Comparison of the Vaginal and Labial Dimensions of Ethnic Chinese and Western Nullipara.

INTRODUCTION AND HYPOTHESIS: Vaginal dimensions have clinical and surgical implications. We sought to quantify the differences between vaginal and labial dimensions in healthy ethnic Chinese and Western women with normal pelvic organ support. METHODS: This is a cross-sectional study of a convenience sample of ethnic Chinese nulliparas (n = 33) and Western nulliparas (n = 33) recruited for research purposes. For each subject, magnetic resonance imaging was used to quantify the vaginal and labial dimensions. Specifically, we identified the anterior and posterior vaginal wall, the outline of the cervix in the mid-sagittal and coronal planes, and the distance from the labia majora to the hymenal ring at the urethral meatus. RESULTS: There were significant differences in age and weight between groups. Substantial variation in vaginal and labial dimensions was found within each group. The vaginal and labial dimensions of ethnic Chinese women ranged from 9-21% smaller than those of Western women; In the ethnic Chinese group, increasing weight and BMI correlated with greater labial distance (r = 0.66 and r = 0.63 respectively); as did height and the distance from the vaginal opening to the cervical os (r = 0.5). In the Western group, only weight correlated with the labial distance (r = 0.51). CONCLUSIONS: Significant group differences in vaginal and labial dimensions were found, with the dimensions of Chinese nulliparas being up to 21% smaller than those of Western nulliparas.

Extracorporeal membrane oxygenation in severe traumatic brain injury: Is it safe?

BACKGROUND: Patients with severe traumatic brain injury (TBI) are at an increased risk of respiratory failure refractory to traditional therapies. The safety of extracorporeal membrane oxygenation (ECMO) in this population remains unclear. We aimed to examine outcomes following ECMO compared with traditional management in severe TBI patients. METHODS: We performed a retrospective cohort study using the Trauma Quality Improvement Program (2017-2020). We identified patients 18 years or older with severe TBI (Abbreviated Injury Score head, ≥3) who underwent ECMO or had either in-hospital cardiac or acute respiratory distress syndrome during their hospitalization. The study excluded pPatients who arrived without signs of life, had a prehospital cardiac arrest, had an unsurvivable injury, were transferred out within 48 hours of arrival, or were received as a transfer and died within 12 hours of arrival Patients with missing information regarding in-hospital mortality were also excluded. Outcomes included mortality, in-hospital complications, and intensive care unit length of stay. To account for patient and injury characteristics, we used 1:1 propensity matching. We performed a subgroup analysis among ECMO patients, comparing patients who received anticoagulants with those who did not. RESULTS: We identified 10,065 patients, of whom 221 (2.2%) underwent ECMO. In the propensity-matched sample of 134 pairs, there was no difference in mortality. Extracorporeal membrane oxygenation was associated with a higher incidence of cerebrovascular accidents (9% vs. 1%, p = 0.006) and a lower incidence of ventilator-associated pneumonia. In the subgroup analysis of 64 matched pairs, patients receiving anticoagulation had lower mortality, higher unplanned return to the operating room, and longer duration of ventilation and intensive care unit length of stay. CONCLUSION: Extracorporeal membrane oxygenation use in severe TBI patients was not associated with higher mortality and should be considered a potential intervention in this patient population. Systemic anticoagulation showed mortality benefit, but further work is required to elucidate the impact on neurological outcomes, and the appropriate dosing and timing of anticoagulation. LEVEL OF EVIDENCE: Therapeutic; Level IV.

Functional Lipids and Cardiovascular Disease Reduction: A Concise Review.

Functional lipids are dietary substances that may have an impact on human health by lowering the risk of chronic illnesses and enhancing the quality of life. Numerous functional lipids have been reported to have potential health benefits in the prevention, management, and treatment of cardiovascular disease, the leading cause of death in the United States. However, there is still insufficient and contradictory information in the literature about their effectiveness and associated mechanisms of action. The objective of this review, therefore, is to evaluate available literature regarding these functional lipids and their health benefits. Various studies have been conducted to understand the links between functional lipids and the prevention and treatment of chronic diseases. Recent studies on phytosterols have reported that CLA, medium-chain triglycerides, and omega-3 and 6 fatty acids have positive effects on human health. Also, eicosanoids, which are the metabolites of these fatty acids, are produced in relation to the ratio of omega-3 to omega-6 polyunsaturated fatty acids and may modulate disease conditions. These functional lipids are available either in dietary or supplement forms and have been proven to be efficient, accessible, and inexpensive to be included in the diet. However, further research is required to properly elucidate the dosages, dietary intake, effectiveness, and their mechanisms of action in addition to the development of valid disease biomarkers and long-term effects in humans.

