Search Results (6)

Background/Objectives: Colorectal cancer (CRC) with hepatic (CRLM) and pulmonary metastases (CRLU) presents a significant clinical challenge, leading to poor prognosis. Surgical resection of these metastases remains controversial because of limited evidence supporting its long-term benefits. To evaluate the impact of surgical resection of both hepatic and pulmonary metastases on long-term survival in patients with multivisceral metastatic colorectal cancer, this retrospective cohort study included 192 patients with UICC stage IV CRC treated at a high-volume academic center. Methods: Patients were divided into two groups: those who underwent surgical resection of both hepatic and pulmonary metastases (n = 100) and those who received non-surgical treatment (n = 92). Propensity score matching was used to adjust for baseline differences. The primary outcome was overall survival (OS). Results: Unadjusted analysis showed a significant OS benefit in the surgical group (median OS: 6.97 years) compared with the conservative group (median OS: 2.17 years). After propensity score matching, this survival advantage persisted (median OS: 5.58 years vs. 2.35 years; HR: 0.3, 95% CI: 0.18–0.47, p < 0.0001). Conclusions: Surgical resection of hepatic and pulmonary metastases in multivisceral metastatic CRC significantly improves long-term survival, supporting an aggressive surgical approach in selected patients. Full article

Kaposi’s sarcoma (KS) is an AIDS-defining illness caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) predominantly in the context of HIV-related immune suppression. We aimed to explore the usefulness of KSHV DNA viral load (VL) measurement in predicting the severity, response to treatment and outcome of KS. We retrospectively assessed a cohort of KS patients (n = 94) receiving treatment at Groote Schuur Hospital, Cape Town, South Africa. Demographic and clinical data, KS staging and response to treatment were extracted from patient files, while long-term survival was ascertained from hospital records. KSHV serology and VL and hIL-6 were determined empirically from patients’ blood. All patients were HIV-positive adults, the majority of whom were on HAART at the time of recruitment. KSHV VL was detectable in 65 patients’ blood (median: 280.5/10⁶ cells (IQR: 69.7–1727.3)) and was highest in patients with S1 HIV-related systemic disease (median 1066.9/10⁶ cells, IQR: 70.5–11,269.6). KSHV VL was associated with the S1 stage in a binomial regression controlling for confounders (adjusted odds ratio 5.55, 95% CI: 1.28–24.14, p = 0.022). A subset of six patients identified to have extremely high KSHV VLs was predominantly T₁ stage with pulmonary KS, and most had died at follow-up. In our cohort, elevated KSHV VL is associated with systemic HIV-related illness in KS disease. Extremely high KSHV VLs warrant further investigation for patients potentially requiring intensive treatment and investigation for progression or diagnosis of concurrent KSHV lytic syndromes. Full article

Therapeutic options for metastatic colorectal cancer (mCRC) are very limited, and the prognosis using combination therapy with a chemotherapeutic drug and a targeted agent, e.g., epidermal growth factor receptor or tyrosine kinase, remains poor. Therefore, mCRC is associated with a poor median overall survival (mOS) of only 25–30 months. Current immunotherapies with checkpoint inhibitor blockade (ICB) have led to a substantial change in the treatment of several cancers, such as melanoma and non-small cell lung cancer. In CRC, ICB has only limited effects, except in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, which comprise about 15% of sporadic CRC patients and about 4% of patients with metastatic CRC. The vast majority of sporadic CRCs are microsatellite-stable (MSS) tumors with low levels of infiltrating immune cells, in which immunotherapy has no clinical benefit so far. Immunotherapy with checkpoint inhibitors requires the presence of infiltrating T cells into the tumor microenvironment (TME). This makes T cells the most important effector cells in the TME, as evidenced by the establishment of the immunoscore—a method to estimate the prognosis of CRC patients. The microenvironment of a tumor contains several types of T cells that are anti-tumorigenic, such as CD8⁺ T cells or pro-tumorigenic, such as regulatory T cells (Tregs) or T helper 17 (Th17) cells. However, even CD8⁺ T cells show marked heterogeneity, e.g., they can become exhausted, enter a state of hyporesponsiveness or become dysfunctional and express high levels of checkpoint molecules, the targets for ICB. To kill cancer cells, CD8⁺ T cells need the recognition of the MHC class I, which is often downregulated on colorectal cancer cells. In this case, a population of unconventional T cells with a γδ T cell receptor can overcome the limitations of the conventional CD8⁺ T cells with an αβT cell receptor. γδ T cells recognize antigens in an MHC-independent manner, thus acting as a bridge between innate and adaptive immunity. Here, we discuss the effects of different T cell subsets in colorectal cancer with a special emphasis on γδ T cells and the possibility of using them in CAR-T cell therapy. We explain T cell exclusion in microsatellite-stable colorectal cancer and the possibilities to overcome this exclusion to enable immunotherapy even in these “cold” tumors. Full article

