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Leukocytes express a number of proteinases which play critical roles in physiologic processes during wound healing. However, if the activity of these proteinases is uncontrolled, they can contribute to devastating tissue injury that can affect most organ systems. Until recently, little was known about the mechanisms by which leukocytes retain the activity of their proteinases within the extracellular space which contains highly effective proteinase inhibitors. Studies of the cell biology of leukocyte proteinases have begun to identify the mechanisms by which proteinases can circumvent the effects of physiologic proteinase inhibitors. Herein, we will review the cell biology of leukocyte proteinases, and we will discuss the mechanisms by which leukocyte proteinases can contribute to physiologic processes occurring during wound healing, as well as their roles in pathologic processes. [ABSTRACT FROM AUTHOR]

Background & Aims: Noninvasive variceal risk stratification systems have not been validated in patients with hepatocellular carcinoma (HCC), which presents logistical barriers for patients in the setting of systemic HCC therapy. We aimed to develop and validate a noninvasive algorithm for the prediction of varices in patients with unresectable HCC., Methods: We performed a retrospective cohort study in 21 centers in the United States including adult patients with unresectable HCC and Child-Pugh A5-B7 cirrhosis diagnosed between 2007 and 2019. We included patients who completed an esophagogastroduodonoscopy (EGD) within 12 months of index imaging but before HCC treatment. We divided the cohort into a 70:30 training set and validation set, with the goal of maximizing negative predictive value (NPV) to avoid EGD in low-risk patients., Results: We included 707 patients (median age, 64.6 years; 80.6% male; 74.0% White). Median time from HCC diagnosis to EGD was 47 (interquartile range, 114) days, with 25.0% of patients having high-risk varices. A model using clinical variables alone achieved an NPV of 86.3% in the validation cohort, whereas a model integrating clinical and imaging variables had an NPV 97.4% in validation. The clinical and imaging model would avoid EGDs in more than half of low-risk patients while misclassifying 7.7% of high-risk patients., Conclusions: A model incorporating clinical and imaging data can accurately predict the absence of high-risk varices in patients with HCC and avoid EGD in many low-risk patients before the initiation of systemic therapy, thus expediting their care and avoiding treatment delays., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Despite immunization, patients on antineoplastic and immunomodulating agents have a heightened risk of COVID-19 infection. However, accurately attributing this risk to specific medications remains challenging., Methods: An observational cohort study from December 11, 2020 to September 22, 2022, within a large healthcare system in San Diego, California, USA was designed to identify medications associated with greatest risk of postimmunization SARS-CoV-2 infection. Adults prescribed WHO Anatomical Therapeutic Chemical (ATC) classified antineoplastic and immunomodulating medications were matched (by age, sex, race, and number of immunizations) with control patients not prescribed these medications yielding a population of 26 724 patients for analysis. From this population, 218 blood samples were collected from an enrolled subset to assess serological response and cytokine profile in relation to immunization., Results: Prescription of WHO ATC classified antineoplastic and immunomodulatory agents was associated with elevated postimmunization SARS-CoV-2 infection risk (HR 1.50, 95% CI 1.38 to 1.63). While multiple immunization doses demonstrated a decreased association with postimmunization SARS-CoV-2 infection risk, antineoplastic and immunomodulatory treated patients with four doses remained at heightened risk (HR 1.23, 95% CI 1.06 to 1.43). Risk variation was identified among medication subclasses, with PD-1/PD-L1 inhibiting monoclonal antibodies, calcineurin inhibitors, and CD20 monoclonal antibody inhibitors identified to associate with increased risk of postimmunization SARS-CoV-2 infection. Antineoplastic and immunomodulatory treated patients also displayed a reduced IgG antibody response to SARS-CoV-2 epitopes alongside a unique serum cytokine profile., Conclusions: Antineoplastic and immunomodulating medications associate with an elevated risk of postimmunization SARS-CoV-2 infection in a drug-specific manner. This comprehensive, unbiased analysis of all WHO ATC classified antineoplastic and immunomodulating medications identifies medications associated with greatest risk. These findings are crucial in guiding and refining vaccination strategies for patients prescribed these treatments, ensuring optimized protection for this susceptible population in future COVID-19 variant surges and potentially for other RNA immunization targets., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body's temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31-60 days PSO. By 61-90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1-4 days PSO with 86% positivity observed at 5-7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Renee Higgins, Florence Lee and Dena Marrinucci are employees of Truvian Sciences, the company that sells Easy Check. Kiang-Teck J. Yeo is a member of the Scientific Advisory Board of Truvian and has received honoraria and equities from Truvian. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The human microbiome encompasses a variety of microorganisms that change dynamically and are in close contact with the body. The microbiome influences health and homeostasis, as well as the immune system, and any significant change in this equilibrium (dysbiosis) triggers both acute and chronic health conditions. Microbiome research has surged, in part, due to advanced sequencing technologies enabling rapid, accurate, and cost-effective identification of the microbiome. A major prerequisite for stool sample collection to study the gut microbiome in longitudinal prospective studies requires standardized protocols that can be easily replicated. However, there are still significant bottlenecks to stool specimen collection that contribute to low patient retention rates in microbiome studies. These barriers are further exacerbated in solid organ transplant recipients where diarrhea is estimated to occur in up to half the patient population. We sought to test two relatively easy sample collection methods (fecal swab and wipes) and compare them to the more cumbersome "gold" standard collection method (scoop) using two different sequencing technologies (16S ribosomal RNA sequencing and shotgun metagenomics). Our comparison of the collection methods shows that both the swabs and the wipes are comparable to the scoop method in terms of bacterial abundance and diversity. The swabs, however, were closer in representation to the scoop and were easier to collect and process compared to the wipes. Potential contamination of the swab and the wipe samples by abundant skin commensals was low in our analysis. Comparison of the two sequencing technologies showed that they were complementary, and that 16S sequencing provided enough coverage to detect and differentiate between bacterial species identified in the collected samples. Our pilot study demonstrates that alternative collection methods for stool sampling are a viable option in clinical applications, such as organ transplant studies. The use of these methods may result in better patient retention recruitment rates in serial microbiome studies.