Post-discharge Outcomes and Healthcare Utilization Among Hispanic/Latinx Injury Survivors: English Language Proficiency Matters.

OBJECTIVE: We sought to compare post-discharge outcomes and healthcare utilization between English-speaking non-Hispanic White (NHW), English-speaking Hispanic/Latinx (ESHL), and Spanish-speaking Hispanic/Latinx (SSHL) survivors of traumatic injury. BACKGROUND: While there is evidence of racial and ethnic disparities in healthcare utilization and post-discharge outcomes after injury, the role of English language proficiency in these disparities remains unclear. METHODS: Moderate to severely injured adults from three level-1 trauma centers completed an interview in English or Spanish between 6-12 months post-injury to assess physical health-related quality of life (SF-12-PCS), return to work, and post-discharge healthcare utilization. The language used in the interview was used as a proxy for English-language proficiency, and participants were categorized as either NHW (reference), ESHL, or SSHL. Multivariable regression models estimated independent associations between language and race/ethnicity with SF-12-PCS, return to work, and post-discharge healthcare utilization outcomes. RESULTS: 3,304 injury survivors were followed: 2,977 (90%) NHW, 203 (6%) ESHL, and 124 (4%) SSHL. In adjusted analyses, no significant differences were observed between ESHL and NHW injury survivors for any outcomes at 6-12 months post-injury. However, SSHL injury survivors exhibited a lower mean SF-12-PCS (41.6 vs. 38.5), -3.07 (95% CI=-5.47, -0.66; P=0.012), decreased odds of returning to work (OR=0.47; CI=0.27 to 0.81; P=0.007), and were less likely to engage in non-injury related outpatient visits, such as primary care visits (OR=0.45; 95% CI 0.28, 0.73; P=0.001), compared to NHW patients. CONCLUSION: Hispanic/Latinx injury survivors have worse post-discharge outcomes and lower non-injury-related healthcare utilization than NHW if they have limited English-language proficiency. Addressing LEP-related barriers to care could help mitigate outcome and healthcare utilization disparities among Hispanic/Latinx injury survivors.

DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction in C. elegans amyloid ß proteotoxicity.

Iron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer's disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals. However, the degree to which iron overload contributes to AD pathogenesis is unclear. Here, we evaluated the involvement of ferroptosis, an iron-dependent cell death process, in mediating AD-like pathologies in C. elegans. Results showed that iron accumulation occurred prior to the loss of neuronal function as worms age. In addition, energetic imbalance was an early event in iron-induced loss of neuronal function. Furthermore, the loss of neuronal function was, in part, due to increased mitochondrial reactive oxygen species mediated oxidative damage, ultimately resulting in ferroptotic cell death. The mitochondrial redox environment and ferroptosis were modulated by pharmacologic processes that exacerbate or abolish iron accumulation both in wild-type worms and worms with increased levels of neuronal amyloid beta (Aß). However, neuronal Aß worms were more sensitive to ferroptosis-mediated neuronal loss, and this increased toxicity was ameliorated by limiting the uptake of ferrous iron through knockout of divalent metal transporter 1 (DMT1). In addition, DMT1 knockout completely suppressed phenotypic measures of Aß toxicity with age. Overall, our findings suggest that iron-induced ferroptosis alters the mitochondrial redox environment to drive oxidative damage when neuronal Aß is overexpressed. DMT1 knockout abolishes neuronal Aß-associated pathologies by reducing neuronal iron uptake.

The Relationship Between Body Mass Index and Long-Term Outcomes Following Traumatic Injury.

