Best practice guidelines have advanced severe traumatic brain injury (TBI) care, however, little currently informs goals of care decisions and processes despite their importance and frequency. Panelists from the Seattle International severe traumatic Brain Injury Consensus Conference (SIBICC) participated in a survey consisting of 24 questions. Questions queried use of prognostic calculators, variability in and responsibility for goals of care decisions, acceptability of neurological outcomes as well as putative means of improving decisions which may limit care. 97.6% of the 42 SIBICC panelists completed the survey. Responses were highly variable to most questions. Overall panelists reported infrequent use of prognostic calculators and observing variability in patient prognostication and goals of care decisions. They felt that it would be beneficial for physicians to improve consensus on what constitutes an acceptable neurological outcome as well as what chance of achieving that outcome is acceptable. Panelists felt that the public should help to define what constitutes a good outcome and expressed some support for a 'nihilism guard'. Over 50% of panelists felt that if it was certain to be enduring, a vegetative state or lower severe disability would justify a withdrawal of care decision while 15% felt that upper severe disability justified such a decision. Whether conceptualizing an ideal or existing prognostic calculator to predict death or an unacceptable outcome, a 64-69% chance of a poor outcome on average was felt to justify treatment withdrawal. These results demonstrate important variability in goals of care decision making and a desire to reduce this variability. Our panel of recognized TBI experts opined on the neurological outcomes and chances of those outcomes which might prompt consideration of care withdrawal, however imprecision of prognostication and existing prognostication tools is a significant impediment to standardizing the approach to care limiting decisions. Keywords: nihilism, withdrawal of care, survey, SIBICC, brain injury, prognosis.
Octogenarians undergoing cystectomy experience higher morbidity and mortality compared to younger patients. Though the non-inferiority of robot-assisted radical cystectomy (RARC) compared to open radical cystectomy (ORC) has been established in a generalized population, the benefits of the robotic approach have not been well studied in an aged population. The National Cancer Database (NCDB) was queried for all patients who underwent cystectomy for bladder cancer from 2010 to 2016. Of these, 2527 were performed in patients age 80 or older; 1988 and 539 underwent ORC and RARC, respectively. On Cox regression analysis, RARC was associated with significantly reduced odds for both 30- and 90-day mortality (HR 0.404, p = 0.004; HR 0.694, p = 0.031, respectively), though the association with overall mortality was not significant (HR 0.877, p = 0.061). The robotic group had a significantly shorter length of stay (LOS) compared to open surgery (10.3 days ORC vs. 9.3 days RARC, p = 0.028). The proportion of cases performed robotically increased over the study period from 12.2% in 2010 to 28.4% in 2016 (p = 0.009, R² = 0.774). The study is limited by a retrospective design and a section bias, which was not completely control for in the analysis. In conclusion, RARC provides improved perioperative outcomes in aged patients compared to ORC and a trend toward greater utilization of this technique was observed.
Childhood trauma is a known risk factor for trauma and stress-related disorders in adulthood. However, limited research has investigated the impact of childhood trauma on brain structure linked to later posttraumatic dysfunction. We investigated the effect of childhood trauma on white matter microstructure after recent trauma and its relationship with future posttraumatic dysfunction among trauma-exposed adult participants (n = 202) recruited from emergency departments as part of the AURORA Study. Participants completed self-report scales assessing prior childhood maltreatment within 2-weeks in addition to assessments of PTSD, depression, anxiety, and dissociation symptoms within 6-months of their traumatic event. Fractional anisotropy (FA) obtained from diffusion tensor imaging (DTI) collected at 2-weeks and 6-months was used to index white matter microstructure. Childhood maltreatment load predicted 6-month PTSD symptoms (b = 1.75, SE = 0.78, 95% CI = [0.20, 3.29]) and inversely varied with FA in the bilateral internal capsule (IC) at 2-weeks (p = 0.0294, FDR corrected) and 6-months (p = 0.0238, FDR corrected). We observed a significant indirect effect of childhood maltreatment load on 6-month PTSD symptoms through 2-week IC microstructure (b = 0.37, Boot SE = 0.18, 95% CI = [0.05, 0.76]) that fully mediated the effect of childhood maltreatment load on PCL-5 scores (b = 1.37, SE = 0.79, 95% CI = [−0.18, 2.93]). IC microstructure did not mediate relationships between childhood maltreatment and depressive, anxiety, or dissociative symptomatology. Our findings suggest a unique role for IC microstructure as a stable neural pathway between childhood trauma and future PTSD symptoms following recent trauma. Notably, our work did not support roles of white matter tracts previously found to vary with PTSD symptoms and childhood trauma exposure, including the cingulum bundle, uncinate fasciculus, and corpus callosum. Given the IC contains sensory fibers linked to perception and motor control, childhood maltreatment might impact the neural circuits that relay and process threat-related inputs and responses to trauma.
