University Medical Center of Southern Nevada

BACKGROUND: This study attempts to validate the American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) for spleen, liver, and kidney injuries using the National Trauma Data Bank (NTDB). STUDY DESIGN: All NTDB entries with Abbreviated Injury Scale codes for spleen, liver, and kidney were classified by OIS grade. Injuries were stratified either as an isolated intraabdominal organ injury or in combination with other abdominal injuries. Isolated abdominal solid organ injuries were additionally stratified by presence of severe head injury and survival past 24 hours. The patients in each grading category were analyzed for mortality, operative rate, hospital length of stay, ICU length of stay, and charges incurred. RESULTS: There were 54,148 NTDB entries (2.7%) with Abbreviated Injury Scale-coded injuries to the spleen, liver, or kidney. In 35,897, this was an isolated abdominal solid organ injury. For patients in which the solid organ in question was not the sole abdominal injury, a statistically significant increase (p < or = 0.05) in mortality, organ-specific operative rate, and hospital charges was associated with increasing OIS grade; the exception was grade VI hepatic injuries. Hospital and ICU lengths of stay did not show substantial increase with increasing OIS grade. When isolated organ injuries were examined, there were statistically significant increases (p < or = 0.05) in all outcomes variables corresponding with increasing OIS grade. Severe head injury appears to influence mortality, but none of the other outcomes variables. Patients with other intraabdominal injuries had comparable quantitative outcomes results with the isolated abdominal organ injury groups for all OIS grades. CONCLUSIONS: This study validates and quantifies outcomes reflective of increasing injury severity associated with increasing OIS grades for specific solid organ injuries alone, and in combination with other abdominal injuries.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Significance Statement Although AKI is an important sequela of coronavirus disease 2019 (COVID-19), data on AKI treated with RRT (AKI-RRT) in patients with COVID-19 are limited. In a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States, one in five patients developed AKI-RRT, 63% of whom died during hospitalization. Among patients who survived to hospital discharge, one in three remained RRT dependent at discharge, and one in six remained RRT dependent 60 days after ICU admission. The study identified several patient-and hospital-level risk factors for AKI-RRT and death. AKI-RRT is common among critically ill patients with COVID-19 and is associated with high mortality and persistent RRT dependence. Background AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). Methods We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. Results A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d -dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1–123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. Conclusions AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of &gt;60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Abstract: Lumbar interbody fusion involves insertion of a structural graft into an intervertebral disc space to promote bony arthrodesis. It is a well-established surgical strategy for multiple spinal disorders ranging from degenerative conditions to trauma, neoplastic diseases, and deformities requiring correction. Since the inception of lumbar interbody fusion, the most established techniques have been two posterior approaches, the posterior lumbar interbody fusion (PLIF) and the transforaminal lumbar interbody fusion (TLIF). Within the past 15 years, multiple anterolateral approaches to the spine have become widely adopted. These approaches can be performed minimally invasively and spare disruption of the paraspinal muscles and posterior spinal column while enabling wide exposure of the disc space for insertion of interbody grafts much larger than PLIF and TLIF instrumentation. This review highlights three minimally invasive anterolateral approaches: the anterior lumbar interbody fusion (ALIF), the transpsoas lateral lumbar interbody fusion (LLIF), and prepsoas or anterior to the psoas oblique lumbar interbody fusion (OLIF). Relevant topics for discussion and comparison include patient selection, surgical techniques, outcomes, and complications for the three surgical approaches.

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS: GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS: The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION: We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING: Gates Foundation.

