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1.
Effect and Safety of Diluted Vasopressin Injection for Bleeding Control During Robot-assisted Laparoscopic Myomectomy in Reproductive Women With Uterine Fibroids: A Randomized Controlled Pilot Trial (VALENTINE Trial)
Park, S. J., Lee, J. W., Hwang, D. W., Lee, S., Yim, G. W., Song, G., Lee, E. J., Kim, H. S.
In vivo (Athens, Greece). 2024;38(1):431-436
Abstract
BACKGROUND/AIM: Vasopressin injected during myomectomy is known to effectively reduce bleeding but is sometimes associated with intraoperative vasoconstriction and hypertension due to systemic absorption. Although there is a growing preference for the use of diluted vasopressin, evidence of its effect and safety is still lacking. PATIENTS AND METHODS We performed a randomized controlled pilot trial to evaluate the effect and safety of vasopressin diluted in a constant volume during robot-assisted laparoscopic myomectomy (RALM), where a total of 39 women with uterine fibroids were randomly assigned into the following three groups (group 1, 0.2 IU/ml; group 2, 0.1 IU/ml; group 3, 0.05 IU/ml with a total of 100 ml of normal saline). The primary endpoint was to compare estimated blood loss (EBL), and the secondary endpoints were to compare postoperative value and drop ratio of hemoglobin, operation time, transfusion, hospitalization, and complications among the three groups. RESULTS There were no differences in the number and largest size of uterine fibroids, total weight of uterine fibroids, console time, and volumes of intravenous fluid administered during RALM among the three groups, whereas combined operation was performed more commonly in group 2 than in groups 1 and 3 (53.9% vs. 0 to 7.7%; p=0.01). The primary and secondary endpoints were also not different among the three groups. However, two patients in group 1 (15.4%) showed vasopressin-related hypertension. CONCLUSION Vasopressin diluted in a volume of 100 ml showed an effective hemostatic effect and safety during RALM (Trial No. NCT04874246 in ClinicalTrial.gov).
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2.
Hemodynamic Effects of Oxytocin and Carbetocin During Elective Cesarean Section in Preeclamptic Patients Under Spinal Anesthesia: A Randomized Double-blind Controlled Study
Bahr, M. H., Abdelaal Ahmed Mahmoud, M. Alkhatip A., Ahmed, A. G., Elgamel, A. F., Abdelkader, M., Hussein, H. A.
Anesthesiology and pain medicine. 2023;13(1):e128782
Abstract
BACKGROUND Oxytocin and carbetocin are uterotonic medications that are used to decrease postpartum hemorrhage (PPH). However, there are not enough clinical data about the hemodynamic side effects of carbetocin. OBJECTIVES This study aimed to compare carbetocin and oxytocin hemodynamic effects in preeclamptic patients undergoing elective cesarean section under spinal anesthesia. METHODS In this double-blind, randomized controlled trial, intravenous oxytocin or carbetocin was administered to 80 women (40 per group). The hemodynamic effects, such as blood pressure (BP), heart rate (HR), and oxygen (O(2)) saturation, were measured before the operation and after 1, 5, 10, and 15 minutes of the administration of both drugs. Intragroup and intergroup comparisons were conducted during statistical analysis. RESULTS Based on the intragroup comparison, there was a significant increase in HR and a reduction in BP from baseline to all intervals after the administration of both interventions. Moreover, based on the intergroup comparison, there was a significantly more increase in HR and a decline in BP and O(2) saturation in the oxytocin group than in the carbetocin group. There were three and seven cases that required another dose of carbetocin and oxytocin, respectively. Moreover, one case developed PPH in the carbetocin group; nevertheless, two cases developed PPH in the oxytocin group. CONCLUSIONS The minimal effect of carbetocin on patients' hemodynamics suggests extending the use of this drug instead of oxytocin as a uterotonic drug in patients with preeclampsia, hemorrhagic risk factors, and/or hypertension.
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3.
