Age-related brain atrophy is not a homogenous process: Different functional brain networks associate differentially with aging and blood factors.

Aging is characterized by a progressive loss of brain volume at an estimated rate of 5% per decade after age 40. While these morphometric changes, especially those affecting gray matter and atrophy of the temporal lobe, are predictors of cognitive performance, the strong association with aging obscures the potential parallel, but more specific role, of individual subject physiology. Here, we studied a cohort of 554 human subjects who were monitored using structural MRI scans and blood immune protein concentrations. Using machine learning, we derived a cytokine clock (CyClo), which predicted age with good accuracy (Mean Absolute Error = 6 y) based on the expression of a subset of immune proteins. These proteins included, among others, Placenta Growth Factor (PLGF) and Vascular Endothelial Growth Factor (VEGF), both involved in angiogenesis, the chemoattractant vascular cell adhesion molecule 1 (VCAM-1), the canonical inflammatory proteins interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα), the chemoattractant IP-10 (CXCL10), and eotaxin-1 (CCL11), previously involved in brain disorders. Age, sex, and the CyClo were independently associated with different functionally defined cortical networks in the brain. While age was mostly correlated with changes in the somatomotor system, sex was associated with variability in the frontoparietal, ventral attention, and visual networks. Significant canonical correlation was observed for the CyClo and the default mode, limbic, and dorsal attention networks, indicating that immune circulating proteins preferentially affect brain processes such as focused attention, emotion, memory, response to social stress, internal evaluation, and access to consciousness. Thus, we identified immune biomarkers of brain aging which could be potential therapeutic targets for the prevention of age-related cognitive decline.

Horizontal versus vertical strategies for infection prevention: current practices and controversies.

PURPOSE OF REVIEW: Healthcare-associated infections (HAIs) represent a major burden on healthcare facilities. Effective infection prevention strategies are essential to prevent the spread of HAIs. These can be broadly classified as vertical and horizontal interventions. Through this review, we aim to assess the merits of these strategies. RECENT FINDINGS: Vertical strategies include active surveillance testing and isolation for patients infected or colonized with a particular organism. These strategies are beneficial to curb the spread of emerging pathogens and during outbreaks. However, the routine use of contact precautions for organisms such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus remains controversial. Horizontal interventions are larger-scale and reduce HAIs by targeting a common mode of transmission shared by multiple organisms. Among these, hand hygiene, chlorhexidine gluconate bathing of select patients and environmental decontamination are the most high-yield and must be incorporated into infection prevention programs. As antimicrobial stewardship is also an effective horizontal strategy, antimicrobial stewardship programs must operate in synergy with infection prevention programs for maximal impact. SUMMARY: Overall, horizontal interventions are considered more cost-effective and have a broader impact. Infection control programs may opt for a combination of vertical and horizontal strategies based on local epidemiology and available resources.

Estradiol effects on an emotional interference task in adolescents with current and remitted depression.

Attentional biases to emotional stimuli are thought to reflect vulnerability for mood disorder onset and maintenance. This study examined the association between the endogenous sex hormone estradiol and emotional attentional biases in adolescent females with either current or remitted depression. Three groups of participants (mean age ± SD) completed the Emotional Interrupt Task: 1) 20 adolescent females (15.1 ± 1.83 years) currently diagnosed with Major Depressive Disorder (MDD), 2) 16 adolescent females (16.4 ± 1.31 years) who had experienced at least one episode of MDD in their lifetime but currently met criteria for MDD in remission, and 3) 30 adolescent female (15.4 ± 1.83 years) healthy controls. Attentional interference (AI) scores were calculated as differences in target response reaction time between trials with emotional facial expressions versus neutral facial expressions. Estradiol levels were assayed by Salimetrics LLC using saliva samples collected within 30 min of waking on assessment days. Robust multiple regression with product terms evaluated estradiol's main effect on AI scores, as well as hypothesized estradiol × diagnostic group interactions. Although neither mean estradiol levels nor mean AI scores in the current-MDD and remitted-MDD groups differed from controls, the relationship between estradiol and overall AI score differed between control adolescents and the remitted-MDD group. Specifically, the remitted-MDD adolescents performed worse (i.e., showed greater attentional interference) when they had higher estradiol; no significant relationship existed in the current-MDD group. Because this finding was driven by angry and not happy stimuli, it appears higher estradiol levels were associated with greater susceptibility to the attention-capturing effects of negatively-valenced emotional content in girls at risk for MDD from prior history.