Abstract Purpose: The purpose of this study is to develop and validate a nomogram model combing radiomics features and clinical characteristics to preoperatively differentiate grade 1 and grade 2/3 tumors in patients with pancreatic neuroendocrine tumors (pNET). Experimental Design: A total of 137 patients who underwent contrast-enhanced CT from two hospitals were included in this study. The patients from the second hospital (n = 51) were selected as an independent validation set. The arterial phase in contrast-enhanced CT was selected for radiomics feature extraction. The Mann–Whitney U test and least absolute shrinkage and selection operator regression were applied for feature selection and radiomics signature construction. A combined nomogram model was developed by incorporating the radiomics signature with clinical factors. The association between the nomogram model and the Ki-67 index and rate of nuclear mitosis were also investigated respectively. The utility of the proposed model was evaluated using the ROC, area under ROC curve (AUC), calibration curve, and decision curve analysis (DCA). The Kaplan–Meier (KM) analysis was used for survival analysis. Results: An eight-feature–combined radiomics signature was constructed as a tumor grade predictor. The nomogram model combining the radiomics signature with clinical stage showed the best performance (training set: AUC = 0.907; validation set: AUC = 0.891). The calibration curve and DCA demonstrated the clinical usefulness of the proposed nomogram. A significant correlation was observed between the developed nomogram and Ki-67 index and rate of nuclear mitosis, respectively. The KM analysis showed a significant difference between the survival of predicted grade 1 and grade 2/3 groups (P = 0.002). Conclusions: The combined nomogram model developed could be useful in differentiating grade 1 and grade 2/3 tumor in patients with pNETs.

OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome. DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol. SETTING: Eight tertiary neonatal intensive care units. PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications. RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.

STUDY DESIGN: Prospective registry. OBJECTIVE: The objective of this study was to examine patient outcomes using a mini-open, lateral approach for the treatment of traumatic thoracic and lumbar fractures. SUMMARY OF BACKGROUND DATA: The high-quality published studies that examine treatment methods for acute traumatic thoracic and lumbar fractures are few and a few that are present contain insufficient samples to make broad conclusions. Despite this, we know that conventional surgical techniques often include large, morbid exposures. More recent advancements in less invasive surgical techniques have greatly decreased the associated morbidities of conventional approaches, namely, thoracotomy. METHODS: A total of 52 patients were treated at 1 of 2 institutions for traumatic thoracic or lumbar fractures with a mini-open lateral approach for corpectomy. Patients were prospectively followed for clinical outcomes, with treatment and in-hospital complications collected retrospectively. RESULTS: The majority of patients (94.2%) presented with traumatic burst fractures with instability and neurologic deficit. Patients were treated with mini-open, lateral corpectomies from T7 to L4, the majority at T12 and L1, and were followed 2 years after surgery. Supplemental internal fixation was used in all patients: 75% anterolateral plating and 46.1% transpedicular fixation (11 [21.2%] patients with combined). Median operative time, estimated blood loss, and hospital stay were 128 minutes, 300 mL, and 4 days, respectively. Complications were observed in 13.5% of patients and no reoperations occurred. Neurologic status, assessed using American Spinal Injury Association categorization, improved significantly postoperatively, with 73% of patients either completely neurologically intact or with only slight residual deficits (American Spinal Injury Association E or D). No patient experienced neurologic deterioration. Expandable wide-footprint titanium cages were used in 34.6% of patients, which resisted radiographic subsidence seen in some patients treated with expandable cylindrical titanium cages. CONCLUSION: The mini-open lateral approach for thoracic and lumbar corpectomy was shown to be safe and effective in this series while avoiding many of the associated morbidities of thoracotomies for anterior column reconstruction and open posterior approaches.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

