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Better employment quality can improve personal well-being, social cohesion, and inclusive growth and development. Yet good quality jobs – associated with greater well-being – are less accessible to women than men. While it is understood that policies balancing family and work lead to greater female labour participation, this paper investigates whether one such policy – increased childcare – improves the quality of jobs where mothers are employed. The context we analyse is a nationwide school reform in Chile that extended school schedules for primary school-aged children, providing childcare services. We combine administrative data of the phase-in of the policy with panel data of individual mothers' employment outcomes and socio-economic characteristics. We estimate a fixed-effects model that controls for mothers' unobserved heterogeneity and identifies the effect of the policy from plausibly exogenous temporal and spatial variations in access to schools with long schedules and exogenous exposure to the policy. We find a positive effect of childcare on several measures of employment quality and gender gaps within the couple. Our evidence suggests that the mechanism driving the impact is the implicit subsidy to the cost of childcare, affecting the opportunity cost of mothers' time. In addition, we find heterogeneous results by mothers' education level. Access to childcare through longer primary school schedules can increase household welfare and can play a role in reducing income and gender inequalities. [ABSTRACT FROM AUTHOR]

PD-(L)1 inhibitors are part of the treatment strategy for non-small cell lung cancer (NSCLC) although its efficacy is limited to certain patients. Our study aimed to identify patients who might benefit from anti-PD-(L)1 inhibitors by analyzing the PD-L1 expression on circulating leukocytes and its evolution during treatment. One hundred thirteen NSCLC patients, according to their radiological response after 10–12 weeks of treatment, were classified into responders, stable, and progressive disease. Percentages of circulating PD-L1+ leukocytes, PD-L1+ platelets (PLTs), and leukocyte-PLT complexes were assessed using flow cytometry, and plasma concentrations of soluble immunomodulatory factors were quantified by ELISA. Responders exhibited significantly higher pre-treatment percentages of PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs than progressors. The percentages of these populations decreased in responders post-treatment, contrasting with stables and progressors. PLTs notably contributed to PD-L1 expression in CD14+ cells and neutrophils. Plasma cytokine analysis revealed baseline differences only in IL-17 concentration among groups, whereas network analyses highlighted distinct association patterns between plasma molecules and PD-L1+ leukocytes after 10–12 weeks of treatment. Our findings suggest that pre-treatment assessment of circulating PD-L1+ neutrophils, PD-L1+ CD14+ cells, and PD-L1+ PLTs may be helpful in identifying NSCLC patients who are potential candidates for anti-PD-(L)1 therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors (ICI) have the potential to induce serious and unpredictable immune-related adverse events (irAEs), the underlying mechanisms of which remain incompletely understood. In this study, we investigated the relationship between irAEs and the expression of IFN-inducible chemokines and cytokines in patients with solid tumours treated with PD-(L)1 inhibitors. We analysed plasma levels of various IFN-related cytokines at different time points in patients categorized by irAE development and severity. We found that patients with serious irAEs showed significant increases in CXCL9, CXCL10, CXCL11, IL-18 and IL-10 at the onset of the irAE compared to patients with mild irAEs and those without irAEs. Additionally, IL-18 emerged as a promising predictive biomarker for serious irAE development. In summary, this study provides valuable insights into the immune responses associated with irAEs and proposes potential predictive markers for their severity. Immune checkpoint inhibitors (ICI) have the potential to trigger unpredictable immune-related adverse events (irAEs), which can be severe. The underlying mechanisms of these events are not fully understood. As PD-L1 is upregulated by IFN, the heightened immune activation resulting from PD-1/PD-L1 inhibition may enhance the IFN response, triggering the expression of IFN-inducible genes and contributing to irAE development and its severity. In this study, we investigated the interplay between irAEs and the expression of IFN-inducible chemokines and cytokines in 134 consecutive patients with solid tumours treated with PD-(L)1 inhibitors as monotherapy or in combination with chemotherapy or other immunotherapy agents. We compared the plasma levels of IFN-associated cytokines (CXCL9/10/11, IL-18, IL-10, IL-6 and TGFβ) at various time points (at baseline, at the onset of irAE and previous to irAE onset) in three patient groups categorized by irAE development and severity: patients with serious irAEs, mild irAEs and without irAEs after PD-(L)1 inhibitors. No differences were observed between groups at baseline. However, patients with serious irAEs exhibited significant increases in CXCL9/10/11, IL-18 and IL-10 levels at the onset of the irAE compared to baseline. A network analysis and correlation patterns highlighted a robust relationship among these chemokines and cytokines at serious-irAE onset. Combining all of the analysed proteins in a cluster analysis, we identified a subgroup of patients with a higher incidence of serious irAEs affecting different organs or systems. Finally, an ROC analysis and a decision tree model proposed IL-18 levels ≥ 807 pg/mL and TGFβ levels ≤ 114 pg/mL as predictors for serious irAEs in 90% of cases. In conclusion, our study elucidates the dynamic changes in cytokine profiles associated with serious irAE development during treatment with PD-(L)1 inhibitors. The study's findings offer valuable insights into the intricate IFN-induced immune responses associated with irAEs and propose potential predictive markers for their severity. [ABSTRACT FROM AUTHOR]

