Magnetic resonance imaging-based radiomics nomogram for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer.

PURPOSE: The aim of this study was to assess the potential application of a radiomics features-based nomogram for predicting therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa). METHODS: Clinicopathologic information was retrospectively collected from 162 patients with high-risk non-metastatic PCa receiving NCHT and radical prostatectomy at our center. The postoperative pathological findings were used as the gold standard for evaluating the efficacy of NCHT. The least absolute shrinkage and selection operator (LASSO) was conducted to develop radiomics signature. Multivariate logistic regression analyses were conducted to identify the predictors of a positive pathological response to NCHT, and a nomogram was constructed based on these predictors. RESULTS: Sixty-three patients (38.89%) experienced positive pathological response to NCHT. Receiver operating characteristic analyses showed that the area under the curve (AUC) of periprostatic fat (PPF) radiomics signature was 0.835 (95% CI, 0.754-0.898), while the AUC of intratumoral radiomics signature was 0.822 (95% CI, 0.739-0.888). Multivariate logistic regression analysis revealed that PSA level, PPF radiomics signature and intratumoral radiomics signature were independent predictors of positive pathological response. A nomogram based on these three predictors was constructed. The AUC was 0.908 (95% CI, 0.839-0.954). The Hosmer-Lemeshow goodness-of-fit test showed that the nomogram was well calibrated. Decision curve analysis revealed the favorable clinical practicability of the nomogram. The nomogram was successfully validated in the validation cohort. Kaplan-Meier analyses showed that nomogram and positive pathological response were significantly related with survival of PCa. CONCLUSION: The radiomics-clinical nomogram based on mpMRI radiomics features exhibited superior predictive ability for positive pathological response to NCHT in high-risk non-metastatic PCa.

Investigating the Association Between Type 2 Diabetes Mellitus and Pathological Responses Among Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

INTRODUCTION: The relationship between type 2 diabetes mellitus (T2DM) and pathological responses after neoadjuvant chemotherapy (NACT) is controversial. In this study, we aim to determine the association of pathological responses in breast cancer women with T2DM after receiving NACT. METHODS: Medical records of breast cancer women with T2DM who received NACT from January 2016 to January 2021 at the medical center in the Gujranwala Institute of Nuclear Medicine and Radiotherapy, Pakistan, were identified and retrieved retrospectively. Variables, including pathological responses, diabetes status, and other clinical data, were collected. Patients were grouped as diabetic and nondiabetic based on the doctor's diagnosis or the diabetic's medication history recorded upon the breast cancer diagnosis. Factors influencing the pathological complete response (pCR) were determined using multivariate logistic regression utilizing IBM SPSS Statistics (version 20). RESULTS: A total of 1372 patient files who received NACT and breast cancer surgery from January 2016 to January 2021 were selected. Out of 1372 breast cancer women receiving NACT, 345 (25.1%) had pre-existing diabetes, while 1027 (74.85%) were without pre-existing diabetes. The most common molecular subtypes of breast cancer were luminal A and B. Two hundred fifty-eight patients (18.8%) had a pCR after receiving NACT. The pCR in diabetic patients was 3.9%, and in nondiabetes, 14.9%. Most women had a pathological partial response (pPR) after the NACT 672 (48.9%). The pPR in diabetic patients was 11.0%, and in nondiabetic patients, it was 38.0%. In nondiabetics, the odds of achieving pPR increase more than pathological no response after the NACT with odd ratio: 1.71 (95% confidence interval: 1.24-2.37). The probability of pCR in patients with luminal B was 1.67 times higher than that in patients with triple-negative breast cancer with odd ratio: 1.67, 95% confidence interval (1.00-2.79), P = 0.05. CONCLUSIONS: The results of the study show that T2DM may have an adverse impact on pCR and pPR following NACT and surgery. Further investigation is needed to explore how changes in blood glucose levels over time impact pathological responses.

Pathological Responses in Asian House Shrews (Suncus murinus) to the Naturally Acquired Orientia tsutsugamushi Infection.

