TREM2 on microglia cell surface binds to and forms functional binary complexes with heparan sulfate modified with 6-O-sulfation and iduronic acid.

The Triggering Receptor Expressed on Myeloid Cells-2 (TREM2), a pivotal innate immune receptor, orchestrates functions such as inflammatory responses, phagocytosis, cell survival, and neuroprotection. TREM2 variants R47H and R62H have been associated with Alzheimer's disease, yet the underlying mechanisms remain elusive. Our previous research established that TREM2 binds to heparan sulfate (HS) and variants R47H and R62H exhibit reduced affinity for HS. Building upon this groundwork, our current study delves into the interplay between TREM2 and HS and its impact on microglial function. We confirm TREM2's binding to cell surface HS and demonstrate that TREM2 interacts with HS, forming HS-TREM2 binary complexes on microglia cell surfaces. Employing various biochemical techniques, including Surface Plasmon Resonance, low molecular weight HS microarray screening, and serial HS mutant cell surface binding assays, we demonstrate TREM2's robust affinity for HS, and the effective binding requires a minimum HS size of approximately 10 saccharide units. Notably, TREM2 selectively binds specific HS structures, with 6-O-sulfation and, to a lesser extent, the iduronic acid residue playing crucial roles. N-sulfation and 2-O-sulfation are dispensable for this interaction. Furthermore, we reveal that 6-O-sulfation is essential for HS-TREM2 ternary complex formation on the microglial cell surface, and HS and its 6-O-sulfation are necessary for TREM2-mediated ApoE3 uptake in microglia. By delineating the interaction between HS and TREM2 on the microglial cell surface and demonstrating its role in facilitating TREM2-mediated ApoE uptake by microglia, our findings provide valuable insights that can inform targeted interventions for modulating microglial functions in Alzheimer's disease.

SARS-CoV-2 infection during pregnancy: clinical characteristics and vertical transmission in a referral hospital in Peru. / Infección por SARS-CoV-2 en el embarazo: características clínicas y trasmisión vertical en un hospital de referencia de Perú.

Motivation for the study. There is a gap in knowledge about vertical transmission of SARS- CoV-2 and its implications for maternal and neonatal health, despite evidence of multisystem involvement in pregnant women with COVID-19. Main findings. The study results suggest low incidence of vertical transmission during pregnancy, with only one PCR-positive case in the placenta and one asymptomatic neonate. Implications. Our results can inform strategies for prevention and management of COVID-19 in pregnant women, as well as guide the development of health policies aimed at protecting maternal and neonatal health during the pandemic. The aim of this study was to analyze the vertical transmission of SARS-CoV-2 in pregnant women with COVID-19 in the Gynecology and Obstetrics Department of the Edgardo Rebagliati Martins National Hospital (HNERM). Twelve pregnant women who met the inclusion criteria were included. Real-time PCR (RT-PCR) tests for SARS-CoV-2 were performed when each woman was admitted to the hospital, placenta samples were collected for pathological evaluation as well. The results showed that vertical transmission of the virus was rare, with an overall low positivity rate in newborns. Although the study has limitations, such as the small number of cases and the lack of electron microscope analysis, it is the first attempt to evaluate vertical transmission in Peru. It is concluded that more research is needed to better understand the relationship between COVID-19 infection and complications during pregnancy.

Se realizó un estudio en el departamento de Ginecología y Obstetricia del Hospital Nacional Edgardo Rebagliati Martins (HNERM) con el objetivo analizar la transmisión vertical del SARS-CoV-2 en mujeres embarazadas con COVID-19. Se incluyeron 12 gestantes que cumplían con los criterios de inclusión. Se realizaron pruebas diagnósticas de PCR en tiempo real (RT-PCR) para SARS-CoV-2 durante la admisión de cada gestante y se recolectaron muestras de placenta para su evaluación anatomopatológica. Los resultados mostraron que la transmisión vertical del virus fue poco común, con una tasa general de positividad baja en los recién nacidos. Aunque el estudio presenta limitaciones, como el número reducido de casos y la falta de análisis con microscopio electrónico, constituye el primer intento en Perú de evaluar la transmisión vertical. Se concluye que se necesita más investigación para comprender mejor la relación entre la infección por la COVID-19 y las complicaciones durante el embarazo. Motivación para realizar el estudio. A pesar de la evidencia de una afectación multisistémica en mujeres embarazadas con la COVID-19, existe un vacío de conocimiento sobre la transmisión vertical del virus y sus implicancias en la salud materna y neonatal. Principales hallazgos. Los resultados del estudio sugieren una baja incidencia de transmisión vertical durante el embarazo, con solo un caso positivo de PCR en la placenta y un neonato asintomático. Implicancias. Este resultado pueden informar las estrategias de prevención y manejo de la COVID-19 en mujeres embarazadas, así como guiar el desarrollo de políticas sanitarias dirigidas a proteger la salud materna y neonatal durante la pandemia.

