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Objective: To determine how the severity of prior history (Hx) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection influences postoperative outcomes after major elective inpatient surgery. Background: Surgical guidelines instituted early in the coronavirus disease 2019 (COVID-19) pandemic recommended a delay in surgery of up to 8 weeks after an acute SARS-CoV-2 infection. This was based on the observation of elevated surgical risk after recovery from COVID-19 early in the pandemic. As the pandemic shifts to an endemic phase, it is unclear whether this association remains, especially for those recovering from asymptomatic or mildly symptomatic COVID-19. Methods: Utilizing the National COVID Cohort Collaborative, we assessed postoperative outcomes for adults with and without a Hx of COVID-19 who underwent major elective inpatient surgery between January 2020 and February 2023. COVID-19 severity and time from infection to surgery were each used as independent variables in multivariable logistic regression models. Results: This study included 387,030 patients, of whom 37,354 (9.7%) were diagnosed with preoperative COVID-19. Hx of COVID-19 was found to be an independent risk factor for adverse postoperative outcomes even after a 12-week delay for patients with moderate and severe SARS-CoV-2 infection. Patients with mild COVID-19 did not have an increased risk of adverse postoperative outcomes at any time point. Vaccination decreased the odds of respiratory failure. Conclusions: Impact of COVID-19 on postoperative outcomes is dependent on the severity of illness, with only moderate and severe disease leading to a higher risk of adverse outcomes. Existing perioperative policies should be updated to include consideration of COVID-19 disease severity and vaccination status. [ABSTRACT FROM AUTHOR]

The demographic composition of modern radiation therapy (RT) clinical trials is incompletely studied. Understanding and minimizing disparities in clinical trials is critical to ensure health equity and the generalizability of research findings. Clinicaltrials.gov was searched to identify RT clinical trials that occurred from 1996 to 2019. A total of 1242 trials were reviewed for patient characteristics. The demographic composition of the studies was summarized by the frequency and percentage of patients by race, gender, and ethnicity. The racial composition of the study population was compared with the 2018 US Census using a 1-sample χ2 test. Subgroup racial composition was compared using χ2 tests of independence. Analyses used a complete case approach. A total of 122 trials met the inclusion criteria, and 121 of these (99.1%) reported race. Trial subgroups included 63 trials in the United States (51.6%), 9 proton therapy trials (7.4%), 34 RT toxicity mitigation or prevention trials (27.9%), 24 trials for female cancer (19.7%), and 17 trials for male cancer (13.9%). US clinical trials overall, US RT toxicity mitigation or prevention trials, US trials for female cancer, and US trials for male cancer had significantly different racial compositions compared with the 2018 US Census data (P <.001 for all). Compared with all clinical trials, those for proton therapy had the largest magnitude of significantly lower enrollment of participants who identified their race as Black, Asian, or other (P <.001). This study characterized the racial composition of prospective RT clinical trials in a modern cohort. The racial population represented across multiple categories in the United States differed significantly from US census data and was most pronounced in trials evaluating proton therapy. This is a benchmark study for future efforts to characterize and balance the participation of underrepresented populations in RT clinical trials. [ABSTRACT FROM AUTHOR]

The human cervical spine sustains compressive loading in automotive events and military operational activities, and the contact and noncontact loading are the two primary impact modes. Biomechanical and anatomical studies have shown differences between male and female cervical spines. Studies have been conducted to determine the human tolerance in terms of forces from postmortem human subject (PMHS) specimens from male and female spines; however, parametric risk curves specific to female spines are not available from contact loading to the head-neck complex under the axial mode. This study was conducted to develop female-spine based risk curves from PMHS tests. Data from experiments conducted by the authors using PMHS upright head-spines were combined with data from published studies using inverted head-spines. The ensemble consisted of 20 samples with ages ranging from 29 to 95 years. Except one, all specimens sustained neck injuries, consisting of fractures to cervical vertebrae, and disruptions to the intervertebral disc and facet joints, and ligaments. Parametric survival analysis was used to derive injury probability curves using the compressive force, uncensored for injury and right censored for noninjury data points. The specimen age was used as the covariate. Injury probability curves were derived using the best fit distribution, and the ± 95% confidence interval limits were obtained. Results indicated that age is a significant covariate for injury for the entire ensemble. Peak forces were extracted for 35, 45, and 63 (mean) years of age, the former two representing the young (military) and the latter, the automobile occupant populations. The forces of 1.2 kN and 2.9 kN were associated with 5% and 50% probability of injury at 35 years. These values at 45 years were 1.0 kN and 2.4 kN, and at 63 years, they were 0.7 kN and 1.7 kN. The normalized widths of the confidence intervals at these probability levels for the mean age were 0.74 and 0.48. The preliminary injury risk curves presented should be used with appropriate caution. This is the first study to develop risk curves for females of different ages using parametric survival analysis, and can be used to advance human safety, and design and develop manikins for military and other environments. [ABSTRACT FROM AUTHOR]