OBJECT: Symptomatic herniated thoracic discs remain a surgical challenge and historically have been associated with significant complications. While neurological outcomes have improved with the abandonment of decompressive laminectomy, the attempt to minimize surgical complications and associated morbidities continues through less invasive approaches. Many of these techniques, such as thoracoscopy, have not been widely adopted due to technical difficulties. The current study was performed to examine the safety and early results of a minimally invasive lateral approach for symptomatic thoracic herniated intervertebral discs. METHODS: Sixty patients from 5 institutions were treated using a mini-open lateral approach for 75 symptomatic thoracic herniated discs with or without calcification. The mean age was 57.9 years (range 23-80 years), and 53.3% of the patients were male. Treatment levels ranged from T4-5 to T11-12, with 1-3 levels being treated (mean 1.3 levels). The most common levels treated were T11-12 (14 cases [18.7%]), T7-8 (12 cases [16%]), and T8-9 (12 cases [16%]). Symptoms included myelopathy in 70% of cases, radiculopathy in 51.7%, axial back pain in 76.7%, and bladder and/or bowel dysfunction in 26.7%. Instrumentation included an interbody spacer in all but 6 cases (10%). Supplemental internal fixation included anterolateral plating in 33.3% of cases and pedicle screws in 10%; there was no supplemental internal fixation in 56.7% of cases. Follow-up ranged from 0.5 to 24 months (mean 11.0 months). RESULTS: The median operating time, estimated blood loss, and length of stay were 182 minutes, 290 ml, and 5.0 days, respectively. Four major complications occurred (6.7%): pneumonia in 1 patient (1.7%); extrapleural free air in 1 patient (1.7%), treated with chest tube placement; new lower-extremity weakness in 1 patient (1.7%); and wound infection in posterior instrumentation in 1 patient (1.7%). Reoperations occurred in 3 cases (5%): one for posterior reexploration, one for infection in posterior instrumentation, and one for removal of symptomatic residual disc material. Back pain, measured using the visual analog scale, improved 60% from the preoperative score to the last follow-up, that is, from 7.8 to 3.1. Excellent or good overall outcomes were achieved in 80% of the patients, a fair or unchanged outcome resulted in 15%, and a poor outcome occurred in 5%. Moreover, myelopathy, radiculopathy, axial back pain, and bladder and/or bowel dysfunction improved in 83.3%, 87.0%, 91.1%, and 87.5% of cases, respectively. CONCLUSIONS: The authors' early experience with a large multicenter series suggested that the minimally invasive lateral approach is a safe, reproducible, and efficacious procedure for achieving adequate decompression in thoracic disc herniations in a less invasive manner than conventional surgical techniques and without the use of endoscopes. Symptom resolution was achieved at similar rates using this approach as compared with the most efficacious techniques in the literature, and with fewer complications in most circumstances.

OBJECTIVE: Relatively little research has examined the role of antiemetic agents in the treatment of acute gastroenteritis. The use of the selective 5-HT3 receptor antagonists (eg, ondansetron) offers a potentially valuable treatment option. The objective of this study was to evaluate the efficacy of ondansetron for the treatment of vomiting associated with acute gastroenteritis in children. METHODS: A randomized, double blind, placebo-controlled trial was conducted in the emergency department of a tertiary-care children's hospital. Eligible patients were 1 month to 22 years old and required intravenous fluids for gastroenteritis. Of 172 patients approached, 107 were enrolled (54 to intravenous ondansetron, 53 to placebo). The mean age was 5.3 years, and 53% of the patients were male. The frequency of vomiting, admission rate, and occurrence of complications were measured. RESULTS: After drug administration, 38 (70%) of the 54 patients in the ondansetron group had complete cessation of vomiting compared with 27 (51%) of the 53 patients in the placebo group. Sixteen (30%) of the 53 patients in the placebo group required admission compared with 14 (26%) of the 54 in the ondansetron group. An analysis of previously untreated patients with a measured serum carbon dioxide > or =15 mEq/L showed that 11 (23%) of the 47 who received placebo were admitted compared with 3 (7%) of the 43 who received ondansetron. No significant complications were detected. CONCLUSIONS: Intravenous ondansetron decreases vomiting in children with gastroenteritis. In addition, ondansetron reduces the need for admission in those who are treated at an initial visit to the emergency department and have a measured serum carbon dioxide > or =15 mEq/L. The safety and low cost of this therapy suggests that ondansetron can be valuable in treating gastroenteritis in children.