The presence of erionite in North American geologies and the estimated mesothelioma potency by region.

OBJECTIVE: Erionite is a naturally occurring fibrous mineral found in soils in some geographical regions. Known for its potency for causing mesothelioma in the Cappadocia region of Turkey, the erionite fiber has attracted interest in the United States due to its presence in a band of rock that extends from Mexico to Montana. There are few toxicology studies of erionite, but all show it to have unusually high chronic toxicity. Despite its high potency compared to asbestos fibers, erionite has no occupational or environmental exposure limits. This paper takes what has been learned about the chemical and physical characteristics of the various forms of asbestos (chrysotile, amosite, anthophyllite, and crocidolite) and predicts the potency of North American erionite fibers. MATERIALS AND METHODS: Based on the fiber potency model in Korchevskiy et al. (2019) and the available published information on erionite, the estimated mesothelioma potency factors (the proportion of mesothelioma mortality per unit cumulative exposure (f/cc-year)) for erionites in the western United States were determined. RESULTS AND DISCUSSION: The model predicted potency factors ranged from 0.19 to 11.25 (average ∼3.5), depending on the region. For reference, crocidolite (the most potent commercial form of asbestos) is assigned a potency factor ∼0.5. CONCLUSION: The model predicted mesothelioma potency of Turkish erionite (4.53) falls in this same range of potencies as erionite found in North America. Although it can vary by region, a reasonable ratio of average mesothelioma potency based on this model is 3,000:500:100:1 comparing North American erionite, crocidolite, amosite, and chrysotile (from most potent to least potent).

Coated Cast Saw Blades Decrease Blade Temperature During Cast Removal.

BACKGROUND: Thermal injuries can occur during cast removal with an oscillating saw. The purpose of this study is to describe the effect of blade material, blade wear, and cast material on blade temperature. METHODS: Short arm plaster and fiberglass casts were cured overnight and bivalved with either new or worn stainless-steel or tungsten-disulfide coated blades. Blade use was defined as removing 1 short arm cast. Blades used to remove more than 20 casts were defined as worn. Ten trials were performed with each combination of blade material, blade wear, and cast material, except for the combination of fiberglass and a worn stainless-steel blade due to complete erosion of cutting teeth. Thirty casts were removed with stainless-steel blades, and 40 casts were removed with coated blades. Blade temperature was measured continuously at 5 Hz using a T-type thermocouple and microcontroller board. A Mann-Whitney U test was used to compare the mean maximum temperature between groups. RESULTS: For plaster casts, new and worn stainless-steel blades produced mean maximum temperatures of 51.4°C and 63.7°C ( P =0.003), respectively. New stainless-steel blades produced significantly higher mean maximum temperatures on fiberglass casts than plaster casts (95.9°C vs. 51.4°C, P <.001). For plaster casts, new and worn coated blades produced mean maximum temperatures of 56.9°C and 53.8°C ( P =0.347). For fiberglass casts, new and worn coated blades produced mean maximum temperatures of 76.6°C and 77.7°C ( P =0.653). As with new stainless-steel blades, new coated blades produced significantly higher mean maximum temperatures on fiberglass than plaster (76.6°C vs. 56.9°C, P <0.001). Mean maximum temperatures between new stainless-steel and coated blades during removal of plaster casts were 51.4°C and 56.9°C ( P =0.131), respectively. However, new coated blades demonstrated significantly lower mean maximum temperatures during fiberglass cast removal compared to new stainless-steel blades (76.6°C vs. 95.9°C, P =0.016). CONCLUSIONS: Coated blades outperformed stainless-steel in nearly all combinations. We recommend limited use of stainless-steel blades to minimize blade temperatures during cast removal. CLINICAL RELEVANCE: Appropriate selection of blade material and monitoring blade wear minimizes blade temperature during cast removal.

Occupational exposures to asbestos in the steel industry: An analysis of the AISI sampling campaign (1989-1997).