In rheumatoid arthritis (RA) synovium, ATP, and ADP are released, sparking inflammation. Ectoenzymes CD39 and CD73 metabolize these purine nucleotides, generating anti-inflammatory adenosine. Therefore, dysregulated CD39 and CD73 expression may impact RA development. We assessed CD39 and CD73 expression in peripheral blood from 15 healthy controls (Cs) and 35 RA patients at baseline and after 3 and 6 months of tocilizumab treatment using flow cytometry. Additionally, ectoenzyme expression was examined on cultured T cells to understand activation and IL-6 effects. At baseline, RA patients exhibited a lower CD8+CD39−CD73+ cell percentage, which inversely correlated with DAS28. Additionally, they had lower percentages of Treg CD39+CD73+ and CD39−CD73− cells. Good responders tended to have lower B CD39+CD73+ cell percentages at baseline and 3 months. Additionally, Treg, CD8+ T and B cells inversely correlated with DAS28. T-cell activation increased CD39 and decreased CD73 expression, regardless of IL-6. IL-6 reduced IFNγ-secreting CD4+ T-cell percentage in Cs, but increased the percentage of IFNγ-secreting CD4+ and CD8+ T cells in RA patients. These findings indicate differing CD39 and CD73 expression in RA and Cs, influenced by T-cell activation and IL-6. Correlations between these molecules and RA activity suggest their role in dysregulated inflammation in RA. [ABSTRACT FROM AUTHOR]

The aim of our pilot study was to compare the performance of the RS-MRI protocol combined with skull radiography versus CT for the detection of skull fractures, scalp hematomas, and intracranial hemorrhage in patients with abusive head trauma (AHT). Additionally, our study aimed to determine whether the presence of scalp hematoma predicts concurrent skull fracture. We conducted a pilot study through retrospective chart review of 24 patients between ages 0 and 15 months who experienced AHT and who received CT, MRI, and skull radiography between May 2020 and August 2021. Two blinded board certified neuroradiologists reviewed the skull radiographs alongside the rapid trauma MRI. Their impressions were documented and compared with findings derived from CT. Combination imaging detected ten out of the 12 skull fractures noted on CT (sensitivity 83.3%, specificity 100%, p=0.48). RS-MRI detected 15 out of the 16 intracranial hemorrhages detected by CT (sensitivity 93.75%, p >0.9). When scalp hematoma was detected on RS-MRI, nine out of the 12 had associated skull fractures when reviewed by radiologist 1 (sensitivity 75%, specificity 100%, p=0.22), and seven out of the 12 had associated skull fractures when reviewed by radiologist 2 (sensitivity 58%, specificity 92%, p=0.25). In pediatric patients with suspected AHT, we found that RS-MRI combined with skull radiographs was not significantly different than CT for the detection of skull fractures, scalp hematomas, and intracranial hemorrhage. This combination has the potential to replace the use of CT as a screening tool for abusive head trauma, while avoiding the risks of sedation often required for routine MRI. [ABSTRACT FROM AUTHOR]

This study aims to investigate the impact of hormonal imbalances during menopause, compounded by the natural ageing process, on bone health. Specifically, it examines the effects of increased bone turnover and focal bone balance on bone mass. A three-dimensional computational bone remodeling model was employed to simulate the response of the femur to habitual loads over a 19-year period, spanning premenopause, menopause, and postmenopause. The model was calibrated using experimental bone mineral density data from the literature to ensure accurate simulations. The study reveals that individual alterations in bone turnover or focal bone balance do not fully account for the observed experimental outcomes. Instead, simultaneous changes in both factors provide a more comprehensive explanation, leading to increased porosity while maintaining the material-to-apparent density ratio. Additionally, different load scenarios were tested, demonstrating that reaching the clinical osteoporosis threshold is independent of the timing of load changes. However, underload scenarios resulted in the threshold being reached approximately 6 years earlier than overload scenarios. These findings hold significant implications for strategies aimed at delaying the onset of osteoporosis and minimizing fracture risks through targeted mechanical stimulation during the early stages of menopause. [ABSTRACT FROM AUTHOR]