We describe the implementation of an electronic medical record “hard stop” to decrease inappropriate Clostridioides difficile testing across a 5-hospital health system, effectively reducing the rates of healthcare-facility–onset C. difficile infection. This novel approach included expert consultation with medical director of infection prevention and control for test-order override.
Over 645 million people worldwide have been infected with SARS-CoV-2, the virus that causes COVID-19. Critical knowledge gaps regarding the characteristics, duration, and impact of symptoms due to “long COVID”. This study evaluated the persistence of symptoms at one year following hospitalization with COVID-19, comparing responses on standardized measurement tools to population norms. Adults hospitalized with COVID-19 March-October 2020 during the initial emergence period in Southeast Michigan were eligible. A detailed survey was conducted via telephone 9-15 months after hospital discharge. Questions assessed fatigue, dyspnea, and physical functioning related to their COVID-19 illness. The median World Health Organization Disability Assessment Schedule (WHODAS) polytomous score placed 50% (n=20/40) of participants in the 90 percentile of disability based on population norms. The mean SF-36 physical functioning score was almost nine points below population norms (mean=70.6, standard deviation=27.4). Additionally, 47.5% of individuals (n=19) were severely emotionally affected by their health condition. Over half of participants surveyed were still impacted a year after initial infection, experiencing limited functional ability, fatigue, and emotional difficulties. Given the impact of these symptoms on day-to-day quality of life, further studies are needed to develop strategies for treatment and management of post-COVID conditions.
Although breast density decline with tamoxifen therapy is associated with greater therapeutic benefit, limited data suggest that endocrine symptoms may also be associated with improved breast cancer outcomes. However, it is unknown whether endocrine symptoms are associated with reductions in breast density after tamoxifen initiation. We evaluated treatment-associated endocrine symptoms and breast density change among 74 women prescribed tamoxifen in a 12-month longitudinal study. Treatment-associated endocrine symptoms and sound speed measures of breast density, assessed via novel whole breast ultrasound tomography (m/s), were ascertained before tamoxifen (T0) and at 1–3 (T1), 4–6 (T2), and 12 months (T3) after initiation. CYP2D6 status was genotyped, and tamoxifen metabolites were measured at T3. Using multivariable linear regression, we estimated mean change in breast density by treatment-associated endocrine symptoms adjusting for age, race, menopausal status, body mass index, and baseline density. Significant breast density declines were observed in women with treatment-associated endocrine symptoms (mean change (95% confidence interval) at T1:−0.26 m/s (−2.17,1.65); T2:−2.12 m/s (−4.02,−0.22); T3:−3.73 m/s (−5.82,−1.63); p -trend = 0.004), but not among women without symptoms ( p -trend = 0.18) ( p -interaction = 0.02). Similar declines were observed with increasing symptom frequency ( p -trends for no symptoms = 0.91; low/moderate symptoms = 0.03; high symptoms = 0.004). Density declines remained among women with detectable tamoxifen metabolites or intermediate/efficient CYP2D6 metabolizer status. Emergent/worsening endocrine symptoms are associated with significant, early declines in breast density after tamoxifen initiation. Further studies are needed to assess whether these observations predict clinical outcomes. If confirmed, endocrine symptoms may be a proxy for tamoxifen response and useful for patients and providers to encourage adherence.
