Correcting Posterior Paraspinal Muscle Computed Tomography Density for Intravenous Contrast Material Independent of Sex and Vascular Phase.

PURPOSE: Intravenous contrast poses challenges to computed tomography (CT) muscle density analysis. We developed and tested corrections for contrast-enhanced CT muscle density to improve muscle analysis and the utility of CT scans for the assessment of myosteatosis. MATERIALS AND METHODS: Using retrospective images from 240 adults who received routine abdominal CT imaging from March to November 2020 with weight-based iodine contrast, we obtained paraspinal muscle density measurements from noncontrast (NC), arterial, and venous-phase images. We used a calibration sample to develop 9 different mean and regression-based corrections for the effect of contrast. We applied the corrections in a validation sample and conducted equivalence testing. RESULTS: We evaluated 140 patients (mean age 52.0 y [SD: 18.3]; 60% female) in the calibration sample and 100 patients (mean age 54.8 y [SD: 18.9]; 60% female) in the validation sample. Contrast-enhanced muscle density was higher than NC by 8.6 HU (SD: 6.2) for the arterial phase (female, 10.4 HU [SD: 5.7]; male, 6.0 HU [SD:6.0]) and by 6.4 HU [SD:8.1] for the venous phase (female, 8.0 HU [SD: 8.6]; male, 4.0 HU [SD: 6.6]). Corrected contrast-enhanced and NC muscle density was equivalent within 3 HU for all correctionns. The -7.5 HU correction, independent of sex and phase, performed well for arterial (95% CI: -0.18, 1.80 HU) and venous-phase data (95% CI: -0.88, 1.41 HU). CONCLUSIONS: Our validated correction factor of -7.5 HU renders contrast-enhanced muscle density statistically similar to NC density and is a feasible rule-of-thumb for clinicians to implement.

Outbreak.info Research Library: a standardized, searchable platform to discover and explore COVID-19 resources.

Outbreak.info Research Library is a standardized, searchable interface of coronavirus disease 2019 (COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) publications, clinical trials, datasets, protocols and other resources, built with a reusable framework. We developed a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public application programming interface (API) and R package.

Corrigendum: Myosteatosis as a Shared Biomarker for Sarcopenia and Cachexia Using MRI and Ultrasound.

[This corrects the article DOI: 10.3389/fresc.2022.896114.].

Myosteatosis as a Shared Biomarker for Sarcopenia and Cachexia Using MRI and Ultrasound.

Purpose: Establish bedside biomarkers of myosteatosis for sarcopenia and cachexia. We compared ultrasound biomarkers against MRI-based percent fat, histology, and CT-based muscle density among healthy adults and adults undergoing treatment for lung cancer. Methods: We compared ultrasound and MRI myosteatosis measures among young healthy, older healthy, and older adults with non-small cell lung cancer undergoing systemic treatment, all without significant medical concerns, in a cross-sectional pilot study. We assessed each participant's rectus femoris ultrasound-based echo intensity (EI), shear wave elastography-based shear wave speed, and MRI-based proton density fat-fraction (PDFF). We also assessed BMI, rectus femoris thickness and cross-sectional area. Rectus femoris biopsies were taken for all older adults (n = 20) and we analyzed chest CT scans for older adults undergoing treatment (n = 10). We determined associations between muscle assessments and BMI, and compared these assessments between groups. Results: A total of 10 young healthy adults, 10 older healthy adults, and 10 older adults undergoing treatment were recruited. PDFF was lower in young adults than in older healthy adults and older adults undergoing treatment (0.3 vs. 2.8 vs. 2.9%, respectively, p = 0.01). Young adults had significantly lower EI than older healthy adults, but not older adults undergoing treatment (48.6 vs. 81.8 vs. 75.4, p = 0.02). When comparing associations between measures, PDFF was strongly associated with EI (ρ = 0.75, p < 0.01) and moderately negatively associated with shear wave speed (ρ = -0.49, p < 0.01) but not BMI, whole leg cross-sectional area, or rectus femoris cross-sectional area. Among participants with CT scans, paraspinal muscle density was significantly associated with PDFF (ρ = -0.70, p = 0.023). Histological markers of inflammation or degradation did not differ between older adult groups. Conclusion: PDFF was sensitive to myosteatosis between young adults and both older adult groups. EI was less sensitive to myosteatosis between groups, yet EI was strongly associated with PDFF unlike BMI, which is typically used in cachexia diagnosis. Our results suggest that ultrasound measures may serve to determine myosteatosis at the bedside and are more useful diagnostically than traditional weight assessments like BMI. These results show promise of using EI, shear wave speed, and PDFF proxies of myosteatosis as diagnostic and therapeutic biomarkers of sarcopenia and cachexia.

The effect of computed tomography parameters on sarcopenia and myosteatosis assessment: a scoping review.