INTRODUCTION: Little is known about the relationship between body mass index (BMI), a function of mass and height (masskg/height2m) and long-term outcomes among traumatic injury survivors. In this prospective cohort study, we investigate the relationship between BMI and long-term health outcomes in the trauma population. METHODS: Adult trauma survivors with an injury severity score ≥9 admitted to one of three level 1 trauma centers, from January 1, 2015 to December 31, 2022, were surveyed via telephone between 6 and 12 mo postinjury. Participants were stratified into one of five groups by BMI at the time of trauma: L-BMI (BMI <18.5), N-BMI (BMI 18.5-24.9), H1-BMI (BMI 25-29.9), H2-BMI (BMI 30-34.9), and H3-BMI (BMI ≥35); N-BMI was used as the referent. Mental and physical health-related quality of life scores, pain, new functional limitations, and hospital readmissions were evaluated. Univariate and multivariate analyses were used to compare outcomes between study groups. RESULTS: 3830 patients were included. Of those, 124 were L-BMI (3.2%), 1495 N-BMI (39%), 1318 H1-BMI (34.4%), 541 H2-BMI (14.1%), and 352 H3-BMI (9.2%). L-BMI was associated with adverse physical (b = -3.13, CI = -5.71 to -0.55, P = 0.017) and mental health (b = -3.17, CI = -5.87 to -0.46, P = 0.022) outcomes 6-12 mo postinjury compared to the referent. H1-BMI and H2-BMI had higher odds of wo`rse physical outcomes (b = -1.47, CI = -2.42 to -0.52, P = 0.002; b = -3.11, CI = - 4.33 to -1.88, P ≤ 0.001, respectively) and chronic pain (adjusted odds ratio (aOR) = 1.24, CI = 1.04-1.47, P = 0.016; aOR = 1.52, CI = 1.21-1.90, P ≤ 0.001, respectively). Patients with H3-BMI had higher odds of worse physical outcomes compared to N-BMI (b = -4.82, CI = -6.28 to -3.37, P ≤ 0.001), chronic pain (aOR = 2.11, CI = 1.61-2.78, P ≤ 0.001), all-cause hospital readmissions (aOR = 1.62, CI = 1.10-2.34, P = 0.013), and new functional limitations (aOR = 1.39, CI = 1.08-1.79, P = 0.01). CONCLUSIONS: BMI variance above or below N-BMI is associated with worse long-term outcomes following traumatic injury.

Fish-inspired tracking of underwater turbulent plumes.

Autonomous ocean-exploring vehicles have begun to take advantage of onboard sensor measurements of water properties such as salinity and temperature to locate oceanic features in real time. Such targeted sampling strategies enable more rapid study of ocean environments by actively steering towards areas of high scientific value. Inspired by the ability of aquatic animals to navigate via flow sensing, this work investigates hydrodynamic cues for accomplishing targeted sampling using a palm-sized robotic swimmer. As proof-of-concept analogy for tracking hydrothermal vent plumes in the ocean, the robot is tasked with locating the center of turbulent jet flows in a 13,000-liter water tank using data from onboard pressure sensors. To learn a navigation strategy, we first implemented RL on a simulated version of the robot navigating in proximity to turbulent jets. After training, the RL algorithm discovered an effective strategy for locating the jets by following transverse velocity gradients sensed by pressure sensors located on opposite sides of the robot. When implemented on the physical robot, this gradient following strategy enabled the robot to successfully locate the turbulent plumes at more than twice the rate of random searching. Additionally, we found that navigation performance improved as the distance between the pressure sensors increased, which can inform the design of distributed flow sensors in ocean robots. Our results demonstrate the effectiveness and limits of flow-based navigation for autonomously locating hydrodynamic features of interest.

Racial and Ethnic Disparities in Emergency General Surgery Outcomes Among Older Adult Patients.

