Urinalysis in Suspected Child Abuse Evaluation in the Emergency Department.

BACKGROUND: Intra-abdominal injury (IAI) is the second leading cause of mortality in abused children. It is challenging to identify in young patients due to their limited verbal skills, delayed symptoms, less muscular abdominal wall, and limited bruising. METHODS: We conducted a retrospective cohort study of children aged 0 to 12 months who were evaluated in the emergency department for suspected child abuse with a skeletal survey and urinalysis between January 1, 2015, and December 31, 2017. Our primary objective was to identify the proportion of IAI cases identified by urinalysis alone (>10 RBC/HPF) and not by examination findings or other laboratory results. A secondary objective was to quantify potential delay in disposition while waiting for urinalysis results, calculated as the length of time between receiving skeletal survey and laboratory results and receiving urinalysis results. RESULTS: Six hundred thirteen subjects met our inclusion criteria; two subjects had hematuria, one of whom had a urinary tract infection. The other was determined to have blood from a catheterized urine specimen. One subject was found to have an IAI. We further found that urinalysis was delayed for 78% of subjects and took a median of 93 [interquartile range, 46-153] minutes longer than imaging and/or laboratories. CONCLUSIONS: No subjects were diagnosed with abdominal trauma based on urinalysis during evaluation in the emergency department who would not have been identified by other standard testing. In addition, patients' disposition was delayed while waiting for urinalysis.

Universal Suicidality Screening in a Pediatric Emergency Department to Improve Mental Health Safety Risk.

INTRODUCTION: Suicide is the second leading cause of death for youth 12 to 18 years of age. Suicidal ideation can be predictive of suicide attempt, so screening for suicidal ideation by emergency nurses can help identify those at risk and facilitate timely intervention. This study evaluates the use of a universal suicide screening using the Patient Safety Screener 3 and the Columbia Suicide Severity Rating Scale to identify youth ages 12 to 18 years experiencing suicide risk and assess factors predictive of suicide risk level. METHODS: We conducted a retrospective cohort study using data from patients presenting to the emergency department at an acute care hospital that uses a universal screening program for suicide risk. We determined the frequency of positive screens and performed multivariate analyses to identify predictive factors of scoring high on the Columbia Suicide Severity Rating Scale. RESULTS: Notably, 9.1% of patients were experiencing some level of suicide risk; 10% of those with positive scores had no mental health history and were not presenting for a mental health reason. After controlling for other independent variables, insurance status, mental health presentation, and known mental health history were significantly associated with Columbia Suicide Severity Rating Scale score. DISCUSSION: Universal screening for suicide risk in pediatric emergency departments by nurses is critical for all patients older than 12 years, given that we identified patients at risk of suicide who presented for non-mental health reasons. These patients may not have been identified or referred to treatment if they were not screened for suicidality increasing risk of future suicide attempt.

A qualitative content analysis study using electronic medical records to understand youth suicide attempts.

PROBLEM: Suicide is the second leading cause of death for people aged 10-24 in the United States. The purpose of this study was to examine circumstances youth self-reported when presenting to hospitals due to a suicide attempt. METHODS: A qualitative content analysis of clinicians' notes identified major themes of patients' lived experiences and circumstances leading up to suicide attempt. FINDINGS: A total of 231 unique patient encounters were included in this study. Mean age of participants was 14.71 (SD = 2.04) the majority being female (75%) and Non-Hispanic White (48%). Four themes characterized contributing factors: (1) trauma, (2) relationship quality, (3) risky behaviors, and (4) personal emotions and symptoms. CONCLUSIONS: Findings suggest commonalities among these youths' circumstances and experiences which may have precipitated a suicide attempt. These data will aid nurses and other health-care providers in understanding the complex, and often traumatic, histories of youth who attempt suicide. Improved knowledge in this area has the potential to direct improved screening, treatment, and referral protocols as well as suggest areas to focus prevention efforts.

DNA and modified vaccinia Ankara prime-boost vaccination generates strong CD8+ T cell responses against minor histocompatibility antigen HA-1.