The American Iron and Steel Institute (AISI) gathered data between 1989 and 1997 to build an "objective database" to further understand the occupational exposures generated by the few asbestos-containing materials remaining at various steelmaking companies at this time. This paper analyzed the 520 samples from this campaign which occurred at five different steel manufacturers: Georgetown Steel Company, Inland Steel Company, Ling-Temco-Vought (LTV) Corporation, United States Steel Corporation, and Weirton Steel Corporation. This database is believed to have never previously been systematically organized. Samples were grouped based on sampling times to determine whether they should most appropriately be compared to the OSHA short-term excursion limit (EL) or the 8-hr time-weighted average (TWA) permissible exposure limit (PEL). Sampling times of 30 min or less were considered short-term samples, and samples of 180 min or greater were considered representative workday samples. Samples that did not fit into either category, with sampling times between 31 and 179 min, were considered task samples. Overall, the data indicated that the airborne concentrations were quite low in 1989 and they continued to be low through the study period which ended in 1997. Only seven out of 286 (approximately 2.5%) short-term or representative workday samples were in exceedance of the current OSHA OELs that were implemented in 1994 (short-term samples being compared to the 1 f/cc EL and representative workday samples being compared to the 0.1 f/cc 8-hr TWA PEL). Consistent with prior data, analysis of this dataset supports the view that materials containing asbestos were not used in many applications in the steel industry, and measured airborne concentrations of asbestos were almost always below the occupational exposure limits (OELs) in the post-OSHA era (1972-2000).

Are contact precautions "essential" for the prevention of healthcare-associated methicillin-resistant Staphylococcus aureus?

The recently updated SHEA/IDSA/APIC practice recommendations for MRSA prevention in acute care facilities list contact precautions (CP) for patients known to be infected or colonized with MRSA as an "essential practice", meaning that it should be adopted in all acute care facilities. We argue that existing evidence on benefits and harms associated with CP do not justify this recommendation. There are no controlled trials that support broad use of CP for MRSA prevention. Data from hospitals that have discontinued CP for MRSA have found no impact on MRSA acquisition or infection. The burden and harms of CP remain concerning, including the environmental impact of increased gown and glove use. We suggest that CP be included among other "additional approaches" to MRSA prevention that can be implemented under specific circumstances (e.g. outbreaks, evidence of ongoing transmission despite application of essential practices).

Three-Dimensional Energy Transfer in Space Plasma Turbulence from Multipoint Measurement.

A novel multispacecraft technique applied to Magnetospheric Multiscale Mission data in the Earth's magnetosheath enables evaluation of the energy cascade rate from the full Yaglom's equation. The method differs from existing approaches in that it (i) is inherently three-dimensional, (ii) provides a statistically significant number of estimates from a single data stream, and (iii) allows visualization of energy flux in turbulent plasmas. This new "lag polyhedral derivative ensemble" technique exploits ensembles of tetrahedra in lag space and established curlometerlike algorithms.

Subsequent cancers within 5 years from initial diagnosis of childhood cancer. Patterns and risks in the population of Great Britain.

BACKGROUND: Patterns and risks of subsequent primary tumours (SPTs) among long-term survivors of childhood cancer have been extensively described, but much less is known about early SPTs (ESPTs) occurring within 5 years after initial diagnosis. PROCEDURE: We carried out a population-based study of ESPTs following childhood cancer throughout Britain, using the National Registry of Childhood Tumours. The full study series comprised all ESPTs occurring among 56,620 children whose initial cancer diagnosis was in the period 1971-2010. Frequencies of ESPT were calculated for the entire cohort. For analyses of risk, follow-up began 92 days after initial diagnosis. RESULTS: ESPT developed in 0.4% of children overall, 0.52% of those initially diagnosed at age less than 1 year and 0.38% of those diagnosed at age 1-14 years. Standardised incidence ratio (SIR) was 7.7 (95% confidence interval [CI]: 6.7-8.9), overall 9.5 (95% CI: 7.1-12.5) for children initially diagnosed in 1981-1990 and 6.5-7.5 for those from earlier and later decades. SIR by type of first cancer ranged from 4.4 (95% CI: 1.8-9.1) for Wilms tumour to 13.1 (95% CI: 7.7-21.0) for non-Hodgkin lymphoma. SIR by type of ESPT ranged from 2.0 (95% CI: 1.0-3.4) for acute lymphoblastic leukaemia to 66.6 (95% CI: 52.3-83.6) for acute myeloid leukaemia. Predisposition syndromes were known to be implicated in 21% of children with ESPT and suspected in another 5%. CONCLUSIONS: This study provides an overview of the patterns and risks of ESPTs in a large population where many children received therapy that is still in widespread use. Further research will be needed to monitor and understand changes in risk as childhood cancer treatment continues to evolve.