INTRODUCTION: Racial and ethnic disparities in emergency general surgery (EGS) patients have been well described in the literature. Nonetheless, the burden of these disparities, specifically within the more vulnerable older adult population, is relatively unknown. This study aims to investigate racial and ethnic disparities in clinical outcomes among older adult patients undergoing EGS. METHODS: This retrospective analysis used data from 2013 to 2019 American College of Surgeons National Surgery Quality Improvement Program database. EGS patients aged 65 y or older were included. Patients were categorized based on their self-reported race and ethnicity. The primary outcomes evaluated were in-hospital mortality, 30-d mortality, and overall morbidity. Multivariable logistic regression was performed to examine the relationship between race/ethnicity and postoperative outcomes while adjusting for relevant factors including age, comorbidities, functional status, preoperative conditions, and surgical procedure. RESULTS: A total of 54,132 patients were included, of whom 79.8% identified as non-Hispanic White, 9.5% as non-Hispanic Black (NHB), 5.8% as Hispanic, and 4.2% as non-Hispanic Asian. After risk adjustment, compared to non-Hispanic White patients, NHB, non-Hispanic Asian, and Hispanic patients had decreased odds of 30-d mortality. For 30-d readmission and reoperation, differences among groups were comparable. However, NHB patients had significantly increased odds of overall morbidity (adjusted odds ratio, 1.18; 95% confidence interval: 1.10-1.26; P < 0.001) and postoperative complications including sepsis, venous thromboembolism, and unplanned intubation. Hispanic ethnicity was associated with lower odds of postoperative myocardial infarction and stroke. CONCLUSIONS: Among older adult patients undergoing emergency general surgery, minority patients experienced higher morbidity rates, but paradoxical disparities in mortality were detected. Further research is necessary to identify the cause of these disparities and develop targeted interventions to eliminate them.

The impact of comorbidities and functional status on outcomes in the older adult emergency general surgery patient.

BACKGROUND: The aim of this study is to quantify the relative contribution of comorbidities and pre-operative functional status on outcomes in geriatric emergency general surgery (EGS) patients. METHODS: This is a retrospective study of older-adult EGS patients at an academic medical center between 2017 and 2018. Patients ≥65 years were included. The primary outcomes examined were 30-day mortality, 30-day morbidity, and length of stay (LOS). RESULTS: 734 patients were included. The mean age was 76, and 48.9 â€‹% received non-operative management. The median LOS was 6.8 days; 11.8 â€‹% of patients died within 30 days, and 40.6 â€‹% developed morbidities. Lacking capacity to consent on admission was independently associated with 30-day mortality (OR: 2.63, [1.32-5.25], p â€‹= â€‹0.006). Comorbidities associated with developing morbidity were CVA with neurologic deficit (OR: 2.29, [1.20-4.36], p â€‹= â€‹0.012), CHF (OR: 2.60, [1.64-4.11], p â€‹< â€‹0.001), in addition to pre-operative delirium (OR: 3.42, [1.43-8.14], p â€‹= â€‹0.006). CONCLUSIONS: A significant contribution to outcomes is determined by pre-admission comorbidities and cognitive and functional status. Opportunities exist for collaboration between Acute Care Surgery and geriatric medicine teams for the optimization of comorbidities.

The Optimal Approach to Surgical Management of Goblet Cell Carcinoid of the Appendix: A Systematic Review.

INTRODUCTION: Goblet cell carcinoid (GCC) is a rare and poorly understood appendiceal neoplasm, exhibiting mixed histological and aggressive clinical features. Current guidelines recommend right hemicolectomy in all cases, although there is conflicting evidence that appendicectomy alone may be sufficient. This review aims to identify the optimal surgical management for appendiceal GCC. METHODS: A systematic review was performed by searching MEDLINE, Embase, Scopus and the Cochrane Register of Controlled Trials. Randomised controlled trials, cohort studies or large case series (>5 patients) reporting clinical outcomes for patients undergoing surgical management of GCC of the appendix were included. Outcomes extracted included participant and tumour characteristics, type of surgery and survival data. RESULTS: A total of 1341 studies were retrieved. After duplicate removal, 796 titles were screened for relevance prior to abstract and full text review. A total of six studies were included for analysis, comprising 3177 patients-1629 females and 1548 males. The median age ranged from 51 to 72 years. A total of 2329 patients underwent right hemicolectomy, while 824 were treated with appendicectomy only. Overall, the included studies report increased survival in patients undergoing right hemicolectomy compared to appendicectomy alone. A meta-analysis was not possible due to insufficient data reported in the published literature to date. CONCLUSIONS: There is no consensus regarding the optimal surgical management of appendiceal GCC, as outcomes-based data comparing surgical interventions are lacking. It is possible that some patients with favourable features are overtreated. The absence of robust evidence to support a more conservative approach means that right hemicolectomy remains the standard of care for all patients, in keeping with current international guidelines. The rarity of this condition and limited data in the published studies remain barriers to evidence-based best clinical practice.

Measure of 90Y-glass microspheres residue post-TARE using PET/CT and potential impact on tumor absorbed dose in comparison 99mTc-MAA SPECT/CT dosimetry.