Allogeneic immune responses underlie the graft-versus-leukaemia effect of stem cell transplantation, but disease relapse occurs in many patients. Minor histocompatibility antigen (mHAg) peptides mediate alloreactive T cell responses and induce graft-versus-leukaemia responses when expressed on patient haematopoietic tissue. We vaccinated nine HA-1-negative donors against HA-1 with a 'prime-boost' protocol of either two or three DNA 'priming' vaccinations prior to 'boost' with modified vaccinia Ankara (MVA). HA-1-specific CD8+ T cell responses were observed in seven donors with magnitude up to 1·5% of total CD8+ T cell repertoire. HA-1-specific responses peaked two weeks post-MVA challenge and were measurable in most donors after 12 months. HA-1-specific T cells demonstrated strong cytotoxic activity and lysed target cells with endogenous HA-1 protein expression. The pattern of T cell receptor (TCR) usage by HA-1-specific T cells revealed strong conservation of T cell receptor beta variable 7-9 (TRBV7-9) usage between donors. These findings describe one of the strongest primary peptide-specific CD8+ T cell responses yet recorded to a DNA-MVA prime-boost regimen and this may reflect the strong immunogenicity of mHAg peptides. Prime-boost vaccination in donors or patients may prove of substantial benefit in boosting graft-versus-leukaemia responses.

Accuracy of ICD-10-CM coding for physical child abuse in a paediatric level I trauma centre.

This retrospective study examined the accuracy of the International Classification of Diseases, Clinical Modification (ICD-10-CM) coding for physical child abuse among patients less than 18 years of age who were evaluated due to concern for physical abuse by a multidisciplinary child protection team (MCPT) during 2016-2017 (N=312) in a paediatric level I trauma centre. Sensitivity, specificity, predictive values and diagnostic OR for ICD-10-CM coding were calculated and stratified by admission status, using as a reference standard the abuse determination of the MCPT recorded in a hospital registry. Among inpatients, child physical abuse coding sensitivity was 55.6% (95% CI 41.4% to 69.1%) and specificity was 78.6% (95% CI 59.0% to 91.7%), with diagnostic OR of 4.58 (95% CI 1.64 to 12.70). Among outpatients, sensitivity was 22.2% (95% CI 15.5% to 30.2%) and specificity was 86.3% (95% CI 77.7% to 92.5%), with diagnostic OR of 1.80 (95% CI 0.89 to 3.64). Use of ICD-10-CM coded data sets alone for surveillance may significantly underestimate the occurrence of physical child abuse.

Predictors of Traumatic Suicide Attempts in Youth Presenting to Hospitals with Level I Trauma Centers.

BACKGROUND: Limited research exists examining the predictors of suicide attempts by mechanism. OBJECTIVE: The purpose of this study was to examine predictors of traumatic suicide attempts in youth. METHODS: Data came from patients 5-18 years of age presenting because of a suicide attempt at 2 hospitals in Central Texas with level I trauma centers. Univariate logistic regression examined the association between traumatic suicide attempts and variables describing the patient's demographic, mental health, and social information. We used the Mann-Whitney U test to examine the association between traumatic suicide attempts and the continuous variable of age. RESULTS: Of 231 patients included in this study, most were female (75.8%), non-Hispanic white (48.1%), and had a median age of 15.0 years (interquartile range 14-16). Compared with patients presenting because of an intentional overdose, patients presenting because of traumatic suicide attempts were associated with a reported criminal history (odds ratio [OR] 14.50 [95% confidence interval {CI} 3.84-54.82]), reported Child Protective Services history (OR 3.26 [95% CI 0.99-10.77]), being publicly insured or uninsured (OR 1.80 [95% CI 1.02-3.19]), male (OR 2.37 [95% CI 1.28-4.38]), and identifying as Hispanic (OR 2.01 [95% CI 1.10-3.68). CONCLUSIONS: Our findings inform targeted preventative resources and education efforts to populations of greatest need.

Evaluation of an After-Hours Child Passenger Safety Resource Guide.

