Label-free optical imaging for brain cancer assessment.

Advances in label-free optical imaging offer a promising avenue for brain cancer assessment, providing high-resolution, real-time insights without the need for radiation or exogeneous agents. These cost-effective and intricately detailed techniques overcome the limitations inherent in magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) scans by offering superior resolution and more readily accessible imaging options. This comprehensive review explores a variety of such methods, including photoacoustic imaging (PAI), optical coherence tomography (OCT), Raman imaging, and IR microscopy. It focuses on their roles in the detection, diagnosis, and management of brain tumors. By highlighting recent advances in these imaging techniques, the review aims to underscore the importance of label-free optical imaging in enhancing early detection and refining therapeutic strategies for brain cancer.

KRAS inhibition activates an actionable CD24 'don't eat me' signal in pancreas cancer.

KRAS G12C inhibitor (G12Ci) has produced encouraging, albeit modest and transient, clinical benefit in pancreatic ductal adenocarcinoma (PDAC). Identifying and targeting resistance mechanisms to G12Ci treatment is therefore crucial. To better understand the tumor biology of the KRAS G12C allele and possible bypass mechanisms, we developed a novel autochthonous KRAS G12C -driven PDAC model. Compared to the classical KRAS G12D PDAC model, the G12C model exhibit slower tumor growth, yet similar histopathological and molecular features. Aligned with clinical experience, G12Ci treatment of KRAS G12C tumors produced modest impact despite stimulating a 'hot' tumor immune microenvironment. Immunoprofiling revealed that CD24, a 'do-not-eat-me' signal, is significantly upregulated on cancer cells upon G12Ci treatment. Blocking CD24 enhanced macrophage phagocytosis of cancer cells and significantly sensitized tumors to G12Ci treatment. Similar findings were observed in KRAS G12D -driven PDAC. Our study reveals common and distinct oncogenic KRAS allele-specific biology and identifies a clinically actionable adaptive mechanism that may improve the efficacy of oncogenic KRAS inhibitor therapy in PDAC. Significance: Lack of faithful preclinical models limits the exploration of resistance mechanisms to KRAS G12C inhibitor in PDAC. We generated an autochthonous KRAS G12C -driven PDAC model, which revealed allele-specific biology of the KRAS G12C during PDAC development. We identified CD24 as an actionable adaptive mechanisms in cancer cells induced upon KRAS G12C inhibition and blocking CD24 sensitizes PDAC to KRAS inhibitors in preclinical models.

Ocrelizumab B-cell repopulation-guided extended interval dosing versus standard dosing - similar clinical efficacy with decreased immunoglobulin M deficiency rates.

BACKGROUND: Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody used in treatment of multiple sclerosis. The standard dosing (SD) regimen consists of OCR maintenance infusions every 6 months. In B-cell repopulation-guided extended interval dosing (EID), repeat infusions are delayed until there is evidence for B-cell repopulation. OBJECTIVES: To compare frequencies of 'no evidence of disease activity' (NEDA-3) and immunoglobulin G (hypo-IgG; <600 mg/dL) and M (hypo-IgM; <40 mg/dL) deficiencies in persons with multiple sclerosis (PwMS) treated with OCR B-cell repopulation-guided EID versus SD. METHODS: Two-center retrospective study comparing frequencies of NEDA-3 and hypo-IgG and hypo-IgM in PwMS treated with OCR B-cell repopulation-guided EID versus SD using a multivariate generalized linear model adjusted for age, sex, and treatment duration. RESULTS: A total of 112 OCR-treated PwMS were included (B-cell repopulation-guided EID n = 52; SD n = 60) with average infusion intervals of 319 (246-485) days (EID) and 184 (170-218) days (SD). There was no significant difference in NEDA-3 (EID: 47/52 [90.4 %]; SD: 50/60 [83.3 %]; p = 0.161) or hypo-IgG (EID: 1/52 [1.9 %]; SD: 4/60 [6.7 %]; p = 0.298) rates. Hypo-IgM was significantly less common in EID (EID: 9/52 [17.3 %] vs. SD: 34/60 [55 %]; p<0.001) upon assessment 1099 (475-1436) days (EID) and 980 (409-1846) days (SD) post-initiation of OCR. Hypo-IgM was associated with average infusion interval length (p = 0.005) and total number of OCR cycles (p = 0.003). CONCLUSIONS: OCR B-cell repopulation-guided EID may be a safe alternative to traditional SD with similar efficacy and significantly less hypo-IgM rates.