Computed tomography (CT) is a valuable assessment method for muscle pathologies such as sarcopenia, cachexia, and myosteatosis. However, several key underappreciated scan imaging parameters need consideration for both research and clinical use, specifically CT kilovoltage and the use of contrast material. We conducted a scoping review to assess these effects on CT muscle measures. We reviewed articles from PubMed, Scopus, and Web of Science from 1970 to 2020 on the effect of intravenous contrast material and variation in CT kilovoltage on muscle mass and density. We identified 971 articles on contrast and 277 articles on kilovoltage. The number of articles that met inclusion criteria for contrast and kilovoltage was 11 and 7, respectively. Ten studies evaluated the effect of contrast on muscle density of which nine found that contrast significantly increases CT muscle density (arterial phase 6-23% increase, venous phase 19-57% increase, and delayed phase 23-43% increase). Seven out of 10 studies evaluating the effect of contrast on muscle area found significant increases in area due to contrast (≤2.58%). Six studies evaluating kilovoltage on muscle density found that lower kilovoltage resulted in a higher muscle density (14-40% increase). One study reported a significant decrease in muscle area when reducing kilovoltage (2.9%). The use of contrast and kilovoltage variations can have dramatic effects on skeletal muscle analysis and should be considered and reported in CT muscle analysis research. These significant factors in CT skeletal muscle analysis can alter clinical and research outcomes and are therefore a barrier to clinical application unless better appreciated.

Outbreak.info Research Library: A standardized, searchable platform to discover and explore COVID-19 resources.

To combat the ongoing COVID-19 pandemic, scientists have been conducting research at breakneck speeds, producing over 52,000 peer-reviewed articles within the first year. To address the challenge in tracking the vast amount of new research located in separate repositories, we developed outbreak.info Research Library, a standardized, searchable interface of COVID-19 and SARS-CoV-2 resources. Unifying metadata from sixteen repositories, we assembled a collection of over 350,000 publications, clinical trials, datasets, protocols, and other resources as of October 2022. We used a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public API, and R package. Finally, we discuss the challenges inherent in combining metadata from scattered and heterogeneous resources and provide recommendations to streamline this process to aid scientific research.

Combination of DXA and BIS Predicts Jump Power Better Than Traditional Measures of Sarcopenia.

Traditional diagnostic criteria for sarcopenia use dual-energy X-ray absorptiometry (DXA)-measured appendicular lean mass (ALM), normalized to height (ALM/ht2) or body mass index (ALM/BMI) to define low muscle mass. However, muscle function declines with aging before the loss of muscle mass is detected by ALM. This is likely due, in part, to qualitative muscle changes such as extracellular and intracellular fluid compartment shifts uncaptured by DXA. We propose combining bioimpedance spectroscopy (BIS), which estimates extracellular and intracellular compartment volume, with DXA to more accurately predict muscle function. This combination may help incorporate muscle quality, thereby improving sarcopenia diagnosis. We cross-sectionally analyzed data from 248 Black and White participants aged 25 to 75 years from the Midlife in the United States Refresher Cohort. We proposed two novel muscle measures: ALM corrected by the BIS-derived whole-body extracellular to intracellular fluid ratio (E/I) and leg lean mass (LLM) corrected by leg-specific E/I, creating (ALM/(E/I)W) and (LLM/(E/I)L), respectively. We compared the associations of traditional muscle measures, ALM/(E/I)W, and LLM/(E/I)L, with grip strength and lower limb power using jumping mechanography. LLM/(E/I)L explained jump power best at R 2 = 0.803 compared with ALM/(E/I)W (p < 0.0001) and all other measures. ALM/(E/I)W explained jump power second best (R 2 = 0.759) but not significantly better than traditional muscle measures. No muscle measure performed better than covariates when predicting handgrip strength. LLM/(E/I)L outperformed ALM/ht2 and ALM/BMI when predicting jump power. We propose LLM/(E/I)L is a powerful and clinically relevant method that accounts for muscle quality. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Ionic Strength-Dependent, Reversible Pleomorphism of Recombinant Newcastle Disease Virus.

