Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers ...to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC.
CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28).
Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p < 0.001), but not in PER. Furthermore, immunohistochemical validation demonstrated that the mean CIB1 expression in HEP was 80% higher than in M0 (p < 0.001).
Gene expression analysis revealed that CIB1 is significantly overexpressed in CRC leading to liver metastases compared to M0 and PER. Thus, the present results suggest that CIB1 may play a crucial role for hematogenous spread to the liver but not for peritoneal carcinomatosis. Consequently, CIB1 seems to be a promising prognostic marker and a potential tool for future targeted therapies as well as early diagnostics and follow-up.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Increasing evidence indicates that angiogenesis is crucial in the development and progression of gastric cancer (GC). This study aimed to develop a prognostic relevant angiogenesis-related gene (ARG) ...signature and a nomogram. The expression profile of the 36 ARGs and clinical information of 372 GC patients were extracted from The Cancer Genome Atlas (TCGA). Consensus clustering was applied to divide patients into clusters 1 and 2. Least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to identify the survival related ARGs and establish prognostic gene signatures, respectively. The Asian Cancer Research Group (ACRG) (
= 300) was used for external validation. Risk score of ARG signatures was calculated, and a prognostic nomogram was developed. Gene set enrichment analysis of the ARG model risk score was performed. Cluster 2 patients had more advanced clinical stage and shorter survival rates. ARG signatures carried prognostic relevance in both cohorts. Moreover, ARG-risk score was proved as an independent prognostic factor. The predictive value of the nomogram incorporating the risk score and clinicopathological features was superior to tumor, lymph node, metastasis (TNM) staging. The high-risk score group was associated with several cancer and metastasis-related pathways. The present study suggests that ARG-based nomogram could serve as effective prognostic biomarkers and allow a more precise risk stratification.
Osteoporotic proximal femur fractures are on the rise due to demographic change. The most dominant surgical treatment option for per/subtrochanteric fractures is cephalomedullary nailing. As it has ...been shown to increase primary stability, cement augmentation has become increasingly popular in the treatment of osteoporotic per/subtrochanteric femur fractures. The ultimate goal is to achieve stable osteosynthesis, allowing for rapid full weight-bearing to reduce possible postoperative complications. In recent years, bioresorbable bone cements have been developed and are now mainly used to fill bone voids. The aim of this study was to evaluate the biomechanical stability as well as the micro-structural behaviour of bioresorbable bone cements compared to conventional polymethylmethacrylate (PMMA)-cements in a subtrochanteric femur fracture model. Biomechanical as well as micro-computed tomography morphology analysis revealed no significant differences in both bone cements, as they showed equal mechanical stability and tight interdigitation into the spongious bone of the femoral head. Given the positive risk/benefit ratio for bioresorbable bone cements, their utilisation should be evaluated in future clinical studies, making them a promising alternative to PMMA-bone cements.
Background: Gluteal muscle fatty atrophy (gMFA) might impair pelvic stability and negatively influence remobilization in patients with fragility fractures of the pelvis (FFP). This study aimed to ...investigate the association between gMFA and surgical indication in patients with FFP. Methods and materials: A retrospective analysis of 429 patients (age ≥80) diagnosed with FFP was performed. gMFA of the gluteus maximus, medius, and minimus was evaluated using a standard scoring system based on computer tomography images. Results: No significant difference was found in gMFA between genders or among FFP types. The severity of gMFA did not correlate with age. The severity of gMFA in the gluteus medius was significantly greater than in the gluteus maximus, whereas the most profound gMFA was found in the gluteus minimus. gMFA was significantly more severe in patients who underwent an operation than in conservatively treated patients with type-III FFP, and an independent correlation to surgical indication was found using logistic regression. Conclusion: Our findings imply that gMFA is an independent factor for surgical treatment in patients with type-III FFP. Besides focusing on the fracture pattern, the further evaluation of gMFA could be a feasible parameter for decision making toward either conservative or surgical treatment of type-III FFP.
Adoptive T cell transfer (ACT) is currently under investigation for the treatment of metastatic cancer. Recent evidence suggests that the coinhibitory PD-1-PD-L1 axis plays a major role in ACT ...failure. We hypothesized that a new fusion receptor reverting PD-1-mediated inhibition into CD28 costimulation may break peripheral tolerance.
Different PD-1-CD28 fusion receptor constructs were created and retrovirally transduced into primary T cell receptor transgenic murine CD8(+) T cells specific for ovalbumin (OT-1). Cytokine release, proliferation, cytotoxicity, and tumor recognition were analyzed in vitro. Antitumor efficacy and mode of action were investigated in mice bearing subcutaneous tumors induced with the pancreatic carcinoma cell line Panc02 expressing the model antigen ovalbumin (Panc-OVA). For antitumoral efficacy, six to eight mice per group were used. All statistical tests are two-sided.