Progressive multifocal leukoencephalopathy without overt immunosuppression.

Progressive multifocal leukoencephalopathy (PML) is a central nervous system disease caused by the human polyomavirus 2 that usually occurs in a setting of immunodeficiency. PML without overt immunosuppression is considered a rare occurrence but has been described in multiple previous case reports and series. Its prevalence, overall frequency, and prognosis are largely unknown. This is a single-center retrospective review of all University of Florida cases with the ICD10 PML diagnosis code (A81.2). PML without overt immunosuppression was defined as absence of human immunodeficiency virus (HIV) infection, hematological malignancy, immunomodulatory/-suppressive medications, autoimmune conditions with a propensity for PML (sarcoidosis, systemic lupus erythematosus). Cases that did not fulfill criteria for clinically or histologically definite PML were excluded. Of 52 patients with the ICD10 code A 81.2, 17 fulfilled definite diagnostic criteria for PML. Overt immunosuppression was identified in 15/17 (88.2%) cases (10/17 (58.8%): human immunodeficiency virus; 5/17 (29.4%): immunomodulatory/-suppressive medication). Two/seventeen (11.8%) cases were consistent with PML without overt immunosuppression. Possible contributing factors were a preceding dog bite and mild hypogammaglobulinemia M (39 mg/dL) in case 1 and significant alcohol use without evidence for liver disease in case 2. Both cases were fatal within 6 (case 1) and 2 (case 2) months. The results suggest that PML without overt immunosuppression may be more common than previously described. Therefore, PML should be considered even in the absence of overt immunosuppression if clinical and radiographic findings are suggestive of the diagnosis.

Injury trends aboard US Navy vessels: A 50-year analysis of mishaps at sea.

BACKGROUND: Maritime activities have been associated with unique dangers to civilian and military sailors. We performed a retrospective cohort study analyzing injury mechanisms and clinical outcomes of casualties onboard US naval ships to determine common injury mechanisms, trends, and outcomes. We hypothesized there would be a downward trend of injuries and fatalities on US naval ships during the study period. METHODS: All mishaps recorded by the Naval Safety Command aboard active service US naval ships from 1970 through 2020 were reviewed. Only mishaps resulting in injury or fatality were included. Over time, injury mechanisms and casualty incidence rates were trended and compared based on medical capabilities. Ships without surgical capabilities were categorized as Role 1, and those with surgical capabilities as Role 2. RESULTS: There were a total of 3,127 casualties identified and analyzed, with 1,048 fatalities and 2,079 injuries. The injury mechanisms associated with the highest mortality included electrocution, blunt head trauma, fall from height, man overboard, and explosion. There was a decrease in the trend of mishaps resulting in casualties, fatalities, and injuries over the 50-year study period. The mortality rate for select severe injury mechanisms was higher on Role 1 capable platforms, compared with Role 2 (0.334 vs. 0.250, p < 0.05). CONCLUSION: Casualty incidences decreased over 50 years. However, mortality still remains high for certain mechanisms no matter the operational platform. Furthermore, Role 1 capable vessels have a higher overall mortality rate for severe injuries compared with Role 2. The authors propose training, process improvement, and technology-related solutions to improve outcomes on Role 1 capable naval vessels. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

The Impact of the Maritime Deployment Cycle on the Surgeon's Knowledge, Skills, and Abilities.

INTRODUCTION: The U.S. Navy routinely deploys aircraft carriers and amphibious assault ships throughout the world in support of U.S. strategic interests, each with an embarked single surgeon team. Surgeons and their teams are required to participate in lengthy pre-deployment shipboard certifications before each deployment. Given the well-established relationship of surgeon volume to patient outcome, we aim to compare the impact of land vs. maritime deployments on Navy general surgeon practice patterns. MATERIALS AND METHODS: Case logs and pre-deployment training initiation of land-based (n = 8) vs. maritime-based (n = 7) U.S. Navy general surgeons over a 3-year period (2017-2020) were compared. Average cases per week were plotted over 26 weeks before deployment. Student's t-test was utilized for all comparisons. RESULTS: Cases declined for both groups in the weeks before deployment. At 6 months (26 weeks) before deployment, land-based surgeons performed significantly more cases than their maritime colleagues (50.3 vs. 14.0, P = .009). This difference persisted at 16 weeks (13.1 vs. 1.9, P = .011) and 12 weeks (13.1 vs. 1.9, P = .011). Overall, surgeon operative volume fell off earlier for maritime surgeons (16 weeks) than land-based surgeons (8 weeks). Within 8 weeks of deployment, both groups performed a similarly low number of cases as they completed final deployment preparations. CONCLUSIONS: Surgeons are a critical component of combat causality care teams. In this analysis, we have demonstrated that both land- and maritime-based U.S. Navy surgeons have prolonged periods away from clinical care before and during deployments; for shipboard surgeons, this deficit is large and may negatively impact patient outcomes in the deployed maritime environment. The authors describe this discrepancy and provide practical doctrinal solutions to close this readiness gap.

Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer's disease.

BACKGROUND: Regulatory T cells (Tregs) play a neuroprotective role by suppressing microglia and macrophage-mediated inflammation and modulating adaptive immune reactions. We previously documented that Treg immunomodulatory mechanisms are compromised in Alzheimer's disease (AD). Ex vivo expansion of Tregs restores and amplifies their immunosuppressive functions in vitro. A key question is whether adoptive transfer of ex vivo expanded human Tregs can suppress neuroinflammation and amyloid pathology in a preclinical mouse model. METHODS: An immunodeficient mouse model of AD was generated by backcrossing the 5xFAD onto Rag2 knockout mice (5xFAD-Rag2KO). Human Tregs were expanded ex vivo for 24 days and administered to 5xFAD-Rag2KO. Changes in amyloid burden, microglia characteristics and reactive astrocytes were evaluated using ELISA and confocal microscopy. NanoString Mouse AD multiplex gene expression analysis was applied to explore the impact of ex vivo expanded Tregs on the neuroinflammation transcriptome. RESULTS: Elimination of mature B and T lymphocytes and natural killer cells in 5xFAD-Rag2KO mice was associated with upregulation of 95 inflammation genes and amplified number of reactive microglia within the dentate gyrus. Administration of ex vivo expanded Tregs reduced amyloid burden and reactive glial cells in the dentate gyrus and frontal cortex of 5xFAD-Rag2KO mice. Interrogation of inflammation gene expression documented down-regulation of pro-inflammatory cytokines (IL1A&B, IL6), complement cascade (C1qa, C1qb, C1qc, C4a/b), toll-like receptors (Tlr3, Tlr4 and Tlr7) and microglial activations markers (CD14, Tyrobp,Trem2) following Treg administration. CONCLUSIONS: Ex vivo expanded Tregs with amplified immunomodulatory function, suppressed neuroinflammation and alleviated AD pathology in vivo. Our results provide preclinical evidences for Treg cell therapy as a potential treatment strategy in AD.

Between the devil and the deep blue sea: A review of 25 modern naval mass casualty incidents with implications for future Distributed Maritime Operations.

ABSTRACT: In the future, United States Navy Role 1 and Role 2 shipboard medical departments will be caring for patients during Distributed Maritime Operations in both contested and noncontested austere environments; likely for prolonged periods of time. This literature review examines 25 modern naval mass casualty incidents over a 40-year period representative of naval warfare, routine naval operations, and ship-based health service support of air and land operations. Challenges, lessons learned, and injury patterns are identified to prepare afloat medical departments for the future fight. LEVEL OF EVIDENCE: Literature Review, level V.

Military deployment's impact on the surgeon's practice.

BACKGROUND: As the United States withdraws from overseas conflicts, general surgeons remain deployed in support of global operations. Surgeons and surgical teams are foundational to combat casualty care; however, currently, there are few casualty producing events. Low surgical volume and acuity can have detrimental effects on surgical readiness for those frequently deployed. The surgical team cycle of deployment involves predeployment training, drawdown of clinical practice, deployment, postdeployment reintegration, and rebuilding of a patient panel. This study aims to assess these effects on typical general surgeon practices. Quantifying the overall impact of deployment may help refine and implement measures to mitigate the effects on skill retention and patient care. METHODS: Surgeon case logs of eligible surgeons deploying between January 1, 2017, and January 1, 2020, were included from participating military treatment facilities. Eligible surgeons were surgeons whose case logs were primarily at a single military treatment facility 26 weeks before and after deployment and whose deployment duration, location, and number of deployed cases were obtainable. RESULTS: Starting 26 weeks prior to deployment, analyzing in 1-week intervals toward deployment time, case count decreased by 4.8% (p < 0.0001). With each 1-week interval, postdeployment up to the 26-week mark, case count increased by 6% (p < 0.0001). Cases volumes most prominently drop 3 weeks prior to deployment and do not reach normal levels until approximately 7 weeks postdeployment. Case volumes were similar across service branches. CONCLUSION: There is a significant decrease in the number of cases performed before deployment and increase after return regardless of military branch. The perideployment surgical volume decline should be understood and mitigated appropriately; predeployment training, surgical skill retention, and measures to safely reintegrate surgeons back into their practice should be further developed and implemented. LEVEL OF EVIDENCE: Economic/Decision, Level III.

