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Background Medical 3D printing as a component of care for adults with cardiovascular diseases has expanded dramatically. A writing group composed of the Radiological Society of North America (RSNA) Special Interest Group on 3D Printing (SIG) provides appropriateness criteria for adult cardiac 3D printing indications. Methods A structured literature search was conducted to identify all relevant articles using 3D printing technology associated with a number of adult cardiac indications, physiologic, and pathologic processes. Each study was vetted by the authors and graded according to published guidelines. Results Evidence-based appropriateness guidelines are provided for the following areas in adult cardiac care; cardiac fundamentals, perioperative and intraoperative care, coronary disease and ischemic heart disease, complications of myocardial infarction, valve disease, cardiac arrhythmias, cardiac neoplasm, cardiac transplant and mechanical circulatory support, heart failure, preventative cardiology, cardiac and pericardial disease and cardiac trauma. Conclusions Adoption of common clinical standards regarding appropriate use, information and material management, and quality control are needed to ensure the greatest possible clinical benefit from 3D printing. This consensus guideline document, created by the members of the RSNA 3D printing Special Interest Group, will provide a reference for clinical standards of 3D printing for adult cardiac indications.

Hepatitis B virus (HBV) causes a potentially life-threatening liver infection that frequently results in life-long chronic infection. HBV is responsible for 887,000 deaths each year, most resulting from chronic liver diseases and hepatocellular carcinoma. Presently, there are 250 million chronic HBV carriers worldwide who are at a high risk for developing cirrhosis and hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer with a strong association with HBV infection. HBV transmission through blood transfusions and perinatal transfer from infected mother to child have been common routes of infection. In the present study, we describe the development of a synthetic DNA plasmid encoding an anti-HBV human monoclonal antibody specific for the common “a determinant region” of HBsAg of hepatitis B virus and demonstrate the ability of this platform at directing in vivo antibody expression. In vivo delivery of this DNA encoded monoclonal antibody (DMAb) plasmid in mice resulted in expression of human IgG over a period of one month following a single injection. Serum antibody was found to recognize the relevant conformational epitope from plasma purified native HBsAg as well as bound HBV in HepG2.2.15 cells. The serum DMAb efficiently neutralized HBV and prevented infection of HepaRG cells in vitro. Additional study of these HBV-DMAb as a possible therapy or immunoprophylaxis for HBV infection is warranted.

Background and Objectives Communities of practice (CoPs) represent effective models to achieve quality outcomes in health care. We report the development and evaluation of a CoP to improve stem cell donor recruitment in Canada. Materials and Methods In September 2017, we invited national stakeholders in stem cell donor recruitment to participate in a Facebook group and regular e-meetings. E-meetings involved speakers and roundtable discussion on topics related to donor recruitment. The Facebook group facilitated sharing of resources. We evaluated stakeholder perspective of the CoP and the impact on recruitment outcomes. Results As of December 2020, the CoP included 382 members who published 243 posts to the Facebook group about patient/donor stories (40%), resources (27%), updates/questions (21%) and recruitment outcomes (12%). In January 2020, we surveyed 44 CoP participants; the majority felt that the Facebook group (86%) and e-meetings (59%) supported the community, and that the CoP fostered collaboration (82%), improved their donor recruitment knowledge (75%) and practice (77%) and improved their ability to recruit needed donors (64%). The launch of the CoP correlated with improved donor recruitment outcomes. In 2016-2017, CoP participants recruited 2918 registrants (46% male; 55.9% non-Caucasian) compared to 4531 registrants in 2018-2019 (52.9% male; 62.7% non-Caucasian). Members of the CoP developed innovative resources to support recruitment efforts and led national campaigns securing coverage in major media outlets. Conclusion We describe the first CoP in stem cell donor recruitment to be formally evaluated. The CoP model may be adopted by donor recruitment organisations, registries and blood banks worldwide to improve recruitment outcomes. HIGHLIGHTS: • A community of practice (CoP) in stem cell donor recruitment was valued by participants and supported efforts to improve recruitment outcomes. • The CoP model may be adopted by donor recruitment organizations, donor registries, and blood banks worldwide to improve recruitment outcomes.

Sialic acid-binding Immunoglobulin-like lectin-9 (Siglec-9) is a glyco-immune negative checkpoint expressed on several immune cells. Siglec-9 exerts its inhibitory effects by binding to sialoglycan ligands expressed on cancer cells, enabling them to evade immunosurveillance. We developed a panel of human anti-Siglec-9 hybridoma clones by immunizing mice with Siglec-9-encoding DNA and Siglec-9 protein. The lead antibodies, with high specificity and functionality against Siglec-9, were identified through screening of clones. The in vitro cytotoxicity assays showed that our lead antibody enhances anti-tumor immune activity. Further, in vivo testing utilizing ovarian cancer humanized mouse model showed a drastic reduction in tumor volume. Together, we developed novel antibodies that augment anti-tumor immunity through interference with Siglec-9-mediated immunosuppression.

