Artificial intelligence based system for predicting permanent stoma after sphincter saving operations.

Although the goal of rectal cancer treatment is to restore gastrointestinal continuity, some patients with rectal cancer develop a permanent stoma (PS) after sphincter-saving operations. Although many studies have identified the risk factors and causes of PS, few have precisely predicted the probability of PS formation before surgery. To validate whether an artificial intelligence model can accurately predict PS formation in patients with rectal cancer after sphincter-saving operations. Patients with rectal cancer who underwent a sphincter-saving operation at Taipei Medical University Hospital between January 1, 2012, and December 31, 2021, were retrospectively included in this study. A machine learning technique was used to predict whether a PS would form after a sphincter-saving operation. We included 19 routinely available preoperative variables in the artificial intelligence analysis. To evaluate the efficiency of the model, 6 performance metrics were utilized: accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiving operating characteristic curve. In our classification pipeline, the data were randomly divided into a training set (80% of the data) and a validation set (20% of the data). The artificial intelligence models were trained using the training dataset, and their performance was evaluated using the validation dataset. Synthetic minority oversampling was used to solve the data imbalance. A total of 428 patients were included, and the PS rate was 13.6% (58/428) in the training set. The logistic regression (LR), Gaussian Naïve Bayes (GNB), Extreme Gradient Boosting (XGB), Gradient Boosting (GB), random forest, decision tree and light gradient boosting machine (LightGBM) algorithms were employed. The accuracies of the logistic regression (LR), Gaussian Naïve Bayes (GNB), Extreme Gradient Boosting (XGB), Gradient Boosting (GB), random forest (RF), decision tree (DT) and light gradient boosting machine (LightGBM) models were 70%, 76%, 89%, 93%, 95%, 79% and 93%, respectively. The area under the receiving operating characteristic curve values were 0.79 for the LR model, 0.84 for the GNB, 0.95 for the XGB, 0.95 for the GB, 0.99 for the RF model, 0.79 for the DT model and 0.98 for the LightGBM model. The key predictors that were identified were the distance of the lesion from the anal verge, clinical N stage, age, sex, American Society of Anesthesiologists score, and preoperative albumin and carcinoembryonic antigen levels. Integration of artificial intelligence with available preoperative data can potentially predict stoma outcomes after sphincter-saving operations. Our model exhibited excellent predictive ability and can improve the process of obtaining informed consent.

Hydrogel-Based Strategies for the Management of Osteomyelitis.

Osteomyelitis is a type of bone infection caused by bacteria, with Staphylococcus sepsis being responsible for most cases. Osteomyelitis treatment generally requires a multifaceted approach that may include intervention of surgery and administration of antibacterial agents, where several materials have been utilized as delivery vehicles for antibiotics and other antibacterial materials. Hydrogel has become a popular candidate for osteomyelitis treatment due to its biocompatibility, water-containing porous structure, and adaptable physicochemical properties. In this review, we discuss several hydrogel-based strategies for osteomyelitis treatment and categorized them based on the encapsulated cargos (i.e., antibiotics, silver nanoparticles, protein and bacteriophage, and reactive oxygen species (ROS) generator). Several representative examples of osteomyelitis treatment using hydrogels are described here, focusing on their design, preparation, properties, and outcomes. We also provide our perspectives on the remaining concerns regarding fabricating advanced hydrogels for osteomyelitis treatment. This review will be valuable to the hydrogel community and inspire researchers to develop next-generation hydrogels for specific and practical clinical applications in osteomyelitis.

Clinical assessment for non-reversal stoma and stoma re-creation after reversal surgery for patients with rectal cancer having undergoing sphincter-saving operation.

BACKGROUND: This study aimed to identify the risk factors for permanent stoma (PS) in patients who underwent sphincter-saving operations for rectal cancer. METHODS: We retrospectively reviewed 597 consecutive patients with rectal cancer from January 2012 to December 2020 at Taipei Medical University Hospital. Univariate and multivariable analyses were used to analyze risk factors for PS. RESULTS: After a mean follow-up of 47.3 months (range 7-114 months), 59 patients (15.1%) were alive with a PS, including 46 patients who did not undergo reversal surgery and 13 patients who underwent stoma re-creation after reversal surgery. The mean period between primary surgery and stoma reversal was 6.0 months. Multivariate analysis revealed that the risk factors for PS were local recurrence [odd ratio (OR), 25.58; 95% confidence interval (CI), 4.428-147.761; p < 0.001], perirectal abscess [OR, 154.34; 95% CI, 15.806 - >999; p < 0.001], anastomosis site stenosis [OR, 187.081; 95% CI, 22.193 - >999; p < 0.001], perineural invasion [OR, 4.782; 95% CI, 1.22-18.736; p = 0.025], and operation time (min) [OR, 1.008; 95% CI, 1.002-1.014; p = 0.01]. CONCLUSIONS: Local recurrence, perirectal abscess, anastomosis site stenosis, perineural invasion, and operation time were independent risk factors for PS. Therefore, before a patient undergoes surgery for rectal cancer, surgeons should consider the possibility of the need for a PS, and patients should be informed before the operation that closure of the temporary stoma may not always be possible.