A genetically modified, recombinant form of Newcastle disease virus (rNDV) undergoes ionic strength-dependent changes in morphology, as observed by cryo-electron microscopy (cEM). In hypotonic solutions with ionic strengths ranging from < 0.01 to 0.02 M, rNDV virions are spherical or predominantly spherical. In isotonic and hypertonic solutions, rNDV displays pleomorphism and contains a mixed population of spherical and elongated particles, indicating that a change from spherical to elongated shape is induced with increasing salt concentration. This ionic strength-dependent transition is largely reversible, as determined by cEM. Concomitantly, we measured infectious titers of these same rNDV samples at different ionic strengths using a fluorescent focus assay (FFA). The infectivity of oncolytic rNDV was found to be independent of ionic strength, ranging from 0.01 M to approximately 0.5 M. These structural and functional observations, in combination, suggest that infectivity (and, by inference, oncolytic activity) of rNDV virions is fully maintained in their pleomorphic forms.IMPORTANCE Oncolytic viruses are being developed for cancer therapy, as they selectively target, infect, and kill cancer cells. NDV is particularly attractive because while it is pathogenic to avians (e.g., chickens), it does not cause significant viremia in humans. We have developed a genetically modified recombinant NDV (rNDV) that has much reduced pathogenicity in chickens but is highly oncolytic. The morphology of rNDV transitions from spherical at very low salt concentrations to a heterogeneous population of spherical and elongated virions in isotonic (physiologic salt concentration) and hypertonic solutions. The infectivity (cell-killing activity by infecting cells) of rNDV is unaltered by changes in salt concentration despite morphological changes. These observations are significant for purification and formulation of rNDV, as exposure to different salt concentrations may be needed. Importantly, at physiological salt concentration, relevant to clinical testing, infectivity and, therefore, oncolytic activity will not be compromised despite morphological heterogeneity.

Monoclonal antibody based in vitro potency assay as a predictor of antigenic integrity and in vivo immunogenicity of a Respiratory Syncytial Virus post-fusion F-protein based vaccine.

The post-fusion form of Respiratory Syncytial Virus (RSV) fusion (F) protein has been used recently in clinical trials as a potential vaccine antigen with the objective of eliciting protective immune response against RSV. In this paper, in vitro antigenicity and in vivo immunogenicity of recombinant, soluble F protein of RSV (RSVsF) were evaluated by several assays. In Vitro Relative Potency (IVRP) of RSVsF was measured in a sandwich ELISA using two antibodies, each specific for epitope site A or C. Therefore, IVRP reflected the integrity of the antigen in terms of changes in antibody binding affinity of either or both of these sites. RSVsF samples with a wide range of IVRP values were generated by applying UV irradiation (photo) and high temperature (heat) induced stress for varying lengths of time. These samples were characterized in terms of stress induced modifications in primary and secondary structures as well as aggregation of RSVsF. Immunogenicity, also referred to as In vivo potency, was measured by induction of total F-protein specific IgG and RSV-neutralizing antibodies in mice dosed with these RSVsF samples. Comparison of results between IVRP and these immunogenicity assays revealed that IVRP provided a sensitive read-out of the integrity of epitope sites A and C, and a conservative and reliable evaluation of the potency of RSVsF as a vaccine antigen. This high throughput and fast turn-around assay allowed us to efficiently screen many different RSVsF antigen lots, thereby acting as an effective filter for ensuring high quality antigen that delivered in vivo potency. In vitro and in vivo potencies were further probed at the level of individual epitope sites, A and C. Results of these experiments indicated that site A was relatively resistant to stress induced loss of potency, in vitro or in vivo, compared to site C.

In vitro infectivity of oncolytic Newcastle Disease Virus: Correlation between plaque and fluorescent focus assays.

Newcastle Disease Virus (NDV) is an avian paramyxovirus that has no significant pathogenicity in humans. Cancer cells with impaired immune defense mechanisms are susceptible to infection and lysis by NDV. A recombinant construct of a lentogenic form of NDV (rNDV) containing an insertion of granulocyte macrophage colony stimulating factor (GMCSF) transgene was earlier reported and shown to have acceptably low avian pathogenicity as well as oncolytic potential. Reliable measurement of infectious titer is key to determining the effectiveness of virus preparations to infect and lyse cells. We report here a comparative evaluation of two infectious titer assays as applied to rNDV: plaque assay and fluorescent focus assay (FFA). Optimization of assay conditions for both titer methods has produced concordant results spanning several orders of magnitude. While plaque formation is the gold standard measure of virus titer, FFA provides higher throughput and faster turn-around. FFA has been further evaluated on two different instrument platforms, for automated versus manual foci recognition and counting, with equivalent results. These results point to amenability of FFA to transfer between different laboratories and analysts, without introducing significant subjectivity in data analysis.

Sexual Health and Language Dominance Among Hispanic/Latino Women and Men: Analysis of a Nationally Representative Sample.

This study assessed the prevalence of sexual behaviors among a nationally representative sample of Latino men and women in the United States (US) (N = 432) including Spanish language data collection. Prior studies of sexual health among US Latinos have consisted of convenience samples, and focused mainly on assessing risk behaviors. We consider a broader range of sexual behaviors, subjective sexual experiences (e.g. pleasure and arousal), and STI testing behaviors. Analyses by language dominance and gender indicate a higher variability in sexual behaviors for English-dominant participants and a link between overall STI testing to regular medical examinations, especially women. Higher rates of pleasure, orgasms and arousal was reported by Spanish-dominant men and women, relative to the English-dominant group. Results represent a nuanced examination of internal differentiation among US Latinos and provides applicable data for reducing sexual health disparities in this population.