Introduction: PICU hospitalization can have a profound impact on child survivors and their families. There is limited research on children's long-term recovery within the context of the family following critical illness. This study aimed to explore children's and parents' perceptions of long-term psychological and behavioral responses within the context of the family one year following PICU hospitalization.Materials and Methods: Caring Intensively is a mixed methods multi-site prospective cohort study that aims to examine children's psychological and behavioral responses over a 3-year period following PICU hospitalization. In this study, part of the qualitative arm of Caring Intensively, an interpretive descriptive design was used to explore children's recovery one year post-discharge. Purposive sampling was used to select 17 families, including 16 mothers, 6 fathers, and 9 children. Semi-structured, audio-recorded interviews were conducted. Data were analyzed iteratively using the constant comparison method.Results: Families described efforts to readapt to routine life and find a new normal following PICU hospitalization. Finding a New Normal consisted of four major themes: (1) Processing PICU Reminders and Memories, (2) Changing Perceptions of Health and Illness, (3) We Are Not the Same, and (4) Altered Relationships. Participants described significant emotional and behavioral changes during the year following discharge. The psychological impact of individual family members' experiences led to changes in their sense of self, which affected family dynamics. PICU memories and reminders impacted participants' perceptions of childhood health and illness and resulted in increased vigilance. Parents and siblings demonstrated increased concern for the child survivor's health, and the experience of long absences and new or altered caregiving roles resulted in changes in relationships and family dynamics.Conclusion: PICU hospitalization impacted the psychological well-being of all family members as they sought to re-establish a sense of normalcy one year following discharge. Parent and child experiences and responses were closely interconnected. Findings highlight the importance of increased follow-up care aimed at supporting the family's psychological recovery.

A new pandemic is ongoing in several parts of the world. The agent responsible is the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The symptoms associated with this virus are known as the coronavirus disease-2019 (COVID-19). In this review, we summarize the published data on virus specific antibodies in hospitalized patients with COVID-19 disease, patients recovered from the disease and the individuals who are asymptomatic with SARS-CoV-2 infections. The review highlights the following: i) an adjunct role of antibody tests in the diagnosis of COVID-19 in combination with RT-PCR; ii) status of antibodies from COVID-19 convalescent patients to select donors for plasma therapy; iii) the potential confounding effects of other coronaviruses, measles, mumps and rubella in antibody testing due to homology of certain viral genes; and iv) the role of antibody testing for conducting surveillance in populations, incidence estimation, contact tracing and epidemiologic studies., Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2); Diagnosis of COVID-19; Antibody tests; RT-PCR.

Simple Summary The FDA recently approved a fourth approach (in addition to surgery, radiation therapy, and chemotherapy) for treating glioblastoma; namely, tumor treating fields (TTFields), a form of alternating electric fields (AEF) therapy that is delivered to the tumor via electrodes placed on the scalp. Despite prolonging overall survival by 5 months when combined with standard chemotherapy in patients with newly diagnosed glioblastoma, the mechanisms of action of TTFields are not fully understood and primarily involve its interruption of mitotic spindle formation which impairs cancer cell division. A novel mechanism of action of TTFields at the cell membrane was recently identified, in which TTFields increases cancer cell membrane permeability. This finding could be exploited to enhance drug delivery to cancer cells. Here, we review the likely mechanisms by which TTFields permeabilize cancer cell membranes, i.e., voltage-gated ion channels, bioelectrorheological effects, and electroporation. Finally, we discuss an explanatory formulation that incorporates all three models. Abstract The biological impact of exogenous, alternating electric fields (AEFs) and direct-current electric fields has a long history of study, ranging from effects on embryonic development to influences on wound healing. In this article, we focus on the application of electric fields for the treatment of cancers. In particular, we outline the clinical impact of tumor treating fields (TTFields), a form of AEFs, on the treatment of cancers such as glioblastoma and mesothelioma. We provide an overview of the standard mechanism of action of TTFields, namely, the capability for AEFs (e.g., TTFields) to disrupt the formation and segregation of the mitotic spindle in actively dividing cells. Though this standard mechanism explains a large part of TTFields’ action, it is by no means complete. The standard theory does not account for exogenously applied AEFs’ influence directly upon DNA nor upon their capacity to alter the functionality and permeability of cancer cell membranes. This review summarizes the current literature to provide a more comprehensive understanding of AEFs’ actions on cell membranes. It gives an overview of three mechanistic models that may explain the more recent observations into AEFs’ effects: the voltage-gated ion channel, bioelectrorheological, and electroporation models. Inconsistencies were noted in both effective frequency range and field strength between TTFields versus all three proposed models. We addressed these discrepancies through theoretical investigations into the inhomogeneities of electric fields on cellular membranes as a function of disease state, external microenvironment, and tissue or cellular organization. Lastly, future experimental strategies to validate these findings are outlined. Clinical benefits are inevitably forthcoming.