The effect of platelet G proteins on platelet extravasation and tumor growth in the murine model of ovarian cancer.

We and other investigators have shown that platelets promote metastasis and the growth of tumors. Our rationale for conducting this study is that platelets' prometastatic and progrowth effects depend on a close encounter between platelets and cancer cells. This interaction occurs inside blood vessels with circulating tumor cells and outside blood vessels with cancer cells residing in the tumor parenchyma. Our hypothesis was that platelet extravasation is required for the effect of platelets on tumor growth. Platelets respond to environmental stimuli by activation of G protein-coupled receptors on their surface. We investigated the impact of various platelet G proteins on the growth of ovarian cancer tumors and platelet extravasation. We used mice with platelet-specific deficiency of Gαi2 (Gi), Gα13 (G13), or Gαq (Gq) in a syngeneic ovarian cancer model. We measured the total weight of tumor nodules resected from tumor-bearing mice. We developed methods for automated whole-slide image acquisition and unbiased computerized image analysis to quantify extravasated platelets. We compared the number of platelets inside tumor nodules of platelet G protein-deficient tumor-bearing mice. We found that deficiency of Gi and G13, but not Gq, in platelets resulted in smaller tumors compared with those in corresponding littermates. Deficiency of Gi and G13 in platelets reduced the number of extravasated platelets by >90%, but deficiency of Gq did not reduce the number of extravasated platelets significantly. The lack of Gi or G13 in platelets reduced platelet extravasation into the tumor and tumor growth.

An imageomics and multi-network based deep learning model for risk assessment of liver transplantation for hepatocellular cancer.

INTRODUCTION: Liver transplantation (LT) is an effective treatment for hepatocellular carcinoma (HCC), the most common type of primary liver cancer. Patients with small HCC (<5 cm) are given priority over others for transplantation due to clinical allocation policies based on tumor size. Attempting to shift from the prevalent paradigm that successful transplantation and longer disease-free survival can only be achieved in patients with small HCC to expanding the transplantation option to patients with HCC of the highest tumor burden (>5 cm), we developed a convergent artificial intelligence (AI) model that combines transient clinical data with quantitative histologic and radiomic features for more objective risk assessment of liver transplantation for HCC patients. METHODS: Patients who received a LT for HCC between 2008-2019 were eligible for inclusion in the analysis. All patients with post-LT recurrence were included, and those without recurrence were randomly selected for inclusion in the deep learning model. Pre- and post-transplant magnetic resonance imaging (MRI) scans and reports were compressed using CapsNet networks and natural language processing, respectively, as input for a multiple feature radial basis function network. We applied a histological image analysis algorithm to detect pathologic areas of interest from explant tissue of patients who recurred. The multilayer perceptron was designed as a feed-forward, supervised neural network topology, with the final assessment of recurrence risk. We used area under the curve (AUC) and F-1 score to assess the predictability of different network combinations. RESULTS: A total of 109 patients were included (87 in the training group, 22 in the testing group), of which 20 were positive for cancer recurrence. Seven models (AUC; F-1 score) were generated, including clinical features only (0.55; 0.52), magnetic resonance imaging (MRI) only (0.64; 0.61), pathological images only (0.64; 0.61), MRI plus pathology (0.68; 0.65), MRI plus clinical (0.78, 0.75), pathology plus clinical (0.77; 0.73), and a combination of clinical, MRI, and pathology features (0.87; 0.84). The final combined model showed 80 % recall and 89 % precision. The total accuracy of the implemented model was 82 %. CONCLUSION: We validated that the deep learning model combining clinical features and multi-scale histopathologic and radiomic image features can be used to discover risk factors for recurrence beyond tumor size and biomarker analysis. Such a predictive, convergent AI model has the potential to alter the LT allocation system for HCC patients and expand the transplantation treatment option to patients with HCC of the highest tumor burden.