Nomogram to predict permanent stoma in rectal cancer patients after sphincter-saving surgery.

BACKGROUND: Approximately 20 percent of patients with a tumour localized in the low rectum still encounter the possibility of requiring permanent stoma (PS), which can cause drastic changes in lifestyle and physical perceptions. AIM: To determine the risk factors for PS and to develop a prediction model to predict the probability of PS in rectal cancer patients after sphincter-saving surgery. METHODS: A retrospective cohort of 421 rectal cancer patients who underwent radical surgery at Taipei Medical University Hospital between January 2012 and December 2020 was included in this study. Univariate and multivariate analyses were performed to identify the independent risk factors for PS. A nomogram was developed according to the independent risk factors obtained in the multivariate analysis. The performance of the nomogram was assessed using a receiver operating characteristic curve and a calibration curve. RESULTS: The PS rate after sphincter-saving surgery was 15.1% (59/391) in our study after a median follow-up of 47.3 mo (range 7-114 mo). Multivariate logistic regression analysis demonstrated that local recurrence, perirectal abscess, anastomosis site stenosis, perineural invasion, tumor size and operative time were independent risk factors for PS. These identified risk factors were incorporated into the nomogram, and the concordance index of this model was 0.903 (95%CI: 0.851-0.955). According to the calibration curves, the nomogram represents a perfect prediction model. CONCLUSION: Several risk factors for PS after sphincter-saving surgery were identified. Our nomogram exhibited perfect predictive ability and will improve a physician's ability to communicate the benefits and risks of various treatment options in shared decision making.

Transcatheter arterial chemoembolization improves the resectability of malignant breast phyllodes tumor with angiosarcoma component: a case report.

BACKGROUND: A giant phyllodes tumor of the breast is a rare fibroepithelial lesion, and its treatment is controversial. Many case reports have reported performing skin graft reconstruction after tumor excision. Chest wall resection may be required if the tumor has invaded the chest muscle layer. We speculated that transcatheter arterial chemoembolization (TACE) can improve the resectability of malignant phyllodes tumor of the breast without requiring skin grafting. The English literature contains only one case report similar to our experience. CASE PRESENTATION: We report a rare case of a 51-year-old woman who had a giant malignant phyllodes tumor with heterologous sarcomatous differentiation in her right breast. The tumor was 19.43 × 12.98 × 21.47 cm. Whole-body computed tomography (CT) and bone scan did not reveal distant metastasis. Chest magnetic resonance imaging showed chest wall tumor invasion. Considering that skin defects after mastectomy can be extensive, we administered four courses of chemoembolization in the 5 weeks before surgery (30 mg of epirubicin and embozene microspheres [400, 500, and 700 µm]/week). Each process was well tolerated, with no serious complications. Only fever and local pain at the tumor site were noted, and these symptoms resolved with time. The follow-up CT scan showed a 45% reduction in tumor volume. Therefore, simple mastectomy was performed without skin grafting reconstruction. Wound healing was satisfactory, and the patient was discharged 1 week after surgery. Pathological and immunohistochemistry (IHC) findings showed a malignant phyllodes tumor with an angiosarcoma component. Because of tumor invasion of the chest wall, we recommended the patient receive radiotherapy, but she refused. Two months after surgery, recurrence of the malignant phyllodes tumor with right axillary lymph node involvement and lung metastasis was confirmed. CONCLUSION: Initial surgical resection of giant phyllodes tumors is often challenging. For initial presentation with unresectable giant phyllodes tumor, we recommend to perform TACE prior to surgery. In our patient, preoperative TACE was effective and safe. If the tumor has invaded the chest wall, early radiotherapy after surgery may be recommended for preventing recurrence.

Magnetic and Thermal-sensitive Poly(N-isopropylacrylamide)-based Microgels for Magnetically Triggered Controlled Release.