BACKGROUND: Transarterial radio-embolization (TARE) became a routine procedure for non-resectable liver tumor mainly hepatocellular carcinoma (HCC). Personalized dosimetry to the index lesion increased tumor response rate. However, there is no requirement to measure the precise activity injected during TARE. We measured 90Y-glass microspheres residue (90Y-Res) in the application system after TARE and assessed its potential impact on the tumor absorbed dose (AD) previously planned with 99mTc MAA SPECT/CT. METHODS: We measured 90Y-Res using PET/CT in all patients that underwent TARE using 90Y-glass-microspheres for non-resectable liver tumors over one year. RESULTS: 90Y-Res was measured in 34 patients (HCC n = 22) with 61 injections, 93.1 ± 94.6 MBq [2-437] that was 4.8 ± 3.5% [0.2-13.7] in comparison to the activity measured in the sealed TheraSphere™ vial (ρ = 0.697; p < 0.001). CONCLUSION: We reported an average of 5% 90Y-Res using PET/CT after TARE with the strongest association to the activity in the TheraSphere™ vial. Therefore, when a high 90Y-Res is suspected on the survey meter, a 90Y-PET/CT scan of 90Y-Res might be useful as a first step to estimate if the target lesion received the recommended AD, especially in HCC patients with borderline tumor dosimetry on the pre-treatment 99mTc-MAA SPECT/CT.

The correlation of CT-derived muscle density, skeletal muscle index, and visceral adipose tissue with nutritional status in severely injured patients.

BACKGROUND: This study explored if computerized tomography-derived body composition parameters (CT-BCPs) are related to malnutrition in severely injured patients admitted to the Intensive Care Unit (ICU). METHODS: This prospective cohort study included severely injured (Injury Severity Score ≥ 16) patients, admitted to the ICU of three level-1 trauma centers between 2018 and 2022. Abdominal CT scans were retrospectively analyzed to assess the CT-BCPs: muscle density (MD), skeletal muscle index (SMI), and visceral adipose tissue (VAT). The Subjective Global Assessment was used to diagnose malnutrition at ICU admission and on day 5 of admission, and the modified Nutrition Risk in Critically ill at admission was used to assess the nutritional risk. RESULTS: Seven (11%) of the 65 analyzed patients had malnutrition at ICU admission, increasing to 23 patients (35%) on day 5. Thirteen (20%) patients had high nutritional risk. CT-BCPs were not related to malnutrition at ICU admission and on day 5. Patients with high nutritional risk at admission had lower MD (median (IQR) 32.1 HU (25.8-43.3) vs. 46.9 HU (37.7-53.3); p < 0.01) and higher VAT (median 166.5 cm2 (80.6-342.6) vs. 92.0 cm2 (40.6-148.2); p = 0.01) than patients with low nutritional risk. CONCLUSION: CT-BCPs do not seem related to malnutrition, but low MD and high VAT may be associated with high nutritional risk. These findings may prove beneficial for clinical practice, as they suggest that CT-derived parameters may provide valuable information on nutritional risk in severely injured patients, in addition to conventional nutritional assessment and screening tools. LEVEL OF EVIDENCE: Level III, Prognostic/Epidemiological.

Renal angioembolization vs. surgery for high-grade renal trauma: a nationwide comparative analysis.

PURPOSE: Renal angioembolization (RAE) is widely employed in low-grade renal injuries and associated with improved patient outcomes, while surgery remains the mainstay for managing high-grade injuries. We compared the outcomes following surgery and RAE in high-grade renal trauma (HGRT). METHODS: We used the ACS TQIP 2016-2020 to identify patients ≥ 16 years with HGRT who underwent RAE or surgery. Morbidity was the primary outcome, while mortality and lengths of stay were secondary outcomes. We accounted for clinically relevant characteristics using multilevel logistic regression analyses. RESULTS: We included 591 patients, of whom 279 (47.2%) underwent RAE. After adjusting, there was no difference in morbidity, hospital LOS, or ICU LOS. The surgery cohort had increased odds of mortality (aOR 4.93; [95% CI] 1.53-15.82; p = 0.007) compared to RAE. In the penetrating injury subgroup, no associations between management and outcomes were observed. In the grade V injury subgroup, morbidity was significantly higher after surgery (aOR 4.64; [95% CI] 1.49-14.47; p = 0.008). CONCLUSION: Overall, RAE did not significantly impact morbidity but was associated with improved mortality. RAE could safeguard renal function by augmenting the efficacy of concurrent non-operative interventions. Randomized studies are needed to further validate the utility of RAE in HGRT.