Traumatic brain injury (TBI) represents a major determining factor of outcome in severely injured patients. However, reliable brain-damage-monitoring markers are still missing. We therefore assessed brain-specific beta-synuclein as a novel blood biomarker of synaptic damage and measured the benchmarks neurofilament light chain (NfL), as a neuroaxonal injury marker, and glial fibrillary acidic protein (GFAP), as an astroglial injury marker, in patients after polytrauma with and without TBI. Compared to healthy volunteers, plasma NfL, beta-synuclein, and GFAP were significantly increased after polytrauma. The markers demonstrated highly distinct time courses, with beta-synuclein and GFAP peaking early and NfL concentrations gradually elevating during the 10-day observation period. Correlation analyses revealed a distinct influence of the extent of extracranial hemorrhage and the severity of head injury on biomarker concentrations. A combined analysis of beta-synuclein and GFAP effectively discriminated between polytrauma patients with and without TBI, despite the comparable severity of injury. Furthermore, we found a good predictive performance for fatal outcome by employing the initial plasma concentrations of NfL, beta-synuclein, and GFAP. Our findings suggest a high diagnostic value of neuronal injury markers reflecting distinct aspects of neuronal injury for the diagnosis of TBI in the complex setting of polytrauma, especially in clinical surroundings with limited imaging opportunities. Full article

Due to the fact that legal and market requirements are becoming stricter, fan noise reduction, in addition to energy efficiency, represent a challenge for fan product designers. Most experimental studies are associated with trial-and-error approaches. Therefore, numerical methods are mostly preferable. However, the quantitative prediction of the noise emitted by radial fans via numerical simulations remains challenging. The Lattice Boltzmann method (LBM) is a relatively new approach that promises a direct calculation of the aerodynamics coupled with the aeroacoustics. This article presents an LBM simulation of a centrifugal fan using the commercial Lattice Boltzmann Code SIMULIA PowerFLOW of Dassault Systèmes. The simulation model includes both the fan impeller and the spiral housing. In accordance with the experimental setup, the fan was mounted in a test bench to analyze four different operating points. The results of the LBM simulation were validated by experimental measurements. Flow information in terms of pressure rise and efficiency of the centrifugal fan as a function of the flow rate are in a good agreement. Considering the acoustic spectra and the blade passing frequency, the simulation was able to precisely predict the noise of the centrifugal fan. The simulation results are also used to visualize the flow and acoustic field inside of the fan to detect noise-generating flow features. By evaluating the filtered pressure fluctuation in the fluid volume and on the wall, four main noise sources of the centrifugal fan can be identified. Full article

Cardiovascular risk factors may act by modulating the composition and function of the adventitia. Here we examine how age affects perivascular adipose tissue (PVAT) and its paracrine activities during neointima formation. Aortic tissue and PVAT or primary aortic smooth muscle cells from male C57BL/6JRj mice aged 52 weeks (“middle-aged”) were compared to tissue or cells from mice aged 16 weeks (“adult”). Vascular injury was induced at the carotid artery using 10% ferric chloride. Carotid arteries from the middle-aged mice exhibited smooth muscle de-differentiation and elevated senescence marker expression, and vascular injury further aggravated media and adventitia thickening. Perivascular transplantation of PVAT had no effect on these parameters, but age-independently reduced neointima formation and lumen stenosis. Quantitative PCR analysis revealed a blunted increase in senescence-associated proinflammatory changes in perivascular tissue compared to visceral adipose tissue and higher expression of mediators attenuating neointima formation. Elevated levels of protein inhibitor of activated STAT1 (PIAS1) and lower expression of STAT1- or NFκB-regulated genes involved in adipocyte differentiation, inflammation, and apoptosis/senescence were present in mouse PVAT, whereas PIAS1 was reduced in the PVAT of patients with atherosclerotic vessel disease. Our findings suggest that age affects adipose tissue and its paracrine vascular activities in a depot-specific manner. PIAS1 may mediate the age-independent vasculoprotective effects of perivascular fat. Full article