Svenssonmadsen5593
Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile neutropenia, and this study now extends and modifies the previous model as well as tests its external validity.
We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm.
A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use.
Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.
Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.
Nigella sativa (N. sativa) exhibits anti-inflammatory, antioxidant, antidiabetic, antimetastatic and antinociceptive effects and has been used to treat dozens of diseases. Thymoquinone (TQ) is an important and active component isolated from N. sativa seeds. Inhibition of cancer-associated activating PIK3CA mutations is a new prospective targeted therapy in personalized metastatic breast cancer (MBC). TQ is reported to be an effective inhibitor of the PI3K/Akt1 pathway in MBC. This study aimed to evaluate the in vitro antitumor effect of TQ in the context of two PIK3CA hotspot mutations, p. H1047R and p. H1047L.
Molecular dynamics, free energy landscapes and principal component analyses were also used to survey the mechanistic effects of the p. H1047R and p. H1047L mutations on the PI3K/Akt1 pathway. Our findings clearly confirmed that the p. FM19G11 in vitro H1047R and p. H1047L mutants could reduce the inhibitory effect of ΔNp63α on the kinase domain of PIK3CA, resulting in increased activity of PI3K downstream signals. Structurally, the partial disruption of the interaction between the ΔNp63α DNA binding domain and the PIK3CA kinase domain at residues 114-359 and 797-1068 destabilizes the conformation of the activation loop and modifies the PIK3CA/ΔNp63α complex. Alongside these structural changes, we found that TQ treatment resulted in high PI3K/Akt1 pathway inhibition in p. H1047R and p. H1047L-expressing cells versus wild-type cells.
These two PIK3CA hotspot mutations therefore not only contribute to tumor progression in patients with MBC but may also serve as targets for the development of novel small molecule therapeutic strategies.
These two PIK3CA hotspot mutations therefore not only contribute to tumor progression in patients with MBC but may also serve as targets for the development of novel small molecule therapeutic strategies.
To reveal the clinical significance of preoperative haematological inflammatory markers in the diagnosis of abdominal wall hernias with strangulation.
The data of 200 patients who underwent surgery for incarcerated hernia were retrospectively analysed. The patients were grouped into three groups; Group 1; only surgical reduction and hernia repair, Group 2; small bowel resection and Group 3; omentum resection. Age, gender, hernia type, the presence of radiological bowel obstruction and preoperative complete blood count data were obtained. Neutrophil-leukocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), haematological inflammatory index (HII) and systemic immune-inflammation index (SII) values were calculated.
The study was consisted of; Group 1 119 patients (59.5%), Group 2 46 patients (23%) and Group 3 35 patients (17.5%). Advanced age (p = 0.001), female gender (p = 0.036), incisional hernias (p = < 0.001) and the presence of bowel obstruction (p = < 0.001) were found to be statistically significant in terms of strangulation. NLR, PLR and SII values were significantly higher in Group 2 compared to Group 1, and PLR values were significantly higher in Group 2 compared with Group 3 (p < 0.05).
The preoperative elevated NLR, PLR and SII values may indicate strangulation and possible intestinal resection, in incarcerated abdominal wall hernias.
The preoperative elevated NLR, PLR and SII values may indicate strangulation and possible intestinal resection, in incarcerated abdominal wall hernias.
Medial unicompartmental knee arthroplasty (mUKA) requires full-thickness cartilage in the lateral compartment, but slight damage of the cartilage surface can be ignored. However, as this statement lacks literature support, we investigated whether slight cartilage damages in the weight-bearing area of the lateral femoral condyle would affect the outcome of mUKAs.
Outerbridge grading was performed on the cartilage in the weight-bearing area of the lateral femoral condyle intraoperatively. The patients, grouped as normal or as having lateral condyle cartilage of Outerbridge grade 1-2 (slight cartilage damage), underwent mUKA. Full-length lower extremity radiographs were taken and hip-knee-ankle angles (HKAAs) were measured both preoperatively and postoperatively. Using magnetic resonance imaging, the lateral meniscal extrusion distance was also measured. In addition, the Oxford Knee Score (OKS) was assessed preoperatively and at the last follow-up, in addition to the patient satisfaction assessment.
We enr medial mobile-bearing UKA.