Introduction: Prenatal and early-life dog exposure has been linked to reduced childhood allergy and asthma. A potential mechanism includes altered early immune development in response to changes in the gut microbiome among dog-exposed infants. We thus sought to determine whether infants born into homes with indoor dog(s) exhibit altered gut microbiome development. Methods: Pregnant women living in homes with dogs or in pet-free homes were recruited in southeast Michigan. Infant stool samples were collected at intervals between 1 week and 18 months after birth and microbiome was assessed using 16S ribosomal sequencing. Perinatal maternal vaginal/rectal swabs and stool samples were sequenced from a limited number of mothers. Mixed effect adjusted models were used to assess stool microbial community trajectories comparing infants from dog-keeping versus pet-free homes with adjustment for relevant covariates. Results: Infant gut microbial composition among vaginally born babies became less similar to the maternal vaginal/rectal microbiota and more similar to the maternal gut microbiota with age-related accumulation of bacterial species with advancing age. Stool samples from dog-exposed infants were microbially more diverse (p = .041) through age 18 months with enhanced diversity most apparent between 3 and 6 months of age. Statistically significant effects of dog exposure on β-diversity metrics were restricted to formula-fed children. Across the sample collection period, dog exposure was associated with Fusobacterium genera enrichment, as well as enrichment of Collinsella, Ruminococcus, Clostridaceae and Lachnospiraceae OTUs. Conclusion: Prenatal/early-life dog exposure is associated with an altered gut microbiome during infancy and supports a potential mechanism explaining lessened atopy and asthma risk. Further research directly linking specific dog-attributable changes in the infant gut microbiome to the risk of allergic disorders is needed.
Background: Single-kV CT imaging is one of the primary imaging methods in radiology practices. However, it does not provide material basis images for some subtle lesion characterization tasks in clinical diagnosis. Purpose: To develop a quality-checked and physics-constrained deep learning (DL) method to estimate material basis images from single-kV CT data without resorting to dual-energy CT acquisition schemes. Methods: Single-kV CT images are decomposed into two material basis images using a deep neural network. The role of this network is to generate a feature space with 64 template features with the same matrix dimensions of the input single-kV CT image. These 64 template image features are then combined to generate the desired material basis images with different sets of combination coefficients, one for each material basis image. Dual-energy CT image acquisitions with two separate kVs were curated to generate paired training data between a single-kV CT image and the corresponding two material basis images. To ensure the obtained two material basis images are consistent with the encoded spectral information in the actual projection data, two physics constraints, i.e., (1) effective energy of each measured projection datum that characterizes the beam hardening in data acquisitions and (2) physical factors of scanners such as detector and tube characteristics, are incorporated into the end-to-end training. The entire architecture is referred to as Deep-En-Chroma in this paper. In the application stage, the generated material basis images are sent to a deep quality check (Deep-QC) network to assess the quality of estimated images and to report the pixel-wise estimation errors for users. The models were developed using 5,592 training and validation pairs generated from 48 clinical cases. Additional 1,526 CT images from another 13 patients were used to evaluate the quantitative accuracy of water and iodine basis images estimated by Deep-En-Chroma. Results: For the iodine basis images estimated by Deep-En-Chroma, the mean difference with respect to dual-energy CT is -0.25 mg/mL, and the agreement limits are [-0.75 mg/mL, +0.24 mg/mL]. For the water basis images estimated by Deep-En-Chroma, the mean difference with respect to dual-energy CT is 0.0 g/mL, and the agreement limits are [-0.01 g/mL, 0.01 g/mL]. Across the test cohort, the median [25th, 75th percentiles] root mean square errors between the Deep-En-Chroma and dual-energy material images are 14 [12, 16] mg/ml for the water images and 0.73 [0.64, 0.80] mg/ml for the iodine images. When significant errors are present in the estimated material basis images, Deep-QC can capture these errors and provide pixel-wise error maps to inform users whether the DL results are trustworthy. Conclusions: The Deep-En-Chroma network provides a new pathway to estimating the clinically relevant material basis images from single-kV CT data and the Deep-QC module to inform end-users of the accuracy of the DL material basis images in practice. This article is protected by copyright. All rights reserved.
