Healthcare Workers' Experiences and Challenges in Managing Gender-Based Violence Among HIV-Positive Women Living in Southern, Tanzania: A Qualitative Study.

Introduction: Healthcare workers (HCW) play an important role in managing women living with HIV (WLHIV) with gender-based violence (GBV) experience, but little is known about their experience in screening and managing GBV among WLHIV. This study explored the perceptions and experience of the HCWs on screening and managing GBV cases among WLHIV. Patients and Methods: We performed a descriptive phenomenological qualitative study to elicit the views and experience of HCW on GBV screening and management for WLHIV. The study was conducted in the semi-urban setting in Morogoro Region, Tanzania. Ten in-depth interviews (IDIs) were administered to HCW selected purposefully based on their roles at an HIV care and treatment center. Data were transcribed using patterns matching study aim and then merged into relevant themes for analysis and interpretation. NVIVO software version 12 was used for data coding and analysis. Results: We found that HCW experienced multiple challenges in GBV screening and management, including limited capacity for GBV screening and management; inadequate training on assessment and handling GBV cases, limited resources (time, GBV guidelines and screening tools), inadequate GBV referral and monitoring systems; referral forms for GBV survivors to social support centers and follow-up mechanisms to trace survivors, mental aspects; HCWs' fear of being stressed by listening to women's' GBV traumatic experiences, HCWs' fear of causing problems to the women's families and HCW biased notions on women disclosure of GBV; the believes that women will not report their GBV experiences. Conclusion: We identified context-specific challenges preventing HCW to deliver optimal services of GBV to WLHIV, stressing the necessity to strengthen HCW capacity and resources for GBV services and to integrate psychosocial services into HIV care. Policy and programs should be developed to support GBV screening and management for WLHIV.

Renal health: Evaluation of the spontaneous use of a new m-health technology and validation of its content to support patients undergoing peritoneal dialysis.

INTRODUCTION: Chronic kidney disease is a worldwide public health problem, with a high prevalence of patients on dialysis. mHealth technologies can greatly support the treatment and monitoring of these patients. Thus, this study aimed to evaluate the spontaneous use of the application (app) Renal Health, a previously available technology, for patients on hemodialysis and validate content to support patients undergoing peritoneal dialysis. METHODS: The first stage consisted of evaluating the spontaneous use of the app, and the second stage consisted of methodological research for the development, evaluation, and improvement of a technological instrument for use in clinical practice as a support for patients undergoing peritoneal dialysis (PD). The association between categorical variables was performed using the chi-square test, adopting a significance level of 5%. RESULTS: The app was accessed by 753 users and of these, 34 % accessed the hemodialysis section. Most accesses were in the state of São Paulo/Brazil and performed by women. The records of biochemical tests did not vary according to gender and age group (p > 0.05). The developed and validated PD section enables section control, allowing the user to manage their sessions. The analysis of the technology by the specialists showed good results for the global content validity index (CVI) regarding objectives (CVI = 0.95), structure (CVI = 0.97), and relevance (CVI = 1.0). CONCLUSION: It is concluded that the hemodialysis section of the Renal Health app aroused the interest of the population and that the developed peritoneal dialysis section was validated by specialists.

Assessment of Phthalate Esters and Physiological Biomarkers in Bottlenose Dolphins (Tursiops truncatus) and Killer Whales (Orcinus orca).

There is growing concern about the potential adverse health effects of phthalates (PAEs) on human health and the environment due to their extensive use as plasticizers and additives in commercial and consumer products. In this study, we assessed PAE concentrations in serum samples from aquarium-based delphinids (Tursiops truncatus, n = 36; Orcinus orca, n = 42) from California, Florida, and Texas, USA. To better understand the physiological effects of phthalates on delphinids, we also explored potential correlations between phthalates and the biomarkers aldosterone, cortisol, corticosterone, hydrogen peroxide, and malondialdehyde while accounting for sex, age, and reproductive stage. All PAEs were detected in at least one of the individuals. ΣPAE ranges were 5.995-2743 ng·mL-1 in bottlenose dolphins and 5.372-88,675 ng·mL-1 in killer whales. Both species displayed higher mean concentrations of DEP and DEHP. PAEs were detected in newborn delphinids, indicating transference via placenta and/or lactation. Linear mixed model results indicated significant correlations between aldosterone, month, location, status, and ΣPAEs in killer whales, suggesting that aldosterone concentrations are likely affected by the cumulative effects of these variables. This study expands on the knowledge of delphinid physiological responses to PAEs and may influence management and conservation decisions on contamination discharge regulations near these species.