Transduction of the PD-1-CD28 receptor constructs mediated enhanced cytokine release, T cell proliferation, and T cell-induced lysis of target tumor cells. The PD-1-CD28 receptor function was dependent on two of the CD28-signaling motifs and IFN-γ release. Treatment of mice with established Panc-OVA tumors with fusion receptor-transduced OT-1 T cells mediated complete tumor regression. Mice rejecting the tumor were protected upon subsequent rechallenge with either ovalbumin-positive or -negative tumors, indicative of a memory response and epitope spreading in nine of 11 mice vs none of the six naïve mice (P < .001). Treatment efficacy was associated with accumulation of IFN-γ-producing T cells and an increased ratio of CD8(+) T cells to immunosuppressive myeloid-derived suppressor cells in the tumors.
Transduction of T cells with this new PD-1-CD28 receptor has the potential of breaking the PD-1-PD-L1-immunosuppressive axis in ACT.
Introduction
Since the introduction of e-scooters in Germany in 2019, they are becoming more and more popular and associated injuries have increased significantly. The aim of this study was to assess ...the injury patterns after e-scooter accidents.
Materials and Methods
From May 2019 to October 2022, all consecutive patients who presented at our emergency department (ED) following e-scooter accidents were included in our study and retrospectively analyzed.
Results
A total of 271 patients were included in our study. The mean age was 33 years. 38% of the patients were female and 62% were male. Most common injuries were traumatic brain injuries in 38% of the patients together with fractures affecting the upper limb (17%). An operative treatment was necessary in 40 patients. Most of the patients presented at night and about 30% were under the influence of alcohol.
Conclusions
Our study shows one of the largest cohort of patients suffering e-scooter accidents in Europe. Compulsory helmet use, stricter alcohol controls and locking periods could contribute significantly to safety.
First experience with continuous glucose monitoring after pancreatic surgery Lampert, Christopher; Weniger, Max; Karcz, Konrad ...
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... et al.,
June 2018, 2018-06-00, 20180601, Letnik:
18, Številka:
4
Journal Article
Immunosuppression leaves transplanted patients at particular risk for severe acute respiratory syndrome 2 (SARS‐CoV‐2) infection. The specific features of coronavirus disease 2019 (COVID‐19) in ...immunosuppressed patients are largely unknown and therapeutic experience is lacking. Seven transplanted patients (two liver, three kidneys, one double lung, one heart) admitted to the Ludwig‐Maximilians‐University Munich because of COVID‐19 and tested positive for SARS‐CoV‐2 were included. The clinical course and the clinical findings were extracted from the medical record. The two liver transplant patients and the heart transplant patient had an uncomplicated course and were discharged after 14, 18, and 12 days, respectively. Two kidney transplant recipients were intubated within 48 hours. One kidney and the lung transplant recipients were required to intubate after 10 and 15 days, respectively. Immunosuppression was adapted in five patients, but continued in all patients. Compared to non‐transplanted patients at the ICU (n = 19) the inflammatory response was attenuated in transplanted patients, which was proven by decreased IL‐6 blood values. This analysis might provide evidence that continuous immunosuppression is safe and probably beneficial since there was no hyperinflammation evident. Although transplanted patients might be more susceptible to an infection with SARS‐CoV‐2, their clinical course seems to be similar to immunocompetent patients.
Pancreatic ductal adenocarcinoma (PDAC) is frequently associated with severe pain. Given the almost inevitably fatal nature of the disease, pain control is crucial. However, data on quality of pain ...management in PDAC is scarce.
This is a multi-center, prospective study to evaluate the quality of pain management in PDAC. Insufficient pain treatment (undertreatment) was prevalent if there was an incongruence between the patients level of pain and the potency of analgesic drug therapy. Determinants of pain and undertreatment were identified using multivariable logistic regression.
139 patients with histologically confirmed PDAC were analyzed. The prevalence of pain was 63%, with approximately one third of the patients grading their pain as moderate to severe. Palliative stage (OR: 3.37, 95%CI: 1.23–9.21, p = 0.018) and localization of the primary tumor in the body or tail (OR: 2.57, 95%CI: 1.05–6.31, p = 0.039) were independent determinants of pain. Of those reporting pain, 60% were undertreated and in 89% pain interfered with activities and emotions. Age ≥ 70 years (OR: 3.20, 95%CI: 1.09–9.41, p = 0.035) was an independent predictor of undertreatment. Patients with longer-known PDAC ( ≥ 30 days) showed improved pain management compared to new cases (OR: 0.19, 95%CI: 0.05–0.81, p = 0.025). Treatment by gastroenterologists (OR: 0.22, 95%CI: 0.05–0.89, p = 0.034) was associated with less undertreatment.
The results show a high proportion of PDAC patients with pain, pain interference and undertreatment, whose characteristics could help to identify patients at risk in the future. Several changes in the management of cancer-related pain are necessary to overcome barriers to optimal treatment.
PDF
