostic yield for CMA and WES in a population-based ASD sample stratified in 3 phenotypic groups. RESULTS: Of 258 probands, 24 (9.3%, 95%CI, 6.1%-13.5%) received a molecular diagnosis from CMA and 8 of 95 (8.4%, 95%CI, 3.7%-15.9%) from WES. The yields were statistically different between the morphological groups. Among the children who underwent both CMA and WES testing, the estimated proportion with an identifiable genetic etiology was 15.8% (95%CI, 9.1%-24.7%; 15/95 children). This included 2 children who received molecular diagnoses from both tests. The combined yield was significantly higher in the complex group when compared with the essential group (pairwise comparison, P = .002). [table: see text]. CONCLUSIONS AND RELEVANCE: Among a heterogeneous sample of children with ASD, the molecular diagnostic yields of CMA and WES were comparable, and the combined molecular diagnostic yield was higher in children with more complex morphological phenotypes in comparison with the children in the essential category. If replicated in additional populations, these findings may inform appropriate selection of molecular diagnostic testing for children affected by ASD.

Learning curves in abdominal wall reconstruction with components separation: one step closer toward improving outcomes and reducing complications.

INTRODUCTION: Learning curves are characterized by incremental improvement of a process, through repetition and reduction in variability, but can be disrupted with the emergence of new techniques and technologies. Abdominal wall reconstruction continues to evolve, with the introduction of components separation in the 1990s and biologic mesh in the 2000s. As such, attempts at innovation may impact the success of reconstructive outcomes and yield a changing set of complications. The purpose of this project was to describe the paradigm shift that has occurred in abdominal wall reconstruction during the past 10 years, focusing on the incorporation of new materials and methods. METHODS: We reviewed 150 consecutive patients who underwent abdominal wall reconstruction of midline defects with components separation, from 2000 to 2010. Both univariate and multivariate logistic regression analyses were performed to identify risk factors for complications. Patients were stratified into the following periods: early (2000-2003), middle (2004-2006), and late (2007-2010). RESULTS: From 2000 to 2010, we performed 150 abdominal wall reconstructions with components separation [mean age, 50.2 years; body mass index (BMI), 30.4; size of defect, 357 cm; length of stay, 9.6 days; follow-up, 4.4 years]. Primary fascial closure was performed in 120 patients. Mesh was used in 114 patients in the following locations: overlay (n = 28), inlay (n = 30), underlay (n = 54), and unknown (n = 2). Complications occurred in a bimodal distribution, highest in 2001 (introduction of biologic mesh) and 2008 (conversion from underlay to overlay location). Age, sex, history of smoking, defect size, and length of stay were not associated with incidence of complications. Unadjusted risk factors for seroma (16.8%) were elevated BMI, of previous hernia repairs, use of overlay mesh, and late portion of the learning curve, with logistic regression supporting only late portion of the learning curve [odds ratio (OR), 4.3; 95% confidence interval (CI), 1.0-18.6] and BMI (OR, 1.17; 95% CI, 1.06-1.29). The only unadjusted risk factor for recurrence was location of mesh. Logistic regression, comparing underlay, inlay, and overlay mesh to no mesh, revealed that the use of underlay mesh predicted recurrence (OR, 3.0; 95% CI, 1.04-8.64). All P values were less than 0.05. CONCLUSIONS: The overall learning curve for a specific procedure, such as abdominal wall reconstruction, can be quite volatile, especially as innovative techniques and new technologies are introduced and incorporated into the surgeon's practice. Our current practice includes primary repair myofascial flap of the components separation and the use of biologic mesh as an overlay graft, anchored to the external oblique. This process of outcome improvement is not gradual but is often punctuated by periods of failure and redemption.

The Study of the Prevention of Anal Cancer (SPANC): design and methods of a three-year prospective cohort study.

BACKGROUND: The incidence of human papillomavirus (HPV)-associated anal cancer is increasing in men who have sex with men (MSM). Screening for the presumed cancer precursor, high-grade anal squamous intraepithelial lesions (HSIL) in a manner analogous to cervical cancer screening has been proposed. Uncertainty remains regarding anal HPV natural history and the role of anal cytology and high-resolution anoscopy (HRA) as screening tests. Well-designed cohort studies are required to address these issues. METHODS/DESIGN: The SPANC study is a prospective study of the epidemiology of low-risk and high-risk anal HPV infection and related cytological and histological abnormalities in HIV-negative and HIV-positive homosexual men aged 35 years and over. The study aims to recruit 600 men from community-based settings in Sydney, Australia. There are six study visits over three years. At the first five visits men undergo a digital ano-rectal examination (DARE), an anal "Papanicolaou" (Pap) test for HPV detection, genotyping and anal cytology, followed by HRA and directed biopsy of any visible abnormalities. The men also complete a behavioural questionnaire before each visit. Questions include a detailed history of sexual behaviour, of anal symptoms, possible anal cancer risk factors and validated quality of life and psychosocial questions. Questionnaires are also completed 2 weeks and 3 months following the provision of test results and include questions on participant experience during the procedure and post-procedure symptoms, including pain and bleeding in addition to quality of life/ psychosocial outcomes. DISCUSSION: Recruitment for the study began in September 2010 and will conclude in mid-2015, with follow up continuing to 2018. Thus far, over 350 men have been recruited from a variety of community-based settings and are broadly representative of the target screening population. The SPANC study is one of only a small number of cohort studies globally to perform HPV, cytology and HRA screening on all participants over multiple time points. The study results will contribute to understanding of the natural history of anal HPV and inform the possible development of guidelines for implementing anal cancer screening programs in this population.