A Comparative Study of the Efficacy of Intraoperative Intravenous Oxytocin and Intramuscular Oxytocin Versus Conventional Intramuscular Oxytocin for Third-Stage Labour in Elective Cesarean Section
Behuria S, Sahu M, Mohanty M, Behera S, Mohapatra K, Patnaik R, Jena S
Cureus. 2023;15(2):e35026
Abstract
Objective To study the efficacy of intraoperative IV oxytocin and intramuscular (IM) oxytocin versus conventional intramuscular oxytocin alone for active management of the third stage of labor in lower segment cesarean section (CS). The study was performed to determine the effect of 5 IU (International Unit) oxytocin infusion at the time of skin incision and that of 10 IU IM oxytocin infusion after delivery in reducing blood loss during and after CS, in comparison with the effect of administrating conventional 10 IU IM oxytocin in the same time period. In addition, it assessed the ability of the IV+IM oxytocin group to reduce the need for additional uterotonic as well as its safety determination and postoperative blood transfusion in CS. Materials and methods It is a randomized control study. The effect of 5 IU of oxytocin infusion at the time of skin incision and 10 IU of IM oxytocin (IV+IM) in reducing blood loss during and after the CS was compared to conventional 10 IU IM oxytocin. Results The study showed that the IV+IM group had a mean blood loss of 316.5 ± 74.36 ml, while the IM group had a mean loss of 403.90 ± 107.2 ml (p-value < 0.001) from placental delivery to the end of CS. A total of 90% of the patients in the IV+IM group had blood loss <50 ml compared to 95% of patients in the IM group who had a blood loss between 50 and 100 ml range from the end of cesarean to two hours postpartum. When total blood loss was compared in both groups, 84% of patients had a blood loss between 300 and 400 ml, compared to 81% of the patients in the IM group who had blood loss of 400-500 ml. Total blood loss in the IM group was 483.20 ± 115.86 ml, which was significantly higher compared to the IV group, 362.60 ± 78.07 ml (p-value=<0.001). Conclusion 5IU oxytocin infusion at the time of skin incision and 10 IU IM oxytocin after delivery of the baby significantly reduced the amount of blood loss, need for blood transfusion, and additional uterotonics during and after lower segment CS.
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4.
Treatment of unfavorable bleeding patterns in contraceptive implant users: a randomized clinical trial of curcumin
Edelman A, Boniface E, Schrote K, Messerle-Forbes M, O'Donnell A, Jensen JT, Han L
American journal of obstetrics and gynecology. 2023
Abstract
BACKGROUND Some users of the etonogestrel contraceptive implant experience bothersome bleeding which can reduce contraceptive satisfaction and continuation. Few strategies exist to manage this bleeding. The exact mechanism of progestin-induced bleeding is unknown but it is likely multi-factorial (e.g. impaired angiogenesis, 'leaky' fragile vasculature, and inflammation). Curcumin, the active ingredient in turmeric, has anti-inflammatory, anti-proliferative, and anti-angiogenic proprieties which may make it a useful agent for implant-associated bothersome bleeding. OBJECTIVE To evaluate whether curcumin decreases frequent or prolonged bleeding or spotting in contraceptive implant users. STUDY DESIGN The study was a randomized, double blind, placebo-controlled trial. We enrolled etonogestrel implant users with frequent or prolonged bleeding or spotting and randomized them to either 600 mg Theracumin HP (Immunovites, Las Vegas, NV) or placebo daily for 30 days. We defined "frequent" as two or more independent bleeding or spotting episodes and "prolonged" as 7 or more consecutive days of bleeding or spotting in a 30-day interval. Implant use was confirmed by clinical exam as well as a negative gonorrhea/chlamydia and pregnancy test. Enrolled participants initiated study treatmentfollowing three consecutive days of bleeding or spotting; if no bleeding or spotting occurred within 30-days of enrollment, subjects were withdrawn from the study. Study treatments were encapsulated to maintain a similar appearance. Participants used text messages to record daily bleeding patterns and study drug compliance. We defined bleeding as a day that required the use of protection with a pad, tampon, or liner, and spotting as a day with minimal blood loss that did not require the use of any protection. Our primary outcome was the total number of days without bleeding or spotting during the 30 days of study drug or placebo exposure. Secondary outcomes including total number of bleeding-free days, bleeding episodes, and satisfaction. A sample size of 22 per group provided 80% power at an alpha 0.05 to demonstrate a 6-day difference between groups. RESULTS From February 2021 to November 2022, 58 individuals enrolled in the study with 93% (n=54) completing 30 days of treatment (curcumin 26, placebo 28). One individual in the curcumin arm did not experience a qualifying bleeding event and thus never initiated treatment and, per protocol, was withdrawn from the study. Participant characteristics did not differ between groups including length of implant use at study enrollment [placebo: 521 days (SD 305), curcumin 419 days (SD 264)]. Study groups did not differ in regard to any bleeding-related outcome [mean days without bleeding or spotting: curcumin 16.7 (SD 6.9), placebo 17.5 (SD 4.8), p = 0.62; mean bleeding-free days: curcumin 23.4 (SD 4.9), placebo 22.4 (SD 4.5), p = 0.44; bleeding episodes: curcumin 2.0 (SD 0.8), placebo 2.1 (SD 0.8), p = 0.63]. Satisfaction with the implant as contraception and acceptability of bleeding over the study period also did not differ by study group (p = 0.54 and p = 0.30, respectively). CONCLUSION Daily use of curcumin did not improve bleeding patterns in users of the etonorgestrel contraceptive implant experiencing frequent or prolonged bleeding patterns.
