Growth inhibition and apoptosis of human multiple myeloma cells induced by 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid derivatives.

Multiple myeloma is a blood cell cancer and can cause symptoms such as bone loss and fatigue. Recent studies have shown that the bone marrow microenvironment may mediate tumor proliferation, drug resistance, and migration of the multiple myeloma cells. Synthetic triterpenoids have been used for the treatment of cancer due to their antiproliferative and anti-inflammatory effects. The objective of this study is to examine the effect of 2-cyano-3, 12 dioxoolean-1,9-dien-28-oic acid (CDDO) derivatives on human multiple myeloma cells. Three CDDO derivatives, such as CDDO-methyl ester, CDDO-trifluroethyl amide, and CDDO-imidazolide (Im), were tested on the growth of human multiple myeloma cells. Our results show that all CDDO derivatives decrease the viability of multiple myeloma cells in a dose- and time-dependent manner, with CDDO-Im being the most potent. CDDO-Im was selected to investigate whether its inhibitory effect on multiple myeloma cell growth is due to cell cycle arrest and induction of apoptosis. The results suggest that CDDO-Im may inhibit cell cycle progression in the G0/G1 phase and induce the intrinsic apoptotic pathway. The effect of CDDO-Im on multiple myeloma cells was evaluated in a Transwell model using myeloma cells co-culturing with human HS-5 stromal cells to simulate the bone marrow microenvironment in vitro. The results showed that CDDO-Im induced multiple myeloma cell apoptosis in the presence of HS-5 cells, albeit to a lower extent than in multiple myeloma cells cultured alone. In conclusion, our data suggest that CDDO-Im inhibits the growth of multiple myeloma cells, either cultured alone or co-cultured with bone marrow stromal cells, through the induction of apoptosis.

Arresting post-partum hemorrhage using the novel trans-vaginal uterine artery clamp.

OBJECTIVES: Post-partum hemorrhage (PPH) continues to be the leading cause of maternal mortality in low-resource settings. The commonest variant - Atonic PPH, is managed by additional pharmacological measures which may fail. Additional surgical interventions for hemostasis take time and are not universally available. Immediate arrest of bleeding was deemed essential and a novel Transvaginal Uterine Artery Clamp (TVUAC) was explored for its effectiveness in achieving immediate hemostasis in atonic and mixed post-partum hemorrhage. STUDY DESIGN: A retrospective chart review was performed for all patients, who underwent vaginal delivery and developed immediate post-partum atonic PPH, in a tertiary care center in South India, between 1st April 2015 and 31st December 2020. As soon as excess bleeding was observed, two TVUACs were applied trans-vaginally at 3' and 9'o clock position of the cervix to occlude the uterine arteries where it joins the isthmus of the uterus. RESULTS: Of 3999 vaginal deliveries, there were 251 patients who developed primary atonic PPH during the study period, of which 89 were managed by medical measures alone. Out of the remaining 162 patients, in 153 (94.4%) TVUAC helped to achieve hemostasis; with TVUAC alone in 120 patients (78.43%) and with an additional second line surgical intervention in 33 patients. In nine patients, TVUAC was not readily available and hence second line interventions alone were used. None required any third line surgical interventions (laparotomies) for hemostasis nor were there any incident of maternal mortality or consumptive coagulopathy. TVUAC was applied for a mean duration of 25 ± 10 min. Only 11.6% (29/251, 95% C.I 7.9-16.1%) of the patients required a blood transfusion with a median of 2 (1-4) units of packed RBC. No procedure related complications were reported up to a scheduled 6th week in-person follow-up. CONCLUSION: The novel TVUAC shows potential in limiting third line interventions, maternal morbidity and mortality. Its effectiveness and safety may be further explored as a first line surgical adjunct to medical measures, in PPH protocols in low-resource settings.

Managing placenta accreta spectrum in low-resource settings using a novel dissection-free aorta clamp: Operative technique.

OBJECTIVE: Surgical management of Placenta accreta spectrum (PAS) is associated with profuse bleeding and increased risk of operative injury to the adherent pelvic structures. We propose using a novel aorta clamp that can occlude the abdominal aorta without retroperitoneal dissection, thereby making it easy for an obstetrician-gynecologist to use it. The novel Paily aorta clamp (PAC) is applied just above the bifurcation of the abdominal aorta. METHODS: This was a retrospective study of 33 women with varying grades of histopathology-confirmed PAS, who were managed as an elective or emergency procedure in a tertiary center in India. RESULTS: Twenty-nine women with advanced grades of PAS underwent sub-total/total hysterectomies, while four women with low-grade PAS underwent a conservative procedure. The procedures were associated with median estimated intra-operative blood loss of 1000 ± 1500 ml, with only 21.2% (n = 7) requiring a transfusion of four or more units packed red blood cells. PAC was applied for a median of 55 ± 20 min and was not associated with any perioperative aortic wall injury or distal thromboembolic phenomenon. CONCLUSION: Our experience using the novel PAC, in the current series and across multiple centers in India, demonstrates that the sizeable abdominal aorta can be clamped safely and effectively without retroperitoneal dissection-with no incidence of vascular injury so far. However, we would urge only designated centers with experienced obstetrician-gynecologists-backed by a urologist, adequate blood bank and intensive care facilities-to tackle PAS procedures using the PAC technique.