Chromophobe renal cell carcinoma (CRCC) is not amenable to International Society for Urologic Pathology-endorsed nucleolar grading. Novel grading approaches were proposed, but the rarity of adverse pathology hampers their discriminatory value. We investigate simple linear micrometer measurements and a proposed immunostain in CRCCs. 32 patients' CRCCs were studied: 12 adverse cases (stage pT3, recurrence, or metastasis), 15 controls (stage ≤pT2, no recurrence or metastasis after >3 years), and 8 metastases (3 were paired with primary adverse cases). The ratio of greatest dimensions of largest and smallest nuclei, in each of 5 “worst” high-power fields, excluding those with degenerative features, was designated variation in nuclear size (VNS). Percent multinucleate cells (PMC) were also counted. Mouse anti PD-L2 monoclonal antibody immunostaining was performed. Mean VNS measured in adverse primary and control primary tumors were 3.7 ± 0.5 and 2.4 ± 0.4 respectively ( P  < .001), and 3.4 ± 0.4 for metastases ( P  < .001). Optimal VNS cut-off was 2.5, with sensitivity and specificity 0.85 and 0.81, respectively. PMCs were 6.0 ± 3.0 for adverse group, 5.7 ± 2.7 for controls, and 4.1 ± 1.6 for metastases ( P  = NS). PD-L2 could not discriminate adverse versus good primary tumors (χ 2 1.6, P  = .2), but was higher in metastases (χ 2 6.9, P  < .01), or metastases plus adverse primary tumors (χ 2 4.8, P  = .03), compared to good-pathology primary tumors. In conclusion, VNS is an easily obtained measurement that can predict adverse behavior of chromophobe RCC, and may impart value for needle biopsy reporting and the choice of active surveillance. PD-L2 was elevated in metastases but was less useful for primary tumors. [ABSTRACT FROM AUTHOR]

Objective Biomechanical data from post mortem human subject (PMHS) experiments are used to derive human injury probability curves and develop injury criteria. This process has been used in previous and current automotive crashworthiness studies, Federal safety standards, and dummy design and development. Human bone strength decreases as the individuals reach their elderly age. Injury risk curves using the primary predictor variable (e.g., force) should therefore account for such strength reduction when the test data are collected from PMHS specimens of different ages (age at the time of death). This demographic variable is meant to be a surrogate for fracture, often representing bone strength as other parameters have not been routinely gathered in previous experiments. However, bone mineral densities (BMD) can be gathered from tested specimens (presented in this manuscript). The objective of this study is to investigate different approaches of accounting for BMD in the development of human injury risk curves. Methods Using simulated underbody blast (UBB) loading experiments conducted with the PMHS lower leg-foot-ankle complexes, a comparison is made between the two methods: treating BMD as a covariate and pre-scaling test data based on BMD. Twelve PMHS lower leg-foot-ankle specimens were subjected to UBB loads. Calcaneus BMD was obtained from quantitative computed tomography (QCT) images. Fracture forces were recorded using a load cell. They were treated as uncensored data in the survival analysis model which used the Weibull distribution in both methods. The width of the normalized confidence interval (NCIS) was obtained using the mean and ± 95% confidence limit curves. Principal results The mean peak forces of 3.9 kN and 8.6kN were associated with the 5% and 50% probability of injury for the covariate method of deriving the risk curve for the reference age of 45 years. The mean forces of 5.4 kN and 9.2 kN were associated with the 5% and 50% probability of injury for the pre-scaled method. The NCIS magnitudes were greater in the covariate-based risk curves (0.52–1.00) than in the risk curves based on the pre-scaled method (0.24–0.66). The pre-scaling method resulted in a generally greater injury force and a tighter injury risk curve confidence interval. Although not directly applicable to the foot-ankle fractures, when compared with the use of spine BMD from QCT scans to pre-scale the force, the calcaneus BMD scaled data produced greater force at the same risk level in general. Conclusions Pre-scaling the force data using BMD is an alternate, and likely a more accurate, method instead of using covariate to account for the age-related bone strength change in deriving risk curves from biomechanical experiments using PMHS. Because of the proximity of the calcaneus bone to the impacting load, it is suggested to use and determine the BMD of the foot-ankle bone in future UBB and other loading conditions to derive human injury probability curves for the foot-ankle complex. [ABSTRACT FROM AUTHOR]