Why Opportunities for Tenure Matter for Minoritized Faculty in Academic Medicine.

Academic medicine continues to characterize the experiences of Black and other minoritized faculty in medicine to enhance their careers and promote their advancement. An issue of discussion is tenure and its role in the advancement and retention of this group. Tenure is a sign of national presence, command of an area of study, and can demonstrate support from the institution in terms of permanent employment, eligibility to apply for awards, sit or vote on certain committees or qualify for certain leadership opportunities. Anecdotally there have been reports that tenure is a thing of the past that has lost relevance prompting some to end tenure in their institutions. Reasons for this are complex, however the literature does not include minoritized faculty as a reason for the need to revise or eliminate tenure and tenure earning tracks. The authors discuss 3 reasons why Black and other minoritized faculty should be afforded the opportunity to achieve permanent status in their academic health centers. They include histories of being denied freedom, having information concealed or being giving false information, and being denied permanent academic employment status.

Revisión narrativa del modelo de desarrollo positivo para adultos emergentes chilenos / A narrative review of the positive development model for Chilean emerging adults / Revisão narrativa do modelo de desenvolvimento positivo para adultos emergentes chilenos

Introducción: El desarrollo positivo es un estadio de ajuste psicosocial que acentúa las potencialidades y los recursos entre jóvenes y sus contextos próximos. En Australia, se desarrolló el primer modelo de desarrollo positivo para adultos emergentes, el cual consta de cinco componentes (competencia social, satisfacción con la vida, confianza y tolerancia con los otros, confianza hacia autoridades e instituciones, acción y compromiso cívico), pero no ha sido investigado en Chile. Objetivo: Analizar la evidencia disponible en la literatura científica sobre los cinco componentes del modelo de desarrollo positivo en adultos emergentes universitarios de Chile. Materiales y métodos: Revisión narrativa de la literatura publicada entre 2013 y 2023, en bases de datos Web of Science, Scopus, SciELO, Redalyc y Dialnet. Resultados: Se obtuvieron 83 artículos, de los cuales 53 cumplieron los requisitos de inclusión; en su mayor parte fueron estudios cuantitativos (81,13%) y en español (75,47%). Se evidenció una disparidad en la cantidad de estudios por temática; se encuentra mayor investigación en satisfacción con la vida y acción y compromiso cívico. Conclusiones: Existen brechas en la literatura científica chilena en el estudio del desarrollo positivo; además de que se discuten particularidades idiosincrásicas y desafíos asociados a la etapa de adultez emergente.

Introduction: Positive development is a stage of psychosocial adjustment that accentuates the potentials and resources of young people and their close contexts. The first positive development model for emerging adulthood was developed in Australia, which includes five components: social; life satisfaction; trust and tolerance of others; trust in the authorities and institutions; and action and civic engagement. However, this model has not been investigated in Chile. Objective: To analyze the evidence available in the scientific literature on the five components of the positive development model in emerging adults universities. Materials and methods: A narrative review of the literature published between 2013 and 2023 in the Web of Science, Scopus, SciELO, Redalyc, and Dialnet databases was conducted. Results: 83 articles were selected, of which 53 met the inclusion criteria; most of them were qualitative studies (81.13%) and in Spanish (75.47%). There is an evident disparity in terms of the number of studies and topics, e.g., there is more research on life satisfaction and civic action and commitment. Conclusions: There are gaps in the Chilean scientific literature in the study of positive development. In addition, idiosyncratic particularities and challenges associated with the stages of emerging adulthood are discussed.