Motor vehicle crashes are a leading cause of unintentional injury deaths for children in the United States. Child safety seats are effective in reducing the rate and severity of injury for children. Families seen in an emergency department (ED) outside of injury prevention (IP) operational hours may not have the same opportunity to obtain a child safety seat due to the unavailability of IP resources. This study evaluated the effectiveness of a resource guide that assists the ED staff to screen and provide the appropriate child safety seat. Two retrospective cohort analyses were conducted to assess the following: (1) patients seen in the ED who were eligible to be screened through the resource guide; and (2) patients who were screened and received a restraint system through the resource guide. Records for both cohorts were reviewed from May 1, 2015, to February 29, 2016. Descriptive statistics were used to describe each cohort. In Cohort 1, 10.6% of the 113 patients meeting criteria were screened for a restraint system. In Cohort 2, 20 patients received a restraint system through the resource guide and 90% of these received the appropriate restraint system for their age and weight. Our results demonstrate the need for an algorithm to increase consistency of the resource guide's utilization. Algorithm development to identify screening candidates, further refinement of the guide's restraint identification process, and staff training may improve this tool to ensure that all patients, despite the availability of IP staff, are screened for the appropriate child safety seat.

Youth Suicide Attempt Nomenclature Used in Two Central Texas Hospitals.

BACKGROUND: Surveillance systems capturing instances of self-directed violence (SDV) continue to lack uniform nomenclature and classification methodology. AIMS: To apply and compare two retrospective surveillance approaches to youth experiencing SDV presenting to two urban hospitals with Level I Trauma Centers. METHOD: Two suicide attempt surveillance methods where retrospectively applied to our SDV cohort: (a) a rigorous method facilitated by medical record review and application of standardized classification; and (b) a common surveillance method conducted by systematic queries of suicide attempt key terms and diagnosis codes among hospital databases. RESULTS: Rigorous surveillance identified 249 patients attempting suicide. The common method's querying suicide attempt in the chief complaint field had a high positive predictive value and specificity; however, sensitivity was low. LIMITATIONS: Authors were unable to determine whether all SDV encounters during the study timeframe were identified for initial screening owing to the hospital's lack of a uniform nomenclature or classification system. CONCLUSION: Results showed underreporting of suicide attempt cases, inadequate sensitivity and specificity in common surveillance methods, and skewed demographic representation compared with the rigorous surveillance method. This study elucidates the negative impact of inconsistent SDV nomenclature including impeding effective patient identification, treatment, surveillance, and generalizable research.

Risk Factors Associated With Emergency Department Return Visits Following Trauma System Discharge.

OBJECTIVES: Little evidence exists in the pediatric trauma literature regarding what factors are associated with re-presentation to the hospital for patients discharged from the emergency department (ED). METHODS: This was a retrospective cohort study of trauma system activations at a pediatric trauma center from June 30, 2007, through June 30, 2013, who were subsequently discharged from the ED or after a brief inpatient stay. Returns within 30 days were reviewed. χ, Student t test, and univariate logistical regression were used to compare predictive factors for those returning and not. RESULTS: One thousand eight hundred sixty-three patient encounters were included in the cohort. Seventy-two patients (3.9%) had at least 1 return visit that was related to the original trauma activation. Age, sex, language, race/ethnicity, ED length of stay, arrival mode, level of trauma activation, and transfer from an outside hospital did not vary significantly between the groups. Patients with public insurance were almost 2 times more likely to return compared with those with private insurance (odds ratio, 1.92; 95% confidence interval, 1.11-3.35). Income by zip code was associated with the risk of a return visit, with patients in neighborhoods at less than the 50th percentile income twice as likely to return to the ED (odds ratio, 2.15; 95% confidence interval, 1.30-3.54). CONCLUSIONS: Patients with public insurance and those from low-income neighborhoods were significantly more likely to return to the ED after trauma system activation. These data can be used to target interventions to decrease returns in high-risk trauma patients.

'We don't have anyone with dementia here': a case for better intersectoral collaboration for remote Indigenous clients with dementia.