BACKGROUND: Smoking is the leading behavioural risk factor for mortality globally, accounting for more than 175 million deaths and nearly 4·30 billion years of life lost (YLLs) from 1990 to 2021. The pace of decline in smoking prevalence has slowed in recent years for many countries, and although strategies have recently been proposed to achieve tobacco-free generations, none have been implemented to date. Assessing what could happen if current trends in smoking prevalence persist, and what could happen if additional smoking prevalence reductions occur, is important for communicating the effect of potential smoking policies. METHODS: In this analysis, we use the Institute for Health Metrics and Evaluation's Future Health Scenarios platform to forecast the effects of three smoking prevalence scenarios on all-cause and cause-specific YLLs and life expectancy at birth until 2050. YLLs were computed for each scenario using the Global Burden of Disease Study 2021 reference life table and forecasts of cause-specific mortality under each scenario. The reference scenario forecasts what could occur if past smoking prevalence and other risk factor trends continue, the Tobacco Smoking Elimination as of 2023 (Elimination-2023) scenario quantifies the maximum potential future health benefits from assuming zero percent smoking prevalence from 2023 onwards, whereas the Tobacco Smoking Elimination by 2050 (Elimination-2050) scenario provides estimates for countries considering policies to steadily reduce smoking prevalence to 5%. Together, these scenarios underscore the magnitude of health benefits that could be reached by 2050 if countries take decisive action to eliminate smoking. The 95% uncertainty interval (UI) of estimates is based on the 2·5th and 97·5th percentile of draws that were carried through the multistage computational framework. FINDINGS: Global age-standardised smoking prevalence was estimated to be 28·5% (95% UI 27·9-29·1) among males and 5·96% (5·76-6·21) among females in 2022. In the reference scenario, smoking prevalence declined by 25·9% (25·2-26·6) among males, and 30·0% (26·1-32·1) among females from 2022 to 2050. Under this scenario, we forecast a cumulative 29·3 billion (95% UI 26·8-32·4) overall YLLs among males and 22·2 billion (20·1-24·6) YLLs among females over this period. Life expectancy at birth under this scenario would increase from 73·6 years (95% UI 72·8-74·4) in 2022 to 78·3 years (75·9-80·3) in 2050. Under our Elimination-2023 scenario, we forecast 2·04 billion (95% UI 1·90-2·21) fewer cumulative YLLs by 2050 compared with the reference scenario, and life expectancy at birth would increase to 77·6 years (95% UI 75·1-79·6) among males and 81·0 years (78·5-83·1) among females. Under our Elimination-2050 scenario, we forecast 735 million (675-808) and 141 million (131-154) cumulative YLLs would be avoided among males and females, respectively. Life expectancy in 2050 would increase to 77·1 years (95% UI 74·6-79·0) among males and 80·8 years (78·3-82·9) among females. INTERPRETATION: Existing tobacco policies must be maintained if smoking prevalence is to continue to decline as forecast by the reference scenario. In addition, substantial smoking-attributable burden can be avoided by accelerating the pace of smoking elimination. Implementation of new tobacco control policies are crucial in avoiding additional smoking-attributable burden in the coming decades and to ensure that the gains won over the past three decades are not lost. FUNDING: Bloomberg Philanthropies and the Bill & Melinda Gates Foundation.

PURPOSE: Patients with advanced papillary renal cell cancer (pRCC) have poor survival after systemic therapy; the reported median survival time is 7 to 17 months. In this trial, we evaluated the efficacy of erlotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor in patients with advanced pRCC, a tumor type associated with wild-type von Hippel Lindau gene. PATIENTS AND METHODS: Patients with histologically confirmed, advanced, or metastatic pRCC were treated with erlotinib 150 mg orally once daily. A RECIST (Response Evaluation Criteria in Solid Tumors) response rate (RR) of > or = 20% was considered a promising outcome. Secondary end points included overall survival and 6-month probability of treatment failure. RESULTS: Of 52 patients registered, 45 were evaluable. The overall RR was 11% (five of 45 patients; 95% CI, 3% to 24%), and the disease control rate was 64% (ie five partial response and 24 stable disease). The median overall survival time was 27 months (95% CI, 13 to 36 months). Probability of freedom from treatment failure at 6 months was 29% (95% CI, 17% to 42%). There was one grade 5 adverse event (AE) of pneumonitis, one grade 4 thrombosis, and nine other grade 3 AEs. CONCLUSION: Although the RECIST RR of 11% did not exceed prespecified estimates for additional study, single-agent erlotinib yielded disease control and survival outcomes of interest with an expected toxicity profile. The design of future trials of the EGFR axis in pRCC should be based on preclinical or molecular data that define appropriate patient subgroups, new drug combinations, or potentially more active alternative schedules.