Scrub typhus is a re-emerging disease caused by Orientia tsutsugamushi, transmitted by mites belonging to the family Trombiculidae. Humans and rodents acquire the infection by the bite of larval mites/chiggers. Suncus murinus, the Asian house shrew, has been reported to harbor the vector mites and has been naturally infected with O. tsutsugamushi. The present study aimed to localize and record O. tsutsugamushi in the tissues and the host response in shrews naturally infected with O. tsutsugamushi. Sheehan's modified May-Grunwald Giemsa staining was carried out in 365 tissues from 87 animals, and rickettsiae were documented in 87 tissues from 20 animals. Immunohistochemical (IHC) staining, using polyclonal antibodies raised against selected epitopes of the 56-kDa antigen, was carried out, and 81/87 tissue sections were tested positive for O. tsutsugamushi. By IHC, in addition to the endothelium, the pathogen was also demonstrated by IHC in cardiomyocytes, the bronchiolar epithelium, stroma of the lungs, hepatocytes, the bile duct epithelium, the epithelium and goblet cells of intestine, the tubular epithelium of the kidney, and splenic macrophages. Furthermore, the pathogen was confirmed by real-time PCR using blood (n = 20) and tissues (n = 81) of the IHC-positive animals. None of the blood samples and only 22 out of 81 IHC-positive tissues were tested positive by PCR. By nucleotide sequencing of the 56-kDa gene, Gilliam and Karp strains were found circulating among these animals. Although these bacterial strains are highly virulent and cause a wide range of pathological alterations, hence exploring their adaptive mechanisms of survival in shrews will be of significance. Given that the pathogen localizes in various organs following a transient bacteremia, we recommend the inclusion of tissues from the heart, lung, intestine, and kidney of reservoir animals, in addition to blood samples, for future molecular surveillance of scrub typhus.

Genitourinary cancer neoadjuvant therapies: current and future approaches.

Neoadjuvant therapies can improve tolerability, reduce tumor volume to facilitate surgery, and assess subsequent treatment response. Therefore, there is much enthusiasm for expanding the benefits of cancer therapies to the neoadjuvant setting to reduce recurrence and improve survival in patients with localized or locally advanced genitourinary (GU) cancer. This approach is clinically pertinent because these treatments are administered primarily to treatment-naive patients and can elicit the greatest drug response. In addition, the results are not impacted by other anticancer treatments. While neoadjuvant therapies have been the standard treatment for bladder cancer in the past, they are presently restricted to clinical trials for renal and prostate cancer (PCa); however, changes are imminent. Precision neoadjuvant therapies will be ushered in by biomarker-stratified neoadjuvant trials with appropriate survival endpoints and comprehensive correlative and imaging studies. This review discusses neoadjuvant studies in GU malignancies and how they inform future study design considerations.

Head-to-head comparisons of [68Ga]Ga-PSMA-11 PET/CT, multiparametric MRI, and prostate-specific antigen for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer patients: a prospective study.

PURPOSE: The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa. METHODS: This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters. RESULTS: All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT. CONCLUSIONS: [68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.

MicroRNAs Involved in Oxidative Stress Processes Regulating Physiological and Pathological Responses.

Oxidative stress influences several physiological and pathological cellular events, including cell differentiation, excessive growth, proliferation, apoptosis, and inflammatory response. Therefore, oxidative stress is involved in the pathogenesis of various diseases, including pulmonary fibrosis, epilepsy, hypertension, atherosclerosis, Parkinson's disease, cardiovascular disease, and Alzheimer's disease. Recent studies have shown that several microRNAs (miRNAs) are involved in the development of various diseases caused by oxidative stress and that miRNAs may be useful to determine the inflammatory characteristics of immune responses during infection and disease. In this review, we describe the known effects of miRNAs on reactive oxygen species to induce oxidative stress and miRNA regulatory mechanisms involved in the uncoupling of Keap1-Nrf2 complexes. Finally, we summarized the functions of miRNAs in several antioxidant genes. Understanding the crosstalk between miRNAs and oxidative stress-inducing factors during physiological and pathological cellular events may have implications for the design of more effective treatments for immune diseases.

Comparisons of Pathological Responses in Carrot to Root-knot Nematodes.

Carrot (Dacus carota var. sativus) is one of the top-ten most economically important vegetable crops produced worldwide, and the root-knot nematodes, Meloidogyne spp., are one of the most important pests in the carrot. In Korea, M. hapla and M. incognita are presumed to be the major root-knot nematodes distributing mostly in open carrot fields and greenhouses, respectively. In our study, currently-developed and commercial carrot cultivars and the parental lines were examined for their pathological responses to M. incognita and M. hapla 7 weeks after inoculation with about 1,000 second-stage juveniles (J2) of the nematodes. All the carrot cultivars and lines showed susceptible responses to both nematodes with the gall index (GI) of 2.4-4.4, which were always higher on the carrot plants infected with M. incognita than M. hapla. Gall sizes were remarkably larger with more serious reduction of the root growths in the plants infected with M. incognita than M. hapla, suggesting the carrot lines examined in our study were more susceptible to the former than the latter. In the infection sites of the root tissues, giant cells were more extensively formed, occupying larger stellar regions with the prominent destruction of adjacent xylem vessels by M. incognita than M. hapla. All of these results suggest M. incognita affect more seriously on the carrot plants that are grown in greenhouses, compared to M. hapla that has a major distribution in open carrot fields, which would be used for determining cropping systems based on target nematode species, their damage and pathological characteristics.