Search

Background: Identification of serum proteins that track with disease course in sarcoidosis may have clinical and pathologic importance. We previously identified up-regulated transcripts for interferon-inducible chemokines CXCL9, and CXCL10, in blood of sar

Background: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes., Methods: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO 2 :FiO 2  > 300 or (ii) SpO2: FiO 2  > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described., Results: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001)., Conclusions: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials., (© 2024. The Author(s).)

Angiopoietin-2 (Ang-2) is associated with vascular endothelial injury and permeability in the acute respiratory distress syndrome (ARDS) and sepsis. Elevated circulating Ang-2 levels may identify critically ill patients with distinct pathobiology amenable to targeted therapy. We hypothesized that plasma Ang-2 measured shortly after hospitalization among patients with sepsis would be associated with the development of ARDS and poor clinical outcomes. To test this hypothesis, we measured plasma Ang-2 in a cohort of 757 patients with sepsis, including 267 with ARDS, enrolled in the emergency department or early in their ICU course before the COVID-19 pandemic. Multivariable models were used to test the association of Ang-2 with the development of ARDS and 30-day morality. We found that early plasma Ang-2 in sepsis was associated with higher baseline severity of illness, the development of ARDS, and mortality risk. The association between Ang-2 and mortality was strongest among patients with ARDS and sepsis as compared to those with sepsis alone (OR 1.81 vs. 1.52 per log Ang-2 increase). These findings might inform models testing patient risk prediction and strengthen the evidence for Ang-2 as an appealing biomarker for patient selection for novel therapeutic agents to target vascular injury in sepsis and ARDS., (© 2023. The Author(s).)

Brain movement during an impact can elicit a traumatic brain injury, but tissue kinematics vary from person to person and knowledge regarding this variability is limited. This study examines spatio-temporal brain-skull displacement and brain tissue deformation across groups of subjects during a mild impact in vivo . The heads of two groups of participants were imaged while subjected to a mild (less than 350 rad s -2 ) impact during neck extension (NE, n = 10) and neck rotation (NR, n = 9). A kinematic atlas of displacement and strain fields averaged across all participants was constructed and compared against individual participant data. The atlas-derived mean displacement magnitude was 0.26 ± 0.13 mm for NE and 0.40 ± 0.26 mm for NR, which is comparable to the displacement magnitudes from individual participants. The strain tensor from the atlas displacement field exhibited maximum shear strain (MSS) of 0.011 ± 0.006 for NE and 0.017 ± 0.009 for NR and was lower than the individual MSS averaged across participants. The atlas illustrates common patterns, containing some blurring but visible relationships between anatomy and kinematics. Conversely, the direction of the impact, brain size, and fluid motion appear to underlie kinematic variability. These findings demonstrate the biomechanical roles of key anatomical features and illustrate common features of brain response for model evaluation.

Background: Alternative tobacco product (ATP) use has bee linked to critical illness, however, few studies have examined the use of these substances in critically ill populations. We sought to examine ATP use within critically ill patients and to define barriers in accurately assessing use within this population. Methods: We prospectively studied 533 consecutive patients from the Early Assessment of Renal and Lung Injury study, enrolled between 2013 and 2016 at a tertiary referral center and a safety-net hospital. ATP use information (electronic cigarettes, cigars, pipes, hookahs/waterpipes, and snus/chewing tobacco) was obtained from the patient or surrogate using a detailed survey. Reasons for non-completion of the survey were recorded, and differences between survey responders vs. non-responders, self- vs. surrogate responders, and ATP users vs. non-users were explored. Results: Overall, 80% ( n = 425) of subjects (56% male) completed a tobacco product use survey. Of these, 12.2% ( n = 52) reported current ATP use, while 5.6% reported using multiple ATP products. When restricted to subjects who were self-responders, 17% reported ATP use, while 10% reported current cigarette smoking alone. The mean age of ATP users was 57 ± 17 years. Those who did not complete a survey were sicker and more likely to have died during admission. Subjects who completed the survey as self-responders reported higher levels of ATP use than ones with surrogate responders ( p < 0.0001). Conclusion: ATP use is common among critically ill patients despite them being generally older than traditional users. Survey self-responders were more likely than surrogate responders to report use. These findings highlight the importance of improving our current methods of surveillance of ATP use in older adults in the outpatient setting.