Cartilage damage of Outerbridge grade 1 and grade 2 in the weight-bearing area of the lateral femoral condyle will not compromise the short-term outcome of medial mobile-bearing UKA.Natural killer (NK) cells are cytotoxic lymphocytes that play a major role in the innate immune system. NK cells exhibit potent cytotoxic activity against cancer cells and virally infected cells without antigen priming. These unique cytotoxic properties make NK cells a promising therapeutic against cancer. Limitations of NK cell therapy include deficiencies in high clinical efficacy often due to a need for a high NK cell to target cell ratio to achieve effective killing. In order to address the suboptimal efficacy of current adoptive NK cell therapy, a high throughput screen (HTS) was designed and performed to identify drug-like compounds that increase NK cytotoxic activity against tumor cells without affecting the normal cells. This screen was performed in a 384-well plate format utilizing an expanded primary NK cell product and ovarian cancer cells as a target cell (TC) line. Of the 8000 diverse small molecules screened, 16 hits were identified (0.2% hit rate) based on both a robust Z (RZ) score less then -3 and a greater than 10% increase in NK cell killing. A validation screen had a confirmation rate of 70%. Select compounds were further validated and characterized by additional cytotoxicity assays including activity against multiple blood cancer and solid tumor cell lines, with no effect on primary human T cells. This work demonstrates that high-throughput screening can be reliably used to identify compounds that increase NK tumoricidal activity in vitro that can be further investigated and translated for potential clinical application. Précis Our work led to the identification of promising compound that potently increases NK cell-mediated killing of a variety of different cancer cells, but no impact on the killing of normal cells. This compound demonstrates the utility of this assay.An increasingly popular approach to the analysis of neural data is to treat activity patterns as being constrained to and sampled from a manifold, which can be characterized by its topology. The persistent homology method identifies the type and number of holes in the manifold, thereby yielding functional information about the coding and dynamic properties of the underlying neural network. In this work, we give examples of highly nonlinear manifolds in which the persistent homology algorithm fails when it uses the Euclidean distance because it does not always yield a good approximation to the true distance distribution of a point cloud sampled from a manifold. To deal with this issue, we instead estimate the geodesic distance which is a better approximation of the true distance distribution and can therefore be used to successfully identify highly nonlinear features with persistent homology. To document the utility of the method, we utilize a toy model comprised of a circular manifold, built from orthogonal sinusoidal coordinate functions and show how the choice of metric determines the performance of the persistent homology algorithm. Furthermore, we explore the robustness of the method across different manifold properties, like the number of samples, curvature and amount of added noise. We point out strategies for interpreting its results as well as some possible pitfalls of its application. Subsequently, we apply this analysis to neural data coming from the Visual Coding-Neuropixels dataset recorded at the Allen Institute in mouse visual cortex in response to stimulation with drifting gratings. We find that different manifolds with a non-trivial topology can be seen across regions and stimulus properties. Finally, we interpret how these changes in manifold topology along with stimulus parameters and cortical region inform how the brain performs visual computation.
We investigated whether or not computed tomographic colonography (CTC) is a viable alternative to double-contrast barium enema (BE) for a preoperative rectal cancer evaluation.
The size and distance from the anal canal to the lower or upper tumor borders were laterally measured in 147 patients who underwent CTC and BE. Measurements were grouped into early cancer, advanced, and after chemoradiation therapy (CRT).
In the early and advanced cancer groups, all lesions were visualized by BE. In contrast, 3 (7.8%) early and 8 (7.3%) advanced cases, located at the anterior wall near the anal canal, were not visualized by CTC because of liquid level formation. In the CRT group, 16 (23.5%) and 4 (5.8%) cases were not visualized by CTC and BE, respectively. The BE and CTC size measurements were similar among cohorts. However, the distance from the anal canal's superior margin tended to be longer with BE, especially in early cancer. The differences in distance from the anal canal were significantly larger in the early cancer group than in the other two groups (p = 0.0024).
CTC may be a viable alternative imaging modality in some cases. However, BE should be employed in anterior wall cases near the anal canal and CRT cases.
CTC may be a viable alternative imaging modality in some cases. However, BE should be employed in anterior wall cases near the anal canal and CRT cases.