A classification system for fat necrosis in autologous breast reconstruction.

PURPOSE: Fat necrosis (FN) is a common complication of autologous breast reconstruction, yet no classification system exists to describe it. We sought to develop and validate a tool for meaningful reporting, comparison of techniques, and treatment planning. Our hypothesis was that a valid classification system would demonstrate higher grades of FN for pedicled transverse rectus abdominus myocutaneous (pTRAM) flaps as compared to free flaps (FF). METHODS: A classification system for FN was developed: grade I, radiologic evidence only; grade II, palpable but not visible FN; grade III, palpable and visible FN; and grade IV, symptomatic FN. For validation, we applied this system to patients who had undergone pTRAM flaps from 2002 to 2006 and FF from 2006 to 2010 at our institution. RESULTS: We performed 93 pTRAM flaps in 69 patients and 102 FF in 69 patients. One patient had grade I FN and was observed. Of the 29 patients with grade II FN, 48% were observed, 17% had biopsy, and 35% underwent debridement. Of the 9 patients with grade III FN, 11% underwent biopsy and 89% had debridement. All patients with grade IV FN underwent debridement. The distribution of FN differed between pTRAM and FF. The mean FN grade for patients undergoing pTRAM was 1.4 versus 0.4 for those undergoing FF (P < 0.05). Fat necrosis requiring reoperation was more frequent in the pTRAM group (23.7% vs 5.9%, P < 0.05). CONCLUSIONS: Our validation study confirmed that FN grade was associated with the need for surgery and was higher for pedicled flaps as compared to FFs. As it is similar to the Baker grading system for capsular contracture, this classification system is familiar to all plastic surgeons. It is simple, easy to remember, clinically oriented, and could be readily incorporated into outcome studies of autologous breast reconstruction.

Delabeling, safety, and impact of ß-lactam allergy testing: A systematic review.

Background: To improve ß-lactam delabeling outcomes, we need to understand current practice and the evidence base regarding its outcomes, safety, and impact. Objectives: We sought to assess the existing published evidence reporting on the effectiveness of penicillin allergy testing and delabeling. Methods: We conducted a systematic review of studies reporting ß-lactam delabeling practices and outcomes after testing, including ß-lactam use and patient understanding of the delabeling result. Searches of the PubMed, Scopus, and Embase databases; clinical trial registries; and websites of professional organizations were conducted. Data were extracted from the included studies in duplicate, with a third extraction if discrepancies remained. Results: We included 284 publications (covering 98,316 participants); 173 were prospective studies, with no randomized controlled trials. The overall study quality was low. In all, 95.6% of individuals who underwent provocation testing were delabeled. Factors associated with successful delabeling could not be determined because of significant heterogeneity between studies. Anaphylaxis due to testing occurred in 0.3% of participants (95 of 31,667). Subjects who did not undergo skin testing (6,980 patients in 31 studies) before challenge had higher rates of provocation test positivity (8.8% vs 4.1% [P < .0001]) and anaphylaxis (15.9% vs 2.7% [P < .0001]) than those subjects who underwent skin testing (51,607 patients in 177 studies). Six studies (2.1%) followed patients after testing to assess their adherence to prescribing recommendations. In all, 136 participants (20.6%) were actively avoiding ß-lactams despite delabeling. Conclusions: The available data suggest that penicillin allergy testing is safe and effective in delabeling most individuals, but the evidence base is incomplete and more work is required to assess the role of skin testing and the impact that delabeling is having on prescribing habits.

The impact of preoperative CT angiography on breast reconstruction with abdominal perforator flaps.