Rationale/objectives: Genetic studies suggest SOX17 deficiency increases pulmonary arterial hypertension (PAH) risk. Based on pathological roles of estrogen and hypoxia inducible factor 2α (HIF-2α) signaling in PA endothelial cells (PAECs), we hypothesized that SOX17 is a target of estrogen signaling that promotes mitochondrial function and attenuates PAH development via HIF-2α inhibition. Methods: We used metabolic (seahorse) and promoter lucifer assays in PAECs along with the chronic hypoxia murine model to test the hypothesis. Measurements and main results: Sox17 expression was reduced in PAH tissues (rodent models and from patients). Chronic hypoxic PH was exacerbated by mice with conditional Tie2-Sox17 (Sox17EC-/-) deletion and attenuated by transgenic Tie2-Sox17 over-expression (Sox17Tg). Based on untargeted proteomics, metabolism was the top pathway altered by SOX17 deficiency in PAECs. Mechanistically, we found HIF-2α levels were increased in the lungs of Sox17EC-/- and reduced in those from Sox17Tg mice. Increased SOX17 promoted oxidative phosphorylation and mitochondrial function in PAECs, which were partly attenuated by HIF-2α overexpression. Rat lungs in males displayed higher Sox17 expression versus females, suggesting repression by estrogen signaling. Supporting 16alpha-hydroxyestrone (16αOHE, a pathologic estrogen metabolite)-mediated repression of SOX17 promoter activity, Sox17Tg mice attenuated 16αOHE-mediated exacerbations of chronic hypoxic PH. Finally, in adjusted analyses in patients with PAH, we report novel associations between a SOX17 risk variant, rs10103692, with reduced plasma citrate levels (n=1326). Conclusions: Cumulatively, SOX17 promotes mitochondrial bioenergetics and attenuates PAH, in part, via inhibition of HIF-2α. 16αOHE mediates PAH development via downregulation of SOX17, linking sexual dimorphism and SOX17 genetics in PAH. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Peritoneal metastases from colon cancer are a particularly challenging disease process given the limited response to systemic chemotherapy. In patients with isolated peritoneal metastases, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy offers a potential treatment option to these patients with limited peritoneal metastases as long as a complete cytoreduction is achieved. Decision about a patient's candidacy for this treatment modality should be undertaken by a multidisciplinary group at expert centers.
Methods for collection of placental tissue at room temperature for metabolic profiling are described. Specimens were excised from the maternal side of the placenta and immediately flash frozen or fixed and stored for 1, 6, 12, 24, or 48 h in 80% methanol. Untargeted metabolic profiling was performed on both the methanol-fixed tissue and the methanol extract. Data were analyzed using Gaussian generalized estimating equations, two sample t-tests with false discovery rate (FDR) corrections, and principal components analysis. Methanol-fixed tissue samples and methanol extracts had a similar number of metabolites (p = 0.45, p = 0.21 in positive vs. negative ion mode). In positive ion mode, when compared to flash frozen tissue, both the methanol extract and methanol-fixed tissue (6 h) had a higher number of metabolites detected (146 additional metabolites, pFDR = 0.020; 149 additional metabolites, pFDR = 0.017; respectively), but these associations were not found in negative ion mode (all pFDR ≥ 0.05). Principle components analysis demonstrated separation of the metabolite features in the methanol extract, but similarity between methanol-fixed tissue and flash frozen tissue. These results show that placental tissue samples collected in 80% methanol at room temperature can yield similar metabolic data to flash frozen specimens.
