Angiosarcoma: clinical outcomes and prognostic factors, a single-center analysis.

PURPOSE: This study sought to investigate oncological outcomes and prognostic factors for patients with angiosarcomas (AS). METHODS: This single-center, retrospective cohort study, analyzed histopathologically confirmed AS cases. Primarily diagnosed, locally recurrent and metastatic AS were included. Overall survival (OS), local control (LC) and local progression-free survival (LPFS) were assessed by Kaplan-Meier estimator. Multivariable Cox regression analysis was performed to detect factors associated with OS and LPFS. RESULTS: In total, 118 patients with a median follow-up of 6.6 months were included. The majority presented with localized disease (62.7%), followed by metastatic (31.4%) and locally recurrent (5.9%) disease. Seventy-four patients (62.7%) received surgery, of which 29 (39.2%) were treated with surgery only, 38 (51.4%) with surgery and perioperative radiotherapy or chemotherapy, and 7 (9.4%) with surgery, perioperative radiotherapy and chemotherapy. Multivariable Cox regression of OS showed a significant association with age per year (hazard ratio (HR): 1.03, p = 0.044) and metastatic disease at presentation (hazard ratio: 3.24, p = 0.015). For LPFS, age per year (HR: 1.04, p = 0.008), locally recurrent disease at presentation (HR: 5.32, p = 0.013), and metastatic disease at presentation (HR: 4.06, p = 0.009) had significant associations. Tumor size, epithelioid components, margin status, and perioperative RT and/or CTX were not significantly associated with OS or LPFS. CONCLUSION: Older age and metastatic disease at initial presentation status were negatively associated with OS and LPFS. Innovative and collaborative effort is warranted to overcome the epidemiologic challenges of AS by collecting multi-institutional datasets, characterizing AS molecularly and identifying new perioperative therapies to improve patient outcomes.

The Roles of AGTRAP, ALKBH3, DIVERSIN, NEDD8 and RRM1 in Glioblastoma Pathophysiology and Prognosis.

This study determined the expression of five novel biomarker candidates in IDH wild-type glioblastoma (GBM) tissues compared to non-malign brain parenchyma, as well as their prognostic relevance for the GBM patients' outcomes. The markers were analysed by immunohistochemistry in tumour tissues (n = 186) and healthy brain tissues (n = 54). The association with the patients' overall survival (OS) and progression-free survival (PFS) was assessed by Kaplan-Meier and log-rank test. The prognostic value of the markers was determined using multivariate Cox proportional hazard models. AGTRAP, DIVERSIN, cytoplasmic NEDD8 (NEDD8c) and RRM1 were significantly overexpressed in tumour tissues compared to the healthy brain, while the opposite was observed for ALKBH3. AGTRAP, ALKBH3, NEDD8c and RRM1 were significantly associated with OS in univariate analysis. AGTRAP and RRM1 were also independent prognostic factors for OS in multivariate analysis. For PFS, only AGTRAP and NEDD8c reached significance in univariate analysis. Additionally, AGTRAP was an independent prognostic factor for PFS in multivariate models. Finally, combined analysis of the markers enhanced their prognostic accuracy. The combination AGTRAP/ALKBH3 had the strongest prognostic value for the OS of GBM patients. These findings contribute to a better understanding of the GBM pathophysiology and may help identify novel therapeutic targets in this type of cancer.

Differences in Osseous Shoulder Morphology, Scapulothoracic Orientation, and Muscle Volume in Patients With Constitutional Static Posterior Shoulder Instability (Type C1) Compared With Healthy Controls.

BACKGROUND: Constitutional static posterior humeral decentering (type C1 according to ABC Classification) has been recognized as a pre-osteoarthritic deformity that may lead to early-onset posterior decentering osteoarthritis at a young age. Therefore, it is important to identify possible associations of this pathologic shoulder condition to find more effective treatment options. PURPOSE: To perform a comprehensive analysis of all parameters reported to be associated with a C1 shoulder-including the osseous shoulder morphology, scapulothoracic orientation, and the muscle volume of the shoulder girdle in a single patient cohort. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: A retrospective, comparative study was conducted analyzing 17 C1 shoulders in 10 patients who underwent magnetic resonance imaging (MRI) with the complete depiction of the trunk from the base of the skull to the iliac crest, including both humeri. The mean age of the patients was 33.5 years, and all patients were men. To measure and compare the osseous shoulder morphology (glenoid version, glenoid offset, humeral torsion, anterior acromial coverage, posterior acromial coverage, posterior acromial height, and posterior acromial tilt) and scapulothoracic orientation (scapular protraction, scapular internal rotation, scapular upward rotation, scapular translation, scapular tilt, and thoracic kyphosis), these patients were matched 1 to 4 according their age, sex, and affected side with shoulder-healthy patients who had received positron emission tomography (PET)-computed tomography. To measure and compare the muscle volume of the shoulder girdle (subscapularis, infraspinatus/teres minor, supraspinatus, trapezius, deltoid, latissimus dorsi/teres major, pectoralis major, and pectoralis minor), patients were matched 1 to 2 with patients who had received PET-MRI. Patients with visible pathologies of the upper extremities were excluded. RESULTS: The C1 group had a significantly higher glenoid retroversion, increased anterior glenoid offset, reduced humeral retrotorsion, increased anterior acromial coverage, reduced posterior acromial coverage, increased posterior acromial height, and increased posterior acromial tilt compared with controls (P < .05). Decreased humeral retrotorsion showed significant correlation with higher glenoid retroversion (r = -0.742; P < .001) and higher anterior glenoid offset (r = -0.757; P < .001). Significant differences were found regarding less scapular upward rotation, less scapular tilt, and less thoracic kyphosis in the C1 group (P < .05). The muscle volume of the trapezius and deltoid was significantly higher in the C1 group (P < .05). CONCLUSION: Patients with C1 shoulders differ from healthy controls regarding osseous scapular and humeral morphology, scapulothoracic orientation, and shoulder girdle muscle distribution. These differences may be crucial in understanding the delicate balance of glenohumeral centering.