OBJECTIVE: This paper reports on findings related to intersectoral collaboration stemming from an evaluation of a dementia awareness resource for use in remote Aboriginal communities*. The resource includes a DVD in English and three (3) Aboriginal languages of the Northern Territory. DESIGN: A qualitative evaluation was conducted in four Northern Territory Aboriginal communities/organisations where the resource had been implemented by external dementia educators. The method included five focus groups with Indigenous aged care workers, community members and aged care service users (n = 26), individual interviews with health care professionals and service coordinators (n = 5), and observation. Data were analysed thematically. RESULTS: Specific findings relating to intersectoral collaboration as a key enabling factor of effective dementia awareness and care are discussed in this paper. In addition to context variables such as understaffing and under-resourcing, there might be a lack of knowledge or interest on the part of some health practitioners concerning clients with dementia within remote communities. CONCLUSION: Dementia awareness in remote communities needs to be tackled from a 'whole system' perspective and not be the exclusive domain of the aged care services. Strategies that increase the critical mass of informed caregivers as well as health professionals will contribute to better services.

Fetal-specific CD8+ cytotoxic T cell responses develop during normal human pregnancy and exhibit broad functional capacity.

Tolerance of the semiallogeneic fetus presents a significant challenge to the maternal immune system during human pregnancy. T cells with specificity for fetal epitopes have been detected in women with a history of previous pregnancy, but it has been thought that such fetal-specific cells were generally deleted during pregnancy as a mechanism to maintain maternal tolerance of the fetus. We used MHC-peptide dextramer multimers containing an immunodominant peptide derived from HY to identify fetal-specific T cells in women who were pregnant with a male fetus. Fetal-specific CD8(+) T lymphocytes were observed in half of all pregnancies and often became detectable from the first trimester. The fetal-specific immune response increased during pregnancy and persisted in the postnatal period. Fetal-specific cells demonstrated an effector memory phenotype and were broadly functional. They retained their ability to proliferate, secrete IFN-γ, and lyse target cells following recognition of naturally processed peptide on male cells. These data show that the development of a fetal-specific adaptive cellular immune response is a normal consequence of human pregnancy and that unlike reports from some murine models, fetal-specific T cells are not deleted during human pregnancy. This has broad implications for study of the natural physiology of pregnancy and for the understanding of pregnancy-related complications.

CD8(+) T-cell immunity against cancer-testis antigens develops following allogeneic stem cell transplantation and reveals a potential mechanism for the graft-versus-leukemia effect.

BACKGROUND: Allogeneic stem cell transplantation is associated with a powerful 'graft-versus-leukemia' effect that is generally considered to result from an alloreactive T-cell immune response. However, disease remission can also be observed after syngeneic transplantation and we investigated whether a T-cell immune response to cancer-testis antigens can be detected in patients in the post-transplant period. DESIGN AND METHODS: The T-cell immune response against cancer-testis antigens was studied in a cohort of 41 patients who underwent allogeneic stem cell transplantation for the management of acute myeloid leukemia or multiple myeloma. The cytokine secretion assay was combined with magnetic selection to allow detection of an interferon-gamma-secreting T-cell response to a panel of cancer-testis antigen peptides. RESULTS: A cancer-testis antigen-specific CD8(+) T-cell immune response was observed in the peripheral blood of five patients with an average magnitude of 0.045% of the CD8(+) T-cell repertoire. Four of these patients had undergone reduced intensity conditioning transplantation with alemtuzumab for the treatment of acute myeloid leukemia and three remain in long-term remission. T-cell immunity was focused against peptides derived from MAGE proteins and was markedly increased within the bone marrow. CONCLUSIONS: Functional cancer-testis antigen-specific CD8(+) T-cell immune responses develop in the early period following reduced intensity allogeneic stem cell transplantation and are preferentially localized to bone marrow. These immune responses are likely to contribute to the cellular basis of the graft-versus-leukemia effect.

Patients with Wegener's granulomatosis demonstrate a relative deficiency and functional impairment of T-regulatory cells.