Importance: Cataract surgery is one of the most commonly performed surgeries across medicine and an integral part of ophthalmologic care. Complex cataract surgery requires more time and resources than simple cataract surgery, yet it remains unclear whether the incremental reimbursement for complex cataract surgery, compared with simple cataract surgery, offsets the increased costs. Objective: To measure the difference in day-of-surgery costs and net earnings between simple and complex cataract surgery. Design, setting, and participants: This study is an economic analysis at a single academic institution using time-driven activity-based costing methodology to determine the operative-day costs of simple and complex cataract surgery. Process flow mapping was used to define the operative episode limited to the day of surgery. Simple and complex cataract surgery cases (Current Procedural Terminology codes 66984 and 66982, respectively) at the University of Michigan Kellogg Eye Center from 2017 to 2021 were included in the analysis. Time estimates were obtained using an internal anesthesia record system. Financial estimates were obtained using a mix of internal sources and prior literature. Supply costs were obtained from the electronic health record. Main outcomes and measures: Difference in day-of-surgery costs and net earnings. Results: A total of 16 092 cataract surgeries were included, 13 904 simple and 2188 complex. Time-based day-of-surgery costs for simple and complex cataract surgery were $1486.24 and $2205.83, respectively, with a mean difference of $719.59 (95% CI, $684.09-$755.09; P < .001). Complex cataract surgery required $158.26 more for costs of supplies and materials (95% CI, $117.00-$199.60; P < .001). The total difference in day-of-surgery costs between complex and simple cataract surgery was $877.85. Incremental reimbursement for complex cataract surgery was $231.01; therefore, complex cataract surgery had a negative earnings difference of $646.84 compared with simple cataract surgery. Conclusions and relevance: This economic analysis suggests that the incremental reimbursement for complex cataract surgery undervalues the resource costs required for the procedure, failing to cover increased costs and accounting for less than 2 minutes of increased operating time. These findings may affect ophthalmologist practice patterns and access to care for certain patients, which may ultimately justify increasing cataract surgery reimbursement.
Background The renal mechanisms involved in the maintenance of human hypertension and resistance to treatment are not well understood. Animal studies suggest that chronic renal inflammation contributes to hypertension. We studied cells shed in first‐morning urine samples from individuals who were hypertensive who exhibited difficult‐to‐control blood pressure (BP). We performed bulk RNA sequencing of these shed cells to develop transcriptome‐wide associations with BP. We also analyzed nephron‐specific genes and used an unbiased bioinformatic approach to find signaling pathways activated in difficult‐to‐control hypertension. Methods and Results Participants who completed the SPRINT (Systolic Blood Pressure Intervention Trial) at a single trial site were recruited, and cells shed in first‐morning urine samples collected. A total of 47 participants were divided into 2 groups based on hypertension control. The BP‐difficult group (n=29) had systolic BP>140 mm Hg, >120 mm Hg after intensive treatment for hypertension, or required more than the median number of antihypertensive drugs used in SPRINT. The easy‐to‐control BP group (n=18) comprised the remainder of the participants. A total of 60 differentially expressed genes were identified with a >2‐fold change in the BP‐difficult group. In BP‐difficult participants, 2 of the most upregulated genes were associated with inflammation: Tumor Necrosis Factor Alpha Induced Protien 6 (fold change, 7.76; P =0.006) and Serpin Family B Member 9 (fold change, 5.10; P =0.007). Biological pathway analysis revealed an overrepresentation of inflammatory networks, including interferon signaling, granulocyte adhesion and diapedesis, and Janus Kinase family kinases in the BP‐difficult group ( P <0.001). Conclusions We conclude that transcriptomes from cells shed in first‐morning urine identify a gene expression profile in difficult‐to‐control hypertension that associates with renal inflammation.