SpDamID: Marking DNA Bound by Protein Complexes Identifies Notch-Dimer Responsive Enhancers.

We developed Split DamID (SpDamID), a protein complementation version of DamID, to mark genomic DNA bound in vivo by interacting or juxtapositioned transcription factors. Inactive halves of DAM (DNA adenine methyltransferase) were fused to protein pairs to be queried. Either direct interaction between proteins or proximity enabled DAM reconstitution and methylation of adenine in GATC. Inducible SpDamID was used to analyze Notch-mediated transcriptional activation. We demonstrate that Notch complexes label RBP sites broadly across the genome and show that a subset of these complexes that recruit MAML and p300 undergo changes in chromatin accessibility in response to Notch signaling. SpDamID differentiates between monomeric and dimeric binding, thereby allowing for identification of half-site motifs used by Notch dimers. Motif enrichment of Notch enhancers coupled with SpDamID reveals co-targeting of regulatory sequences by Notch and Runx1. SpDamID represents a sensitive and powerful tool that enables dynamic analysis of combinatorial protein-DNA transactions at a genome-wide level.

Cooperative approaches in catalytic hydrogenation and dehydrogenation.

Metal-ligand cooperativity (MLC) is an established strategy for developing effective hydrogenation and dehydrogenation catalysts. Metal-metal cooperativity (MMC) in bimetallic complexes is not as well understood, and to date has had limited implementation in (de)hydrogenation. Herein we use (de)hydrogenation processes as a platform to examine modes of cooperativity, with a particular focus on catalytic mechanisms. We investigate how lessons learnt from the extensive development of metal-ligand cooperative catalysts can aid the ongoing development of metal-metal cooperative catalysts.

Nutritional assessment and dietetic resource for children and young people with cancer in the United Kingdom.

BACKGROUND: Both under- and overnutrition may have adverse impact on outcome of cancer in children and teenagers/young adults (CTYA). Previous studies confirm that screening for nutritional risk and detection of nutritional abnormality is inconsistently undertaken in practice. METHODS: We undertook a survey of dietetic resource and nutritional assessment in CTYA principal treatment centres (PTC) in the United Kingdom. Responses were received from 95% children's and 69% TYA PTC. RESULTS: Only 13/18 (72%) children's PTC, and one of 11 (9%) TYA PTC, met national standards for dietetic resource; one of 18 (6%) paediatric and six of 11(54%) TYA PTC had no such resource. While resources were greater in larger paediatric PTC, who were also most likely to undertake stem cell transplantation, resources in TYA PTC were too low to assess relationship to centre size. Most centres focused resources on inpatient care and <50% considered staffing adequate; 82% used nutritional screening tools but without consistency in the tool used. Weight and height were the principal method for assessment, but with inconsistency in the frequency of measurement and use in different clinical settings. Measures derived from weight and height, including body mass index (BMI), were inconsistently utilised. The use of arm anthropometry was rare despite evidence that use increases recognition of undernutrition. Detailed nutritional assessment was infrequently attempted. CONCLUSION: Barriers to adequate nutritional assessment and treatment for all patients include resource limitations (particularly TYA), training for staff, and uncertainty about detailed assessment of nutritional status. There is a need to harmonise screening and assessment of nutritional status in CTYA with cancer.

Copper and Zinc Complexes of 2,7-Bis(6-methyl-2-pyridyl)-1,8-naphthyridine─A Redox-Active, Dinucleating Bis(bipyridine) Ligand.

The ligand 2,7-bis(6-methyl-2-pyridyl)-1,8-naphthyridine (MeL) acts as a dinucleating analogue of ubiquitous 2,2'-bipyridine ligands. Coordination of MeL to [Cu(NCMe)4]PF6 and Zn(OAc)2 led to isolation of monometallic [Zn(OAc)2(MeL)], homobimetallic [Cu2(MeL)2][PF6]2, and heterobimetallic [CuZn(µ-OAc)2(MeL)]PF6 complexes. The redox-active nature of the ligand enables access to four redox states of the complex [Cu2(MeL)2][PF6]2. DFT studies indicate that these comprise a metal-centered oxidative and ligand-centered reductive processes.

A mock circulation loop to evaluate differential hypoxemia during peripheral venoarterial extracorporeal membrane oxygenation.