Prostate cancer is a prevalent cancer in men and consists of both indolent and aggressive phenotypes. While active surveillance is recommended for the former, current treatments for the latter include surgery, radiation, chemo and hormonal therapy. It has been observed that the recurrence in the treated patients is high and results in castration resistant prostate cancer for which treatment options are limited. This scenario has prompted us to consider immunotherapy with synthetic DNA vaccines, as this approach can generate antigen-specific tumor-killing immune cells. Given the multifocal and heterogeneous nature of prostate cancer, we hypothesized that synthetic DNA vaccines targeting different prostate specific antigens are likely to induce broader and improved immunity who are at high risk as well as advanced clinical stage of prostate cancer, compared to a single antigen approach. Utilizing a bioinformatics approach, synthetic enhanced DNA vaccine (SEV) constructs were generated against STEAP1, PAP, PARM1, PSCA, PCTA and PSP94. Synthetic enhanced vaccines for prostate cancer antigens were shown to elicit antigen-specific immune responses in mice and the anti-tumor activity was evident in a prostate tumor challenge mouse model. These studies support further evaluation of the DNA tools for immunotherapy of prostate cancer and perhaps other cancers.

OBJECTIVES: Health care providers (HCPs) require ongoing support to meet the evolving care needs of children with medical complexity (CMC). Project Extension for Community Healthcare Outcomes (ECHO) is a model for delivering technology-enabled medical education and cultivating a community of practice. In this study, we focused on developing, implementing, and evaluating the first ECHO program dedicated to the care of CMC. Specific objectives were to evaluate the program feasibility (participation and acceptability) and impact on perceived HCP knowledge, self-efficacy, and clinical practice after 6 months. METHODS: A needs assessment was conducted to inform an interprofessional CMC curriculum. This curriculum was delivered through monthly virtual TeleECHO clinics (didactic and case-based learning) from January 2018 to 2020. The program was available at no cost to HCPs throughout Ontario. Surveys were distributed at baseline and 6 months to assess program acceptability, knowledge, self-efficacy, and practice impact by using 7-point Likert scales. Descriptive and inferential data analyses were conducted. RESULTS: Twenty-four clinics were completed with a mean of 19 ± 6 attendees. Acceptability scores (n = 27) ranged from 5.0 ± 1.1 to 6.4 ± 0.6. Participants reported an improvement in their knowledge and self-efficacy across all probed topics and skills (P values ranged from CONCLUSIONS: Project ECHO is a feasible and acceptable model for virtual education of interprofessional HCPs in managing CMC. This program has the potential to increase system capacity to provide quality care to CMC close to home.