Introdução: O desenvolvimento positivo é uma fase de ajustamento psicossocial que acentua o potencial e os recursos dos jovens e dos seus contextos imediatos. Na Austrália, foi desenvolvido o primeiro modelo de desenvolvimento positivo para adultos emergentes, que consiste em cinco componentes (social, satisfação com a vida, confiança e tolerância com os outros, confiança nas autoridades e instituições, ação e envolvimento cívico), mas ainda não foi investigado no Chile. Objetivo: Analisar as evidências disponíveis na literatura científica sobre os cinco componentes do modelo de desenvolvimento positivo em adultos universitários emergentes no Chile. Materiais e métodos: Revisão narrativa da literatura publicada entre 2013 e 2023, nas bases de dados Web of Science, Scopus, SciELO, Redalyc e Dialnet. Resultados: foram obtidos 83 artigos, dos quais 53 atenderam aos requisitos de inclusão; A maioria deles eram estudos quantitativos (81,13%) e em espanhol (75,47%). Ficou evidente uma disparidade no número de estudos por tema; Há mais pesquisas sobre satisfação com a vida e ação e compromisso cívico. Conclusões: Existem lacunas na literatura científica chilena no estudo do desenvolvimento positivo; Além disso, são discutidas particularidades e desafios idiossincráticos associados à fase da idade adulta emergente.

Surgical Care Through a Community Free Clinic-Ambulatory Surgical Center Partnership.

BACKGROUND: Disparities secondary to underinsurance present throughout the surgical care continuum. Community free clinics are uniquely capable to provide health care services to the medically underserved, but surgery often falls outside their scope of care. METHODS: Retrospective chart review was conducted on consecutive community free clinic patients receiving free surgical services via referral to a partnering ambulatory surgery center between March 2016 and September 2021. Those with documented contact information were recruited 1-3 years post-procedure for long-term quality-of-life (LTQOL) outcomes assessment via modified Veterans RAND 12-item health survey. RESULTS: Of 142 included patients, 95.7% identified as Hispanic/Latino and 75.6% were uninsured. Twelve patients had cancerous or precancerous lesions detected and/or removed through diagnostic or definitive procedures. 3.5% experienced postoperative complication including bacterial (n = 2) or fungal (n = 1) surgical site infection and wound dehiscence (n = 2). With a 48.9% response rate, no significant differences in sociodemographic or clinical characteristics were found between surveyed vs non-surveyed patients. Of surveyed patients, 59.7% and 52.2% reported pre-/post-operative improvement in physical health and emotional health, respectively. DISCUSSION: Free diagnostic screening procedures provided timely diagnoses while free definitive surgeries safely and positively impacted long-term patient-reported physical health. Longitudinal, multidisciplinary follow-up and social support may be warranted to concurrently improve emotional and mental health in similarly underinsured populations.

The impact of post-operative enteral nutrition on duodenal injury outcomes: A post hoc analysis of an EAST multicenter trial.

BACKGROUND: Leak following surgical repair of traumatic duodenal injuries results in prolonged hospitalization and oftentimes nil per os(NPO) treatment. Parenteral nutrition(PN) has known morbidity; however, duodenal leak(DL) patients often have complex injuries and hospital courses resulting in barriers to enteral nutrition(EN). We hypothesized EN alone would be associated with 1)shorter duration until leak closure and 2)less infectious complications and shorter hospital length of stay(HLOS) compared to PN. METHODS: This was a post-hoc analysis of a retrospective, multicenter study from 35 Level-1 trauma centers, including patients >14 years-old who underwent surgery for duodenal injuries(1/2010-12/2020) and endured post-operative DL. The study compared nutrition strategies: EN vs PN vs EN + PN using Chi-Square and Kruskal-Wallis tests; if significance was found pairwise comparison or Dunn's test were performed. RESULTS: There were 113 patients with DL: 43 EN, 22 PN, and 48 EN + PN. Patients were young(median age 28 years-old) males(83.2%) with penetrating injuries(81.4%). There was no difference in injury severity or critical illness among the groups, however there were more pancreatic injuries among PN groups. EN patients had less days NPO compared to both PN groups(12 days[IQR23] vs 40[54] vs 33[32],p = <0.001). Time until leak closure was less in EN patients when comparing the three groups(7 days[IQR14.5] vs 15[20.5] vs 25.5[55.8],p = 0.008). EN patients had less intra-abdominal abscesses, bacteremia, and days with drains than the PN groups(all p < 0.05). HLOS was shorter among EN patients vs both PN groups(27 days[24] vs 44[62] vs 45[31],p = 0.001). When controlling for predictors of leak, regression analysis demonstrated EN was associated with shorter HLOS(ß -24.9, 95%CI -39.0 to -10.7,p < 0.001). CONCLUSION: EN was associated with a shorter duration until leak closure, less infectious complications, and shorter length of stay. Contrary to some conventional thought, PN was not associated with decreased time until leak closure. We therefore suggest EN should be the preferred choice of nutrition in patients with duodenal leaks whenever feasible. LEVEL OF EVIDENCE: IV.