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5.
Evaluation of collagen turnover biomarkers as an objective measure for efficacy of treatment with rurioctocog alfa pegol in Hemophilia A patients: a secondary analysis of a randomized controlled trial
Manon-Jensen, T., Tangada, S., Bager, C., Chowdary, P., Klamroth, R., von Drygalski, A., Windyga, J., Escobar, M., Frederiksen, P., Engl, W., et al
Journal of thrombosis and haemostasis : JTH. 2023
Abstract
BACKGROUND Hemophilia patients with recurrent hemarthroses develop hemophilic arthropathy (HA). Regular prophylaxis with factor VIII (FVIII) can reduce HA, but there is a need for objective outcome measures to evaluate treatment efficacy. METHODS Joint remodeling was assessed by analyzing serum levels of collagen remodeling products at baseline and months 3, 6, 9, and 12 in a 98 patient subset receiving pharmacokinetics-guided prophylaxis with rurioctocog alfa pegol, targeting FVIII trough levels of 1-3 IU/dL or 8-12 IU/dL (PROPEL study, NCT0285960). RESULTS Basement membrane metabolism-related type 4 collagen remodeling products (C4M and PRO-C4) decreased after 3 months at all time points by up to 25% at 1-3 IU/dL (p=.049, p<.0001) and 8-12 IU/dL FVIII trough levels (p=.0002, p<.0001). Interstitial tissue metabolism-related type 3 (C3M) and 5 (PRO-C5) collagen remodeling products decreased after 3 months, by up to 19% at 1-3 IU/dL FVIII trough level (p=.0001, p=.009) and 23% at 8-12 IU/dL FVIII trough level (p=.0002, p=.001). An increase of up to 12% was seen for cartilage metabolism-related type 2 collagen product (PRO-C2, not C2M) after 6 months at both trough levels (p=.01, p=.005). When stratified by prior treatment, changes in C3M (p=.03) and C4M (p=.02) levels were observed between trough levels for prior on-demand treatment but not for prophylaxis prior to study entry. CONCLUSION Joint improvement measured by collagen remodelling biomarkers specific to the basement membrane, interstitial matrix, and cartilage was seen with pharmacokinetics-guided prophylaxis. These collagen remodeling biomarkers warrant further exploration as biomarkers to guide treatment toward improvement in HA.
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6.
The efficacy of three regimes of uterotonic agents for prevention of postpartum blood loss at undergoing cesarean section: a prospective randomized clinical trial
Çetin, Ç, Dural, H. R., Özcan, P., Tanoğlu, F. B., Kütük, M. S., Pasin, Ö, Ateş, S.
Ginekologia polska. 2023
Abstract
OBJECTIVES To compare the efficacy of three regimes of uterotonic agents on PPH in women undergoing cesarean section in our RCT. MATERIAL AND METHODS This study was a randomized controlled study (NCT05083910) performed at the Bezmialem Vakif University between July 2021 and January 2022. All women were randomly allocated into three groups: Group I (n = 52) - oxytocin only; Group II (n = 52) - the combination of oxytocin plus intrauterine misoprostol; Group III (n = 52) - carbetocin only. The primary outcome measures were: PPH to evaluate with the change between the concentrations of preoperative and postoperative hemoglobin, hematocrit and intraoperative blood loss. RESULTS The blood loss characteristics, including the change in hemoglobin and the change in hematocrit concentration, intraoperative blood loss, intraoperative additional hemostatic uterine sutures and the need for additional uterotonics, were lowest in group III, although all groups were comparable in terms of blood loss parameters. Group III had the highest blood loss ratio, exceeding 1000 mL. For the combination of oxytocin and intrauterine misoprostol, the ARR was 3.8% (95% CI 20.02-12.33), with a RR of 1.18 (95% CI 0.58-2.39) and a NNT of 26 (95% CI 8.1-4.9); for carbetocin, the ARR was 5.8% (95% CI 22.15-10.61), with a RR of 1.27 (95% CI 0.63-2.53) and a NNT of 17 (95% CI 9.41-4.51). CONCLUSIONS Our results demonstrate that carbetocin shows no superiority in the prevention of PPH in women undergoing cesarean section. Oxytocin still seems to be a highly effective alternative to prevent PPH.
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7.