INTRODUCTION: Peripheral veno-arterial extracorporeal membrane oxygenation (VA ECMO) creates a retrograde flow along the aorta competing with the left ventricle (LV) in the so-called 'mixing zone' (MZ). Detecting it is essential to understand which of the LV or the ECMO flow perfuses the upper body - particularly the brain and the coronary arteries - in case of differential hypoxemia (DH). METHODS: We described a mock circulation loop (MCL) that enabled experimental research on DH. We recreated the three clinical situations relevant to clinicians: where the brain is either totally perfused by the ECMO or the LV or both. In a second step, we used this model to investigate two scenarios to diagnose DH: (i) pulse pressure and (ii) thermodilution via injection of cold saline in the ECMO circuit. RESULTS: The presented MCL was able to reproduce the three relevant mixing zones within the aortic arch, thus allowing to study DH. Pulse pressure was unable to detect location of the MZ. However, the thermodilution method was able to detect whether the brain was totally perfused by the ECMO or not. CONCLUSION: We validated an in-vitro differential hypoxemia model of cardiogenic shock supported by VA ECMO. This MCL could be used as an alternative to animal studies for research scenarios.

Impact of the Centers for Medicare and Medicaid Services Sepsis Core Measure on Antibiotic Use.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) implemented a core measure sepsis (SEP-1) bundle in 2015. One element was initiation of broad-spectrum antibiotics within 3 hours of diagnosis. The policy has the potential to increase antibiotic use and Clostridioides difficile infection (CDI). We evaluated the impact of SEP-1 implementation on broad-spectrum antibiotic use and CDI occurrence rates. METHODS: Monthly adult antibiotic data for 4 antibiotic categories (surgical prophylaxis, broad-spectrum for community-acquired infections, broad-spectrum for hospital-onset/multidrug-resistant [MDR] organisms, and anti-methicillin-resistant Staphylococcus aureus [MRSA]) from 111 hospitals participating in the Clinical Data Base Resource Manager were evaluated in periods before (October 2014-September 2015) and after (October 2015-June 2017) policy implementation. Interrupted time series analyses, using negative binomial regression, evaluated changes in antibiotic category use and CDI rates. RESULTS: At the hospital level, there was an immediate increase in the level of broad-spectrum agents for hospital-onset/MDR organisms (+2.3%, P = .0375) as well as a long-term increase in trend (+0.4% per month, P = .0273). There was also an immediate increase in level of overall antibiotic use (+1.4%, P = .0293). CDI rates unexpectedly decreased at the time of SEP-1 implementation. When analyses were limited to patients with sepsis, there was a significant level increase in use of all antibiotic categories at the time of SEP-1 implementation. CONCLUSIONS: SEP-1 implementation was associated with immediate and long-term increases in broad-spectrum hospital-onset/MDR organism antibiotics. Antimicrobial stewardship programs should evaluate sepsis treatment for opportunities to de-escalate broad therapy as indicated.

Male-derived copulatory plugs enhance implantation success in female Mus musculus.

Among a wide diversity of sexually reproducing species, male ejaculates coagulate to form what has been termed a copulatory plug. A number of functions have been attributed to copulatory plugs, including the inhibition of female remating and the promotion of ejaculate movement. Here we demonstrate that copulatory plugs also influence the likelihood of implantation, which occurs roughly 4 days after copulation in mice. Using a bead transfer method to control for differences in ejaculate retention and fertilization rates, we show that implantation rates significantly drop among females mated to genetically engineered males incapable of forming plugs (because they lack functional transglutaminase 4, the main enzyme responsible for its formation). Surprisingly, this result does not correlate with differences in circulating progesterone levels among females, an important hormone involved in implantation. We discuss three models that connect male-derived copulatory plugs to implantation success, including the hypothesis that plugs contribute to a threshold amount of stimulation required for females to become receptive to implantation.

Spatially clustered count data provide more efficient search strategies in invasion biology and disease control.