The rapid deformation of brain tissue in response to head impact can lead to traumatic brain injury. In vivo measurements of brain deformation during non-injurious head impacts are necessary to understand the underlying mechanisms of traumatic brain injury and compare to computational models of brain biomechanics. Using tagged magnetic resonance imaging (MRI), we obtained measurements of three-dimensional strain tensors that resulted from a mild head impact after neck rotation or neck extension. Measurements of maximum principal strain (MPS) peaked shortly after impact, with maximal values of 0.019-0.053 that correlated strongly with peak angular velocity. Subject-specific patterns of MPS were spatially heterogeneous and consistent across subjects for the same motion, though regions of high deformation differed between motions. The largest MPS values were seen in the cortical gray matter and cerebral white matter for neck rotation and the brainstem and cerebellum for neck extension. Axonal fiber strain (Ef) was estimated by combining the strain tensor with diffusion tensor imaging data. As with MPS, patterns of Ef varied spatially within subjects, were similar across subjects within each motion, and showed group differences between motions. Values were highest and most strongly correlated with peak angular velocity in the corpus callosum for neck rotation and in the brainstem for neck extension. The different patterns of brain deformation between head motions highlight potential areas of greater risk of injury between motions at higher loading conditions. Additionally, these experimental measurements can be directly compared to predictions of generic or subject-specific computational models of traumatic brain injury.

Objective: To obtain dense spatiotemporal measurements of brain deformation from two distinct but complementary head motion experiments: linear and rotational accelerations., Methods: This study introduces a strategy for integrating harmonic phase analysis of tagged magnetic resonance imaging (MRI) and finite-element models to extract mechanically representative deformation measurements. The method was calibrated using simulated as well as experimental data, demonstrated in a phantom including data with image artifacts, and used to measure brain deformation in human volunteers undergoing rotational and linear acceleration., Results: Evaluation methods yielded a displacement error of 1.1 mm compared to human observers and strain errors between [Formula: see text] for linear acceleration and [Formula: see text] for rotational acceleration. This study also demonstrates an approach that can reduce error by 86% in the presence of corrupted data. Analysis of results shows consistency with 2-D motion estimation, agreement with external sensors, and the expected physical behavior of the brain., Conclusion: Mechanical regularization is useful for obtaining dense spatiotemporal measurements of in vivo brain deformation under different loading regimes., Significance: The measurements suggest that the brain's 3-D response to mild accelerations includes distinct patterns observable using practical MRI resolutions. This type of measurement can provide validation data for computer models for the study of traumatic brain injury.

Background Cardiovascular intensive care units ( CICUs ) have evolved from coronary care wards into distinct units for critically ill patients with primary cardiac diseases, often suffering from illnesses that cross multiple disciplines. Mounting evidence has demonstrated improved survival with the incorporation of dedicated CICU providers with expertise in critical care medicine ( CCM ). This is the first study to systematically survey dual certified physicians in order to assess the relevance of CCM training to contemporary CICU care. Methods and Results Utilizing American Board of Internal Medicine data through 2014, 397 eligible physicians had obtained initial certification in both cardiovascular disease and CCM . A survey to delineate the role of critical care training in the CICU was provided to these physicians. Among those surveyed, 120 physicians (30%) responded. Dual certified physicians reported frequent use of their CCM skills in the CICU , highlighting ventilator management, multiorgan dysfunction management, end-of-life care, and airway management. The majority (85%) cited these skills as the reason CCM training should be prioritized by future CICU providers. Few (17%) agreed that general cardiology fellowship alone is currently sufficient to care for patients in the modern CICU . Furthermore, there was a consensus that there is an unmet need for cardiologists trained in CCM (70%) and that CICU s should adopt a level system similar to trauma centers (61%). Conclusions Citing specific skills acquired during CCM training, dual certified critical care cardiologists reported that their additional critical care experience was necessary in their practice to effectively deliver care in the modern CICU .