Bibliometric analysis of nursing education reviews.

BACKGROUND: While the number of reviews of nursing education research has increased over the years, bibliometric studies about these reviews are limited. OBJECTIVES: The purposes were to: (1) examine the number of reviews of nursing education research published from 2018 through 2022, (2) identify journals publishing these reviews, (3) identify the types and topics of reviews in nursing education, and (4) analyze how these reviews are labeled (standard versus nonstandard). DESIGN: This was a bibliometric study of reviews in nursing education. METHODS: The search for reviews in nursing education was done using CINAHL Complete via the EBSCO host platform and was limited to articles published in peer reviewed journals. The results were imported into EndNote, and the title or abstract was used to identify the review type. The categorized reviews were then exported into Microsoft Excel. The titles and abstracts were searched to identify reviews in nursing education, resulting in 600 articles analyzed in this study. The topics of the reviews were identified via natural language processing techniques based on the Medical Subject Headings biomedical vocabulary in the manual tags with each article. RESULTS: The number of reviews has steadily increased over the years. The top journal in which reviews were published was Nurse Education Today (n = 197). Nearly a quarter (n = 149, 24.8 %) of the reviews were integrative, followed by systematic (n = 117, 19.5 %), scoping (n = 117, 19.5 %), and literature (n = 85, 14.2 %). There were 12 main topics: most reviews were on simulation, followed by critical thinking methods and the academic achievement of nursing students. CONCLUSION: This study documented an increase in the number of reviews of nursing education research over the last five years. The most common type was an integrative review, followed by systematic, scoping, and literature. Reviews on simulation were most common.

Atherosclerosis Is a Smooth Muscle Cell-Driven Tumor-Like Disease.

BACKGROUND: Atherosclerosis, a leading cause of cardiovascular disease, involves the pathological activation of various cell types, including immunocytes (eg, macrophages and T cells), smooth muscle cells (SMCs), and endothelial cells. Accumulating evidence suggests that transition of SMCs to other cell types, known as phenotypic switching, plays a central role in atherosclerosis development and complications. However, the characteristics of SMC-derived cells and the underlying mechanisms of SMC transition in disease pathogenesis remain poorly understood. Our objective is to characterize tumor cell-like behaviors of SMC-derived cells in atherosclerosis, with the ultimate goal of developing interventions targeting SMC transition for the prevention and treatment of atherosclerosis. METHODS: We used SMC lineage tracing mice and human tissues and applied a range of methods, including molecular, cellular, histological, computational, human genetics, and pharmacological approaches, to investigate the features of SMC-derived cells in atherosclerosis. RESULTS: SMC-derived cells in mouse and human atherosclerosis exhibit multiple tumor cell-like characteristics, including genomic instability, evasion of senescence, hyperproliferation, resistance to cell death, invasiveness, and activation of comprehensive cancer-associated gene regulatory networks. Specific expression of the oncogenic mutant KrasG12D in SMCs accelerates phenotypic switching and exacerbates atherosclerosis. Furthermore, we provide proof of concept that niraparib, an anticancer drug targeting DNA damage repair, attenuates atherosclerosis progression and induces regression of lesions in advanced disease in mouse models. CONCLUSIONS: Our findings demonstrate that atherosclerosis is an SMC-driven tumor-like disease, advancing our understanding of its pathogenesis and opening prospects for innovative precision molecular strategies aimed at preventing and treating atherosclerotic cardiovascular disease.

14-Year Epidemiologic study of Pseudomonas aeruginosa bloodstream infection incidence and resistance in the Veterans Health Administration system, 2009-2022.