Geographic profiling, a mathematical model originally developed in criminology, is increasingly being used in ecology and epidemiology. Geographic profiling boasts a wide range of applications, such as finding source populations of invasive species or breeding sites of vectors of infectious disease. The model provides a cost-effective approach for prioritizing search strategies for source locations and does so via simple data in the form of the positions of each observation, such as individual sightings of invasive species or cases of a disease. In doing so, however, classic geographic profiling approaches fail to make the distinction between those areas containing observed absences and those areas where no data were recorded. Absence data are generated via spatial sampling protocols but are often discarded during the inference process. Here we construct a geographic profiling model that resolves these issues by making inferences via count data, analyzing a set of discrete sentinel locations at which the number of encounters has been recorded. Crucially, in our model this number can be zero. We verify the ability of this new model to estimate source locations and other parameters of practical interest via a Bayesian power analysis. We also measure model performance via real-world data in which the model infers breeding locations of mosquitoes in bromeliads in Miami-Dade County, Florida, USA. In both cases, our novel model produces more efficient search strategies by shifting focus from those areas containing observed absences to those with no data, an improvement over existing models that treat these areas equally. Our model makes important improvements upon classic geographic profiling methods, which will significantly enhance real-world efforts to develop conservation management plans and targeted interventions.

Evaluation of a point-of-care molecular detection device for Leishmania spp. and intercurrent fungal and mycobacterial organisms in Peruvian patients with cutaneous ulcers.

PURPOSE: Overlapping clinical features of cutaneous leishmaniasis (CL) with ulcers caused by fungi and mycobacteria necessitate confirmatory diagnostic testing. We evaluated a handheld battery-operated device for detection of CL and common fungal and mycobacterial causes of ulcers. METHODS: We validated Palm PCR™ for detection of common ulcerative skin pathogens using ATCC® reference and clinical strains of Leishmania, mycobacteria, and fungi in the lab and field. Amplified products were Sanger sequenced. Performance characteristics were calculated using conventional PCR as a reference standard. RESULTS: Palm PCR™ detected 100% of ATCC® strains of Leishmania, fungi, and mycobacteria, with sensitivity and specificity of 90% and 91.7%, respectively. In the field, the sensitivity for detection of Leishmania in patients with suspected CL was 100%. In 61% of CL patients, co-colonization with genera such as Malassezia, Aspergillus, Candida, and Cladosporium was detected. In 50% of CL patients with an inflammatory (secondarily infected) phenotype, detected fungal species had known associations with human cutaneous disease. CONCLUSIONS: Palm PCR™ performs comparably to conventional PCR for detection of Leishmania, fungi, and mycobacteria. This work has implications for the diagnostic approach to tropical ulcers, and has the potential to improve field detection of ulcerative pathogens in resource constrained areas.

Be still, my beating heart: reading pulselessness from Shakespeare to the artificial heart.

Today, patients with heart failure can be kept alive by an artificial heart while they await a heart transplant. These modern artificial hearts, or left ventricular assist devices (LVADs), remove the patient's discernible pulse while still maintaining life. This technology contradicts physiological, historical and sociocultural understandings of the pulse as central to human life. In this essay, we consider the ramifications of this contrast between the historical and cultural importance placed on the pulse (especially in relation to our sense of self) and living with a pulseless LVAD. We argue that the pulse's relationship to individual identity can be rescripted by examining its representation in formative cultural texts like the works of William Shakespeare. Through an integration of historical, literary and biomedical engineering perspectives on the pulse, this paper expands interpretations of pulselessness and advocates for the importance of cultural-as well as biomedical-knowledge to support patients with LVADs and those around them. In reconsidering figurative and literal representations of the heartbeat in the context of technology which removes the need for a pulse, this essay argues that narrative and metaphor can be used to reconceptualise the relationship between the heartbeat and identity.

The Fibrosis-4 Index Is Associated With Need for Mechanical Ventilation and 30-Day Mortality in Patients Admitted With Coronavirus Disease 2019.

The Fibrosis-4 Index (FIB-4), developed to predict fibrosis in liver disease, was used to identify patients with coronavirus disease 2019 who will require ventilator support as well as those associated with 30-day mortality. Multivariate analysis found obesity (odds ratio [OR], 4.5), diabetes mellitus (OR, 2.55), and FIB-4 ≥2.67 (OR, 3.09) independently associated with need for mechanical ventilation. When controlling for ventilator use, sex, and comorbid conditions, FIB-4 ≥2.67 was also associated with increased 30-day mortality (OR, 8.4 [95% confidence interval, 2.23-31.7]). Although it may not be measuring hepatic fibrosis, its components suggest that increases in FIB-4 may be reflecting systemic inflammation associated with poor outcomes.