Trauma-Sensitive Yoga Interventions and Posttraumatic Stress and Depression Outcomes Among Women: A Systematic Review and Analysis of Randomized Control Trials.

Research shows that most people experience at least one traumatic event in their lifetimes, and between 6% and 8% of those with a history of trauma will develop posttraumatic stress disorder (PTSD) and/or related mental health conditions. Women face a greater threat of trauma exposure and have a higher risk of PTSD and depression than men. Trauma-Sensitive Yoga (TSY), a body-based adjunctive therapy, has shown potential in several studies as an effective method for reducing PTSD and depression symptoms. However, existing research and systematic reviews vary widely in their methodological rigor and comparison samples. Thus, in this systematic review we examined the effectiveness of TSY among women with a history of trauma and depression who had participated in randomized control trials with clear control and experimental groups. Findings in fixed- and mixed-effects meta-analysis models suggest marginally significant to no effects of TSY on PTSD and depression outcomes. Our systematic review highlights critical questions and significant gaps in the existing literature about the rationale and best practices of TSY intervention duration.

Current challenges in military trauma readiness: Insufficient relevant surgical case volumes in military treatment facilities.

BACKGROUND: The management of battlefield trauma requires a specific skill set, which is optimized by regular trauma experience. As military casualties from the prolonged conflicts in the Middle East decrease, challenges exist to maintain battlefield trauma readiness. Military surgeons must therefore depend on the Military Health System. The purpose of the study was to evaluate the frequency of surgical cases relevant to deployed combat casualty care performed at military treatment facilities (MTFs). METHODS: Combat casualty care relevant cases (CCC-RCs) were defined as emergent, open surgical cases in which the patient required a blood transfusion. Case logs from four military treatment centers with surgical residency training programs were used. Twenty-four months of case records between January 1, 2017, and January 1, 2019, were included to determine total numbers of CCC-RCs at each institution. The results were compared with San Antonio Military Medical Center's, the Department of Defense's only American College of Surgeons-verified level 1 trauma center. RESULTS: Fifty-one trauma/general surgeons and six vascular surgeons case logs were examined. Thirty (0.3%) of 10,529 cases performed by trauma/general and vascular surgeons over the 2-year study period were considered CCC-RCs. These results were in contrast to San Antonio Military Medical Center, which had a significantly higher proportion of CCC-RCs (113 of 320 cases, 35.3%, p < 0.0001). CONCLUSION: A cross-section of MTF surgical case complexity demonstrates a lack of cases considered to be CCC-RCs. At the MTFs evaluated, surgical case surrogates for combat trauma and combat casualty care is close to zero. These data are potentially representative of other military treatment centers, which focus on beneficiary care. For readiness purposes, MTFs that care primarily for Tricare beneficiaries without a significant trauma population should not be considered meaningful sources of CCC-RCs for trauma/general and vascular surgeons. LEVEL OF EVIDENCE: Therapeutic/care management study, level V.

The ABC's of Pancreatic Trauma: Airway, Breathing, and Computerized Tomography Scan?

OBJECTIVES: Missed pancreatic injury carries significant morbidity. Computerized tomography (CT) imaging is useful, but may lack sensitivity to identify pancreatic injury. New-generation CT scanners should improve sensitivity, but this has not been studied. A previous study published in 2002 evaluating the sensitivity for identifying pancreatic injury with single-slice CT scanners yielded a 68% correlation between operative and CT findings. We aim to study the accuracy of modern CT for diagnosis and grading of pancreatic injury. METHODS: All trauma admissions from 2008 and 2012 were retrospectively reviewed. Patients with a pancreatic injury, either on CT or intraoperatively, were included (n = 96). Sensitivity and specificity were calculated using Student's t test. RESULTS: 48 patients had injuries noted on CT and in the operating room. In this group, 68.8% had CT findings discordant with operative findings. Of these, 78.8% had no injury noted on CT, of which 26.9% required surgical intervention. Seven patients with injury on CT had none identified in the operating room. Based on these results, the sensitivity for CT imaging to identify an injury is 36.4% with a positive predictive value of 68.2%. CONCLUSIONS: Our results indicate that despite advances in CT technology, the sensitivity and specificity for identifying pancreatic injury remains low. Although CT scans remain critical in trauma evaluation, awareness of this diagnostic gap is important. Further analysis is required to determine any impact on patient outcomes.

