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Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS, only limited inferences can be drawn from imaging data regarding therapy response. To date there are no established and evidence-based diagnostic biomarkers for STS due to their rarity and diversity. In a proof-of-concept study, circulating tumor DNA (ctDNA) was quantified in (n = 25) plasma samples obtained from (n = 3) patients with complex karyotype STS collected over three years. Genotyping of tumor tissue was performed by exome sequencing. Patient-individual mini-panels for targeted next-generation sequencing were designed encompassing up to 30 mutated regions of interest. Circulating free DNA (cfDNA) was purified from plasma and ctDNA quantified therein. ctDNA values were correlated with clinical parameters. ctDNA concentrations correlated with the tumor burden. In case of full remission, no ctDNA was detectable. Patients with a recurrence at a later stage showed low levels of ctDNA during clinical remission, indicating minimal residual disease. In active disease (primary tumor or metastatic disease), ctDNA was highly elevated. We observed direct response to treatment, with a ctDNA decline after tumor resections, radiotherapy, and chemotherapy. Quantification of ctDNA allows for the early detection of recurrence or metastases and can be used to monitor treatment response in STS. Therapeutic decisions can be made earlier, such as the continuation of a targeted adjuvant therapy or the implementation of extended imaging to detect recurrences. In metastatic disease, therapy can be adjusted promptly in case of no response. These advantages may lead to a survival benefit for patients in the future. [ABSTRACT FROM AUTHOR]

Simple Summary: Atypical fibroxanthoma and pleomorphic dermal sarcoma represent two tumors on the spectrum of a rare dermal sarcoma entity. Close clinical presentation and nearly identical histologic features but distinct prognoses make proper treatment strategies challenging. We performed a retrospective analysis of 32 patients with AFX or PDS in the scalp to provide guidance regarding the extent of radical excision to achieve stable oncological outcomes and whether radical tumor resection on the scalps required complex soft-tissue reconstruction. Compared to AFX, PDS shows a more aggressive growth pattern with frequent satellite metastases and distant metastases. These require extensive resections for local control to achieve long-term remission in most PDS patients. Despite the limited elasticity of the scalp, plastic reconstructive procedures can obtain reliable soft tissue reconstruction, even for complete scalp defects. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center. Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are two distinct designations for a rare dermal sarcoma entity. These tumors arise predominantly in the sun-damaged skin of elderly patients. Although both AFX and PDS have a similar clinical presentation and nearly identical genetic features, they significantly differ in prognosis. Here we present a retrospective single-center chart review analyzing the outcomes of patients treated for dermal sarcoma. The radicality of the tumor-resection extent and soft-tissue reconstructive options were assessed. Patients between January 2010 and August 2021 were included. We recorded resection margins, tumor recurrence, overall survival, number of operations until complete tumor resection, and reconstructive procedures; any complications were recorded. Furthermore, we analyzed a subgroup of patients with satellite metastases. A total of 32 patients met the inclusion criteria (30 male, 2 female, median age of 77.5 years (interquartile range (IQR) 74–81)). Histopathology revealed AFX in 14 patients and PDS in 18 patients. Margin-free resection was achieved in 31 cases, and 27 patients were remission free over the reported period. The local recurrence rate was 5, and distant metastasis was detected in four cases. Of all the PDS cases, nine presented with satellite metastasis. No AFX had satellite metastases. Due to their rarity, managing these tumors requires an interdisciplinary setting in a specialized sarcoma center. [ABSTRACT FROM AUTHOR]

Simple Summary: Synovial sarcomas (SS) are rare soft tissue tumors of mesenchymal origin. Following resection of the primary tumor, about one third to half of the patients suffer from recurrence. Detection of local and distant recurrence during follow-up is commonly accomplished by imaging. There are no biomarkers available for routine diagnostics. We employ a highly sensitive targeted next-generation sequencing approach to monitor tumor dynamics by genotyping of circulating free DNA (cfDNA) in SS patients. cfDNA which harbors tumor-specific mutations (circulating tumor-DNA; ctDNA) correlated with the presence of viable tumor tissue. This enables timely and non-invasive detection of tumor recurrence and monitoring of treatment response independent of the anatomic location. Background: Synovial sarcoma (SS) is a malignant soft tissue tumor of mesenchymal origin that frequently occurs in young adults. Translocation of the SYT gene on chromosome 18 to the SSX genes on chromosome X leads to the formation of oncogenic fusion genes, which lead to initiation and proliferation of tumor cells. The detection and quantification of circulating tumor DNA (ctDNA) can serve as a non-invasive method for diagnostics of local or distant tumor recurrence, which could improve survival rates due to early detection. Methods: We developed a subtype-specific targeted next-generation sequencing (NGS) approach specifically targeting SS t(X;18)(p11;q11), which fuses SS18 (SYT) in chromosome 18 to SSX1 or SSX2 in chromosome x, and recurrent point mutations. In addition, patient-specific panels were designed from tumor exome sequencing. Both approaches were used to quantify ctDNA in patients' plasma. Results: The subtype-specific assay allowed detection of somatic mutations from 25/25 tumors with a mean of 1.68 targetable mutations. The minimal limit of detection was determined at a variant allele frequency of 0.05%. Analysis of 29 plasma samples from 15 tumor patients identified breakpoint ctDNA in 6 patients (sensitivity: 40%, specificity 100%). The addition of more mutations further increased assay sensitivity. Quantification of ctDNA in plasma samples (n = 11) from one patient collected over 3 years, with a patient-specific panel based on tumor exome sequencing, correlated with the clinical course, response to treatment and tumor volume. Conclusions: Targeted NGS allows for highly sensitive tumor profiling and non-invasive detection of ctDNA in SS patients, enabling non-invasive monitoring of tumor dynamics. [ABSTRACT FROM AUTHOR]

The impacts of facial nerve disorders on daily life, such as communication and also emotion recognition caused by different underlying conditions, are extremely relevant as well, and are intensively discussed in two articles which devote themselves to the subject of emotion recognition. In conclusion, we can see that the topic of facial nerve palsy offers a vast and dynamic spectrum of developments in the fields of causation, diagnostics, and therapy/rehabilitation. Although there has been a rapid increase in the number of new publications and studies in relation to the diagnostics, impacts and rehabilitation methods of facial nerve disorders, a general structure in evidence-based medicine is still difficult to establish. [Extracted from the article]

XD14 is a 4-acyl pyrrole derivative, which was discovered by a high-throughput virtual screening experiment. XD14 inhibits bromodomain and extra-terminal domain (BET) proteins (BRD2, BRD3, BRD4 and BRDT) and consequently suppresses cell proliferation. In this study, metabolic profiling reveals the molecular effects in the human breast cancer cell line MCF-7 (Michigan Cancer Foundation-7) treated by XD14. A three-day time series experiment with two concentrations of XD14 was performed. Gas chromatography-mass spectrometry (GC-MS) was applied for untargeted profiling of treated and non-treated MCF-7 cells. The gained data sets were evaluated by several statistical methods: analysis of variance (ANOVA), clustering analysis, principle component analysis (PCA), and partial least squares discriminant analysis (PLS-DA). Cell proliferation was strongly inhibited by treatment with 50 μM XD14. Samples could be discriminated by time and XD14 concentration using PLS-DA. From the 117 identified metabolites, 67 were significantly altered after XD14 treatment. These metabolites include amino acids, fatty acids, Krebs cycle and glycolysis intermediates, as well as compounds of purine and pyrimidine metabolism. This massive intervention in energy metabolism and the lack of available nucleotides could explain the decreased proliferation rate of the cancer cells. [ABSTRACT FROM AUTHOR]