Objectives: The purpose of this study is to report the results of open reduction internal fixation of patella fractures (OTA 34 A-C) using cannulated lag screws and FiberWire® (Arthrex, Naples, FL, USA) with regard to union and symptomatic implant removal., Design: Retrospective review of prospectively collected database., Setting: Urban Level 1 trauma center and Level 2 trauma center METHODS: All displaced intra-articular patella fractures (OTA 34 A-C) treated with ORIF by cannulated lag screws and FiberWire® tension band/cerclage between January 1, 2009 and August 1, 2018. Three hundred and eighty seven consecutive patients were identified. Fifty fractures were included in the final analysis., Main Outcome Measurement: All patients were followed to clinical and radiographic union. Nonunion was defined as lack of clinical and radiographic union, fracture displacement, and/or return to OR for revision surgery. Rate of symptomatic implant removal was recorded., Results: Average age was 57.7 years (range 21-86). Average follow up was 20.6 months (range 6-98 months). Average time to clinical and radiographic union was 3.1 months (range 3-7 months). Four fractures were open. There was a 96% (48/50) rate of primary union, with one patients requiring revision surgery to achieve union, and one developing an asymptomatic radiographic nonunion. The rate of symptomatic implant removal was 8% (4/50). Only 1 of the 4 was operated for a prominent suture knot, and the remaining 3 were for prominent screw removal. Knee range of motion averaged 0.37° extension to 119° flexion (range, 0-150°)., Conclusion: Patella fractures can be treated with cannulated lag screws and FiberWire® with a high rate of primary union (96%) and a low rate of symptomatic implant removal (8%). The implant removal rate compares favorably with alternative constructs, with an equivalent rate of fracture union., Competing Interests: Declaration of Competing Interest Authors have no relevant conflict of interest to disclose to this topic., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: To investigate the biomechanical properties of a lateral locked plate alone or in combination with a supplemental medial plate or an intramedullary nail (IMN)., Methods: Intra-articular distal femur fractures with metaphyseal comminution (OTA/AO 33-C) were simulated with a standardized model in 28 synthetic femora and divided into 4 groups. Group I was instrumented with a 4.5-mm lateral locked distal femoral plate alone, group II with a lateral locked plate plus a low-profile precontoured 3.5-mm medial distal tibial plate, group III with a lateral locked plate plus a medial 3.5-mm reconstruction plate, and group IV with a lateral locked plate plus a retrograde IMN. Specimens were then axially loaded and cycled to failure or runout. Outcomes of interest were baseline stiffness, survivability, and cycles to failure., Results: Groups III and IV have a significantly higher baseline stiffness (P < 0.001) when compared with groups I and II. Furthermore, groups III and IV had a higher max load to failure (P < 0.01) when compared with groups I and II. The survivability in groups III and IV was 71% and 100%, respectively, while no specimens in group I or II survived maximum loading. There was no significant difference between group III and IV regarding stiffness, survivability, and cycles to failure., Conclusion: When considering fixation for intra-articular distal femur fractures with metaphyseal comminution (OTA/AO 33-C), we found that supplementation of a lateral locked plate with a medial plate or an IMN to be biomechanically superior to lateral locked plating alone regarding stiffness, survivability, and cycles to failure. A low-profile precontoured plate did not add significantly to the construct stiffness in this study.