The migration and antimicrobial functions of neutrophils seem to be impaired during sepsis and contribute to the dysregulation of immune responses and disease pathogenesis. However, the role of neutrophil extracellular traps (NETs) remains to be clarified. The study aimed to analyse sequential phenotypic and functional changes of neutrophils during the time following the diagnosis of sepsis. We prospectively enrolled 49 septic and 18 non‐septic patients from the intensive care unit (ICU) and emergency room (ER) and 20 healthy volunteers (HV). Baseline blood samples from septic and non‐septic patients were collected within 12 h of admission to the hospital. Additional septic samples were drawn at 24, 48 and 72 h after baseline. Neutrophil phenotype and degranulation capacity were assessed by flow cytometry and NET formation was quantified by fluorescence. Neutrophils from septic patients exhibited increased CD66b, CD11b and CD177 expression but displayed reduced NET formation at baseline compared with non‐septic patients and HV controls. Neutrophils expressing CD177 interacted less with platelets, were related to reduced NETosis and tended to indicate a worse sepsis outcome. In vitro experiments revealed that neutrophil function is compromised by the origin of sepsis, including the pathogen type and the affected organ. Assessing a decision tree model, our study showed that CD11b expression and NETosis values are useful variables to discriminate septic from non‐septic patients. We conclude that sepsis induces changes in neutrophil phenotype and function that may compromise the effective capacity of the host to eliminate pathogens. [ABSTRACT FROM AUTHOR]

The skull base provides a platform for supporting the brain while serving as a conduit for major neurovascular structures. In addition to malignant lesions originating in the skull base, there are many benign entities and developmental variants that may simulate disease. Therefore, a basic understanding of the relevant embryology is essential. Lesions centered in the skull base can extend to the adjacent intracranial and extracranial compartments; conversely, the skull base can be secondarily involved by primary extracranial and intracranial disease. CT and MRI are the mainstay imaging methods and are complementary in the evaluation of skull base lesions. Advances in cross-sectional imaging have been crucial in the management of patients with skull base pathology, as this represents a complex anatomical area that is hidden from direct clinical exam. Furthermore, the clinician must rely on imaging studies for therapy planning and to monitor treatment response. It is crucial to have a thorough understanding of skull base anatomy and its various pathologies, as well as to recognize the appearance of treatment-related changes. In this review, we aim to describe skull base tumors and tumor-like lesions in an anatomical compartmental approach and present imaging methods that aid in diagnosis, management, and follow-up. [ABSTRACT FROM AUTHOR]

Coma is a state of unresponsiveness to external stimuli, which can be secondary to a variety of CNS alterations affecting essential neuronal pathways, particularly the ascending reticular activating system. A comprehensive clinical evaluation is necessary for assessment of motor function and brainstem reflexes but is often insufficient for determination of the underlying etiology and extent of injury. Diagnostic brain imaging is typically needed for management and decision-making, particularly in acute settings where prompt diagnosis of reversible/treatable conditions is essential, as well as for prognostication. Understanding the pathophysiologic mechanisms leading to coma and comalike states and their imaging manifestations will enable selection of appropriate modalities and facilitate a clinically relevant interpretation. For evaluation of brain death, diagnostic imaging has a supportive role, and when indicated, selection of an ancillary diagnostic test is based on multiple factors, including susceptibility to confounding factors and specificity, in addition to safety, convenience, and availability. [ABSTRACT FROM AUTHOR]