An increased proportion of CD4(+) CD25(+) T cells has been reported in Wegener's granulomatosis (WG) and may represent an accumulation of regulatory T cells (Treg). CD25 is also expressed on recently activated effector T cells. We have determined the relative proportion of these subsets in a large patient cohort. The fraction of Treg in peripheral blood mononuclear cells from patients and healthy controls was determined by assessment of Foxp3 expression on CD4(+) CD25(+) T cells. The functional activity of Treg was determined by their ability to suppress proliferation and cytokine production in response to proteinase-3. Although WG patients demonstrated an increased fraction of CD4(+) CD25(+) T cells, the percentage of Foxp3-positive cells was decreased. In addition, the percentage of Treg was inversely related to the rate of disease relapse. CD4(+) CD25(hi) T cells were able to suppress T-cell proliferation to proteinase-3 in healthy controls and anti-neutrophil cytoplasm antibody (ANCA)- negative patients (at time of sampling) but not in ANCA-positive patients. In patients with active disease, an increased proportion of CD4(+) Foxp3(+) cells was associated with a more rapid disease remission. Patients with WG demonstrate abnormalities in the number and function of Treg and this is most pronounced in those with most active disease. This information is of value in understanding the pathogenesis and potential treatment of this disease.

Fetal microchimerism: the cellular and immunological legacy of pregnancy.

During pregnancy there is transplacental traffic of fetal cells into the maternal circulation. Remarkably, cells of fetal origin can then persist for decades in the mother and are detectable in the circulation and in a wide range of tissues. Maternal CD8 T cell responses directed against fetal antigens can also be detected following pregnancy. However, the impact that the persistence of allogenic cells of fetal origin and the maternal immune response towards them has on the mother's health remains unclear and is the subject of considerable investigation. The potentially harmful effects of fetal microchimerism include an association with autoimmune disease and recurrent miscarriage. Beneficial effects that have been explored include the contribution of persistent fetal cells to maternal tissue repair. A link between fetal microchimerism and cancer has also been proposed, with some results supporting a protective role and others, conversely, suggesting a role in tumour development. The phenomenon of fetal microchimerism thus provokes many questions and promises to offer further insights not only into the biology of pregnancy but fields such as autoimmunity, transplantation biology and oncology.

Secondary anchor polymorphism in the HA-1 minor histocompatibility antigen critically affects MHC stability and TCR recognition.

T cell recognition of minor histocompatibility antigens (mHags) underlies allogeneic immune responses that mediate graft-versus-host disease and the graft-versus-leukemia effect following stem cell transplantation. Many mHags derive from single amino acid polymorphisms in MHC-restricted epitopes, but our understanding of the molecular mechanisms governing mHag immunogenicity and recognition is incomplete. Here we examined antigenic presentation and T-cell recognition of HA-1, a prototypic autosomal mHag derived from single nucleotide dimorphism (HA-1(H) versus HA-1(R)) in the HMHA1 gene. The HA-1(H) peptide is restricted by HLA-A2 and is immunogenic in HA-1(R/R) into HA-1(H) transplants, while HA-1(R) has been suggested to be a "null allele" in terms of T cell reactivity. We found that proteasomal cleavage and TAP transport of the 2 peptides is similar and that both variants can bind to MHC. However, the His>Arg change substantially decreases the stability and affinity of HLA-A2 association, consistent with the reduced immunogenicity of the HA-1(R) variant. To understand these findings, we determined the structure of an HLA-A2-HA-1(H) complex to 1.3A resolution. Whereas His-3 is accommodated comfortably in the D pocket, incorporation of the lengthy Arg-3 is predicted to require local conformational changes. Moreover, a soluble TCR generated from HA-1(H)-specific T-cells bound HA-1(H) peptide with moderate affinity but failed to bind HA-1(R), indicating complete discrimination of HA-1 variants at the level of TCR/MHC interaction. Our results define the molecular mechanisms governing immunogenicity of HA-1, and highlight how single amino acid polymorphisms in mHags can critically affect both MHC association and TCR recognition.