Background: Subtalar arthritis is a common consequence following calcaneal fracture, and its development is related to the severity of the fracture. Previous calcaneal fracture models have demonstrated altered contact characteristics when a step-off is created in the posterior facet articular surface. Changes in posterior facet contact characteristics have not been previously characterized for calcaneal fracture gap without step-off., Methods: The contact characteristics (peak pressure, area of contact, and centroid of pressure) of the posterior facet of the subtalar joint were determined in 6 cadaveric specimens. After creating a calcaneal fracture to simulate a Sanders type II fracture, the contact characteristics were determined with the posterior facet anatomically reduced followed by an incremental increase in fracture gap displacement of 2, 3, and 5 mm without a step-off of the articular surface., Results: Peak pressure on the medial fragment was significantly less with a 5-mm gap compared to a 2- or 3-mm gap, or reduced. On the lateral fragment, the peak pressure was significantly increased with a 5-mm gap compared to a 2- or 3-mm gap. Contact area significantly changed with increased gap., Conclusion: In this study, there were no significant differences in contact characteristics between a <3-mm gap and an anatomically reduced fracture, conceding the study limitations including limiting axial loading to 50% of donor body weight., Clinical Relevance: A small amount of articular incongruity without a step-off can be tolerated by the subtalar joint, in contrast to articular incongruity with a step-off present.

Exposure to As, Cd, Pb, and U among older Hispanic adults residing in underserved communities in southern New Mexico was investigated. Personal information was obtained by standardized interview from 188 adults aged 40-85 years. Urinary metal concentrations were measured and compared to results from the National Health and Nutritional Examination Survey (NHANES). Urinary As and U in study participants significantly (p < .05) exceeded NHANES reference values. Elevated urinary As concentration was significantly associated with older age, Latin American birthplace, clinic site, private-well drinking water, higher self-rated health, and diabetes. Higher urinary Cd was significantly associated with older age, clinic site, female sex, agricultural work, and current cigarette smoking. No personal characteristics were significantly associated with urinary Pb or U. Our results suggest elevated levels of As and U in this population.

Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals., Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry., Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd., Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

This article describes the preoperative preparation of patients with neuromuscular disorders. These entities are a relatively rare and diverse group of diseases that can affect various organ systems in addition to the central nervous system. The anesthetic implications for the various comorbidities are varied and can be profound. These patients should be optimized before surgery, with the involvement of a multidisciplinary team of specialists., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Cutaneous metastatic mammary carcinoma may occur in patients with a history of breast carcinoma. Cutaneous metastases typically present as firm papulonodules on the chest. We describe a rare case of cutaneous metastatic mammary carcinoma arising in a 45-year-old woman presenting as painful, indurated plaques with ulceration in the pelvic region.