Introduction/ Background Traditionally, MM harbouring t(11;14) is considered standard risk disease. In the era of novel therapies, however, pts with t(11;14) are reported to have inferior outcomes to other standard risk pts. Evidence of response to the BCL-2 inhibitor, Venetoclax (Ven), has further increased interest in understanding outcomes of t(11;14) pts. In this study, we aimed to describe the historical outcomes of t(11;14) MM and response to Ven in a real-world cohort of Australian pts. Methods This was a retrospective, multicentre study conducted by members of the Australasian Leukaemia and Lymphoma Group, Myeloma Working Party. Cases were identified by interrogation of cytogenetics/FISH database from 2010 to 2019 inclusive. Baseline patient and disease characteristics, treatment exposure and outcomes were extracted from hospital medical records. Descriptive statistics, and survival analyses were performed as appropriate. Results Seventy-four pts [median age 65 years (yrs), range (43-85)] were identified across seven centres. 43% pts had ISS Stage III MM with 88% harbouring additional cytogenetic abnormalities, incl. 13% with gain in 1q and 12% with del(17p). The majority (81%) of pts received proteasome inhibitor (PI)-based 1 st line therapy with 60% having an upfront autologous stem cell transplant (ASCT) and 54% having immunomodulatory drug (IMiD)-based maintenance therapy. Two patients received an allogeneic stem cell transplant after ASCT. The overall response rate (ORR) was 86% with 38% achieving very good partial response (VGPR) or better. The median progression free survival-1 (PFS-1) was 1.91 yrs (95% CI 1.73-2.56) [PI-based, n=60, PFS 1.84yrs (95% CI 1.61-2.41) vs IMiD-based, n=5, PFS 4.58yrs (95% CI 1.16-5.51), HR 0.68 p=0.45] The median overall survival (OS) was 5.35 yrs (95% CI 4.12-6.56). Second and third line therapy was predominantly IMiD-based (see Table 1) with recent introduction of anti-CD38 monoclonal antibodies (mAbs). Median PFS-2 was 0.77 yrs (95% CI 0.39-0.98) while median PFS-3 was 0.65 yrs (95% CI 0.34-1.16). Eleven pts (median 3 prior lines of therapy) were given Ven [Six pts in combination with PI, three with PI and mAbs and two with dexamethasone]. ORR to Ven was 55% with 45% achieving VGPR or better. Median PFS with Ven was 0.54 yrs (85% CI 0.05-2.17). Median PFS for patients with 1-4 lines (n=6) was 1.22 years and median PFS for patients with 5 lines or more (n=5) was 0.54 years, HR 0.56 (95% CI 0.12-2.5). Conclusion For pts harbouring t(11;14), the duration of response to PI-based 1 st line therapy is suboptimal even with the use of ASCT consolidation in the majority of patients. Despite multiple prior lines of therapy, Venetoclax shows promising results and every effort should be made for early identification of this cytogenetic lesion. Further studies are required to examine the impact of novel triplet and quadruplet combination therapy and use of venetoclax early in the disease course of this sub-group of patients. Figure 1 Figure 1. Disclosures Talaulikar: Takeda: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Roche: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Gibbs: Janssen, Celgene, Amgen, Takeda, BMS and Pfizer: Consultancy, Honoraria; AbbVie: Consultancy.

Prostate cancer (PCa) represents the most predominant cancer type among males with an estimated 191,930 cases diagnosed in 2020 with 33,330 deaths globally. Notably, different treatment modalities such as surgery, chemo, radiation and hormone therapy exhibited improved outcomes in early stage PCa patients; however, there exist high recurrence rate in the treated patients and leads to castration resistant prostate cancer, the treatment choices for which are highly restricted. This scenario has pressed us to consider synthetic DNA vaccine-based immunotherapy approach, with ability to induce antigen-specific tumor-killing immune cells. Considering the high heterogeneity of prostate cancer cells, we hypothesized that synthetic DNA vaccines targeting multiple prostate specific antigens would elicit improved immune responses in those who are at high risk as well as advanced stages of prostate cancer. Therefore, we generated synthetic enhanced DNA immunogens as DNA constructs (SEV) targeting STEAP1, PAP, PARM1, PSCA, PCTA and PSP94 through utilization of bioinformatics approaches. The SEVs for prostate cancer antigens elicited potent cellular immunity as well as polyfunctionality of antigen-specific T cells in mice. Further, they were capable of generating robust humoral immune responses to each antigen. The anti-tumor activities of the SEVs were studied in prostate tumor which showed that the induced immune responses delayed tumor progression and enhanced infiltration of anti-tumor CD8+ T cells in the tumor microenvironment in a mouse model challenge system. These data highlight further study of these novel immunogens as synthetic DNA immunogens for immunotherapy of PCa, and perhaps other human cancers. Citation Format: Devivasha Bordoloi, Peng Xiao, Hyeree Choi, Michelle Ho, Alfredo Perales-Puchalt, Makan Khoshnejad, J.Joseph Kim, Laurent Humeau, Alagarsamy Srinivasan, David B. Weiner, Kar Muthumani. Novel synthetic DNA vaccines in prostate cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1915.

Aim Pneumococcus is a common commensal and an important pathogen among children for which immunization is available. Some serotypes occasionally cause severe pneumococcal disease with high mortality and morbidity. We reviewed all pneumococcal serotypes and mortality/morbidity in a pediatric intensive care unit (PICU) following universal pneumococcal conjugate vaccine (PCV) immunization. Methods A 13-valent PCV was introduced in the universal immunization program in late 2011 in Hong Kong. We retrospectively reviewed all pneumococcal serotypes in the pre-(2007-11) and post-(2012-16) 13-valent PCV era. Results There were 29 (1.9%) PICU patients with pneumococcal isolation, of which 6 died (20% motality). Serogroups 6 and 19 predominated before and Serogroup 3 after 2012. In the post-13-valent PCV era, the prevalence of pneumococcus isolation in PICU was increased from 1 to 2% (p = 0.04); Serogroup 3 was the major serotype of morbidity, despite supposedly under vaccine coverage. The majority of pneumococcus were penicillin-sensitive (94%) in the post 13-valent PCV era. All pneumococcus specimens were sensitive to cefotaxime and vancomycin. Binary logistic regression showed that there were reductions in Serogroup 6 (odds ratio [OR], 0.050; 95% confidence interval [CI], 0.004-0.574; p = 0.016) and Serogroup 19 (odds ratio [OR], 0.105; 95% confidence interval [CI], 0.014-0.786; p = 0.028) but not mortality or morbidity for patients admitted after 2012. Conclusions SPD is associated with significant morbidity and mortality, despite treatment with systemic antibiotics and ICU support. The expanded coverage of 13-valent PCV results in the reduction of Serotypes 6 and 19 but not mortality/morbidity associated with SPD in the setting of a PICU.