Outcomes of severe isolated blunt chest trauma in young and geriatric patients.

PURPOSE: Our understanding of the growing geriatric population's risk factors for outcomes after traumatic injury remains incomplete. This study aims to compare outcomes of severe isolated blunt chest trauma between young and geriatric patients and assess predictors of mortality. METHODS: The ACS-TQIP 2017-2020 database was used to identify patients with severe isolated blunt chest trauma. Patients having extra-thoracic injuries, no signs of life upon presentation to the emergency department (ED), prehospital cardiac arrest, or who were transferred to or from other hospitals were excluded. The primary outcome was in-hospital mortality. Univariate and multivariable regression analyses were performed to assess independent predictors of mortality. RESULTS: A total of 189,660 patients were included in the study, with a median age of 58 years; 37.5% were aged 65 or older, and 1.9% died by discharge. Patients aged 65 and older had significantly higher mortality (3.4% vs. 1.0%, p < 0.001) and overall complications (7.0% vs. 4.7%, p < 0.001) compared to younger patients. Age ≥ 65 was independently associated with mortality (OR: 5.45, 95%CI: 4.96-5.98, p < 0.001), prolonged hospitalization, and complications. In the geriatric group, age > 75 was an independent predictor of mortality compared to ages 65-75 (OR: 2.62, 95%CI: 2.37-2.89, p < 0.001). Geriatric patients with an MVC, presenting with a GCS ≤ 8, and having an SBP < 90 had the highest mortality of 56.9%. CONCLUSION: The geriatric trauma patient with isolated severe blunt chest injury has significantly higher mortality and morbidity compared to younger patients and warrants special consideration of multiple factors that affect outcomes. Individual predictors of mortality carry a greater impact on mortality in geriatric patients.

Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders.

BACKGROUND: Noninfectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage-predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations for these differences remain unclear. OBJECTIVE: We sought to understand spatial gene expression characteristics in these disorders. METHODS: We performed spatial transcriptomics in cases of CS, GA, NL, and NXG to compare patterns of immune activation and other molecular features in a spatially resolved fashion. RESULTS: CS is characterized by a polarized, spatially organized type 1-predominant response with classical macrophage activation. GA is characterized by a mixed but spatially organized pattern of type 1 and type 2 polarization with both classical and alternative macrophage activation. NL showed concomitant activation of type 1, type 2, and type 3 immunity with a mixed pattern of macrophage activation. Activation of type 1 immunity was shared among, CS, GA, and NL and included upregulation of IL-32. NXG showed upregulation of CXCR4-CXCL12/14 chemokine signaling and exaggerated alternative macrophage polarization. Histologic alteration of extracellular matrix correlated with hypoxia and glycolysis programs and type 2 immune activation. CONCLUSIONS: Inflammatory cutaneous granulomatous disorders show distinct and spatially organized immune activation that correlate with hallmark histologic changes.

Explaining recovery from coma with multimodal neuroimaging.

The aim of this prospective, observational cohort study was to investigate and assess diverse neuroimaging biomarkers to predict patients' neurological recovery after coma. 32 patients (18-76 years, M = 44.8, SD = 17.7) with disorders of consciousness participated in the study. Multimodal neuroimaging data acquired during the patient's hospitalization were used to derive cortical glucose metabolism (18F-fluorodeoxyglucose positron emission tomography/computed tomography), and structural (diffusion-weighted imaging) and functional connectivity (resting-state functional MRI) indices. The recovery outcome was defined as a continuous composite score constructed from a multivariate neurobehavioral recovery assessment administered upon the discharge from the hospital. Fractional anisotropy-based white matter integrity in the anterior forebrain mesocircuit (r = 0.72, p < .001, 95% CI: 0.87, 0.45), and the functional connectivity between the antagonistic default mode and dorsal attention resting-state networks (r = - 0.74, p < 0.001, 95% CI: - 0.46, - 0.88) strongly correlated with the recovery outcome. The association between the posterior glucose metabolism and the recovery outcome was moderate (r = 0.38, p = 0.040, 95% CI: 0.66, 0.02). Structural (adjusted R2 = 0.84, p = 0.003) or functional connectivity biomarker (adjusted R2 = 0.85, p = 0.001), but not their combination, significantly improved the model fit to predict the recovery compared solely to bedside neurobehavioral evaluation (adjusted R2 = 0.75). The present study elucidates an important role of specific MRI-derived structural and functional connectivity biomarkers in diagnosis and prognosis of recovery after coma and has implications for clinical care of patients with severe brain injury.