Magnetically and thermally sensitive poly(N-isopropylacrylamide) (PNIPAAm)/Fe3O4-NH2 microgels with the encapsulated anti-cancer drug curcumin (Cur) were designed and fabricated for magnetically triggered release. PNIPAAm-based magnetic microgels with a spherical structure were produced via a temperature-induced emulsion followed with physical-crosslinking by mixing PNIPAAm, polyethylenimine (PEI), and Fe3O4-NH2 magnetic nanoparticles. Because of their dispersity, the Fe3O4-NH2 nanoparticles were embedded inside the polymer matrix. The amine groups exposed on the Fe3O4-NH2 and PEI surface supported the spherical structure by physically crosslinking with the amide groups of the PNIPAAm. The hydrophobic anti-cancer drug curcumin can be dispersed in water after encapsulation into the microgels. The microgels were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and UV-Vis spectral analysis. Furthermore, magnetically triggered release was studied under an external high frequency magnetic field (HFMF). A significant "burst release" of curcumin was observed after applying the HFMF to the microgels due to the magnetic inductive heating (hyperthermia) effect. This manuscript describes the magnetically triggered controlled release of Cur-PNIPAAm/Fe3O4-NH2 encapsulated curcumin, which can be potentially applied for tumor therapy.

Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release.

Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

A common polymorphism decreases LRP1 mRNA stability and is associated with increased plasma factor VIII levels.

The low-density lipoprotein receptor-related protein 1 (LRP1) gene is associated with increased levels of plasma factor VIII (FVIII). We aimed to explore eight functional genetic LRP1 variants for their potential roles in regulating FVIII levels and acute ischemic stroke (AIS). This genetic association study enrolled 192 patients with AIS and 134 controls. There were no significant differences in the genetic frequency of the eight functional single-nucleotide polymorphisms (SNPs) between the control and AIS groups. However, while analyzing the association between the eight SNPs and plasma FVIII levels, subjects with T/T genotype of rs1800137 (vs. CC+CT) were found to be associated with higher FVIII levels (23.5IU/dL; 95% confidence interval, 7.4-39.5IU/dL; P=0.0044) after adjusting for age, gender, estimated glomerular filtration rate, O blood type, inflammatory state, and body mass index. An analysis of the mRNA stability and abundance was designed and performed using minigene system transfected into HepG2 cells to assess the possible differences in mRNA stabilities between rs1800137 CC (rs1800137C) and TT (rs1800137T) genotypes. Site-directed mutagenesis revealed that rs1800137T accounts for the observed decrease in mRNA stability. The SNP rs1800137, located in exon 8, has been identified as an exon-splicing enhancer in silico. However, alternative splicing of LRP1 without inclusion of exon 8 was not identified. In transfected HepG2 cells, cycloheximide slowed down the degradation of the rs1800137T-containing minigene. These results demonstrate that synonymous SNP rs1800137 can lead to increased plasma FVIII levels due to decreased mRNA stability via translation-dependent mRNA degradation associated with codon optimality.

Magnetically triggered nanovehicles for controlled drug release as a colorectal cancer therapy.

Magnetic silica core/shell nanovehicles presenting atherosclerotic plaque-specific peptide-1 (AP-1) as a targeting ligand (MPVA-AP1 nanovehicles) have been prepared through a double-emulsion method and surface modification. Amphiphilic poly(vinyl alcohol) was introduced as a polymer binder to encapsulate various drug molecules (hydrophobic, hydrophilic, polymeric) and magnetic iron oxide (Fe3O4) nanoparticles. Under a high-frequency magnetic field, magnetic carriers (diameter: ca. 50 nm) incorporating the anti-cancer drug doxorubicin collapsed, releasing approximately 80% of the drug payload, due to the heat generated by the rapidly rotating Fe3O4 nanoparticles, thereby realizing rapid and accurate controlled drug release. Simultaneously, the magnetic Fe3O4 themselves could also kill the tumor cells through a hyperthermia effect (inductive heating). Unlike their ungrafted congeners (MPVA nanovehicles), the AP1-grafted nanovehicles bound efficiently to colorectal cancer cells (CT26-IL4Rα), thereby displaying tumor-cell selectivity. The combination of remote control, targeted dosing, drug-loading flexibility, and thermotherapy and chemotherapy suggests that magnetic nanovehicles such as MPVA-AP1 have great potential for application in cancer therapy.

Magnetic liposomes for colorectal cancer cells therapy by high-frequency magnetic field treatment.

In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 µM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.