363 Background: 3D printing is a growing tool in surgical education due to the ability to visualize organs, tissue, and masses from multiple angles before operating on a patient. Previous studies using highly detailed and expensive 3D models costing between $1,000-250 per model have been shown to enhance patient and trainee comprehension of tumor characteristics, goals of surgery, and planned surgical procedure for partial nephrectomies. In our study we aim to use simpler and less expensive models in a greater range of patients receiving partial nephrectomies to determine the use of 3D models in patient, resident, and fellow education. Methods: 3D models of the effected kidney, mass, renal artery, and renal vein were created using preoperative imaging of undergoing partial nephrectomies at Thomas Jefferson University Hospital (TJUH) costing $35 per model. Residents and fellows filled out 3 surveys assessing their surgical plan and their confidence in the chosen plan at 3 time points: 1) Before seeing the model, 2) After seeing the model before surgery, and 3) After surgery. Ten patients filled out 2 surveys about their understanding of the kidney, their disease, the surgery they will undergo, and the risks involved with surgery before and after seeing the model. Results: Based on surveys to assess for surgical plan and confidence given to resident and fellow surgeons before and after seeing the 3D model, confidence significantly increased. Surveys given after surgery assessing anatomic and surgical comprehension found that resident and fellow surgeons rated the helpfulness of the models on their anatomical comprehension 7.6 out of 10 and the help of the models on their surgical confidence 7 out of 10. Patient understanding of their kidney, disease, and surgery significantly increased after seeing the 3D model, but the risks associated with surgery did not significantly increase. The extent that the model helped the patients learn about the kidney, their disease, the surgery, and the risks related to surgery were rated an average of 8.33, 9.67, 9.5, and 8.83 out of 10, respectively. Conclusions: Patient-specific 3D models for partial nephrectomies increase resident and fellow confidence in surgical approach and helped patients learn about their disease and feel comfortable going into surgery. Thus, it is important to continue to explore 3D models as an educational tool for both trainees and patients and potentially include 3D models as part of the standard of care. Further research could continue to explore the utility of 3D models as a pre-operative educational tool for both patients and trainees in other surgical fields.

This study explores whether it is possible to reconstruct the frequency of extreme precipitation occurrence across the contiguous United States (CONUS) using the Living Blended Drought Atlas (LBDA), a 500 year paleoclimate reconstruction of the summer (June–August) Palmer Drought Severity Index (PDSI). We first identify regions of the country where the LBDA may reflect the occurrence of extremes based on their seasonality and contribution to total annual moisture delivery. Correlation measures are used to assess the relationship between the frequencies of extreme precipitation occurrence and both the instrumental monthly PDSI and the annual LBDA-estimated PDSI. Extreme precipitation is found to account for a large portion of total precipitation west of the Mississippi River and clusters in particular seasons (winter and summer), supporting a strong relationship with the LBDA without much information loss from the instrumental PDSI data. Dimension reduction techniques are used to explore the joint spatiotemporal structure of extreme precipitation occurrence and LBDA across the country. The primary modes of variability of the LBDA and extreme precipitation occurrence relate remarkably well for a region centered over the southwest that exhibits an ENSO-like time-frequency structure. Generalized linear models (GLMs) are used to demonstrate the feasibility of reconstructing the annual extreme precipitation frequency over the 500 year prehistoric record at two sites in the southwest and Southern Plains. GLM-based reconstructions show a high degree of structured variability in the likelihood of extreme precipitation occurrences over the prehistoric record.

Sickle cell disease (SCD) is characterized by a single point mutation in the seventh codon of the β-globin gene. Site-specific correction of the sickle mutation in hematopoietic stem cells would allow for permanent production of normal red blood cells. Using zinc-finger nucleases (ZFNs) designed to flank the sickle mutation, we demonstrate efficient targeted cleavage at the β-globin locus with minimal off-target modification. By co-delivering a homologous donor template (either an integrase-defective lentiviral vector or a DNA oligonucleotide), high levels of gene modification were achieved in CD34(+) hematopoietic stem and progenitor cells. Modified cells maintained their ability to engraft NOD/SCID/IL2rγ(null) mice and to produce cells from multiple lineages, although with a reduction in the modification levels relative to the in vitro samples. Importantly, ZFN-driven gene correction in CD34(+) cells from the bone marrow of patients with SCD resulted in the production of wild-type hemoglobin tetramers.