Background: Multidrug resistant Pseudomonas aeruginosa (PA) represents a serious threat to hospitalized patients. Characterizing the incidence of PA infection and degree of resistance can inform empiric treatment and preventative measures. Objectives: We sought to describe trends in incidence and resistance characteristics of PA bloodstream infections (BSI) observed within the Veterans Health Administration (VHA) system and identify factors contributing to higher observed mortality within this population. Methods: We characterized demographic and clinical features of unique patients among the VHA population presenting with their first episode of PA-BSI between 2009 and 2022 and summarized trends related to mortality and resistance phenotype based on year and geographical location. We additionally used logistic regression analysis to identify predictors of 30-day mortality among this cohort. Results: We identified 8039 PA-BSIs during the study period, 32.7% of which were hospital onset. Annual PA-BSI cases decreased by 35.8%, and resistance among all antimicrobial classes decreased during the study period, while the proportion of patients receiving early active treatment based on susceptibility testing results increased. Average 30-day mortality rate was 23.3%. Higher Charlson Comorbidity Index, higher mAPACHE score, VHA facility complexity 1b and hospital-onset cases were associated with higher mortality, and early active treatment was associated with lower mortality. Conclusions: PA-BSI resistance decreased across the VHA system during the study period. Further investigation of antimicrobial stewardship measures possibly contributing to the observed decreased resistance in this cohort and identification of measures to improve on the high mortality associated with PA-BSI in the VHA population is warranted.

High-Dimensional Single-Cell Multimodal Landscape of Human Carotid Atherosclerosis.

BACKGROUND: Atherosclerotic plaques are complex tissues composed of a heterogeneous mixture of cells. However, our understanding of the comprehensive transcriptional and phenotypic landscape of the cells within these lesions is limited. METHODS: To characterize the landscape of human carotid atherosclerosis in greater detail, we combined cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing to classify all cell types within lesions (n=21; 13 symptomatic) to achieve a comprehensive multimodal understanding of the cellular identities of atherosclerosis and their association with clinical pathophysiology. RESULTS: We identified 25 cell populations, each with a unique multiomic signature, including macrophages, T cells, NK (natural killer) cells, mast cells, B cells, plasma cells, neutrophils, dendritic cells, endothelial cells, fibroblasts, and smooth muscle cells (SMCs). Among the macrophages, we identified 2 proinflammatory subsets enriched in IL-1B (interleukin-1B) or C1Q expression, 2 TREM2-positive foam cells (1 expressing inflammatory genes), and subpopulations with a proliferative gene signature and SMC-specific gene signature with fibrotic pathways upregulated. Further characterization revealed various subsets of SMCs and fibroblasts, including SMC-derived foam cells. These foamy SMCs were localized in the deep intima of coronary atherosclerotic lesions. Utilizing cellular indexing of transcriptomes and epitopes by sequencing data, we developed a flow cytometry panel, using cell surface proteins CD29, CD142, and CD90, to isolate SMC-derived cells from lesions. Lastly, we observed reduced proportions of efferocytotic macrophages, classically activated endothelial cells, and contractile and modulated SMC-derived cells, while inflammatory SMCs were enriched in plaques of clinically symptomatic versus asymptomatic patients. CONCLUSIONS: Our multimodal atlas of cell populations within atherosclerosis provides novel insights into the diversity, phenotype, location, isolation, and clinical relevance of the unique cellular composition of human carotid atherosclerosis. These findings facilitate both the mapping of cardiovascular disease susceptibility loci to specific cell types and the identification of novel molecular and cellular therapeutic targets for the treatment of the disease.

Metal and metalloid maternal transfer in a newborn West Indian manatee (Trichechus manatus) two years after the northeastern oil spill disaster of 2019 in Brazil.

A large-scale oil spill along the northeastern Brazilian coast in 2019-2020 severely impacted primary manatee habitats in Brazil. This study aimed to assess metal and metalloid contamination in a dead manatee calf found following this oil spill. Several elements were detected, including chromium, iron, nickel, lead, and vanadium, which are crude oil components, and thallium, a component of dispersants used to degrade and dissipate crude oil. The presence of these contaminants in the manatee calf is indicative of maternal exposure, metabolism, and newborn transference via placenta and lactation. This is the first report of mother-calf metal transfer in manatees, highlighting the species' vulnerability and potential long-term population dynamics effects, and the first report for several metals and metalloids in these animals, laying the foundation for future research efforts. These findings highlight the urgent need for continued environmental monitoring, ecotoxicological assessments, and conservation initiatives.

Hemotropic Mycoplasmas (Hemoplasmas) in Free-Ranging Azara's Agoutis (Dasyprocta azarae) from an Urban Area of Southern Brazil.

