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Up to 50 % of dairy cows fail to resolve uterine involution and develop chronic clinical (CE) or subclinical endometritis (SE) 21 days after calving. Clinical endometritis is associated with purulent discharge, while SE is not associated with overt clinical signs. Along with numerous knowledge gaps related to its pathogenesis, SE does not allow for a straightforward and effective therapy. Therefore, it is crucial to unravel differences in the expression of genes among healthy, CE, and SE cows. This might contribute to the discovery of new drug candidates and, in consequence, a potentially effective treatment. In the present study, cows between 21 and 28 days postpartum (PP) were examined using vaginoscopy for the presence of vaginal discharge and endometrial cytology for the determination of the endometrial polymorphonuclear cell (PMN) percentage. Next, an endometrial biopsy sample was taken to investigate the expression of 13 selected candidate genes by qPCR. Uterine health status was assigned to healthy (absence of abnormal vaginal discharge and ≤5 % PMN, n = 13), SE (absence of abnormal vaginal discharge and >5 % PMN, n = 30), and CE (mucopurulent or purulent vaginal discharge and >5 % PMN, n = 9). At the same time, a blood sample was collected to assess serum progesterone concentration and to categorize cows as low (≤1 ng/mL) or high (>1 ng/mL) in progesterone. High expression of IL1B, IL6, IL17A, CXCL8, PTGES, PTGS1, PTGS2, and INHBA genes and low expression of FST was noted in the endometrium of CE compared to healthy cows. Increased endometrial INHBA expression was observed in both SE and CE compared to healthy cows. Interestingly, greater expression of PTGES and PRXL2B genes and lower expression of PTGS2 were characteristic of SE versus CE or healthy. Among cows with no overt clinical symptoms of uterine disease (healthy and SE), the endometrial expression of IL1 B, CXCL8, and PTGES was greater in cows with high versus low serum progesterone. Several genes were differentially expressed among healthy, SE, and CE cows indicating different pathways for the development of different uterine diseases. In conclusion, we found progesterone-independent SE markers, which suggests that low endometrial PTGS2 expression may be indicative of an inadequate immune response and thus contribute to the pathogenesis of SE. • Progesterone concentration did not affect mRNA expression of INHBA, FST, or INHA. • INHBA, POSTN, and FST may play significant roles in endometrial inflammation. • Cytokine expression (IL1B, IL6, IL17A, CXCL8) was upregulated in cows with CE compared to SE. [ABSTRACT FROM AUTHOR]

Abstract: Background and purpose: High dose rate (HDR) brachytherapy is a clinically used procedure in prostate cancer treatment. The purpose of this study was to present the influence of using different optimization algorithms in 3D-CBRT planning on the treatment plan quality. Materials and methods: Treatment plans were calculated for 15 patients – three plans for each patient using: geometrical optimization (GO), inverse optimization (IO) and blind inverse optimization (BIO). For each patient, PTV and OAR volumes, number of needles and geometry of the implant were set equal. Differences between dose distributions were tracked using: D90, V100, V200, Dmax (for prostate); D10, Dmax (for urethra); D10, V100, Dmax (for rectum). Results: The analysis of mean values of D90 and V100 in the prostate showed that inverse algorithms gave the best results (mean D90 was 12.1% for BIO and 9.3% for IO better than for GO, mean V100 was 8.2% for BIO and 6.3% for IO better than for GO). From a clinical point of view, GO diminished the doses in the PTV and urethra in all analyzed parameters. The lowest mean doses in the rectum were achieved for plans optimized with IO and BIO (mean D10: 61.2% for GO, 58.1% for IO, 58.0% for BIO; mean Dmax: 92.8% for GO, 85.1% for IO, 83.6% for BIO). Conclusions: Application of the blind inverse optimization (BIO) algorithm led to clinically best dose parameters for PTV and the rectum. Use of geometrical optimization (GO) led to smaller doses in the urethra, which was however associated with a certain dose decrease also in PTV. [Copyright &y& Elsevier]