Lack of Concordance Between Abbreviated Injury Scale and American Association for the Surgery of Trauma Organ Injury Scale in Patients with High-Grade Solid Organ Injury.

BACKGROUND: The Abbreviated Injury Scale (AIS) is widely utilized for body region-specific injury severity. The AAST-Organ Injury Scale (AAST-OIS) provides organ-specific injury severity but is not included in trauma databases. Previous researchers have used AIS as a surrogate for OIS. This study aims to assess AIS-abdomen concordance with AAST-OIS grade for liver and spleen injuries, hypothesizing concordance in terms of severity (grade of OIS and AIS) and patient outcomes. STUDY DESIGN: This retrospective study (7/2020-6/2022) was performed at three trauma centers. Adult trauma patients with AAST-OIS grade III-V liver and/or spleen injury were included. AAST-OIS grade for each organ was compared to AIS-abdomen by evaluating the percentage of AAST-OIS grade correlating with each AIS score as well as rates of operative intervention for these injuries. Analysis was performed with Chi-square tests and univariate analysis. RESULTS: Of 472 patients, 274 had liver injuries and 205 had spleen injuries grades III-V. AAST-OIS grade III-V liver injuries had concordances rates of 85.5%, 71% and 90.9% with corresponding AIS 3-5 scores. AAST-OIS grade III-V spleen injuries had concordances rates of 89.7%, 87.8% and 87.3%. There was a statistical lack of concordance for both liver and spleen injuries (both p<0.001). Additionally, there were higher rates of operative intervention for AAST-OIS grade IV and V liver injuries and grade III and V spleen injuries versus corresponding AIS scores (p<0.05). CONCLUSION: AIS should not be used interchangeably with OIS due to lack of concordance. AAST-OIS should be included in trauma databases to facilitate improved organ injury research and quality improvement projects.

Prospective Outpatient Follow-Up of Early Cognitive Impairment in Patients with Mild Traumatic Brain Injury and Intracranial Hemorrhage.

INTRODUCTION: Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines (BIG) suggest mTBI patients can be safely discharged from the Emergency Department. Although half of mTBI patients with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients' ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up. METHODS: A single-center prospective cohort study including adult trauma patients with ICH or skull fracture plus a Glasgow coma scale (GCS) of 13-15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as a RLA < 8. We compared ECI and non-ECI groups for demographics, injury profile, computed tomography (CT) imaging (e.g., Rotterdam CT score) and outcomes with bivariate analysis. 30-day follow up phone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms. RESULTS: From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% versus 46.3%, p=0.003) and higher Rotterdam CT score (p=0.004) compared to those without ECI. On 30-day follow up, 6 of 21 patients (26.6%) had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms. CONCLUSION: Over one-third of mTBI patients with ICH had ECI. At 30-day post-discharge follow-up over one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI prior to discharge as a significant portion may have ongoing difficulties reintegrating into work and society.

Association of oral lichen planus and psoriasis: a case-control study.

OBJECTIVE: The aim of the present study was to investigate whether psoriasis disease constitutes a risk factor for OLP, by assessing the prevalance of psoriasis in a test group with OLP and the control group without. METHOD AND MATERIALS: A cohort of consecutive patients diagnosed clinically and histologically with OLP between 2014 and 2022 was analyzed. The results were contrasted with those obtained in control series matched for age and sex. The correlations between OLP and sex, age, tobacco, alcohol consumption, and psoriasis were assessed using Pearson chi-square test. Multivariate regression analysis was performed to evaluate the association between psoriasis and OLP. For the assessment of the quality of the statistical models, the Akaike information criterion was used. RESULTS: The study involved 1,016 patients; 738 women (72.6%) and 278 men (27.4%). The average age was 59.38 ± 12.55 years. Of 508 patients with OLP, 16 (3.15%) had comorbid psoriasis, and this was 5 (0.98%) in the control group. Age, sex, smoking, and alcohol habits were not predictive variables in the relationship between psoriasis and OLP in these patients. There were statistically significant differences in relation to the number of locations, with greater extension in patients with OLP and psoriasis (P = .002). According to the multivariate analysis, the odds ratio of OLP for psoriasis was 3.13 (95% CI 1.20-9.68). CONCLUSIONS: This is the first study showing the potential association between psoriasis and OLP, and the results should be considered to improve knowledge of comorbidity of OLP. Based on the results, it is recommended that clinicians collect data regarding history of psoriasis in patients with OLP, and consider possible multiple intraoral locations.