Hemotropic mycoplasmas (hemoplasmas) are opportunistic bacteria that attach to the erythrocyte surface, causing infectious anemia in several mammalian species, including rodents. Studies surveying native Azara's agoutis (Dasyprocta azarae) in Brazil are lacking. Accordingly, the present study aimed to assess hemoplasmas infection in free-ranging agoutis from an urban environmental conservation area in Curitiba, southern Brazil. Overall, 11/35 (31.43%) agoutis were positive to hemoplasmas by quantitative PCR (cycle threshold≤34.4). Sequencing of the 16S ribosomal RNA gene indicated Mycoplasma haemomuris infection, closely related to M. haemomuris subsp. ratti, suggesting hemoplasma transmission from urban rats to agoutis. Because the main route of M. haemomuris transmission has been direct rodent-to-rodent infection, the relatively lower positivity that we detected may be the result of low intraspecies contact due to the smaller social units of agoutis, generally consisting of two to four individuals, and low interspecies contact due to only sporadic agouti-rat interactions in urban settings, compared with other rodent species interactions. Further studies should be conducted to determine whether the hemoplasma infection that we found can cause clinical onset and life-threatening anemia in agoutis.

Nicotine Metabolite Ratio Decreases After Switching Off Efavirenz-Based Therapy in People With HIV Who Smoke.

Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P < 0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates.

Vimentin at the core of wound healing.

As a member of the large family of intermediate filaments (IFs), vimentin has emerged as a highly dynamic and versatile cytoskeletal protein involved in many key processes of wound healing. It is well established that vimentin is involved in epithelial-mesenchymal transition (EMT) during wound healing and metastasis, during which epithelial cells acquire more dynamic and motile characteristics. Moreover, vimentin participates in multiple cellular activities supporting growth, proliferation, migration, cell survival, and stress resilience. Here, we explore the role of vimentin at each phase of wound healing, with focus on how it integrates different signaling pathways and protects cells in the fluctuating and challenging environments that characterize a healing tissue.

An examination of retracted articles in nursing literature.

INTRODUCTION: The output of scholarly publications in scientific literature has increased exponentially in recent years. This increase in literature has been accompanied by an increase in retractions. Although some of these may be attributed to publishing errors, many are the result of unsavory research practices. The purposes of this study were to identify the number of retracted articles in nursing and reasons for the retractions, analyze the retraction notices, and determine the length of time for an article in nursing to be retracted. DESIGN: This was an exploratory study. METHODS: A search of PubMed/MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, and Retraction Watch databases was conducted to identify retracted articles in nursing and their retraction notices. RESULTS: Between 1997 and 2022, 123 articles published in the nursing literature were retracted. Ten different reasons for retraction were used to categorize these articles with one-third of the retractions (n = 37, 30.1%) not specifying a reason. Sixty-eight percent (n = 77) were retracted because of an actual or a potential ethical concern: duplicate publication, data issues, plagiarism, authorship issues, and copyright. CONCLUSION: Nurses rely on nursing-specific scholarly literature as evidence for clinical decisions. The findings demonstrated that retractions are increasing within published nursing literature. In addition, it was evident that retraction notices do not prevent previously published work from being cited. This study addressed a gap in knowledge about article retractions specific to nursing.

Gene duplication as a major force driving the genome expansion in some giant viruses.

IMPORTANCE: Giant viruses are noteworthy not only due to their enormous particles but also because of their gigantic genomes. In this context, a fundamental question has persisted: how did these genomes evolve? Here we present the discovery of cedratvirus pambiensis, featuring the largest genome ever described for a cedratvirus. Our data suggest that the larger size of the genome can be attributed to an unprecedented number of duplicated genes. Further investigation of this phenomenon in other viruses has illuminated gene duplication as a key evolutionary mechanism driving genome expansion in diverse giant viruses. Although gene duplication has been described as a recurrent event in cellular organisms, our data highlights its potential as a pivotal event in the evolution of gigantic viral genomes.

Association of COVID-19 coinfection with increased mortality among patients with Pseudomonas aeruginosa bloodstream infection in the Veterans Health Administration system.