Contact brachytherapy for non-melanoma skin cancers demonstrates very good treatment results. The main problem is to fit properly a standard applicator to a heavily pleated surface, such as the nasal or orbital region. In order to improve the reproducibility and quality of dose distributions, we have introduced individual custom-designed applicators manufactured on a 3D printer. The purpose of this study was to verify the effect of changing the contoured CTV volume between the pre-plan and the therapeutic plan. For the study, 95 consecutive treatment plans were qualified for patients treated between 2021 and 2023 with individual contact applicators for skin brachytherapy. After the qualification, on the first visit in brachytherapy department, the patient had fiducial radiological markers surrounding the skin lesion placed and the CT scan performed. On the images, the physician contoured the volume of the CTV and critical organs. Based on the CT images and contours, medical physicist prepared the body of the applicator, the position of the catheters and the optimal source dwell positions in treatment planning system. The proposed dose distribution was consulted with the physician for verification. After approval, the DICOM files were exported to software converting DICOM files to printable stl files and the applicator was printed. At the next visit, the patient was CT scanned with the applicator in place and a treatment plan was prepared, based on the recontoured CTV and critical organs. We compared CTV volume values and dose distribution values in reconstructed critical organs and CTV for the pre-plan and approved treatment plan. We considered CTV volume, V100, V150 and D90. For OARs we compared doses in 0.1, 1 and 2 ccm. Since the parameters studied did not show conformity to the normal distribution (the Shapiro-Wilk test was used) we applied the Wilcoxon signed-rank test. The compared parameters for the evaluation of the treatment plan appeared to be consistent with each other within the limits assumed for the tests performed (α=0.05), except for the maximum doses in the lenses. The doses in 0.1 cc of lens in the realized plans were found to be statistically significantly lower than in the plans created at the time of applicator design. Left lens pre-plan D0.1 = 12.86% vs 11.48% (p=0,005441) in treatment plan, right lens pre-plan D.01 = 9.67% vs 8.02% (p=0,005694) in treatment plan. During the preparation of the final treatment plans, physicists suspected physicians to contour larger CTV volumes than during the pre-plan and the applicator design. A surprising result of this study was that although not statistically significant but the mean CTV volume in the pre-plan was higher than in the contour made for the final treatment plan (1.69 ccm vs. 1.61 ccm). The main investigator thought before performing the statistics that the relationship would be the opposite. Treatment plans prepared for delivering skin brachytherapy using personalized applicators manufactured with 3D printing were not statistically different from those prepared during applicator design. Only the maximum doses deposited in the lenses were statistically lower in the treatment plans finally accepted for irradiation than in the pre-plans. Recontouring of the CTV and critical organs did not affect the dose distributions during the preparation of the final plan, which indicates that the individual applicators prepared on the 3D printer were properly fitted to the patient's body surface. [ABSTRACT FROM AUTHOR]

The aim of this work was to analyze the results of palliative HDR brachytherapy in patients with advanced esophageal cancer.Ninety-one patients with unresectable, advanced esophageal cancer were treated palliatively by HDR brachytherapy. All patients received a total dose of 22.5 Gy in three fractions per week. Remissions of dysphagia and other clinical and radiological factors were assessed in the first month posttreatment, and then in the third, sixth, and twelfth months. The survival rate was compared with some chosen clinical factors using a log-rank test and the Kaplan–Meier method.The median survival time among all patients was 8.2 months. The median survival time according to the obtained remission was 14.6, 7.2, and 3.8 months (log-rank p=00001, F Cox p=0.00001) for complete remission (CR), partial remission (PR), and lack of remission (NR), respectively. A longer median survival time was observed when tumor size was less then 5 cm (12.1 months), than between 5 and 10 cm (7.8 months), or longer than 10 cm (6.4 months) (log-rank p=0.002). Longer median survival times were observed in clinical stage II (14.1 months), compared with clinical stage III (7.7 months) and IV (7.2 months) (log-rank p=0.01). Significant correlations were found between survival and the Karnofsky Performance Status, grade of dysphagia, and age.HDR brachytherapy for advanced esophageal cancer allowed for improvement of dysphagia in most patients. The complete or partial remission, the older age of patients, and the lower grade of dysphagia observed in first month posttreatment were the most important prognostic factors allowing for prolonged survival (confirmed by a multivariate analysis). In the univariate analysis, important prognostic factors for prolonged survival were: a higher Karnofsky Performance Status, a lower clinical stage and a small tumor size. [Copyright &y& Elsevier]