Infección por SARS-CoV-2 en el embarazo: características clínicas y trasmisión vertical en un hospital de referencia de Perú / SARS-CoV-2 infection in pregnancy: clinical characteristics and vertical transmission in a reference hospital in Peru

Se realizó un estudio en el departamento de Ginecología y Obstetricia del Hospital Nacional Edgardo Re-bagliati Martins (HNERM) con el objetivo analizar la transmisión vertical del SARS-CoV-2 en mujeres embarazadas con COVID-19. Se incluyeron 12 gestantes que cumplían con los criterios de inclusión. Se realizaron pruebas diagnósticas de PCR en tiempo real (RT-PCR) para SARS-CoV-2 durante la admi-sión de cada gestante y se recolectaron muestras de placenta para su evaluación anatomopatológica. Los resultados mostraron que la transmisión vertical del virus fue poco común, con una tasa general de posi-tividad baja en los recién nacidos. Aunque el estudio presenta limitaciones, como el número reducido de casos y la falta de análisis con microscopio electrónico, constituye el primer intento en Perú de evaluar la transmisión vertical. Se concluye que se necesita más investigación para comprender mejor la relación entre la infección por la COVID-19 y las complicaciones durante el embarazo.

Delineation of functional subdomains of Huntingtin protein and their interaction with HAP40.

The huntingtin (HTT) protein plays critical roles in numerous cellular pathways by functioning as a scaffold for its many interaction partners and HTT knock out is embryonic lethal. Interrogation of HTT function is complicated by the large size of this protein so we studied a suite of structure-rationalized subdomains to investigate the structure-function relationships within the HTT-HAP40 complex. Protein samples derived from the subdomain constructs were validated using biophysical methods and cryo-electron microscopy, revealing they are natively folded and can complex with validated binding partner, HAP40. Derivatized versions of these constructs enable protein-protein interaction assays in vitro, with biotin tags, and in cells, with luciferase two-hybrid assay-based tags, which we use in proof-of-principle analyses to further interrogate the HTT-HAP40 interaction. These open-source biochemical tools enable studies of fundamental HTT biochemistry and biology, will aid the discovery of macromolecular or small-molecule binding partners and help map interaction sites across this large protein.

Progesterone and its metabolite allopregnanolone promote invasion of human glioblastoma cells through metalloproteinase­9 and cSrc kinase.

Glioblastomas are the most aggressive and common primary brain tumors in adults. Glioblastoma cells have a great capacity to migrate and invade the brain parenchyma, often reaching the contralateral hemisphere. Progesterone (P4) and its metabolite, allopregnanolone (3α-THP), promote the migration and invasion of human glioblastoma-derived cells. P4 induces migration in glioblastoma cells by the activation of the proto-oncogene tyrosine-protein kinase Src (cSrc) and focal adhesion kinase (Fak). In breast cancer cells, cSrc and Fak promote invasion by increasing the expression and activation of extracellular matrix metalloproteinases (MMPs). However, the mechanism of action by which P4 and 3a-THP promote invasion in glioblastoma cells remains unclear. The effects of P4 and 3α-THP on the protein expression levels of MMP-2 and -9 and the participation of cSrc in progestin effects in U251 and U87 human glioblastoma-derived cells were evaluated. It was determined by western blotting that the P4 increased the protein expression level of MMP-9 in U251 and U87 cells, and 3α-THP increased the protein expression level of MMP-9 in U87 cells. None of these progestins modified MMP-2 protein expression levels. The increase in MMP-9 expression was reduced when the intracellular progesterone receptor and cSrc expression were blocked with small interfering RNAs. Cell invasion induced by P4 and 3α-THP was also blocked by inhibiting cSrc activity with PP2 or by cSrc gene silencing. These results suggest that P4 and its metabolite 3α-THP induce the invasion of glioblastoma cells by increasing MMP-9 expression through the cSrc kinase family. The results of this study provide information of interest in the context of targeted therapies against molecular pathways involved in glioblastoma invasion.

Design and Implementation of a Culturally-Tailored Randomized Pilot Trial: Puerto Rican Optimized Mediterranean-Like Diet.