Conventional imaging studies of human spine are done in a supine posture in which the axial loading of the spine is not considered. Upright images better reveal the interrelationships between the various internal structures of the spine. The objective of the current study is to determine the cross-sectional areas, radii, and angulations of the psoas, erector spinae, and multifidus muscles of the lumbar spine in the sitting posture. Ten young (mean age 31 ± 4.8 years) asymptomatic female subjects were enrolled. They were seated in an erect posture and weight-bearing T1 and T2 MRIs were obtained. Cross-sectional areas, radii, and angulations of the muscles were measured from L1-L5. Two observers repeated all the measurements for all parameters, and reliability was determined using the inter- and intra-class coefficients. The Pearson product moment correlation was used for association between levels, while level differences were used using a linear regression model. The cross-sectional areas of the psoas and multifidus muscles increased from L1 to L5 (1.9 ± 1.1 to 12.1 ± 2.5 cm2 and 1.8 ± 0.3 to 5.7 ± 1.4 cm2). The cross-sectional area of the erector spinae was greatest at the midlevel (13.9 ± 2.2 cm2) and it decreased in both directions. For the angle, the range for psoas muscles was 75–105°, erector spinae were 39–46° and multifidus was 11–19°. Correlations magnitudes were inconsistent between levels and muscle types. These quantitated data improve our understanding of the geometrical properties in the sitting posture. The weight-bearing MRI-quantified morphometrics of human lumbar spine muscles from this study can be used in biomechanical models for predicting loads on spinal joints under physiological and traumatic situations. [ABSTRACT FROM AUTHOR]

Buried blast explosions create small projectiles which can become lodged in the tissue of personnel as far away as hundreds of meters. Without appropriate treatment, these lodged projectiles can become a source of infection and prolonged injury to soldiers in modern combat. Human cadavers can be used as surrogates for living humans for ballistic penetration testing, but human cadavers are frozen during transport and storage. The process of freezing and thawing the tissue before testing may change the biomechanical properties of the tissue. The goal of the current study was to understand penetration threshold differences between fresh, refrigerated, and frozen tissue and investigate factors that may contribute to these differences. A custom-built pneumatic launcher was used to accelerate 3/16″ stainless steel ball bearings toward porcine legs that were either tested fresh, following refrigerated storage, or following frozen storage. A generalized linear mixed model, accounting for within-animal dependence, owing to repeated observations, was found to be the most appropriate for these data and was used for analysis. The "generalized" model accommodated non-continuous observations, provided a straight-forward way to implement the repeated measures, and provided a risk estimate for projectile penetration. Both storage condition (p = 0.48) and leg (p = 0.07) were shown to be not significant and the confidence intervals for those variables were overlapping. As all covariates were found to be non-significant, a single model containing all impacts was used to develop a V50, or velocity at which 50% of impacts are expected to penetrate. From this model, 50% probability of penetration occurs at 137.3 m/s with 95% confidence intervals at 132.0 and 144.0 m/s. In this study, the fresh legs and previously frozen legs allowed penetration at similar velocities indicating that previously frozen legs were acceptable surrogates for fresh legs. This study only compared the penetration threshold in tissues that had been stored in differing conditions. To truly study penetration, more conditions will need to be studied including the effects of projectile mass and material, the effects of projectile shape, and the effects of clothing or protective layers on penetration threshold. [ABSTRACT FROM AUTHOR]

