Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

Objective: The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. Methods: We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. Results: SWE allowed differentiation between benign PGT (Warthin's Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. Conclusion: MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs

Incidence and survival of HNSCC patients living with HIV compared with HIV-negative HNSCC patients

Purpose: The aim was to analyze the incidence and survival of patients living with HIV (PLWH) with head and neck squamous cell carcinoma (HNSCC) and to compare with a control group of HIV-negative HNSCC patients. Methods: Clinicopathological data and predictors for overall survival (OS) and disease-free survival (DFS) were investigated (2009-2019). Results: 50 of 5151 HNSCC patients (0.97%) were PLWH, and 76% were smokers. Age <= 60 years, HIV-PCR <= 50 copies, CD4 cells <= 200/mm(3), cART treatment, T and UICC classification, oral cavity and nasal/paranasal sinuses, and therapy were significantly associated with OS in univariate analysis. In the multivariate analysis, only age and HIV-PCR independently predicted OS. The OS of the 50 PLWH was not significantly altered compared with the 5101 HIV-negative controls. However, OS and DFS were significantly inferior in advanced tumor stages of PLWH compared with an age-matched control group of 150 HIV-negative patients. Conclusions: PLWH were diagnosed with HNSCC at a significantly younger age compared to HIV-negative patients. Taking into account patient age at initial diagnosis, both OS and DFS rates in PLWH are significantly worse compared with a matched control group of HIV-negative patients in advanced tumor stages UICC III/IV. The prognosis (OS) is improved when taking cART treatment, the HIV viral load is undetectable and CD4 count is high

Does Emotion Dysregulation Mediate the Relationship between Early Maltreatment and Later Substance Dependence? Findings of the CANSAS Study

Background/Aims: Maltreatment in childhood and adolescence is a risk factor for substance use disorders (SUDs) in adulthood. This association has rarely been investigated in the light of emotion dysregulation. To fill this gap, this study examines emotion dysregulation and SUDs among adults with a history of early maltreatment. Methods: Comparison of emotion dysregulation in adults with a history of early abuse and neglect who developed either an SUD (n = 105) or no mental disorder (n = 54). Further, a mediation model for the association between the severity of early maltreatment and SUDs was tested. Participants completed research diagnostic interviews for psychopathology, the Difficulties in Emotion Regulation Scale, and the Childhood Trauma Questionnaire. Results: By using hierarchical regression techniques and mediational analyses controlling for age and gender, it was possible to provide evidence for the mediating role of emotion dysregulation between early emotional and physical maltreatment and later SUDs. Conclusions: Emotion dysregulation is a potential mechanism underlying the relationship between early emotional and physical maltreatment and the development of SUDs. In light of these findings, focusing on the early training of adaptive emotion regulation strategies after childhood maltreatment might be of considerable relevance to prevent the development of SUDs

Anti-Tumor Necrosis Factor α Therapeutics Differentially Affect Leishmania Infection of Human Macrophages

Tumor necrosis factor α (TNFα) drives the pathophysiology of human autoimmune diseases and consequently, neutralizing antibodies (Abs) or Ab-derived molecules directed against TNFα are essential therapeutics. As treatment with several TNFα blockers has been reported to entail a higher risk of infectious diseases such as leishmaniasis, we established an in vitro model based on Leishmania-infected human macrophages, co-cultured with autologous T-cells, for the analysis and comparison of anti-TNFα therapeutics. We demonstrate that neutralization of soluble TNFα (sTNFα) by the anti-TNFα Abs Humira®, Remicade®, and its biosimilar Remsima® negatively affects infection as treatment with these agents significantly reduces Leishmania-induced T-cell proliferation and increases the number of infected macrophages. By contrast, we show that blockade of sTNFα by Cimzia® does not affect T-cell proliferation and infection rates. Moreover, compared to Remicade®, treatment with Cimzia® does not impair the expression of cytolytic effector proteins in proliferating T-cells. Our data demonstrate that Cimzia® supports parasite control through its conjugated polyethylene glycol (PEG) moiety as PEGylation of Remicade® improves the clearance of intracellular Leishmania. This effect can be linked to complement activation, with levels of complement component C5a being increased upon treatment with Cimzia® or a PEGylated form of Remicade®. Taken together, we provide an in vitro model of human leishmaniasis that allows direct comparison of different anti-TNFα agents. Our results enhance the understanding of the efficacy and adverse effects of TNFα blockers and they contribute to evaluate anti-TNFα therapy for patients living in countries with a high prevalence of leishmaniasis

Therapeutic anti-TNFα antibodies differentially affect Leishmania infection of primary human macrophages

Excessive production of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) is associated with the pathophysiology of human autoimmune diseases. As a consequence, neutralizing antibodies or antibody-derived molecules directed against TNFα have emerged as important therapeutics. Despite the great success of anti-TNFα treatment, serious adverse effects remain and complications include a higher risk for infectious diseases such as leishmaniasis. In this study, we developed an in vitro model based on Leishmania-infected human macrophages, co-cultured with autologous T-cells, for the analysis and comparison of currently marketed anti-TNFα agents and their potential to contribute to the onset of leishmaniasis. Using our in vitro model, we identified that neutralization of soluble TNFα (sTNFα) by the anti-TNFα antibodies Remicade®, Remsima® and Humira® negatively affected infection as treatment with these agents significantly reduced Leishmania-induced CD4 T-cell proliferation and increased the number of infected macrophages. In contrast, we showed that blockade of sTNFα by Cimzia® did not affect T-cell proliferation and infection rates. Moreover, compared to Remicade®, the application of Cimzia® did not impair the phenotype and effector functions of T-cells as shown by the expression levels of PD-1, CD45RO and cytolytic effector proteins. The latter are potentially implicated in intracellular killing of parasites. We confirmed that the diverging effects of Remicade® or Cimzia® treatment were independent of Fc-Fcγ receptor interaction. However, our data indicate that Cimzia® supports parasite control through its conjugated PEG moiety as PEGylation of Remicade® enhanced T-cell proliferation and thus improved the clearance of intracellular Leishmania. This effect was associated with complement activation, showing increased C5a expression upon treatment with PEGylated TNFα inhibitors. Altogether, our results enhance the understanding of the effectiveness and adverse effects of anti-TNFα treatment. Considering the emergence of leishmaniasis as complication of anti-TNFα therapy, our findings contribute to evaluate different anti-TNFα agents. Based on our results, we propose that the application of Cimzia® may be beneficial for patients living in countries with a high prevalence of leishmaniasis