Integrase-defective lentiviral vectors (IDLVs) have been of limited success in the delivery of zinc finger nucleases (ZFNs) to human cells, due to low expression. A reason for reduced gene expression has been proposed to involve the epigenetic silencing of vector genomes, carried out primarily by histone deacetylases (HDACs). In this study, we tested valproic acid (VPA), a known HDAC inhibitor (HDACi), for its ability to increase transgene expression from IDLVs, especially in the context of ZFN delivery. Using ZFNs targeting the human adenosine deaminase (ADA) gene in K562 cells, we demonstrated that treatment with VPA enhanced ZFN expression by up to 3-fold, resulting in improved allelic disruption at the ADA locus. Furthermore, three other U.S. Food and Drug Administration-approved HDACis (vorinostat, givinostat, and trichostatin-A) exhibited a similar effect on the activity of ZFN-IDLVs in K562 cells. In primary human CD34(+) cells, VPA- and vorinostat-treated cells showed higher levels of expression of both green fluorescent protein (GFP) as well as ZFNs from IDLVs. A major mechanism for the effects of HDAC inhibitors on improving expression was from their modulation of the cell cycle, and the influence of heterochromatinization was determined to be a lesser contributing factor.

Background Blunt thoracic aortic injury (BTAI) and traumatic brain injury (TBI) are the leading causes of death after blunt trauma, and TBI is common among patients with BTAI. Although aspects of aortic management, such as repair timing and procedural anticoagulation therapy, may complicate TBI, the optimal management of these patients is undefined. Methods Adults with BTAI and moderate to severe TBI admitted to a level I trauma center over 12 years were retrospectively analyzed; patients presenting in extremis were excluded. The primary outcome was neurologic progression within 48 hours of aortic repair. Patients undergoing nonoperative aortic management served as controls for baseline TBI progression. Secondary outcomes were aortic morbidity and mortality and overall inpatient survival. Results Of 309 patients with BTAI, 138 had concurrent TBI, and 75 were included for analysis. Twenty-two (29%) were treated nonoperatively, 29 (39%) had early aortic repair (17 open, 12 endovascular), and 24 (32%) had delayed repair (3 open, 21 endovascular). The severity of TBI was similar between groups. Early aortic repair within 24 hours of admission was independently associated with worsening TBI, regardless of repair modality or anticoagulation use. In contrast, patients undergoing delayed repair had no perioperative neurologic progression despite procedural anticoagulation therapy. Early aortic repair was also associated with increased aortic morbidity and mortality. Conclusions For patients with BTAI and TBI, early aortic intervention is associated with progressive TBI regardless of repair modality, as well as increased aortic morbidity and mortality. Patients not requiring emergent intervention can undergo delayed repair with full anticoagulation therapy.

Mayaro virus (MAYV) of the genus alphavirus is a mosquito-transmitted emerging infectious disease that causes an acute febrile illness, rash, headaches, and nausea that may turn into incapacitating, persistent arthralgias in some victims. Since its discovery in Trinidad in 1954, cases of MAYV infection have largely been confined there and to the northern countries of South America, but recently, MAYV cases have been reported in some island nations in the Caribbean Sea. Accompanying these reports is evidence that new vectors, including Aedes spp. mosquitos, recently implicated in the global spread of Zika and chikungunya viruses, are competent for MAYV transmission, which, if true, could facilitate the spread of MAYV beyond its current range. Despite its status as an emerging virus, there are no licensed vaccines to prevent MAYV infection nor therapeutics to treat it. Here, we describe the development and testing of a novel DNA vaccine, scMAYV-E, that encodes a synthetically-designed consensus MAYV envelope sequence. In vivo electroporation-enhanced immunization of mice with this vaccine induced potent humoral responses including neutralizing antibodies as well as robust T-cell responses to multiple epitopes in the MAYV envelope. Importantly, these scMAYV-E-induced immune responses protected susceptible mice from morbidity and mortality following a MAYV challenge., Author summary Mayaro virus (MAYV) is a mosquito-transmitted virus that causes fever, headache, chills, nausea and joint pain that can last for months after infection. The rising number of cases, due to increased mosquito circulation, and the threat of an epidemic emphasize its importance as an emerging virus, but there are no licensed vaccines to prevent Mayaro infection nor therapeutics to treat it. In this study, we gathered fundamental knowledge on how the immune system responds to MAYV infection, and we evaluated the efficacy of a novel, synthetic DNA envelope vaccine (scMAYV-E) in mice. Analysis of immune responses in mice demonstrated that this vaccine induces potent T cell immunity and antibodies. Mice who receive the vaccine and then are challenged with live MAYV are protected against Mayaro disease. This data provides evidence that the DNA-based MAYV vaccine may be able to prevent Mayaro disease. Thus, the scMAYV-E vaccine is a promising step forward for MAYV vaccine development. Future testing will evaluate whether this vaccine is a viable means to halt the spread of MAYV and protect individuals from Mayaro disease.