Losing a loved one often results in acute grief and depressive symptoms. The vast majority of older individuals are resilient and return to normal functioning within a year after a loss. However, a significant minority develop mental health complications, including prolonged grief disorder and bereavement-related depression. This can lead to adverse consequences, including physical and cognitive decline, impairment in global functioning, and early mortality. The contributing factors that increase the likelihood of adverse mental health outcomes in bereaved individuals have not been fully elucidated. This study explores the relationship of loneliness with grief and depressive symptom trajectories in older adults after an attachment loss. 45 individuals over age 50 and within 13 months following the death of a loved one completed a comprehensive clinical assessment at the baseline visit (week 0), including the UCLA Loneliness Scale-3, the Inventory of Complicated Grief (ICG), and the Hamilton Depression Rating Scale (HAM-D). All participants completed a 6-month longitudinal study; ICG and HAM-D were completed at weeks 8, 16, and 26 (endpoint). Statistical analyses : Two classes of mixed-effects models, where covariates are fixed effects and patient-specific dependents are random effects, were considered. Cross-sectional models were used to investigate relationships between loneliness and grief and depressive symptoms at baseline. Longitudinal models were used to examine the relationship of baseline loneliness scores with grief and depressive symptoms across the 6-month study duration. In longitudinal models, the interactions between time elapsed since baseline and dynamic measurements (complicated grief and depressive symptom scores) were examined. A hierarchical variance-covariance structure for random effects, informed by clustering of clinical trajectories, was used to determine participant trajectories. Age, gender, days since the loss, and cumulative medical illness rating scale for geriatrics scores were included as covariates in all models. The R statistical software (version 3.6.3) was utilized for data analyses. Cross-sectionally, loneliness was positively associated with scores on the ICG (p<0.01) and HAM-D (p<0.01) in separate models, after adjusting for covariates. However, the loneliness-ICG relationship was no longer significant when HAM-D was included as a covariate in an extended model (p=0.32). Mediation analyses revealed that the loneliness-ICG relationship was mediated by baseline HAM-D scores. In contrast, the loneliness-HAM-D relationship remained significant even after including ICG as a covariate (p=0.01). Longitudinally, baseline loneliness scores were associated with worsening HAM-D scores over time (p<0.01); this association persisted over 6 months (p<0.01). The loneliness-ICG longitudinal relationship was not significant. Of additional interest were the co-movement patterns expressed by HAM-D and ICG: adults following a C-shaped trajectory for HAM-D scores were likely to demonstrate a similar trajectory with ICG scores. Loneliness was independently associated with grief and depression symptom severity in older adults following bereavement. However, the baseline loneliness-grief symptom association was mediated by depression. Since loneliness could predict depressive symptom trajectories in older grieving individuals, interventions targeting loneliness may also improve depression outcomes in this study population. Although the co-movement analysis was exploratory (i.e., this was used to inform the structure of the covariance matrix for random effects in analytic models), it has implications for future treatment intervention study designs. This research was funded by NIMH grants R01 MH122490 and R21 MH109807 (Goveas); Costigan Family Foundation (Goveas); and UL1TR001436 [ABSTRACT FROM AUTHOR]

The objective of this study was to determine force-based lumbar spine injury criteria due to vertical impact using Post Mortem Human Surrogate (PMHS) experiments. Mounted personnel in military vehicles sustain loads from the pelvis in combat events such as underbody blast loadings. Forty-three post mortem human subject thoracolumbar spinal columns were obtained, screened for pre-existing trauma, bone mineral densities (BMDs) were determined, pre-test radiological images were taken, fixed at the ends in polymethylmethacrylate, load cells were attached to the ends of the fixation, positioned on custom vertical accelerator device based on a military-seating posture, and impacted at the base. Posttest images were obtained, and gross dissection was done to confirm injuries, classified into single and multilevel groups, groups A and B. Axial and resultant forces at the thoracolumbar (proximal) and lumbosacral (distal) joints were used as response variables to develop lumbar spine injury risk curves using parametric survival analysis. The Brier score metric was used to rank the variables. Age, BMD, column length, and vertebral body and intervertebral disc areas were used as covariates. The optimal metric describing the underlying response to injury was the distal resultant force for group A and proximal axial force for group B specimens. Force-BMD for group A and force-body area for group B were the best combinations. The IRCs with ±95% confidence intervals and quality of risk curves are given in the paper, and they serve as lumbar spine injury criteria. The present human cadaver Injury Risk Curves (IRCs) can be used to conduct matched pair tests to obtain dummy-based injury assessment risk curves/values to predict injury. The present IRCs can be used in human body finite element models. The relationship between covariates and primary forces presented in this study contribute to a better understanding of the role of demographic, geometric, and material factors to impact acceleration loading. [ABSTRACT FROM AUTHOR]

Some patients with cyclic vomiting syndrome (CVS) use cannabis to relieve stress and for its antiemetic properties. However, chronic cannabis use has been associated paradoxically with cannabinoid hyperemesis syndrome (CHS) and some patients with CVS are thought to have CHS. We sought to characterize patterns of cannabis use by patients with CVS and identify those who could be reclassified as having CHS. We performed a cross-sectional study of 140 patients with CVS (72% female; mean age, 37 ± 13 y) seen at a specialized clinic. Patients were screened for cannabis use with the cannabis use disorder identification test. Patients were classified as regular (use ≥4 times/wk) or occasional users (<4 times/wk). Forty-one percent of patients were current cannabis users, with 21% reporting regular use. Regular users were more likely to be male and to report an anxiety diagnosis, and smoked cannabis with higher tetrahydrocannabinol content and for a longer duration. Most users reported that cannabis helped control CVS symptoms. Among all cannabis users, 50 of 57 (88%) reported that they had abstained for longer than 1 month, but only 1 user reported resolution of CVS episodes during the abstinence period. This patient subsequently resumed using cannabis but remains free of symptoms. Cannabis is used commonly among patients with CVS—patients report relief of symptoms with use. We found 21% of patients with CVS to be regular users, but only 1 met the Rome IV criteria for CHS. Longitudinal studies are needed to determine the relationships among cannabis use, hyperemesis, and mood symptoms. [ABSTRACT FROM AUTHOR]