Opioids affect motor and sensory function throughout the gastrointestinal tract, and are frequently associated with a number of gastrointestinal symptoms including constipation, which impairs the quality of life and may limit the dose of opioid or result in discontinuation altogether. Patients with opioid-induced constipation should be assessed by careful history and physical examination, and in some cases where the diagnosis is unclear with select diagnostic tests. Few clinical studies have been conducted to assess the efficacy of various treatments. However, it is generally recommended that first-line therapy begin with opioid rotation, as well as with low-cost and low-risk approaches such as lifestyle changes, consumption of fiber-rich food, stool softeners, and laxatives.

Enterocutaneous fistula (ECF) is an uncommon and poorly studied postoperative complication. The objective of this study was to analyze the incidence and resource utilization of patients who developed an ECF after trauma laparotomy. All patients with an ECF occurring after trauma laparotomy at a Level I trauma center were identified through a review of both the Trauma Registry and the Morbidity and Mortality reports for a 9-year period ending in December 2006. Each ECF case was matched with a control (non-ECF) that did not develop this complication after laparotomy. The matching criteria were: age, gender, mechanism of injury, Injury Severity Score, Abbreviated Injury Score, and damage control laparotomy requiring an open abdomen. Outcomes analyzed were intensive care unit (ICU) and hospital length of stay, mortality, and total hospital charges. During the 9-year period, of 2373 acute trauma laparotomies performed, 36 (1.5%) patients developed an enterocutaneous fistula, and were matched to 36 controls. Patients with an ECF were 31 +/- 12 years of age, were 97 per cent male, had a mean Injury Severity Score of 21 +/- 10, and 75 per cent were penetrating. Eighty-nine per cent of the ECF patients had a hollow viscus injury. The most common was colon (69%), followed by small bowel (53%), duodenum (36%), and stomach (19%). Fifty-six per cent of the ECF patients had multiple hollow viscus injuries. The development of an ECF was associated with significantly increased ICU length of stay (28.5 +/- 30.5 vs 7.6 +/- 9.3 days, P = 0.004), hospital length of stay (82.1 +/- 100.8 vs 16.2 +/- 17.3 days, P < 0.001), and hospital charges ($539,309 vs $126,996, P < 0.001). In conclusion, the development of an enterocutaneous fistula after laparotomy for trauma resulted in a significant impact on resource utilization including longer ICU and hospital length of stay and higher hospital charges. Further investigation into the prevention and treatment of this costly complication is warranted.

BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes. DISCUSSION: This article reviews the evidence from phase 3 clinical trials for each of the 5 GLP-1 receptor agonists by comparing them against one another and with other existing therapies, including metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sulfonylureas. Incretin-based therapies have emerged as attractive agents for the treatment of type 2 diabetes. They target the GLP-1 hormone, which is partly responsible for insulin release and for attenuating hyperglycemia during meals (ie, the incretin effect). The 2 classes of incretin-based therapy currently available are GLP-1 receptor agonists and DPP-4 inhibitors, which prevent the breakdown of GLP-1. Both classes are attractive options, given their glucose-lowering effects without the adverse effects of hypoglycemia and weight gain. The different mechanisms of action of these therapies result in generally greater efficacy with GLP-1 receptor agonists, albeit at the expense of slightly increased gastrointestinal symptoms. These agents exert their effects by improving glucose-dependent insulin release, suppressing glucagon release, suppressing hepatic glucose output, and decreasing the rate of gastric emptying, thereby reducing appetite. Currently, 5 GLP-1 receptor agonists are available, including exenatide, liraglutide, albiglutide, dulaglutide, and lixisenatide; semaglutide may soon become available as the newest agent. With the exception of the investigational oral semaglutide, which has shown promising results, the other 5 agents are administered as subcutaneous injections, at different dosing intervals. CONCLUSION: Currently, 5 GLP-1 receptor agonists are available for use in the United States. Although they are all in the same drug class, some significant differences exist among the various GLP-1 receptor agonists. The choice of a specific GLP-1 receptor agonist will depend on the patient preferences, potential adverse effects, and cost.