Dermoid cysts are benign developmental anomalies. They are postulated to originate from the congenital inclusion of germ layers in the deeper tissues along the lines of embryonic fusion (New and Erich Surg, Gynecol Obstet 65:48–55, 1937). Dermoid cysts can be divided into three types according to their histological characteristics, namely epidermoid, dermoid, and teratoid (Tuffin and Theaker, Int J Oral Maxillofac Surg 20:275, 1991). The majority of dermoid cysts arise in the ovaries. Those occurring in the cervicofacial region are uncommon, accounting for about 7% of all dermoids (De Souza et al., Plast Reconstr Surg 112(7):1972, 2003). Dermoid cysts around the auricular region are rare. To the best of our knowledge, there have been only four cases of post-auricular dermoid cyst reported in literature (Bauer et al., Arch Dermatol 130:913, 1994; De Souza et al., Plast Reconstr Surg 112(7):1972, 2003; Meagher and Morrison, Br J Plast Surg 54:336, 2001; Samper, Plast Reconstr Surg 106:947, 2000. We hereby report the fifth case of this rare condition.

Polysomnograms (PSGs) are not used in most spine centers for children with EOS. There are no standards for PSG referrals, and the yield from PSGs is unknown. We describe referrals for PSGs in 96 children > 5 years old with EOS, their lung functions, types of EOS, and frequency of abnormal PSGs.

Introduction Reconstruction of the weight bearing, thick and durable heel, in soft tissue injuries of the foot remains a difficult and challenging problem. The thick glabrous epidermis and dermis, and the fibrous septae of the subcutaneous layer provide unique properties for withstanding pressure and shock associated with gait.

Objective Clinical practice guideline (CPG) quality assessment is important before applying their recommendations. Determining whether recommendation strength is consistent with supporting quality of evidence is also essential. We aimed to determine quality of critical care pharmacotherapy CPGs and to assess whether high quality evidence supports strong pharmacotherapy recommendations.

Purpose Society relies on family caregivers of children who depend on medical technology (e.g. mechanical ventilation), to provide highly skilled and vigilant care in their homes 24 hours per day. Sleep disturbance is among the most common complaints of these caregivers. The purpose of this review is to systematically examine studies reporting on sleep outcomes in family caregivers of technology dependent children. Methods All relevant databases were systematically searched: MEDLINE, EMBASE, PsycINFO and CINAHL. Given the heterogeneity of the studies, a qualitative analysis was completed and thus results of this review are presented as a narrative. Results Thirteen studies were retrieved that met eligibility criteria for inclusion. All of the studies reported on family caregivers of children with medical complexity living at home. Moreover, all of the studies relied entirely on self-report, not objective sleep measures. No intervention studies were found. Sleep disturbance was found to be common (51-100%) along with caregiver reports of poor sleep quality. Sleep quantity was seldom measured, but was found in the few studies that did, to be approximately 6 hours, or less than recommendations for optimal health and daytime function. Multiple caregiver, child and environmental factors were also identified that may negatively influence caregiver sleep, health and daytime function. Conclusion Findings of this review suggest that family caregivers of children with medical complexity who depend on medical technology achieve poor sleep quality and quantity that may place them at risk of the negative consequences of sleep deprivation. Recommendations for practice include that health care providers routinely assess for sleep disturbance in this vulnerable population. The review also suggests that studies using objective sleep measurement are needed to more fully characterize sleep and inform the development of targeted interventions to promote sleep in family caregivers of technology dependent children.

Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen receptors generates a continual supply of effector T cells, potentially providing superior anticancer efficacy compared with the infusion of terminally differentiated T cells. Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK. Ex vivo analysis of T cells showed antigen- and HLA-restricted effector function against melanoma. Robust engraftment of gene-modified human cells was demonstrated with PET reporter imaging in hematopoietic niches such as femurs, humeri, vertebrae, and the thymus. Safety was demonstrated by the in vivo ablation of PET signal, NY-ESO-1-TCR–bearing cells, and integrated lentiviral vector genomes upon treatment with ganciclovir, but not with vehicle control. Our study provides support for the efficacy and safety of gene-modified HSCs as a therapeutic modality for engineered cancer immunotherapy. Cancer Res; 74(18); 5173–83. ©2014 AACR.

