Brachytherapy in gynecological malignancies at a tertiary care hospital: An analysis.

Purpose: Brachytherapy plays a crucial role in the standard of care for locally advanced gynecological malignancies. In this report, we present the experience from a tertiary teaching hospital, which is a referral center for image-guided brachytherapy (IGBT) in the management of locally advanced gynecological malignancies. Material and methods: This was a retrospective study of 130 patients referred to our hospital for IGBT after receiving initial external beam radiotherapy in their primary healthcare facilities, from January 2021 till January 2023. CT-based planning was done to delineate high-risk clinical target volume (HR-CTV). Dose of 6-7.5 Gy in 3-4 fractions was prescribed. Overall treatment time (OTT) was calculated, and patients were assessed for clinical response and toxicity after three months. Results: All patients received IGBT using an intra-cavitary or interstitial technique. The D90 HR-CTV mean EQD2 dose was 28.34 ±2.78 Gy. The mean EQD2 dose to 2 cc of the bladder, rectum, and sigmoid was 18.31 ±5.19 Gy, 14.14 ±5.76 Gy, and 17.43 ±4.75 Gy, respectively. The median interval time between the last fraction of external beam radiation therapy (EBRT) and first evaluation in the hospital was 19 (range, 13-28) days (interquartile range [IQR]). The median time between the completion of chemoradiation and brachytherapy procedure was 25 (range, 19-33) days (IQR). The mean overall treatment time (OTT) was 63.5 ±14.7 days. Conclusions: This study highlights the established advantages of image-guided interstitial brachytherapy and associated challenges. To optimize the overall treatment duration, it is imperative to prioritize and update the referral processes for brachytherapy centers.

Efficacy of desulfated heparin mitigating inflammation in rat burn wound model.

During skin repair, leukocyte infiltration is the principal inflammatory response which is instrumental in triggering growth factor and cytokine signals that orchestrate together to recruit cells necessary for healing. In severe wounds like burn, when acute inflammation becomes chronic, intervention is required to control inflammation so as to hasten the process of healing. Heparin, a known anticoagulant also possesses anti-inflammatory activity by its ability to interfere with the adhesion of leukocytes to the endothelium. Desulfated heparins (DSH) have subdued anticoagulant activity while possessing increased anti-inflammatory activity. Among which 2,3 DSH is found to have marked potency as an anti-inflammatory agent and has been utilized for this study. In this investigation, a controlled delivery system was designed by incorporating 2,3 DSH in microspheres and embedding in collagen matrix which could serve as a wound dressing in burns. In vivo evaluation of healing process was ascertained in rat burn wound model by qualitative and quantitative estimation of proinflammatory cytokines in serum and granulation tissue and collagen turnover was also assessed as healing progressed. The results of this study suggests that 2,3 DSH could be delivered in a controlled manner to regulate inflammatory events to hasten healing of burn wounds.

Controlled release of 2, 3 desulfated heparin exerts its anti-inflammatory activity by effectively inhibiting E-selectin.

Control of inflammation using appropriate anti-inflammatory agent prevents wound from becoming chronic. Heparin is a heterogeneous mixture of polysaccharide molecules with a mean molecular weight between 12-30 kDa containing 200-300 disaccharide units of glycosaminoglycan chains. Chemical modifications leading to generation of a unique pentasaccharide sequence effectively reduces its anticoagualant activity, while retaining its anti-inflammmatory property. In this study, Standard heparin was partially desulfated to 2, 3 desulfated heparin (2, 3 DSH) and its anti-inflammatory property was determined by assessing its ability to prevent static adhesion of leukocytes to endothelium and clotting assay. The effectiveness of 2, 3 DSH to down regulate E-selectin and key proinflammatory cytokines (IL-1beta and IL-6) was assessed by western blot and immunocytochemistry. These results were compared with commercially available 2-Desulfated Heparin (2DSH) and standard heparin (SH). Finally, a controlled delivery system of 2, 3 DSH was designed using chitosan microspheres and collagen as scaffold. Optimal loading of 2, 3 DSH was achieved and the release kinetics were tuned to follow a controlled release pattern. The steady state concentration of 2, 3 DSH was found to be optimal to elicit anti-inflammatory property and could achieve inhibition of E-selectin expression while unaffecting the normal clotting cascade.