Progesterone Receptor Membrane Component 1 (PGRMC1) Modulates Tumour Progression, the Immune Microenvironment and the Response to Therapy in Glioblastoma.

Progesterone Receptor Membrane Component 1 (PGRMC1) is a tumour-promoting factor in several types of cancer but its role in brain tumours is poorly characterized thus far. Our study aimed to determine the effect of PGRMC1 on glioblastoma (GBM) pathophysiology using two independent cohorts of IDH wild-type GBM patients and stable knockdown GBM models. We found that high levels of PGRMC1 significantly predicted poor overall survival in both cohorts of GBM patients. PGRMC1 promoted the proliferation, anchorage-independent growth, and invasion of GBM cells. We identified Integrin beta-1 (ITGB1) and TCF 1/7 as potential members of the PGRMC1 pathway in vitro. The levels of ITGB1 and PGRMC1 also correlated in neoplastic tissues from GBM patients. High expression of PGRMC1 rendered GBM cells less susceptible to the standard GBM chemotherapeutic agent temozolomide but more susceptible to the ferroptosis inducer erastin. Finally, PGRMC1 enhanced Interleukin-8 production in GBM cells and promoted the recruitment of neutrophils. The expression of PGRMC1 significantly correlated with the numbers of tumour-infiltrating neutrophils also in tissues from GBM patients. In conclusion, PGRMC1 enhances tumour-related inflammation and promotes the progression of GBM. However, PGRMC1 might be a promising target for novel therapeutic strategies using ferroptosis inducers in this type of cancer.

Impact of Individual Spinopelvic Anatomy on the Localization and Severity of Symptomatic Isthmic Spondylolisthesis.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVES: Isthmic spondylolisthesis (iSPL) occurs most commonly in L5/S1 and L4/5. This study investigates the association between spinopelvic anatomy and the pathogenesis of iSPL. METHODS: Spinopelvic parameters as well as severity of slip grade were measured in sagittal spine radiographs of symptomatic patients with iSPL in segments L4/5 and L5/S1. Means were calculated and differences between both groups were analyzed. A correlation between the analyzed parameters and degree of slippage was performed. RESULTS: We included 73 subjects in this study; 11 in L4/5 group and 62 in L5/S1 group. Pelvic anatomy significantly differed between L4/5 and L5/S1 iSPL (Pelvic Incidence (PI) 54.8° vs 66.3°, P value = .006; Pelvic Radius (PR) 124.4 mm vs 137.4 mm; P value = .005 and Sacral Table Angle (STA) 101.0° vs 92.2°, P value < .001). The relative degree of slippage was significantly higher in the L5/S1 group (L4/5 29.1% vs L5/S1 40.1%, P value .022). We also observed a significant correlation between pelvic anatomy and the severity of the slip in iSPL at the L5/S1 level. CONCLUSIONS: Pelvic parameters PI and STA play an important role concerning the level of occurrence and severity of iSPL. Spinopelvic anatomy determines the pathogenesis of iSPL.

Sarcoma Patients Admitted to the Intensive Care Unit (ICU): Predictive Relevance of Common Sepsis and Performance Parameters.

Purpose: Prognosis of sarcoma patients is improving, with a better understanding of sarcomagenesis revealing novel therapeutic targets. However, aggressive chemotherapy remains an essential part of treatment, bearing the risk of severe side effects that require intensive medical treatment. Available data on the characteristics and clinical outcome of sarcoma patients admitted to intensive care units (ICU) are sparse. Patients and Methods: We performed a retrospective analysis of sarcoma patients admitted to the ICU from 2005 to 2022. Patients ≥18 years with histologically proven sarcoma were included in our study. Results: Sixty-six patients were eligible for analysis. The following characteristics had significant impact on overall survival: sex (p=0.046), tumour localization (p=0.02), therapeutic intention (p=0.02), line of chemotherapy (p<0.001), SAPS II score (p=0.03) and SOFA score (p=0.02). Conclusion: Our study confirms the predictive relevance of established sepsis and performance scores in sarcoma patients. For overall survival, common clinical characteristics are also of significant value. Further investigation is needed to optimize ICU treatment of sarcoma patients.