BACKGROUND: Negative nitrogen balance and skeletal muscle loss are common in critically injured patients and may contribute to morbidity, mortality and resource utilization. Juven, an enteral supplement which is a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine (ARG), and glutamine (GLN) has been shown to restore muscle in cachetic acquired immunodeficiency syndrome (AIDS) and cancer patients. More recently HMB has been shown to attenuate cancer-induced muscle loss by decreasing muscle proteolysis. The purpose of this study was to analyze whether HMB alone or in combination with ARG and GLN would have a similar effect on critically injured trauma patients. We hypothesized that nitrogen balance would be improved and muscle proteolysis decreased with HMB and HMB/ARG/GLN supplementation. METHODS: There were 100 adult trauma patients with Injury Severity Score (ISS) >18 were enrolled in this prospective, randomized, blinded study. All patients received standard tube feeds and one of three iso-nitrogenous supplements; HMB, HMB/ARG/ GLN, or placebo (PLAC) for 28 days. Urine, serum, and clinical data were collected for 72 patients receiving at least 7 days of supplementation during the first 14 days of treatment. Urinary 3-methylhistidine (3-MH) was used as a proxy for muscle proteolysis. RESULTS: The three groups were similar in age, gender, mechanism, and severity of injury, with the average ISS being 31.9. Utilizing covariant (ISS) repeated measure (days 1-14) mixed model (SAS) analysis, there was a significant treatment effect (p = 0.05) on nitrogen balance (g/d). Change in nitrogen balance from the first 7 days to the last 7 days was -4.3 for the HMB and -5.6 g/d HMB/ARG/GLN groups compared with -8.9 g/d for the PLAC group. 3-MH to creatinine ratios were not different in the PLAC group as compared with the HMB/ARG/GLN and HMB groups (Treatment Effect, p = 0.80). CONCLUSIONS: These data suggest that supplementation with HMB alone may improve nitrogen balance in critically injured adult patients and that this effect is not a result of lowered muscle protein turnover as originally hypothesized.

In Brief Study Design. Prospective registry. Objective. The objective of this study is to examine procedural and long-term outcomes of a mini-open, lateral approach for tumor removal in the thoracic spine. Summary of Background Data. The majority of spinal tumors present as metastatic tumors in the thoracic spine. Conventional surgical treatments have been associated with high rates of approach-related morbidities as well as difficult working windows for complete tumor excision. Recent advances in minimally invasive techniques, particularly mini-open (minimally invasive, not endoscopic) approaches, help to reduce the morbidities of conventional procedures with comparable outcomes. Methods. Twenty-one consecutively treated patients at 2 institutions were treated between 2007 and 2009. Treatment variables, including operating time, estimated blood loss, length of hospital stay, and complications were collected, as were outcome measures, including the visual analog scale for pain and the Oswestry disability index. Results. Twenty-one patients with thoracic spinal tumors were successfully treated with a minimally invasive lateral approach. Operating time, estimated blood loss, and length of hospital stay were 117 minutes, 291 mL, and 2.9 days, respectively. One (4.8%) perioperative complication occurred (pneumonia). Mean follow-up was 21 months. Two patients had residual tumor at last follow-up. Two patients died during the study as the result of other metastases (spine tumor was secondary). Visual analog scale improved from 7.7 to 2.9 and Oswestry disability index improved from 52.7% to 24.9% from preoperative to the last follow-up. Conclusion. The mini-open lateral approach described here can be performed safely and without many of the morbidities and difficulties associated with conventional and endoscopic procedures. Proper training in minimally invasive techniques and the use of direct-visualization minimally invasive retractors are required to safely and reproducibly treat these complex indications. Conventional surgical approaches for the treatment of thoracic spine tumors carry significant morbidities. This report describes a mini-open lateral technique for access and removal of tumors of the thoracic spine with short operating times, minimal blood loss, low lengths of hospital stay, and complications, as well as significantly improved clinical outcomes.