Background: Adhering to a Mediterranean Diet (MedDiet) is associated with a healthier cardiometabolic profile. However, there are limited studies on the MedDiet benefits for non-Mediterranean racial/ethnic minorities, for whom this diet may be unfamiliar and inaccessible and who have a high risk of chronic diseases. Objectives: To describe the study design of a pilot trial testing the efficacy of a MedDiet-like tailored to adults in Puerto Rico (PR). Methods: The Puerto Rican Optimized Mediterranean-like Diet (PROMED) was a single-site 4-mo parallel two-arm randomized pilot trial among a projected 50 free-living adults (25-65 y) living in PR with at least two cardiometabolic risk factors (clinicaltrials.gov registration #NCT03975556). The intervention group received 1 individual nutritional counseling session on a portion-control culturally-tailored MedDiet. Daily text messages reinforced the counseling content for 2 mo, and we supplied legumes and vegetable oils. Participants in the control group received cooking utensils and one standard portion-control nutritional counseling session that was reinforced with daily texts for 2 mo. Text messages for each group were repeated for two more months. Outcome measures were assessed at baseline, 2 and 4 m. The primary outcome was a composite cardiometabolic improvement score; secondary outcomes included individual cardiometabolic factors; dietary intake, behaviors, and satisfaction; psychosocial factors; and the gut microbiome. Results: PROMED was designed to be culturally appropriate, acceptable, accessible, and feasible for adults in PR. Strengths of the study include applying deep-structure cultural components, easing structural barriers, and representing a real-life setting. Limitations include difficulty with blinding and with monitoring adherence, and reduced timing and sample size. The COVID-19 pandemic influenced implementation, warranting replication. Conclusions: If PROMED is proven efficacious in improving cardiometabolic health and diet quality, the findings would strengthen the evidence on the healthfulness of a culturally-appropriate MedDiet and support its wider implementation in clinical and population-wide disease-prevention programs.

Predictors of Mortality in Trauma patients Receiving massive Transfusion Protocol.

INTRODUCTION: Massive transfusion protocol (MTP) is often defined as the transfusion of ≥10 units of packed red blood cells (PRBCs) in 24 hours. The purpose of this study is to determine which factors most significantly contribute to mortality in patients receiving MTP after trauma. METHODS: An initial database search followed by retrospective chart review was performed on patients treated at four trauma centers in Southern California. Data were collected on all patients who received MTP, defined as at least 10 units PRBCs within the first 24 hours of admission, between January 2015 and December 2019. Patients with isolated head injuries were excluded. Univariate and multivariate analyses were used to determine which factors most significantly influenced mortality. RESULTS: Of 1278 patients who met our inclusion criteria in the database, 596 (46.6%) survived and 682 (53.4%) died. On univariate analysis initial vitals and labs, except for initial hemoglobin and initial platelet count were significant predictors of mortality. A multivariate regression model showed the strongest predictors of mortality were pRBC transfusions at 4 hours (OR 1.073, CI 1.020-1.128, P = .006) and 24 hours (OR 1.045, CI 1.003-1.088, P = .036), and FFP transfusion at 24 hours (OR 1.049, CI 1.016-1.084, P = .003). CONCLUSION: Our data indicates that several factors may contribute to mortality in patients receiving MTP. In particular age, mechanism, initial GCS, and PRBC transfusions at 4 and 24 hours provided the strongest correlation. Further multicenter trials are indicated to provide further guidance in deciding when to discontinue massive transfusion.

Trauma Patients With Cirrhosis Have a Similar Risk of Unplanned Operation and Decreased Associated Risk of Mortality With Venous Thromboembolism Chemoprophylaxis.

INTRODUCTION: Patients with cirrhosis have an increased risk of complications after trauma, including bleeding, unplanned operations, and death. The benefit of venous thromboembolism (VTE) chemoprophylaxis in trauma patients with cirrhosis (CTPs) is not clear, especially since cirrhotic patients are hypercoagulable. We hypothesized that CTPs receiving VTE chemoprophylaxis (vCP) have a lower risk of death with no increased risk for unplanned operations compared to patients with cirrhosis not receiving vCP. METHODS: The 2017-2019 TQIP database was queried for patients with cirrhosis. Patients on outpatient anticoagulant therapy or with a history of bleeding diathesis, interhospital transfers, severe head injury, deaths < 72 hours, and hospitalization < 2 days were excluded. A multivariable logistic regression analysis was performed. RESULTS: From 10,011 CTPs, 6,350 (63.4%) received vCP. Compared to patients without vCP, the vCP group had decreased mortality (4.5% vs. 5.5%, P = 0.03) but a similar rate of unplanned operations (1% vs. 0.6%, P = 0.07). This persisted on multivariable analysis, with a decreased associated risk of mortality (OR 0.54, CI 0.42-0.69, P < 0.001), and a similar risk of unplanned operation (P = 0.85). CONCLUSION: CTPs received VTE chemoprophylaxis in under two-thirds of cases. On multivariable analysis, vCP was associated with a decreased risk of mortality and a similar risk of unplanned operations. These findings suggest that vCP appears safe. Further investigation is needed to confirm this finding.