Introduction: Living donor liver transplantation (LDLT) is a promising option for mitigating the deceased donor organ shortage and reducing waitlist mortality. Despite excellent outcomes and data supporting expanding candidate indications for LDLT, broader uptake throughout the United States has yet to occur. Methods: In response to this, the American Society of Transplantation hosted a virtual consensus conference (October 18-19, 2021), bringing together relevant experts with the aim of identifying barriers to broader implementation and making recommendations regarding strategies to address these barriers. In this report, we summarize the findings relevant to the selection and engagement of both the LDLT candidate and living donor. Utilizing a modified Delphi approach, barrier and strategy statements were developed, refined, and voted on for overall barrier importance and potential impact and feasibility of the strategy to address said barrier. Results: Barriers identified fell into three general categories: 1) awareness, acceptance, and engagement across patients (potential candidates and donors), providers, and institutions, 2) data gaps and lack of standardization in candidate and donor selection, and 3) data gaps regarding post-living liver donation outcomes and resource needs. Conclusions: Strategies to address barriers included efforts towards education and engagement across populations, rigorous and collaborative research, and institutional commitment and resources. This article is protected by copyright. All rights reserved.
This case report describes an ulcerated violaceous nodule on the right nasal ala as well as 3 small ulcers on the neck, back, and buttocks.
Introduction: In October 2021, the American Society of Transplantation (AST) hosted a virtual consensus conference aimed at identifying and addressing barriers to the broader, safe expansion of living donor liver transplantation (LDLT) throughout the United States (US). Methods: A multidisciplinary group of LDLT experts convened to address issues related to financial implications on the donor, transplant center crisis management, regulatory and oversight policies, and ethical considerations by assessing the relative significance of issues in preventing LDLT growth, with proposed strategies to overcome barriers. Results: Living liver donors endure multiple obstacles including financial instability, loss of job security and potential morbidity. These concerns, along with other center, state and federal specific policies can be perceived as significant barriers to expanding LDLT. Donor safety is of paramount importance to the transplant community; however, regulatory and oversight policies aimed at ensuring donor safety can be viewed as ambiguous and complicated leading to time-consuming evaluations that may deter donor motivation and program expansion. Conclusion: Transplant programs need to establish appropriate crisis management plans to mitigate potential negative donor outcomes and ensure program viability and stability. Finally, ethical aspects, including informed consent for high-risk recipients and use of non-directed donors, can be perceived as additional barriers to expanding LDLT. This article is protected by copyright. All rights reserved.
Background Despite efficacy of medication for opioid use disorder, low-income, ethno-racial minoritized populations often experience poor opioid use disorder treatment outcomes. Peer recovery specialists, individuals with lived experience of substance use and recovery, are well-positioned to engage hard-to-reach patients in treatment for opioid use disorder. Traditionally, peer recovery specialists have focused on bridging to care rather than delivering interventions. This study builds on research in other low-resource contexts that has explored peer delivery of evidence-based interventions, such as behavioral activation, to expand access to care. Methods We sought feedback on the feasibility and acceptability of a peer recovery specialist-delivered behavioral activation intervention supporting retention in methadone treatment by increasing positive reinforcement. We recruited patients and staff at a community-based methadone treatment center and peer recovery specialist working across Baltimore City, Maryland, USA. Semi-structured interviews and focus groups inquired about the feasibility and acceptability of behavioral activation, recommendations for adaptation, and acceptability of working with a peer alongside methadone treatment. Results Participants (N = 32) shared that peer recovery specialist-delivered behavioral activation could be feasible and acceptable with adaptations. They described common challenges associated with unstructured time, for which behavioral activation could be particularly relevant. Participants provided examples of how a peer-delivered intervention could fit well in the context of methadone treatment, emphasizing the importance of flexibility and specific peer qualities. Conclusions Improving medication for opioid use disorder outcomes is a national priority that must be met with cost-effective, sustainable strategies to support individuals in treatment. Findings will guide adaptation of a peer recovery specialist-delivered behavioral activation intervention to improve methadone treatment retention for underserved, ethno-racial minoritized individuals living with opioid use disorder.
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Detroit, United States