Purpose: Despite the growing evidence that ecological factors contribute to substance use, the relationship of ecological factors and illicit drugs such as marijuana use is not well understood, particularly among adolescents in Latin America. Guided by social disorganization and social stress theories, we prospectively examined the association of disaggregated neighborhood characteristics with marijuana use among adolescents in Santiago, Chile, and tested if these relationships varied by sex. Methods: Data for this study are from 725 community-dwelling adolescents participating in the Santiago Longitudinal Study, a study of substance using behaviors among urban adolescents in Santiago, Chile. Adolescents completed a two-hour interviewer administered questionnaire with questions about drug use and factors related to drug using behaviors. Results: As the neighborhood levels of drug availability at baseline increased, but not crime or noxious environment, adolescents had higher odds of occasions of marijuana use at follow up, approximately 2 years later (odds ratio [OR] = 1.39, 95% CI = 1.16–1.66), even after controlling for the study’s covariates. No interactions by sex were significant. Discussion: The findings suggest that “poverty”, “crime”, and “drug problems” may not be synonyms and thus can be understood discretely. As Latin American countries re-examine their drug policies, especially those concerning decriminalizing marijuana use, the findings suggest that attempts to reduce adolescent marijuana use in disadvantaged neighborhoods may do best if efforts are concentrated on specific features of the “substance abuse environment”.

Penetrating injuries to the aorta usually result in immediate life-threatening hemorrhage. Because these lesions are typically either fatal or identified and controlled surgically, chronic pseudoaneurysms after penetrating aortic trauma are rare. Most of these patients present with rupture or local complications, and management before the endovascular era has historically been open repair. As such, there are limited data to guide the modern management of an asymptomatic, posttraumatic aortic pseudoaneurysm. Here, we describe a 54-year-old man who was diagnosed with an incidental, supraceliac aortic pseudoaneurysm 14 years after an abdominal stab wound. He underwent successful and uncomplicated endovascular repair.

Secondary corrective osteotomy of malunited craniofacial fractures can be a challenging proposition. The exposure, extrusion, and palpability of the titanium implants used become a genuine concern especially in areas of relatively thin skin, such as the periorbital region. Restoring a satisfactory contour to the midface is another major task for the plastic surgeon. Bone cement used to reconstruct craniofacial defects has existed for many years. However, most applications have been as a substitute for autogenous bone grafts for defects less than 25 cm2. In this article, we present two cases of malunited facial fractures that underwent corrective osteotomy, during which we felt that despite the conventional osteotomy and reduction techniques, there was still either a small remnant step deformity or suboptimal contour smoothness due to prominence of the implants used. We thus used bone cement as a resurfacing medium over titanium implants to restore good malar contour and reduce the palpability and exposure rate of the titanium implants. We report good patient satisfaction with contour correction with no increase in wound infection rates or any delay in wound healing. There was initial chemosis associated with the use of the bone cement, which resolved in both patients within 3 to 4 weeks. Postoperative computed tomography showed some degree of osteointegration but no fraction of the bone cement. Calcium phosphate bone cement thus presents an attractive adjunctive method for midfacial contour resurfacing, when used in conjunction with conventional osteotomy procedures and as an onlay over prominent titanium implants.

The majority of patients with acute myeloid leukemia (AML) will require second-line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. The reported efficacy of second-line regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review of 77 patients receiving therapy between 2001 and 2008 with relapsed, 42, and refractory, 35, AML was performed to determine overall response rate and survival following mitoxantrone (8 mg/m(2)/day), etoposide (100 mg/m(2)/day), and cytarabine (1,000 mg/m(2)/day) chemotherapy administered over 5 days. Among 77 patients (median age of 54 years and 64% intermediate risk karyotype) with median follow-up of 153 days, 18% achieved a complete response and 8% a morphologic leukemia-free state. Fifty-seven (74%) experienced treatment failure, 10 of whom achieved a remission after additional therapy. Median overall survival (OS) was 6.8 months. Among patients achieving a response, 50% received consolidation with allogeneic HCT, autologous HCT (5%), or consolidation chemotherapy alone (45%). A nonsignificant trend in overall response (50%, 27%, and 23.8%) and median OS (8.3, 6.8, and 4.7 months) was observed by cytogenetic stratification into favorable, intermediate, and unfavorable risk. Patients with refractory versus relapsed disease had similar overall responses (20% and 31%, P = 0.41) and median OS (5.3 and 7.6 months, P = 0.36). Despite risk stratification by the European Prognostic Index, our series demonstrates inferior rates of response and survival, illustrating the limited activity of this regimen in our cohort.