Relationship of Obesity and Severe Penetrating Thoracic and Abdominal Injuries in Adolescent Patients.

BACKGROUND: Over 20% of United States adolescents are obese. A thicker layer of subcutaneous adiposity might provide a protective "armor" layer against penetrating wounds. We hypothesized that adolescents with obesity presenting after isolated thoracic and abdominal penetrating trauma have lower rates of severe injury and mortality than adolescents without obesity. METHODS: The 2017-2019 Trauma Quality Improvement Program database was queried for patients between 12 and 17 years old presenting with knife or gunshot wounds. Patients with body mass index (BMI) ≥30 (obese) were compared to patients with BMI <30. Sub-analyses were performed for adolescents with isolated abdominal trauma and isolated thoracic trauma. Severe injury was defined as an abbreviated injury scale grade >3. Bivariate analyses were performed. RESULTS: 12,181 patients were identified; 1603 (13.2%) had obesity. In isolated abdominal gunshot or knife wounds, rates of severe intra-abdominal injuries and mortality were similar (all P > .05) between groups. In isolated thoracic gunshot wounds, adolescents with obesity had a lower rate of severe thoracic injury (5.1% vs 13.4%, P = .005) but statistically similar mortality (2.2% vs 6.3%, P = .053) compared to adolescents without obesity. In isolated thoracic knife wounds, rates of severe thoracic injuries and mortality were similar (all P > .05) between groups. DISCUSSION: Adolescent trauma patients with and without obesity presenting after isolated abdominal or thoracic knife wounds had similar rates of severe injury, operative intervention, and mortality. However, adolescents with obesity presenting after an isolated thoracic gunshot wound had a lower rate of severe injury. This may impact the future work-up and management of adolescents sustaining isolated thoracic gunshot wounds.

Outcomes among trauma patients with duodenal leak following primary versus complex repair of duodenal injuries: An Eastern Association for the Surgery of Trauma multicenter trial.

BACKGROUND: Duodenal leak is a feared complication of repair, and innovative complex repairs with adjunctive measures (CRAM) were developed to decrease both leak occurrence and severity when leaks occur. Data on the association of CRAM and duodenal leak are sparse, and its impact on duodenal leak outcomes is nonexistent. We hypothesized that primary repair alone (PRA) would be associated with decreased duodenal leak rates; however, CRAM would be associated with improved recovery and outcomes when leaks do occur. METHODS: A retrospective, multicenter analysis from 35 Level 1 trauma centers included patients older than 14 years with operative, traumatic duodenal injuries (January 2010 to December 2020). The study sample compared duodenal operative repair strategy: PRA versus CRAM (any repair plus pyloric exclusion, gastrojejunostomy, triple tube drainage, duodenectomy). RESULTS: The sample (N = 861) was primarily young (33 years) men (84%) with penetrating injuries (77%); 523 underwent PRA and 338 underwent CRAM. Complex repairs with adjunctive measures were more critically injured than PRA and had higher leak rates (CRAM 21% vs. PRA 8%, p < 0.001). Adverse outcomes were more common after CRAM with more interventional radiology drains, prolonged nothing by mouth and length of stay, greater mortality, and more readmissions than PRA (all p < 0.05). Importantly, CRAM had no positive impact on leak recovery; there was no difference in number of operations, drain duration, nothing by mouth duration, need for interventional radiology drainage, hospital length of stay, or mortality between PRA leak versus CRAM leak patients (all p > 0.05). Furthermore, CRAM leaks had longer antibiotic duration, more gastrointestinal complications, and longer duration until leak resolution (all p < 0.05). Primary repair alone was associated with 60% lower odds of leak, whereas injury grades II to IV, damage control, and body mass index had higher odds of leak (all p < 0.05). There were no leaks among patients with grades IV and V injuries repaired by PRA. CONCLUSION: Complex repairs with adjunctive measures did not prevent duodenal leaks and, moreover, did not reduce adverse sequelae when leaks did occur. Our results suggest that CRAM is not a protective operative duodenal repair strategy, and PRA should be pursued for all injury grades when feasible. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

The impact of rounds with a psychiatry team in the intensive care unit: A prospective observational pilot study evaluating the effects on delirium incidence and outcomes.