The impact of frailty on long-term functional outcomes in severely injured geriatric patients.

BACKGROUND: The incidence of severe injury in the geriatric population is increasing. However, the impact of frailty on long-term outcomes after injury in this population remains understudied. Therefore, we aimed to understand the impact of frailty on long-term functional outcomes of severely injured geriatric patients. METHODS: We conducted a retrospective cohort study, including patients ≥65 years old with an Injury Severity Score ≥15, who were admitted between December 2015 and April 2022 at one of 3 level 1 trauma centers in our region. Patients were contacted between 6 and 12 months postinjury and administered a trauma quality of life survey, which assessed for the presence of new functional limitations in their activities of daily living. We defined frailty using the mFI-5 validated frailty tool: patients with a score ≥2 out of 5 were considered frail. The impact of frailty on long-term functional outcomes was assessed using 1:1 propensity matching adjusting for patient characteristics, injury characteristics, and hospital site. RESULTS: We included 580 patients, of whom 146 (25.2%) were frail. In a propensity-matched sample of 125 pairs, frail patients reported significantly higher functional limitations than nonfrail patients (69.6% vs 47.2%; P < .001). This difference was most prominent in the following activities: climbing stairs, walking on flat surfaces, going to the bathroom, bathing, and cooking meals. In a subgroup analysis, frail patients with traumatic brain injuries experienced significantly higher long-term functional limitations. CONCLUSION: Frail geriatric patients with severe injury are more likely to have new long-term functional outcomes and may benefit from screening and postdischarge monitoring and rehabilitation services.

Proposals for Revised International Working Group-European LeukemiaNet Criteria for Anemia Response in Myelofibrosis.

With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate inter-study comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to i) account for gender-specific differences in determining hemoglobin levels for eligibility criteria, ii) revise definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices, and iii) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks prior to study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs. non-TDA) and graded (major vs. minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.

Lenacapavir Exhibits Atropisomerism - Mechanistic Pharmacokinetics and Disposition Studies of Lenacapavir Reveal Intestinal Excretion as a Major Clearance Pathway.

Lenacapavir (LEN), a long-acting injectable, is the first approved human immunodeficiency virus type 1 capsid inhibitor and one of a few FDA-approved drugs that exhibit atropisomerism. LEN exists as a mixture of two class 2 atropisomers that interconvert at a fast rate (t1/2 <2 hours) with a ratio that is stable over time and unaffected by enzymes or binding to proteins in plasma. LEN exhibits low systemic clearance (CL) in nonclinical species and humans; however, in all species the observed CL was higher than the in vitro predicted CL. The volume of distribution was moderate in nonclinical species and consistent with the tissue distribution observed by whole body autoradiography in rats. LEN does not distribute to brain, consistent with being a P-glycoprotein (P-gp) substrate. Mechanistic drug disposition studies with [14C]LEN in IV-dosed BDC rats and dogs showed a substantial amount of unchanged LEN (31 - 60% of dose) excreted in feces, indicating that intestinal excretion (IE) was a major clearance pathway for LEN in both species. Coadministration of oral elacridar, a P-gp inhibitor, in rats decreased CL and IE of LEN. Renal excretion was <1% of dose in both species. In plasma, almost all radioactivity was unchanged LEN. Low levels of metabolites in excreta included LEN-conjugates with glutathione, pentose, and glucuronic acid, which were consistent with metabolites formed in vitro in Hµrel® hepatocyte co­cultures and those observed in human. Our studies highlight the importance of IE for efflux substrates that are highly metabolically stable compounds with slow elimination rates. Significance Statement LEN is a long-acting injectable that exists as conformationally stable atropisomers. Due to an atropisomeric interconversion rate that significantly exceeds the in vivo elimination rate, the atropisomer ratio of LEN remains constant in circulation. The disposition of LEN highlights that intestinal excretion has a substantial part in the elimination of compounds that are metabolically highly stable and efflux transporter substrates.