Background: This study employed bibliometric analysis to ascertain the research focus areas among a group of Mexican physicians affiliated with the Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (ISSSTE). ISSSTE, a healthcare institution catering to a diverse range of diseases, offers a distinctive perspective on the investigated specialties within the realm of health. The primary objective was to identify knowledge gaps in medical care disciplines through a comprehensive examination of scholarly publications. Methods: We retrieved Scopus papers affiliated with "ISSSTE" and saved them as.CSV files. Subsequently, we employed VOSviewer, biblioshiny, and bibliometrix for bibliometric analysis. This enabled us to identify prominent institutions, prolific authors, highly cited researchers, and their respective affiliations. Results: Our analysis identified 2063 publications; the specialty internal medicine accounted for the greatest proportion with 831 publications. Original papers accounted for 82% of the total, with 52% of them being written in Spanish. The majority of scientific output, 92%, originated from Mexico City. The annual production has steadily increased since 2010, peaking in 2021 with over 200 publications. However, papers on prevalent conditions, such as metabolic syndrome, received limited citations, and the L0 index (percentage of uncited items) for all papers is close to 60%. Scopus mislabeled one affiliation, and some cases show a low paper-to-author ratio of 0.5 Discussion: Additional concerns, such as honorary authorship due to excessive authors per paper, and the underlying causes of low citation rates in Mexican publications, warrant further examination. Moreover, our research emphasizes the urgency of bolstering research and development funding, which was consistently below 0.5% of GDP for the past four decades, falling short of legal mandates and international benchmarks. We endorse the establishment of robust research collectives in Latin America to address these challenges, foster regional scientific output, and transition from knowledge consumers to knowledge producers, thereby reducing dependence on foreign technology. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Anestesiología is the property of Colegio Mexicano de Anestesiologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Simple Summary: This study provides novel information about the role of neutrophils in malignant pleural effusion (MPE) and hallmarks their clinical relevance. Since these cells have emerged as important regulators of cancer, we characterized their phenotype and functions in MPE microenvironment. We found that neutrophil-derived products (degranulation molecules and neutrophil extracellular traps (NETs)) were increased in MPE. In addition, NETs were associated with a worse outcome in lung adenocarcinoma patients with MPE. Malignant pleural effusion (MPE) is a common severe complication of advanced lung adenocarcinoma (LAC). Neutrophils, an essential component of tumor infiltrates, contribute to tumor progression and their counts in MPE have been associated with worse outcome in LAC. This study aimed to evaluate phenotypical and functional changes of neutrophils induced by MPE to determine the influence of MPE immunomodulatory factors in neutrophil response and to find a possible association between neutrophil functions and clinical outcomes. Pleural fluid samples were collected from 47 LAC and 25 heart failure (HF) patients. We measured neutrophil degranulation products by ELISA, oxidative burst capacity and apoptosis by flow cytometry, and NETosis by fluorescence. The concentration of degranulation products was higher in MPE-LAC than in PE-HF. Functionally, neutrophils cultured with MPE-LAC had enhanced survival and neutrophil extracellular trap (NET) formation but had reduced oxidative burst capacity. In MPE, NETosis was positively associated with MMP-9, P-selectin, and sPD-L1 and clinically related to a worse outcome. This is the first study associating NETs with a worse outcome in MPE. Neutrophils likely contribute to tumor progression through the release of NETs, suggesting that they are a potential therapeutic target in LAC. [ABSTRACT FROM AUTHOR]

Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). However, the relationship between monocyte–PLT conjugates (CD14+PLT+) and clinical and immunological variables and the regulation of this interaction by IL-6 blockage are still unknown. Here, we compared the presence of monocyte–PLT conjugates (CD14+PLT+) and membrane CD162 expression using flow cytometry, and, by ELISA, the markers of PLT activation (sCD62P and sCD40L) in healthy donors (HD) and patients with long-standing RA before TCZ (baseline). We found higher percentages and absolute counts of CD14+PLT+, and higher plasmatic levels of sCD62P and sCD40L but lower CD162 expression on monocytes from RA patients than those from HD. Additionally, the levels of CD14+PLT+ inversely correlated with inflammatory parameters. Interestingly, 95% of patients with lower percentages of CD14+PLT+ and only 63% of patients with higher percentages of CD14+PLT+ achieved a EULAR-defined response at four weeks (p = 0.036). After TCZ, the percentage of CD14+PLT+ increased in 92% of RA patients who achieved 12 w-remission (p < 0.001). Our results suggest that the binding of PLTs has a modulatory effect, accentuated by the increased binding of PLTs to monocytes in response to the therapeutic blockage of IL-6. [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPN) are chronic cancers of the hematopoietic stem cells in the bone marrow, and patients often harbor elevated numbers of circulating platelets (PLT). We investigated the frequencies of circulating PLT-lymphocyte aggregates in MPN patients and the effect of PLT-binding on CD8 T cell function. The phenotype of these aggregates was evaluated in 50 MPN patients and 24 controls, using flow cytometry. In vitro studies compared the proliferation, cytokine release, and cytoxicity of PLT-bound and PLT-free CD8 T cells. Frequencies of PLT-CD8 T cell aggregates, were significantly elevated in MPN patients. Advanced disease stage and CALR mutation associated with the highest aggregate frequencies with a predominance of PLT-binding to antigen-experienced CD8 T cells. PLT-bound CD8 T cells showed reduction in proliferation and cytotoxic capacity. Our data suggest that CD8 T cell responses are jeopardized in MPN patients. JAK2 and CALR exon 9 mutations – the two predominant driver mutations in MPN – are targets for natural T cell responses in MPN patients. Moreover, MPN patients have more infections compared to background. Thus, PLT binding to antigen experienced CD8 T cells could play a role in the inadequacy of the immune system to control MPN disease progression and prevent recurrent infections. [ABSTRACT FROM AUTHOR]