Elder Abuse in Nursing Homes: Do Special Care Units Make a Difference? A Secondary Data Analysis of the Swiss Nursing Homes Human Resources Project

In special care units (SCUs) for residents with advanced dementia, both personnel and organizations are adapted to the needs of residents. However, whether these adaptations have a preventive effect on elder abuse has not yet been explored.; To describe the prevalence of observed emotional abuse, neglect, and physical abuse in Swiss nursing homes, to compare SCUs with non-SCUs concerning the frequency of observed emotional abuse, neglect, and physical abuse, and to explore how resident-related characteristics, staff outcomes/characteristics, and organizational/environmental factors relate to observed elder abuse.; This is a secondary data analysis of the Swiss Nursing Homes Human Resources Project (SHURP), a cross-sectional multicenter study. Data were collected from 2012 to 2013 and are based on observed rather than perpetrated elder abuse. We performed multilevel mixed-effects logistic regressions taking into account the hierarchical structure of the data with personnel nested within units and facilities.; Of 4,599 care workers in 400 units and 156 facilities, 50.8% observed emotional abuse, 23.7% neglect, and 1.4% physical abuse. There was no significant difference between SCUs and non-SCUs regarding observed emotional abuse and neglect. Higher scores for 'workload' and sexual aggression towards care workers were associated with higher rates of emotional abuse and neglect. Verbal and physical resident aggression, however, were only associated with higher rates of emotional abuse. Negative associations were found between 'teamwork and resident safety climate' and both forms of abuse.; Improving teamwork and the safety climate and reducing work stressors might be promising points of intervention to reduce elder abuse. More specific research about elder abuse in SCUs and the interaction between work climate and elder abuse is required

Quantitative Multiparametric Ultrasound (mpUS) in the Assessment of Inconclusive Cervical Lymph Nodes

Background: Enlarged cervical lymph nodes (CLN) are preferably examined by ultrasound (US) by using criteria such as size and echogenicity to assess benign and suspicious CLN, which should be histologically evaluated. This study aims to assess the differentiation of malign and benign CLN by using multiparametric US applications (mpUS). Methods: 101 patients received a standardized US protocol prior to surgical intervention using B-mode&ndash;US, shear-wave elastography (SWE) and contrast-enhanced ultrasound (CEUS). SWE was assessed by 2D real-time SWE conducting a minimum of five measurements, CEUS parameters were assessed with post-processing perfusion software. Histopathological confirmation served as the gold standard. Results: B-mode&ndash;US and SWE analysis of 104 CLN (36 benign, 68 malignant) showed a significant difference between benign and malignant lesions, presenting a larger long axis and higher tissue stiffness (both p &lt; 0.001). Moreover, tissue stiffness assessed by SWE was significantly higher in CLN with regular B-mode&ndash;US criteria (Solbiati Index &gt; 2 and short-axis &lt; 1 cm, p &lt; 0.001). No perfusion parameter on CEUS showed a significant differentiation between benign and malignant CLN. Discussion: As the only multiparametric parameter, SWE showed higher tissue stiffness in malignant CLN, also in subgroups with regular B-mode criteria. This fast and easy application may be a promising noninvasive tool to US examination to ameliorate the sonographic differentiation of inconclusive CLN

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

Objective: The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. Methods: We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. Results: SWE allowed differentiation between benign PGT (Warthin’s Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. Conclusion: MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs

Assessment of Parotid Gland Tumors by Means of Quantitative Multiparametric Ultrasound (mpUS)

Objective: The preoperative diagnostical differentiation of parotid gland tumor (PGT) is not always simple due to several different entities. B-mode-ultrasound (US) remains the imaging modality of choice, while histopathology serves as the gold standard for finalizing the diagnosis. We aimed to evaluate the use of multiparametric US (mpUS) in the assessment of PGT. Methods: We included 97 PGTs from 96 patients. A standardized mpUS protocol using B-mode-US, shear-wave elastography (SWE), and standardized contrast-enhanced ultrasound (CEUS) was performed prior to surgical intervention. SWE was assessed by real-time measurement conducting a minimum of five measurements, while quantitative CEUS parameters were assessed with a post-processing perfusion software. Results: SWE allowed differentiation between benign PGT (Warthin&rsquo;s Tumor (WT) paired with lymph nodes (LN) and pleomorphic adenoma (PA)), and WT and LN were softer compared to PA. WT showed lower velocities than squamous cell carcinoma (SCC): the most common malignant PGT. CEUS parameters showed significant group differences between WT and PA, WT and malignant lesions, WT and SCC, WT paired with LN versus PA, and WT paired with LN versus SCC. Conclusion: MpUS seems to be beneficial in the assessment of PGT characterization, with benign PGT appearing to be softer in SWE than tumors with malignant tendencies. The quantitative CEUS parameter shows higher perfusion in WT than in PA, and malignant PGTs are less vascularized than WTs