The development of methods to detect slowly progressing diseases is often hampered by the time-consuming acquisition of a sufficiently large data set. In this paper, a method is presented to model the change in images acquired by scanning laser polarimetry, for the detection of glaucomatous progression. The model is based on image series of 23 healthy eyes and incorporates colored noise, incomplete cornea compensation and masking by the retinal blood vessels. Additionally, two methods for detecting progression, taking either one or two follow-up visits into account, are discussed and tested on these simulated images. Both methods are based on Student's t-tests, morphological operations and anisotropic filtering. The images simulated by the model are visually pleasing, show corresponding statistical properties to the real images and are used to optimize the detection methods. The results show that detecting progression based on two follow-up visits greatly improves the sensitivity without adversely affecting the specificity.

Matrix metalloproteinase (MMP)-9 secreted by activated polymorphonuclear neutrophils (PMN) may play roles in mediating lung injury by degrading extracellular matrix proteins. However, the mechanisms by which MMP-9 retains activity in the presence of tissue inhibitors of metalloproteinases (TIMPs) are not known. We show that MMP-9 is also expressed on the cell surface of PMN, and proinflammatory mediators induce up to 10-fold increases in cell surface expression of MMP-9. Stimulated human PMN express active forms of cell surface MMP, which cleave the MMP substrate, McaPLGLDpaAR. Loss-of-function studies employing PMN from mice genetically deficient in MMP-9 (MMP-9-/-) demonstrate that membrane-bound MMP-9 contributes substantially to MMP-mediated surface-bound cleavage of McaPLGLDpaAR (approximately 50%) and gelatin (approximately 70%) by stimulated PMN. Like soluble MMP-9, membrane-bound MMP-9 cleaves McaPLGLDpaAR (Kcat/KM = 82,000 M-1s-1), gelatin, type IV collagen, elastin, and alpha1-proteinase inhibitor. However, in contrast to soluble MMP-9, membrane-bound MMP-9 is substantially resistant to inhibition by TIMPs. The IC50 for inhibition of membrane-bound MMP-9 by TIMP-1 and TIMP-2 are approximately 21-fold and approximately 68-fold higher, respectively, than those for inhibition of soluble MMP-9. The binding of MMP-9 to the plasma membrane of PMN enables it to evade inhibition by TIMPs, and thereby may alter the pericellular proteolytic balance in favor of extracellular matrix degradation. Membrane-bound MMP-9 on PMN may play pathogenetic roles in inflammatory lung diseases.

Objective: Determination of glucose concentration from whole blood samples in neonates is confounded by variable hematocrit values, sample source, user technique, and test method, which results in poor correlation with glucose values measured from plasma or serum. Recently developed ion-selective electrodes (ISE) allow measurement of glucose in the water phase of both red blood cells and plasma with a small sample size (200 microliters)., Study Design: The purpose of this study was to compare (1) whole blood and plasma glucose measurements by the ISE method and (2) ISE glucose values with those determined by two chromogen reagent test strip colorimetric methods. Values were determined in 180 different samples obtained from 145 infants., Results: Correlation of whole blood and plasma glucose concentrations determined by the ISE method was excellent (y = 0.99x, R2 = 0.99) and no effect was seen from hematocrit values. The two chromogen test strip methods also revealed good linearity with ISE whole blood and plasma glucose values but had large confidence intervals for individual values. Sensitivity for detecting blood glucose levels < 40 mg/dl by the two test strip methods was 9 of 11 and 9 of 10 with four and one false-positive results, respectively., Conclusion: These data indicate that the ISE method provides an excellent correlation of whole blood and plasma glucose measurement results, overcoming technical problems of differing hematocrit values and serum or plasma sample acquisition in neonates. Chromogen test strip methods have limited value in estimating specific glucose values, but can be useful in screening infants for hypoglycemia.

The HIV epidemic has challenged nursing to rethink the tools it uses and to consider how traditional medical tools may be used in the assessment of nursing problems. This article presents information for the direct care nurse on laboratory tests and how they may be used to meet the traditional needs of physiologic assessment and evaluation and to develop specific nursing interventions. This articles discusses tests used for HIV infection, HIV disease progression, presence of microbiologic agents of opportunistic infections commonly associated with advanced HIV disease, and common laboratory tests and their special relevance to HIV. Nursing implications and interventions are discussed throughout the text.