Background: Anti-PD-(L)1 blocking agents can induce immune-related adverse events (irAEs), which can compromise treatment continuation. Since circulating leukocyte–platelet (PLT) complexes contribute to inflammatory and autoimmune diseases, we aimed to analyze the role of these complexes as predictors of irAEs in non-small cell lung cancer (NSCLC) patients receiving anti-PD-(L)1. Materials and methods: Twenty-six healthy donors (HD) and 87 consecutive advanced NSCLC patients treated with anti-PD-(L)1 were prospectively included. Percentages of circulating leukocyte–PLT complexes were analyzed by flow cytometry and compared between HD and NSCLC patients. The association of leukocyte–PLT complexes with the presence and severity of irAEs was analyzed. Results: NSCLC patients had higher percentages of circulating leukocyte–PLT complexes. Higher percentages of monocytes with bound PLT (CD14 + PLT +) were observed in patients who received prior therapies while CD4 + T lymphocytes with bound PLT (CD4 + PLT +) correlated with platelets counts. The CD4 + PLT + high percentage group presented a higher rate of dermatological irAEs while the CD4 + PLT + low percentage group showed a higher rate of non-dermatological irAEs (p < 0.001). A lower frequency of grade ≥ 2 irAEs was observed in the CD4 + PLT + high percentage group (p < 0.05). Patients with CD4 + PLT + low and CD14 + PLT + high percentages presented a higher rate of grade ≥ 3 irAEs and predominantly developed non-dermatological irAEs (p < 0.01). Conclusions: Our results suggest that circulating leukocyte–PLT complexes and the combination of CD4 + PLT + and CD14 + PLT + percentages can be used as a predictive biomarker of the development and severity of irAEs in advanced NSCLC patients receiving anti-PD-(L)1 agents. [ABSTRACT FROM AUTHOR]

Advances in methods for determining the forces exerted by cells while they migrate are essential for attempting to understand important pathological processes, such as cancer or angiogenesis, among others. Precise data from three-dimensional conditions are both difficult to obtain and manipulate. For this purpose, it is critical to develop workflows in which the experiments are closely linked to the subsequent computational postprocessing. The work presented here starts from a traction force microscopy (TFM) experiment carried out on microfluidic chips, and this experiment is automatically joined to an inverse problem solver that allows us to extract the traction forces exerted by the cell from the displacements of fluorescent beads embedded in the extracellular matrix (ECM). Therefore, both the reconstruction of the cell geometry and the recovery of the ECM displacements are used to generate the inputs for the resolution of the inverse problem. The inverse problem is solved iteratively by using the finite element method under the hypothesis of finite deformations and nonlinear material formulation. Finally, after mathematical postprocessing is performed, the traction forces on the surface of the cell in the undeformed configuration are obtained. Therefore, in this work, we demonstrate the robustness of our computational-based methodology by testing it under different conditions in an extreme theoretical load problem and then by applying it to a real case based on experimental results. In summary, we have developed a new procedure that adds value to existing methodologies for solving inverse problems in 3D, mainly by allowing for large deformations and not being restricted to any particular material formulation. In addition, it automatically bridges the gap between experimental images and mechanical computations. [ABSTRACT FROM AUTHOR]

Patients with chronic inflammatory diseases often exhibit cardiovascular risk. This risk is associated with the systemic inflammation that persists in these patients, causing a sustained endothelial activation. Different mechanisms have been considered responsible for this systemic inflammation, among which activated platelets have been regarded as a major player. However, in recent years, the role of platelets has become controversial. Not only can this subcellular component release pro- and anti-inflammatory mediators, but it can also bind to different subsets of circulating lymphocytes, monocytes and neutrophils modulating their function in either direction. How platelets exert this dual role is not yet fully understood. [ABSTRACT FROM AUTHOR]