PURPOSE: Because of the anatomic variability of the deep inferior epigastric artery, preoperative CT angiography (pCTA) has gained popularity for planning abdominal perforator flap breast reconstruction. This study evaluates how pCTA has affected preoperative planning, operative time, and outcome. METHODS: We performed a retrospective study of abdominal free flap breast reconstruction at our institution over a 4-year period, with pCTA performed routinely after the first year. Operative time and outcomes were compared between procedures with and without pCTA. Incidental findings were recorded. RESULTS: Between 2006 and 2010, 102 abdominal perforator flap surgeries were performed on 69 patients; of whom, 51 patients had pCTA and 18 did not. pCTA changed preoperative planning in 50% of cases by identifying the best perforator in unilateral cases or perforators with long intramuscular course. Preoperative plan based on pCTA corresponded to operative procedures in 89% of cases. The sensitivity and positive predictive value of pCTA to localize perforators were 79% and 92%, respectively. Operative time was significantly reduced with pCTA for both unilateral (636 vs. 496 minutes, P = 0.017) and bilateral cases (746 vs. 629 minutes, P = 0.05). Rates of fat necrosis, partial flap necrosis, and complete flap loss were comparable between the 2 groups. Incidentalomas were found in 36% of patients. CONCLUSIONS: pCTA appears to reduce operative time by minimizing time spent identifying perforators, assisting in side selection for unilateral reconstruction, and optimizing planning when a long intramuscular course is identified. The effect of a learning curve cannot be excluded and is the chief limitation of this study.

To everything there is a season: impact of seasonal change on admissions, acuity of injury, length of stay, throughput, and charges at an accredited, regional burn center.

PURPOSE: Although previous studies have investigated the impact of weather and temporal factors on incidence of trauma admissions, there is a paucity of data describing the effect of seasonal change on burn injury. The purpose of this study was to examine the impact of the changing seasons on admissions to and resource utilization at an accredited burn center, with the goal of optimizing patient throughput and matching supply with demand. METHODS: We performed a retrospective review of all burn admissions to an accredited, regional burn center, from Summer 2009 through Spring 2010. Patients were segregated into the seasonal cohorts of Summer, Fall, Winter, and Spring, based on admission date. Patient demographics included age, gender, mechanism of injury, and total body surface area (TBSA) injured. Main outcome measures included length of intensive care unit (ICU) stay, length of stay (LOS), and hospital charges, which served as a proxy for resource utilization (nursing, wound, and critical care; access to operating room (OR); inpatient rehabilitation). Groups were compared by T tests, with statistical significance assigned to P values <0.05. RESULTS: Seven hundred thirty patients were admitted to the burn center during this annual period, with a mean age of 31.6 years and a TBSA of 8.9%. Although Spring had the greatest the number of admissions at 219 (30%), patients from Summer and Winter had the largest burns, longest length of ICU and hospital stays, and highest hospital charges (P < 0.05). Furthermore, variability of these parameters, as measured by standard deviation, was greatest during Summer and Winter, serving to reduce throughput via uneven demand on resources. Highest throughput occurred during the Spring, which had the highest admission-to-LOS ratio. No differences were observed in age, gender, and incidence of electrical injuries, across the 4 seasons. CONCLUSIONS: Summer and winter were the peak seasons of resource utilization at our burn center, in terms of length and variability of ICU and hospital stays, as well as total hospital charges. Such seasonal change may be related to acuity of burn injury but not number of burn admissions. To improve operational efficiency and maximize patient throughput, resource allocation should be structured to anticipate seasonal changes, so that supply of services matches demand.

The transition from pedicle transverse rectus abdominis myocutaneous to perforator flap: what is the cost of opportunity?

PURPOSE: This study evaluates how the transition from pedicled transverse rectus abdominis myocutaneous (pTRAM) to perforator flaps at an academic center has affected outcome and reimbursement. METHODS: In 2006, our practice transitioned to almost exclusively perforator flaps for breast reconstruction. This study retrospectively compares pTRAM flaps performed from 2002 to 2006 (group 1) with perforator flaps from 2006 to 2010 (group 2). Operative time, complications, and reimbursement were compared between the 2 groups. RESULTS: We performed 93 pTRAM flaps in 69 patients in group 1 and 102 perforator flaps in 69 patients in group 2. Operative time was shorter in group 1 for unilateral breast reconstruction (399 vs. 543 minutes, P = 0.0001), but no significant difference was noted for bilateral cases (547 vs. 658 minutes, P = 0.1). Fat necrosis requiring reoperation (23.7% vs. 5.9%, P = 0.0004) and partial flap necrosis (20.6% vs. 7.2%, P = 0.045) were more frequent in group 1. There was a higher frequency of abdominal hernia (8.8% vs. 1.6%, P = 0.2) but fewer hematomas (1.5% vs. 10%, P = 0.06) in group 1, although statistical significance was not reached between the 2 groups. Mean adjusted payment per case was $3658.67 for group 1 versus $5256.48 for group 2 (P = 0.004), whereas payment per minute was $9.25 for group 1 versus $9.13 for group 2 (P = 0.9). Perforator flaps appear to be as profitable as pTRAM flaps with lower morbidity. CONCLUSIONS: The transition from pTRAM to perforator flap can be done successfully with appropriate resources and support. The development of a perforator flap practice represents an opportunity cost in optimizing patient care and should be an option to patients seeking breast reconstruction.