Objective: Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI. Design: Retrospective cohort study. Setting: Veterans Health Administration. Patients: Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection. Methods: We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 and mortality among patients with PA-BSI. Additional predictors included demographics, comorbidities, disease severity, antimicrobial susceptibility, and treatment. Results: A total of 6,714 patients with PA-BSI were identified. Throughout the study period, PA resistance rates decreased. Mortality decreased during the pre-COVID-19 period and increased during the COVID-19 period. Mortality was not significantly different between pre-COVID-19 (24.5%, 95% confidence interval [CI] 23.3-28.6) and COVID-19 period/COVID-negative (26.0%, 95% CI 23.5-28.6) patients, but it was significantly higher in COVID-19 period/COVID-positive patients (47.2%, 35.3-59.3). In the modified Poisson analysis, COVID-19 coinfection was associated with higher mortality (relative risk 1.44, 95% CI 1.01-2.06). Higher Charlson Comorbidity Index, higher modified Acute Physiology and Chronic Health Evaluation score, and no targeted PA-BSI treatment within 48 h were also predictors of higher mortality. Conclusions: Higher mortality was observed in patients with COVID-19 coinfection among patients with PA-BSI. Future studies should explore this relationship in other settings and investigate potential SARS-CoV-2 and PA synergy.

Exploration of Cyberethics in Health Professions Education: A Scoping Review.

As digital technologies rapidly integrate into Health Professions Education (HPE), understanding cyberethics is increasingly crucial. This scoping review explores the pedagogy of cyberethics in HPE, highlighting a significant gap in explicit definitions and conceptualizations. Additionally, the absence of specific theoretical frameworks in most documents raises concerns about research progression. Only four articles introduce educational interventions in cyberethics, indicating a promising avenue for future research. While comprehensive search methods are employed, limitations, including language biases, exist. Future investigations should broaden the discourse to encompass ethical implications of emerging technologies within HPE. Cultivating comprehensive, culturally sensitive, and inclusive guidelines is vital for ethical digital practices in the health care community.

Mapping the genomic landscape of multidrug resistance in Plasmodium falciparum and its impact on parasite fitness.

Drug-resistant Plasmodium falciparum parasites have swept across Southeast Asia and now threaten Africa. By implementing a P. falciparum genetic cross using humanized mice, we report the identification of key determinants of resistance to artemisinin (ART) and piperaquine (PPQ) in the dominant Asian KEL1/PLA1 lineage. We mapped k13 as the central mediator of ART resistance in vitro and identified secondary markers. Applying bulk segregant analysis, quantitative trait loci mapping using 34 recombinant haplotypes, and gene editing, our data reveal an epistatic interaction between mutant PfCRT and multicopy plasmepsins 2/3 in mediating high-grade PPQ resistance. Susceptibility and parasite fitness assays implicate PPQ as a driver of selection for KEL1/PLA1 parasites. Mutant PfCRT enhanced susceptibility to lumefantrine, the first-line partner drug in Africa, highlighting a potential benefit of opposing selective pressures with this drug and PPQ. We also identified that the ABCI3 transporter can operate in concert with PfCRT and plasmepsins 2/3 in mediating multigenic resistance to antimalarial agents.

Assessing variation in faecal glucocorticoid concentrations in gray whales exposed to anthropogenic stressors.

Understanding how individual animals respond to stressors behaviourally and physiologically is a critical step towards quantifying long-term population consequences and informing management efforts. Glucocorticoid (GC) metabolite accumulation in various matrices provides an integrated measure of adrenal activation in baleen whales and could thus be used to investigate physiological changes following exposure to stressors. In this study, we measured GC concentrations in faecal samples of Pacific Coast Feeding Group (PCFG) gray whales (Eschrichtius robustus) collected over seven consecutive years to assess the association between GC content and metrics of exposure to sound levels and vessel traffic at different temporal scales, while controlling for contextual variables such as sex, reproductive status, age, body condition, year, time of year and location. We develop a Bayesian Generalized Additive Modelling approach that accommodates the many complexities of these data, including non-linear variation in hormone concentrations, missing covariate values, repeated samples, sampling variability and some hormone concentrations below the limit of detection. Estimated relationships showed large variability, but emerging patterns indicate a strong context-dependency of physiological variation, depending on sex, body condition and proximity to a port. Our results highlight the need to control for baseline hormone variation related to context, which otherwise can obscure the functional relationship between faecal GCs and stressor exposure. Therefore, extensive data collection to determine sources of baseline variation in well-studied populations, such as PCFG gray whales, could shed light on cetacean stress physiology and be used to extend applicability to less-well-studied taxa. GC analyses may offer greatest utility when employed as part of a suite of markers that, in aggregate, provide a multivariate measure of physiological status, better informing estimates of individuals' health and ultimately the consequences of anthropogenic stressors on populations.