Penetrating aerodigestive injuries in the neck: a proposed CT-aided modified selective management algorithm.

OBJECTIVES: To determine the specific CT findings of penetrating neck wound profile predicting aerodigestive injuries, diagnostic performance of CTA and to propose a modified selective management algorithm to reduce nontherapeutic invasive procedures. METHODS: We retrospectively evaluated CTAs of 102 patients to determine the presence of various CT signs. "Trajectory"-based signs included trajectory of the wound extending into the aerodigestive tract and trajectory violating the deep neck spaces. "Conventional" signs included transcervical injury; wall defect; air or blood in the deep neck spaces; irregular or thickened aerodigestive tract; and active mucosal bleeding. RESULTS: Trajectory of the wound extending into the aerodigestive tract (sensitivity 76 %, specificity 97 %) and trajectory of the wound violating the suprahyoid deep neck spaces or the infrahyoid visceral space (sensitivity 97 %, specificity 55 %) were the best predictors of injury on regression analysis. The most specific "conventional" CT signs were "wall defect" and "active mucosal bleed", but had very low sensitivity. The sensitivity of CTA for detecting an injury ranged from 89.5 % to 92 %, specificity ranged from 62.5 % to 89 %. CONCLUSION: CTA can be a useful technique in detecting aerodigestive injury. Our proposed management algorithm can exclude an injury with high degree of confidence (sensitivity 97 %). KEY POINTS: • Trajectory-based CT signs predict aerodigestive injury after penetrating neck trauma. • Surgery should be considered when trajectory extends into the infra-arytenoid aerodigestive tract. • Endoscopy or exploration should be considered when trajectory violates deep neck spaces. • This modified approach can decrease negative explorations and invasive diagnostic procedures.

Through the looking glass: early non-invasive imaging in TBI predicts the need for interventions.

BACKGROUND: Early diagnosis and treatment of traumatic brain injury (TBI) lead to better outcomes. It is difficult to predict which patients benefit from specialised centres, leading to over triage or delay in definitive care. We propose that a non-invasive test comprising optic nerve sheath ultrasound, transcranial Doppler and quantitative papillary reactivity is feasible, correlates with CT findings and may allow for accurate early identification of TBI. METHODS: A 1-year, prospective observation study evaluated a low-risk, non-invasive method of assessing brain injury. Patients underwent a non-invasive neurological examination for trauma, including the above assessments. Data from the three examinations were collected within 6 hours of injury and at 24 hours, and were analysed. Demographics, haemodynamic data, imaging results and short-term outcomes/interventions were recorded. RESULTS: Trauma patients over the age of 18 years, with a Glascow coma scale (GCS) of <12 or CT evidence of TBI, and intubated were included (N=100). These were divided into +CT (n=49) and -CT groups (n=51) according to the Marshall CT classification of TBI. The +CT group was older, with worse GCS and higher lactate (p=0.008, p=0.001 and p=0.01) but were otherwise well matched. The +CT group included all TBI types, with 96% of the patients having more than one type of TBI. Pulsatility index and neurologic pupillary index were predictive of a +CT (p=0.04, p=0.02). Area under the receiver-operating curve for the logistic regression model for the prediction of positive radiographic findings was r=0.718. Finally, we suggest a preliminary scoring heuristic for predicting a positive radiological finding in a patient with TBI. CONCLUSIONS: The proposed examination is a feasible, non-invasive tool that may have clinical utility in the early prediction of TBI. If validated, it may improve trauma triage for the brain-injured patient. Further studies are warranted to validate this model.

Deep Brain Stimulation in a Case of Mitochondrial Disease.