Copyright of Cirugía y Cirujanos is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Laryngeal involvement in tuberculosis is rare and may mimic malignancy. We report the case of a 26‐year‐old female who presented with sore throat for several months. CT revealed an infiltrative laryngeal mass and upper lobe pulmonary opacities. Laryngoscopic biopsy confirmed necrotizing granulomatous inflammation with positive culture for Mycobacterium tuberculosis. [ABSTRACT FROM AUTHOR]

Copyright of Revista de Ciencias Economicas is the property of Universidad Nacional del Litoral and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Peters anomaly (PA) is a congenital corneal opacity associated with corneo‐lenticular attachments. PA can be isolated or part of a syndrome with most cases remaining genetically unsolved. Exome sequencing of a trio with syndromic PA and 145 additional unexplained probands with developmental ocular conditions identified a de novo splicing and three novel missense heterozygous CDH2 variants affecting the extracellular cadherin domains in four individuals with PA. Syndromic anomalies were seen in three individuals and included left‐sided cardiac lesions, dysmorphic facial features, and decreasing height percentiles; brain magnetic resonance imaging identified agenesis of the corpus callosum and hypoplasia of the inferior cerebellar vermis. CDH2 encodes for N‐cadherin, a transmembrane protein that mediates cell‐cell adhesion in multiple tissues. Immunostaining in mouse embryonic eyes confirmed N‐cadherin is present in the lens stalk at the time of separation from the future cornea and in the developing lens and corneal endothelium at later stages, supporting a possible role in PA. Previous studies in animal models have noted the importance of Cdh2/cdh2 in the development of the eye, heart, brain, and skeletal structures, also consistent with the patient features presented here. Examination of CDH2 in additional patients with PA is indicated to confirm this association. [ABSTRACT FROM AUTHOR]

Background and objective: The discovery of highly accurate pleural fluid (PF) biomarkers of malignancy remains elusive. We assessed the operating characteristics of the PF epithelial cell adhesion molecule (EpCAM), claudin 4 (CL4) and human epididymis protein 4 (HE4) as potential markers of epithelial malignancies. Methods: The three markers were quantified by immunoassays in the supernatants (s) and cell lysates (cl) of 175 PF samples. The cut‐off values with 100% specificity were selected for malignant–benign discrimination. An immunocytochemical staining index score for each marker was also evaluated on PF cell blocks. The resulting best biomarker was further validated in two independent populations of 73 and 48 patients with pleural effusions (PE). Results: An EpCAM(cl) >98 pg/g total lysate protein yielded 75% sensitivity, 100% specificity, negative likelihood ratio of 0.25 and area under the curve of 0.94 for labelling adenocarcinomatous effusions. Sensitivity reached 88% if EpCAM(cl) was combined with EpCAM immunostaining. One‐third or more of the malignant effusions exhibiting a false‐negative cytological fluid examination were correctly classified by EpCAM(cl) concentrations. Immunoassays for CL4 and HE4 were diagnostically useless. Conclusion: EpCAM(cl) is a new biomarker of adenocarcinomatous PE with meaningful discriminating properties. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with the polyclonal activation of B lymphocytes and the production of autoantibodies that cause immune complex-related inflammation. Immunological factors derived from platelets modulate B cell function in SLE disease. However, platelets do not only modify the immune system by soluble factors. The binding of platelets to lymphocytes can modulate immune response. Thus, we speculate that the binding of platelets to lymphocytes in SLE patients may play a role in abnormal B lymphocyte response and the pathogenesis of SLE. We observed that levels of lymphocytes with bound platelets were higher in SLE patients than in healthy donors (HD). In SLE patients, the percentage of B lymphocytes with bound platelets positively correlated with plasmatic levels of IgG, IgA, IL-10, and soluble CD40L and negatively correlated with IgM levels, though not in HD. Preswitched memory B lymphocytes were the subpopulation with more bound platelets. Lymphocytes with bound platelets from both HD and SLE patients had major levels of CD86 and BAFFR and a greater production of IL-10 than lymphocytes without bound platelets. However, only B lymphocytes with bound platelets from SLE patients had increased levels of IgG and IgA on their surface. SLE patients with a suggestive renal manifestation had the highest levels of B and T lymphocytes with bound platelets. These results suggest that the binding of platelets to lymphocytes plays a role in SLE disease and that controlling this binding may be a promising therapeutic approach. [ABSTRACT FROM AUTHOR]