Muscle coordination patterns of lingual behaviors are synergies generated by deforming local muscle groups in a variety of ways. Functional units are functional muscle groups of local structural elements within the tongue that compress, expand, and move in a cohesive and consistent manner. Identifying the functional units using tagged-magnetic resonance imaging (MRI) sheds light on the mechanisms of normal and pathological muscle coordination patterns, yielding improvement in surgical planning, treatment, or rehabilitation procedures. In this paper, to mine this information, we propose a matrix factorization and probabilistic graphical model framework to produce building blocks and their associated weighting map using motion quantities extracted from tagged-MRI. Our tagged-MRI imaging and accurate voxel-level tracking provide previously unavailable internal tongue motion patterns, thus revealing the inner workings of the tongue during speech or other lingual behaviors. We then employ spectral clustering on the weighting map to identify the cohesive regions defined by the tongue motion that may involve multiple or undocumented regions. To evaluate our method, we perform a series of experiments. We first use two-dimensional images and synthetic data to demonstrate the accuracy of our method. We then use three-dimensional synthetic and in vivo tongue motion data using protrusion and simple speech tasks to identify subject-specific and data-driven functional units of the tongue in localized regions.

Tagged magnetic resonance imaging has been used for decades to observe and quantify motion and strain of deforming tissue. It is challenging to obtain 3-D motion estimates due to a tradeoff between image slice density and acquisition time. Typically, interpolation methods are used either to combine 2-D motion extracted from sparse slice acquisitions into 3-D motion or to construct a dense volume from sparse acquisitions before image registration methods are applied. This paper proposes a new phase-based 3-D motion estimation technique that first computes harmonic phase volumes from interpolated tagged slices and then matches them using an image registration framework. The approach uses several concepts from diffeomorphic image registration with a key novelty that defines a symmetric similarity metric on harmonic phase volumes from multiple orientations. The material property of harmonic phase solves the aperture problem of optical flow and intensity-based methods and is robust to tag fading. A harmonic magnitude volume is used in enforcing incompressibility in the tissue regions. The estimated motion fields are dense, incompressible, diffeomorphic, and inverse-consistent at a 3-D voxel level. The method was evaluated using simulated phantoms, human brain data in mild head accelerations, human tongue data during speech, and an open cardiac data set. The method shows comparable accuracy to three existing methods while demonstrating low computation time and robustness to tag fading and noise.

Displacement fields are important to analyze deformation, which is associated with functional and material tissue properties often used as indicators of health. Magnetic resonance imaging (MRI) techniques like DENSE and image registration methods like Hyperelastic Warping have been used to produce pixel-level deformation fields that are desirable in high-resolution analysis. However, DENSE can be complicated by challenges associated with image phase unwrapping, in particular offset determination. On the other hand, Hyperelastic Warping can be hampered by low local image contrast. The current work proposes a novel approach for measuring tissue displacement with both DENSE and Hyperelastic Warping, incorporating physically accurate displacements obtained by the latter to improve phase characterization in DENSE. The validity of the proposed technique is demonstrated using numerical and physical phantoms, and in vivo small animal cardiac MRI.

Background: Identification of serum proteins that track with disease course in sarcoidosis may have clinical and pathologic importance. We previously identified up-regulated transcripts for interferon-inducible chemokines CXCL9, and CXCL10, in blood of sarcoidosis patients compared to controls. The objective of this study was to determine whether proteins encoded by these transcripts were elevated in serum and identified patients with remitting vs. chronic progressive sarcoidosis longitudinally., Methods: Serum levels of CXCL9, CXCL10, and proteins associated with inflammation and/or disease activity (sIL2R, ACE, ESR and CRP) were measured in a prospective cohort of sarcoidosis subjects and controls. Comparisons were made between groups and clinical course using pulmonary function measures and a severity score developed by Wasfi et al., Results: In a cross-sectional analysis of 36 non-immunosuppressed sarcoidosis subjects, serum CXCL9, CXCL10, and sIL2R were significantly elevated compared to 46 controls (p < 0.0001). CXCL9 and CXCL10 were strongly inter-correlated (p = 0.0009). CXCL10 and CXCL9 were inversely correlated with FVC% predicted and DLCO% predicted, respectively. CXCL10 and CXCL9 significantly correlated with sarcoidosis severity score. sIL2R, ESR, CRP, and ACE serum levels did not correlate with pulmonary function measures or severity score. In the longitudinal analysis of 26 subjects, changes in serum CXCL10 level over time corresponded with progression versus remission of disease., Conclusions: Interferon-γ-inducible chemokines, CXCL9 and CXCL10, are elevated in sarcoidosis and inter-correlated with each other. Chemokine levels correlated with measures of disease severity. Serial measurements of CXCL10 corresponded to clinical course.