This study reviewed the literature for the extent of neuroimaging findings in boxers, indicative of traumatic brain injury (TBI) as identified in magnetic resonance imaging (MRI). The study then utilized a systematic checklist approach to assess 100 unselected consecutive 1.5- and 3.0-Tesla MRI examinations of professional unarmed combatants to determine the extent of identifiable TBI findings. The percentage of positive findings and the localization of lesions were quantified using the checklist that included the MRI findings previously reported in the medical literature. Seventy-six percent of the unarmed combatants had at least one finding that may be associated with TBI: 59% hippocampal atrophy, 43% cavum septum pellucidum, 32% dilated perivascular spaces, 29% diffuse axonal injury, 24% cerebral atrophy, 19% increased lateral ventricular size, 14% pituitary gland atrophy, 5% arachnoid cysts, and 2% had contusions. Statistical relationships were found between number of bouts and lateral ventricular size (tau-b = 0.149, p = 0.0489), with years of fighting correlating with the presence of dilated perivascular spaces (tau-b = 0.167, p = 0.0388) and diffuse axonal injury (tau-b = 0.287, p = 0.0013) findings. The improved resolution and increased signal-to-noise ratio on 1.5- and 3.0-Tesla high-field MRI systems defines the range of pathological variations that may occur in professional unarmed combatants. Additionally, the use of a systematic checklist approach insures evaluation for all possible TBI-related abnormalities. This knowledge can be used to anticipate the regions of potential brain pathology for radiologists and emergency medicine physicians, and provides important information for evaluating unarmed combatants relative to their safety and long-term neurocognitive outcome.

OBJECT: The minimally invasive lateral transpsoas approach for interbody fusion has been increasingly employed to treat various spinal pathological entities. Gaining access to the retroperitoneal space and traversing the abdominal wall poses a risk of injury to the major nervous structures. Nerve injury of the abdominal wall can potentially lead to paresis of the abdominal musculature and bulging of the abdominal wall. Abdominal wall nerve injury resulting from the minimally invasive lateral retroperitoneal transpsoas approach has not been previously reported. The authors describe a case series of patients presenting with paresis and bulging of the abdominal wall after undergoing a minimally invasive lateral retroperitoneal approach. METHODS: The authors retrospectively reviewed all patients who underwent a minimally invasive lateral transpsoas approach for interbody fusion and in whom development of abdominal paresis developed; the patients were treated at 4 institutions between 2006 and 2010. All data were recorded including demographics, diagnosis, operative procedure, positioning, hospital course, follow-up, and complications. The onset, as well as resolution of the abdominal paresis, was reviewed. RESULTS: The authors identified 10 consecutive patients in whom abdominal paresis developed after minimally invasive lateral transpsoas spine surgery out of a total of 568 patients. Twenty-nine interbody levels were fused (range 1-4 levels/patient). There were 4 men and 6 women whose mean age was 54.1 years (range 37-66 years). All patients presented with abdominal paresis 2-6 weeks postoperatively. In 8 of the 10 patients, abdominal wall paresis had resolved by the 6-month follow-up visit. Two patients only had 1 and 4 months of follow-up. No long-term sequelae were identified. CONCLUSIONS: Abdominal wall paresis is a rare but known potential complication of abdominal surgery. The authors report the first case series associated with the minimally invasive lateral transpsoas approach.