While in vivo acoustic radiation force impulse (ARFI)-induced peak displacement (PD) has been demonstrated to have high sensitivity and specificity for differentiating soft from stiff plaque components in patients with carotid plaque, the parameter exhibits poorer performance for distinguishing between plaque features with similar stiffness. To improve discrimination of carotid plaque features relative to PD, we hypothesize that signal correlation and signal-to-noise ratio (SNR) can be combined, outright or via displacement variance. Plaque feature detection by displacement variance, evaluated as the decadic logarithm of the variance of acceleration and termed “log(VoA),” was compared to that achieved by exploiting SNR, cross correlation coefficient, and ARFI-induced PD outcome metrics. Parametric images were rendered for 25 patients undergoing carotid endarterectomy, with spatially matched histology confirming plaque composition and structure. On average, across all plaques, log(VoA) was the only outcome metric with values that statistically differed between regions of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), collagen (COL), and calcium (CAL). Further, log(VoA) achieved the highest contrast-to-noise ratio (CNR) for discriminating between LRNC and IPH, COL and CAL, and grouped soft (LRNC and IPH) and stiff (COL and CAL) plaque components. More specifically, relative to the previously demonstrated ARFI PD parameter, log(VoA) achieved 73% higher CNR between LRNC and IPH and 59% higher CNR between COL and CAL. These results suggest that log(VoA) enhances the differentiation of LRNC, IPH, COL, and CAL in human carotid plaques, in vivo, which is clinically relevant to improving stroke risk prediction and medical management. [ABSTRACT FROM AUTHOR]

Key Points: • Work-energy equation using 4D-flow MRI is a promising technique for non-invasive estimation of trans-stenotic pressure drop in patients with idiopathic intracranial hypertension. • Additional research with larger and multicentric prospective cohorts is needed to validate the results, along with improvement of the segmentation process with automated techniques and shortening of scanning times to allow for practical clinical use. [ABSTRACT FROM AUTHOR]

Purpose Although symptoms are expected to improve after the resection of pituitary macroadenomas, tumor resection volume does not always correlate with the patient’s symptoms. Our objectives were to assess the pre and postoperative volumes of pituitary macroadenomas before, immediately after surgery and at follow-up, and to explore possible associations and correlations among these changes and symptoms. Materials and methods We retrospectively reviewed the clinical records and the preoperative and postoperative magnetic resonance imaging studies at 24 hours and at 3, 6 and 9 months follow-up of 146 patients who underwent surgery for pituitary macroadenomas. We measured tumor volumes before and after surgery and compared changes with symptom improvement. Results The mean preoperative tumor volume was 24.66 cm3 (standard deviation 65.18 cm3, 95% confidence interval (CI) 14–35.32). The most common symptoms were visual/cranial nerve abnormalities (65%) and headaches (56%). Immediately after surgery, symptoms persisted without significant changes in all patients. A progressive tumor volume decrease was noted during follow-up, and symptoms improved in 78% of patients. Despite no imaging evidence of chiasm or cavernous sinus compression, 32 patients showed no symptom improvement. Patients with symptoms for more than 1 year (mean duration of symptoms 26 months, SD 24.3, 95% CI 22.03–29.97 months) had a higher risk of the persistence of symptoms compared to patients with a mean duration of symptoms of less than 1 year (odds ratio 2.5, 95% CI 2.4–3, P < 0.005). Conclusions The duration of symptoms prior of surgery is a more important factor than tumor resection volume alone when considering the long-term outcome of symptoms. Furthermore, lack of symptom improvement in the immediate postoperative period does not necessarily represent an inadequate resection. [ABSTRACT FROM AUTHOR]