Mitigating Racial And Ethnic Bias And Advancing Health Equity In Clinical Algorithms: A Scoping Review.

In August 2022 the Department of Health and Human Services (HHS) issued a notice of proposed rulemaking prohibiting covered entities, which include health care providers and health plans, from discriminating against individuals when using clinical algorithms in decision making. However, HHS did not provide specific guidelines on how covered entities should prevent discrimination. We conducted a scoping review of literature published during the period 2011-22 to identify health care applications, frameworks, reviews and perspectives, and assessment tools that identify and mitigate bias in clinical algorithms, with a specific focus on racial and ethnic bias. Our scoping review encompassed 109 articles comprising 45 empirical health care applications that included tools tested in health care settings, 16 frameworks, and 48 reviews and perspectives. We identified a wide range of technical, operational, and systemwide bias mitigation strategies for clinical algorithms, but there was no consensus in the literature on a single best practice that covered entities could employ to meet the HHS requirements. Future research should identify optimal bias mitigation methods for various scenarios, depending on factors such as patient population, clinical setting, algorithm design, and types of bias to be addressed.

Vimentin takes a hike - Emerging roles of extracellular vimentin in cancer and wound healing.

Vimentin is a cytoskeletal protein important for many cellular processes, including proliferation, migration, invasion, stress resistance, signaling, and many more. The vimentin-deficient mouse has revealed many of these functions as it has numerous severe phenotypes, many of which are found only following a suitable challenge or stress. While these functions are usually related to vimentin as a major intracellular protein, vimentin is also emerging as an extracellular protein, exposed at the cell surface in an oligomeric form or secreted to the extracellular environment in soluble and vesicle-bound forms. Thus, this review explores the roles of the extracellular pool of vimentin (eVIM), identified in both normal and pathological states. It focuses specifically on the recent advances regarding the role of eVIM in wound healing and cancer. Finally, it discusses new technologies and future perspectives for the clinical application of eVIM.

Prognostic Value of Nivolumab Clearance in Non-Small Cell Lung Cancer Patients for Survival Early in Treatment.

INTRODUCTION: Immune checkpoint inhibitors improved survival of advanced stage non-small cell lung cancer patients, but the overall response rate remains low. A biomarker that identifies non-responders would be helpful to allow treatment decisions. Clearance of immune checkpoint inhibitors is related to treatment response, but its prognostic potential early in treatment remains unknown. Our primary aim was to investigate the prognostic potential of nivolumab clearance for overall survival early in treatment. Our secondary aim was to evaluate the performance of nivolumab clearance as prognostic biomarker. PATIENTS AND METHODS: Individual estimates of nivolumab clearances at first dose, 6 and 12 weeks after treatment initiation were obtained via nonlinear mixed-effects modelling. Prognostic value of nivolumab clearance was estimated using univariate Cox regression at first dose and for the ratios between 6 and 12 weeks to first dose. The performance of nivolumab clearance as biomarker was assessed by calculating sensitivity and specificity. RESULTS: During follow-up of 75 months, 69 patients were included and 865 died. Patients with a nivolumab clearance ≥ 7.3 mL/h at first dose were more likely to die compared to patients with a nivolumab clearance < 7.3 mL/h at first dose (hazard ratio [HR] = 3.55, 955 CI 1.75-7.20). The HRs of dose nivolumab clearance ratios showed similar results with a HR of 3.93 (955 CI 1.66-9.32) for 6 weeks to first-dose clearance ratio at a 0.953 cut-point and a HR of 2.96 (955 CI 1.32-6.64) for 12 weeks to first-dose clearance ratio at a cut-point of 0.814. For nivolumab clearance at all early time points, sensitivity was high (≥ 0.95) but specificity was low (0.11-0.29). CONCLUSION: Nivolumab clearance is indicative of survival early in treatment. Our results encourage to further assess the prognostic potential of immunotherapy clearance.