BACKGROUND: DBS has proven to be an effective therapy for Parkinson's disease, essential tremor, and primary dystonia. Mixed results have been reported in case series for other hyperkinetic disorders, and sparse data are available regarding secondary movement disorders. We report on the clinical effects of bilateral globus pallidus internus (GPi) DBS, a progressive mitochondrial cytopathy. METHODS: A single patient with myoclonus and dystonia syndrome secondary to a mitochondrial cytopathy with history of perinatal hypoxia was identified from our University of Florida DBS database. Demographics, clinical, surgical, and DBS data were documented. RESULTS: At 6 months post-DBS, we observed a 32% (361 to 527) improvement on quality of life (36-item Medical Outcome Study Short-Form Health Survey; SF-36). Objective clinical scales revealed a 33% (143 to 96) improvement in the Unified Myoclonus Rating Scale (UMRS) total score. The UMRS action myoclonus subsection revealed a 29% (69 to 46) improvement. No significant changes were observed in the Burke-Fahn-Mardsen Dystonia Rating Scale (BFMDRS). After 1-year follow-up, a worsening of 59% (527 to 215) was observed in the SF-36 scale, of 19% (28.5 to 35) in the BFMDRS, and of 23% (96 to 124) in the UMRS. However, the frequency and intensity of action myoclonus scores remained lower when compared to baseline scores. CONCLUSIONS: Although we observed a loss of benefit in the long term for most quality-of-life and clinical outcomes, the DBS effects on action myoclonus seemed to remain stable. Longer follow-up studies are necessary to confirm our short-term and unblinded findings.

Ratio-driven resuscitation predicts early fascial closure in the combat wounded.

BACKGROUND: Operation Iraqi Freedom and Operation Enduring Freedom have seen the highest rates of combat casualties since Vietnam. These casualties often require massive transfusion (MT) and immediate surgical attention to control hemorrhage. Clinical practice guidelines dictate ratio-driven resuscitation (RDR) for patients requiring MT. With the transition from crystalloid to blood product resuscitation, we have seen fewer open abdomens in combat casualties. We sought to determine the effect RDR has on achieving early definitive abdominal fascial closure in combat casualties undergoing exploratory laparotomy. METHODS: Records of 1,977 combat casualties admitted to a single US military hospital from April 2003 to December 2011 were reviewed. Patients receiving an MT and laparotomy in theater constituted the study cohort. The cohort was divided into RDR, defined as a ratio of 0.8-U to 1.2-U packed red blood cells to 1-U fresh frozen plasma, and No-RDR groups. Age, injury patterns, mechanism of injury, injury severity, blood products, number of laparotomies, and days to fascial closure were collected. Assessed outcomes were number of days (early ≤ 2 days) and number of laparotomies to achieve fascial closure. RESULTS: The mean age of the study cohort (n = 172) was 24.0 years, and mean Injury Severity Score (ISS) was 24.8. Improvised explosive device blast was the most common mechanism of injury (74.4%). The cohort was divided into RDR patients (n = 73) and no RDR (n = 99). There was no difference in mean age, mean ISS, or rate of nontherapeutic exploratory laparotomies between the groups. RDR patients had a significantly lower abdominal injury rate (34.2% vs. 72.7%, p < 0.01), had fewer laparotomies (2.7 vs. 4.3, p = 0.003), and achieved primary fascial closure faster (2.4 days vs. 7.2 days, p = 0.004). On multivariate analysis, RDR (2.74; 95% confidence interval, 1.44-5.2) was an independent predictor for early fascial closure. CONCLUSION: Adherence to RDR guidelines resulted in significantly decreased number of abdominal operations and was identified as an independent predictor for early fascial closure. Further investigation is warranted to validate these findings. LEVEL OF EVIDENCE: Therapeutic study, level III.

Individual and interpersonal risk factors for physical intimate partner violence perpetration by biological sex and ethnicity.

Intimate partner violence (IPV) is a public health problem that reaches across age, sex, and ethnicity. In this study, we examined risk factors for physical IPV perpetration among young adult males and females from four ethnic groups. Data were taken from Waves 1-3 of the National Longitudinal Study of Adolescent Health (Add Health). The sample included 10,141 Wave 3 respondents (ages ranged from 18-27 years old) who reported being in a current romantic relationship. Physical IPV perpetration was reported by 14.10% of White, 23.28% of Black, 18.82% of Latino, and 18.02% of Asian males. Physical IPV perpetration was reported by 19.01% of White, 24.80% of Black, 25.97% of Latina, and 19.21% of Asian females. Following an ecological framework, proximal risk factors at intrapersonal and interpersonal levels were included in the analyses. Despite finding fairly consistent percentage of physical IPV perpetration across sample groups, the risk factors for physical IPV perpetration were rather uncommon across sex and ethnicity. Only 1 factor--psychological IPV perpetration toward a romantic partner--was consistently associated with physical IPV perpetration across all groups. Our findings have implications for tailoring prevention and intervention efforts toward risk factors of physical IPV perpetration that are uniquely associated with biological sex and ethnicity.