Abstract: Ascitic neutrophils from cirrhotic patients with spontaneous bacterial peritonitis (SBP) exhibit an impaired oxidative burst that could facilitate bacterial infection. However, the influence of the cell‐free ascitic fluid of these patients on neutrophil function has not been investigated. To analyze this influence, we determined the ascitic levels of cytokines, resistin, and lactoferrin and their association with neutrophil function, disease severity score, and SBP resolution. We analyzed NETosis induction by microscopy and oxidative burst by the flow cytometry of healthy neutrophils cultured in ascitic fluid from cirrhotic patients with sterile ascites (SA) and with SBP before and after antibiotic treatment. Resistin, IL‐6, IL‐1 receptor antagonist, IL‐1β, and lactoferrin levels were measured in ascitic fluids and supernatants of cultured neutrophils and PBMCs by ELISA. Upon stimulation, healthy neutrophils cultured in SBP ascitic fluid produced lower NETosis and oxidative burst than those cultured in SA. Ascitic resistin levels were negatively correlated with NETosis, oxidative burst, and ascitic glucose levels; and positively correlated with the model for end‐stage liver disease score. After an E. coli or TNF‐α stimulus, neutrophils were the major resistin producers. Resistin indirectly reduced the oxidative burst of neutrophils and directly reduced the inflammatory phenotype of monocytes and TNF‐α production. Bacterial‐induced resistin production can down‐regulate the inflammatory response of macrophages and neutrophil function in ascitic fluid. Consequently, this down‐regulation may jeopardize the elimination of bacteria that translocate to ascitic fluid in patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to determine the value of resistive index (RI) variability in predicting cerebrovascular complications during extracorporeal membrane oxygenation (ECMO). Methods: This retrospective study included 36 infants treated by ECMO. The RI was measured on daily transfontanellar duplex sonography, obtained first without fontanel compression and then after gentle compression with the transducer. The age at ECMO cannulation, sex, gestational age at birth, method of delivery, indication, and type and duration of ECMO were recorded. Results: There was a statistically significant difference in RI variability in infants who developed cerebrovascular complications as opposed to those who did not (P =.002). Resistive index variability of 10% or greater on any day was associated with an increased risk for cerebrovascular complications (P =.0482; χ2 = 3.9). Variability in the first 5 days was significantly higher than on following days (P <.0001). The age at ECMO cannulation showed a significant difference, with mean ± SD values of 1.1 ± 0.9 days in the complications group and 2.7 ± 2.2 days in the no‐complications group (P =.043). Conclusions: Resistive index variability of 10% or greater on any day had a statistically significant risk of cerebrovascular complication development. Extracorporeal membrane oxygenation cannulation at younger than 3 days conferred an increased risk of cerebrovascular complications. [ABSTRACT FROM AUTHOR]

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Chemokine receptors are distinctively exposed on cells to characterize their migration pattern. However, little is known about factors that may regulate their expression. To determine the optimal conditions for an accurate analysis of chemokine receptors, we compared the expression of CCR2, CCR4, CCR5, CCR6, CXCR3 and CXCR4 on different leukocyte subsets using whole blood (WB) plus erythrocyte lysis and density gradient isolation (Ficoll). Most WB monocytes were CCR2+ (93.5±2.9%) whereas 32.8±6.0% of monocytes from Ficoll-PBMC expressed CCR2 (p<0.001). Significant reductions of CCR6 and CXCR3 on monocytes were also observed after Ficoll isolation (WB: 46.4±67.5% and 57.1±5.5%; Ficoll: 29.5±2.2% and 5.4±4.3% respectively) (p<0.01). Although comparable percentages of WB and Ficoll-PBMC monocytes expressed CCR4, CCR5 and CXCR4, Ficoll isolation significantly reduced the levels of CXCR4 (WB: MFI 5±0.4 and Ficoll: MFI 3.3±0.1) (p<0.05). Similarly to monocytes, CCR2, CXCR3 and CXCR4 were also reduced on lymphocytes. In addition, Ficoll isolation significantly reduced the percentage of CCR4 positive lymphocytes (WB: 90.2±4.5% and Ficoll: 55±4.1%) (p<0.01). The loss of expression of chemokine receptors after isolation of monocytes was not dependent on either the anticoagulant or the density gradient method. It was irreversible and could not be restored by LPS activation or in vitro macrophage differentiation. Experiments tagged with anti-CCR2 antibodies prior to density gradient isolation demonstrated that Ficoll internalized chemokine receptors. The method for cell isolation may alter not only the expression of certain chemokine receptors but also the respective functional migration assay. The final choice to analyze their expression should therefore depend on the receptor to be measured [ABSTRACT FROM AUTHOR]

Myoepitheliomas are rare tumors increasingly recognized to occur in the soft tissues. Although the hand and carpal tunnel are exceptional locations, the presence of these lesions in such sites constitutes a potential cause of debilitating symptoms. We report the case of a patient with severe pain secondary to median nerve compression and displacement of flexor tendons caused by a rapidly growing myoepithelioma. This is the first sonographic description of this tumor producing carpal tunnel syndrome and disabling pain. High-resolution sonography allowed evaluation of gross tumor morphology and real-time assessment of its interactions with surrounding structures. [ABSTRACT FROM AUTHOR]