BACKGROUND: Delirium in the intensive care unit (ICU) is a common but serious condition that has been associated with in-hospital mortality and post-discharge psychological dysfunction. The aim of this before and after study is to determine the effect of a multidisciplinary care model entailing daily ICU rounds with a psychiatrist on the incidence of delirium and clinical outcomes. OBJECTIVE: To assess the impact of a proactive psychiatry consultation model in the surgical ICU on the incidence and duration of delirium. METHODS: This was a prospective, single institution, observational controlled cohort pilot study of adult patients admitted to a surgical ICU. A control group that received standard of care (SOC) with daily delirium prevention care bundles in the pre-intervention period was compared to an intervention group, which had a psychiatrist participate in daily ICU rounds (post-intervention period). The primary outcome was delirium incidence. The secondary outcomes were: delirium duration, ventilator days, hospital and ICU length of stay, and in-hospital mortality. RESULTS: A total of 104 patients were enrolled and equally split between SOC and intervention groups; 95 contributed to analysis. The overall incidence of ICU delirium was 19%. SOC and intervention groups had similar rates of delirium (21% vs 18%, p = 0.72). None of the secondary outcomes statistically significantly differed between the two groups. CONCLUSION: Delirium in ICU patients is a potentially preventable condition with serious sequelae. There was no difference in delirium incidence or duration between patients receiving SOC or patients who had multidisciplinary rounds with a psychiatrist.

Detection of antibodies against the huntingtin protein in human plasma.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disorder resulting from a CAG expansion in the huntingtin (HTT) gene, which leads to the production and accumulation of mutant huntingtin (mHTT). While primarily considered a disorder of the central nervous system, multiple changes have been described to occur throughout the body, including activation of the immune system. In other neurodegenerative disorders, activation of the immune system has been shown to include the production of antibodies against disease-associated pathological proteins. However, the existence of mHTT-targeted antibodies has never been reported. In this study, we assessed the presence and titer of antibodies recognizing HTT/mHTT in patients with HD (n = 66) and age- and gender-matched healthy controls (n = 66) using a combination of Western blotting and ELISA. Together, these analyses revealed that antibodies capable of recognizing HTT/mHTT were detectable in the plasma samples of all participants, including healthy controls. When antibody levels were monitored at different disease stages, it was observed that antibodies against full-length mHTT were highest in patients with severe disease while antibodies against HTTExon1 were elevated in patients with mild disease. Combined, these results suggest that antibodies detecting different forms of mHTT peak at different disease stages.

Expression and estrogen regulation of G protein-coupled estrogen receptor in human glioblastoma cells.

Glioblastoma (GB) is the most frequent primary brain tumor with a very poor prognosis. Sex hormones are crucial players in the development of GBs. 17 ß-estradiol (E2) signaling is involved through its corresponding intracellular receptors [estrogen receptor α (ERα) and ß (ERß)] in GB cell proliferation and progression. E2 activates G-protein coupled estrogen receptor (GPER), leading to rapidly occurring effects, independently of gene transcription. GPER activation is involved in tumor progression in various cancer types. Currently, available data concerning the occurrence and role of GPER in GB are very limited. In the present study, it was observed that GPER was expressed in human brain tumor cell lines [U251 (astrocytoma-derived cell line), U87, LN229 and T98 (glioblastoma-derived cell line)]. Immunofluorescence assays revealed that GPER localizes in the plasma membrane, cytoplasm and nucleus. An in silico analysis identified two potential E2 response elements in the promoter region of the GPER gene. E2 increased GPER expression in the U251, U87 and LN229 cell lines. Molecular modeling data derived from in silico analysis predicted the three-dimensional conformation of GPER, and docking analysis identified potential binding sites of E2 and its specific agonist, G1. Taken together, these results indicate that GPER may be differentially expressed in human GB cell lines with E2 possibly upregulating GPER expression. The present study raises further questions about the implications of GPER-mediated E2 signaling in the biology of GBs.