Selective accumulation of virus-specific CD8+ T cells with unique homing phenotype within the human bone marrow.

The bone marrow plays a unique role within the immune system. We compared the phenotype and function of virus-specific CD8(+) T cells from matched samples of human peripheral blood and bone marrow. Analysis of virus-specific memory CD8(+) T cells showed widely divergent partition of antigen-specific populations between blood and bone marrow. T cells specific for Epstein-Barr virus (EBV) lytic antigens were enriched 3-fold in marrow compared with blood, whereas the response to EBV latent epitopes was equivalent between the 2 compartments. No difference in EBV viral load or expression of the EBV lytic protein was observed between blood and bone marrow. In direct contrast, although cytomegalo-virus (CMV)-specific T cells were the largest virus-specific population within peripheral blood, they were reduced by 60% within marrow. Bone marrow T cells were found to exhibit a unique CCR5(+)CXCR6(+)CXCR3(-) homing phenotype which has not been observed on T cells from other secondary lymphoid organs or peripheral organs. Expression of CCR5 and CXCR6 was higher on EBV-specific T cells within peripheral blood compared with CMV-specific populations. These observations identify a novel bone marrow homing phenotype for CD8(+) memory T cells, which necessitates a reevaluation of the magnitude of antigen-specific populations within the lymphoid system.

Differential pattern of CD4+ and CD8+ T-cell immunity to MAGE-A1/A2/A3 in patients with monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma.

The factors that determine progression from monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma are unclear but may include the breakdown of immune surveillance. Cancer testis antigens (CTAgs) are expressed by the majority of myelomas and MGUS tumors and are a potential immune target. We have characterized CD4(+) and CD8(+) T-cell immune responses to MAGE-A1/A2/A3 in these patients. CD4(+) T-cell immunity to MAGE proteins is stronger and more frequent in MGUS compared with myeloma with a predominantly CD45RA(-)CCR7(-) effector memory profile and cytotoxicity against MAGE-positive cell lines. In contrast CD8(+) T-cell immune responses were present almost exclusively in patients with multiple myeloma, correlating with disease, with a CD45RA(+)CCR7(-) memory phenotype, localizing poorly to the bone marrow but were able to lyse myeloma cell lines in vitro. This suggests that the CD4(+) CTAg-specific immune response may play a role in controlling tumor growth, whereas the efficacy of the CD8(+) T-cell response appears to be limited in vivo. Despite this, patients with evidence of a CTAg-specific immune response had a 53% reduction in mortality over a median follow-up of 4 years. These findings have important implications for clinical approaches to CTAg-specific immunotherapy in patients with cancer.

Expression of the Epstein-Barr virus-encoded Epstein-Barr virus nuclear antigen 1 in Hodgkin's lymphoma cells mediates Up-regulation of CCL20 and the migration of regulatory T cells.

In approximately 50% of patients with Hodgkin's lymphoma (HL), the Epstein-Barr virus (EBV), an oncogenic herpesvirus, is present in tumor cells. After microarray profiling of both HL tumors and cell lines, we found that EBV infection increased the expression of the chemokine CCL20 in both primary Hodgkin and Reed-Sternberg cells and Hodgkin and Reed-Sternberg cell-derived cell lines. Additionally, this up-regulation could be mediated by the EBV nuclear antigen 1 protein. The higher levels of CCL20 in the supernatants of EBV-infected HL cell lines increased the migration of CD4(+) lymphocytes that expressed FOXP3, a marker of regulatory T cells (Tregs), which are specialized CD4(+) T cells that inhibit effector CD4(+) and CD8(+) T cells. In HL, an increased number of Tregs is associated with the loss of EBV-specific immunity. Our results identify a mechanism by which EBV can recruit Tregs to the microenvironment of HL by inducing the expression of CCL20 and, by doing so, prevent immune responses against the virus-infected tumor population. Further investigation of how EBV recruits and modifies Tregs will contribute not only to our understanding of the pathogenesis of virus-associated tumors but also to the development of therapeutic strategies designed to manipulate Treg activity.