Idiopathic renal artery and infrarenal aortic aneurysms in a 6-year-old child: case report and literature review.

Multiple arterial aneurysms are distinctly rare in the pediatric population. Most arterial aneurysms in children are secondary to infections, trauma, arteritides, collagen vascular diseases, and other causes. True idiopathic aneurysms are the least common and less than a dozen reports of multiple idiopathic aneurysms have been published. We present a case of an idiopathic, symptomatic renal artery aneurysm with fistulization to the renal vein and a concomitant abdominal aortic aneurysm in a 6-year-old boy. The diagnostic workup, surgical treatment, pathologic findings, and a review of the literature are presented.

A modern analysis of morbidity after pancreatic resection.

Complications after pancreatic resection remain prevalent. Procedure-related morbidity has previously focused on prevention of pancreatic and biliary fistulas (PFs and BFs) with other complications receiving less attention. We examined morbidity and its impact on reoperation, length of stay (LOS), and mortality following pancreatic resection. We retrospectively reviewed patients having elective pancreatectomy at the University of Tennessee affiliated hospitals during a recent 5-year time period. Factors examined included morbidity, mortality, and the need for reoperation. Patient deaths were analyzed with a focus on antecedent complications. Comparisons were made using Student's t test and chi2 analysis where appropriated. From 1997 to 2003, 125 patients had pancreatic resections: 93 Whipple procedures, 27 distal, and 5 total pancreatectomies. Twenty-nine patients (23%) did not have intraperitoneal drainage (IPD). Resections were performed for cancer in 75 per cent. Seventy complications occurred in 55 patients (44%). Morbidity related to an intra-abdominal process resulted in 16 reoperations and 4/6 deaths in this series (overall mortality, 4.8%). There were no BFs. Of 10 patients with PFs (8%), none required reoperation, and there was no PF-related mortality. No patient without IPD developed a PF. The presence of a PF significantly increased LOS when compared to those without (30.9 +/- 13.1 vs 17.4 +/- 12.2 days, P < 0.01). Forty-four per cent of all complications were related to either intra-abdominal abscess (IAA), hemorrhage, or feeding tube placement (18, 8, and 5, respectively). Management of IAA included percutaneous drainage in 16 and reoperation in 2 with 1 associated death. Hemorrhage necessitated reoperation in 6, resulted in 1 patient death, and was followed by IAA in 2. Of 5 jejunostomy tube complications, 4 required reoperation and 2 patients died. LOS was significantly greater in these 28 patients when compared to all others (28.1 +/- 16.9 vs 15.8 +/- 9.9 days, P < 0.001). Following pancreatectomy, 1) BFs should be a rare event; 2) PFs remain important but are most often managed nonoperatively with few sequelae; 3) in this series, IAA and hemorrhage were more common than PF, frequently mandated reoperation, prolonged hospitalization, and were associated with procedure related mortality; 4) feeding tube complications, though rare, are often catastrophic; 5) future efforts should focus on factors that could reduce abscess formation and a reduction in overall complications--many of which are potentially preventable.

Preservation of human pancreatic islet in vivo function after 6-month culture in serum-free media.

BACKGROUND: Culturing human islets in Memphis serum-free media (M-SFM) is associated with excellent postculture recovery, in vitro function, and in vivo survival. The authors investigate the possibility of preserving islet function for extended periods (6 months) in culture and describe the in vitro and in vivo functional outcomes associated with these extended culture times. METHODS: Human islets isolated from three cadaveric donor organs were cultured in M-SFM for 1, 3, or 6 months before transplantation under the kidney capsule of nonobese diabetic (NOD)-severe combined immunodeficiency (SCID) mice. In vitro function was measured by static incubation at the time of transplantation. In vivo function was assessed by measuring human insulin and C-peptide production, and by the ability of 6-month cultured islets to cure streptozotocin-induced diabetes in this mouse model. RESULTS: Islet recovery ratios after 1 month in culture ranged from 85% to 88% and declined to 28% to 53% after 6 months of culture (P <0.01). Insulin stimulation indices did not differ among the fresh or the 6-month cultured preparations. All preparations cultured for 1 to 3 months functioned in the NOD-SCID mice. After 6 months of culture, two of the three preparations demonstrated in vivo function and were able to cure streptozotocin-induced diabetes. CONCLUSIONS: These data demonstrate that human islets can be cultured in M-SFM for extended periods and still retain in vitro and in vivo function and the ability to cure experimental diabetes. The ability to maintain islets in culture for prolonged periods is an important step toward the development of islet tissue repositories and distribution centers.