Effect of intravenous low-dose norepinephrine on blood loss in non-tourniquet total knee arthroplasty under general anesthesia: a randomized, double-blind, controlled, single-center trial
Chen, S., Luo, F., Lin, Y., Yu, G., Luo, J., Xu, J.
Journal of orthopaedic surgery and research. 2023;18(1):933
Abstract
OBJECTIVE This prospective trial aimed to evaluate the effects of low-dose intravenous norepinephrine (NE) on intraoperative blood loss and bleeding from osteotomy sites during non-tourniquet total knee arthroplasty (TKA) under general anesthesia. METHODS A total of 120 patients who underwent TKA between December 2020 and May 2022 were enrolled and randomly assigned to the intravenous low-dose NE Group (NE Group) or the control group (C Group). During surgery, NE Group received 0.05-0.1 μg/(kg min) of NE intravenously to raise and maintain the patient's mean arterial pressure (MAP). C Group received the same dose of saline as placebo. Intraoperative blood loss, bleeding score at osteotomy sites, Δlactate levels (Lac), postoperative complications, and transfusion rate during hospitalization were compared between groups. RESULTS Intraoperative and osteotomy blood loss was significantly lower in the NE Group than in the C Group (P < 0.001). No significant difference was observed in ΔLac between groups (P > 0.05). There was no significant difference in complications between the groups 3 days after surgery (P > 0.05). In addition, there was no significant difference in blood transfusion rates between the two groups during hospitalization (P > 0.05). CONCLUSION In non-tourniquet TKA under general anesthesia, low-dose intravenous NE safely and effectively reduced intraoperative blood loss and provided a satisfactory osteotomy site while maintaining a higher MAP.
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8.
Rilzabrutinib versus placebo in adults and adolescents with persistent or chronic immune thrombocytopenia: LUNA 3 phase III study
Kuter, D. J., Bussel, J. B., Ghanima, W., Cooper, N., Gernsheimer, T., Lambert, M. P., Liebman, H. A., Tarantino, M. D., Lee, M., Guo, H., et al
Therapeutic advances in hematology. 2023;14:20406207231205431
Abstract
BACKGROUND Immune thrombocytopenia (ITP) is characterized by primarily autoantibody-mediated platelet destruction and impaired platelet production resulting in thrombocytopenia and an increased risk of bleeding. Other manifestations include increased risk of thrombosis and diminished quality of life. Current treatment approaches are directed toward lowering the rate of platelet destruction or stimulating platelet production to prevent bleeding. Rilzabrutinib is an oral, reversible, potent Bruton tyrosine kinase inhibitor that was specifically designed to treat immune-mediated diseases and mediates its therapeutic effect through a dual mechanism of action: (1) inhibiting B-cell activation and (2) interrupting antibody-coated cell phagocytosis by Fc gamma receptor in spleen and liver. A 24-week dose-finding phase I/II study of rilzabrutinib in patients with ITP showed a 40% platelet response (⩾2 consecutive platelet counts of ⩾50 × 10(9)/L and increase from baseline ⩾20 × 10(9)/L without rescue medication use) and a well-tolerated safety profile with only grade 1/2 transient adverse events across dose levels. OBJECTIVES Assess the efficacy and safety of oral rilzabrutinib in adult and adolescent patients with persistent or chronic ITP. DESIGN Rilzabrutinib 400 mg BID is being evaluated in the ongoing LUNA 3 multicenter, double-blind, placebo-controlled phase III study. METHODS AND ANALYSIS The primary endpoint is durable platelet response, defined as achieving platelet counts of ⩾50 × 10(9)/L for at least two-thirds of ⩾8 available weekly scheduled platelet measurements during the last 12 weeks (including ⩾2 available measurements within the last 6 weeks) of the 24-week blinded treatment period in the absence of rescue therapy. ETHICS Ethical guidelines and informed consent are followed. DISCUSSION The LUNA 3 trial will further investigate rilzabrutinib's safety and efficacy in adult and adolescent patients, with the primary goal of addressing a major objective in treating patients with ITP: durability of platelet response. TRAIL REGISTRATION ClinicalTrials.gov NCT04562766: https://clinicaltrials.gov/ct2/show/NCT04562766; EU Clinical Trials Register EudraCT 2020-002063-60: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-002063-60.
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9.
Low-Dose vasopressin and renal perfusion in pediatric cardiac surgery
Kumar, A., Ghotra, G. S., Raj, S., Tiwari, N., Ramamurthy, H. R.
Annals of cardiac anaesthesia. 2023;26(3):309-317
Abstract
BACKGROUND Congenital heart surgeries are associated with post-bypass renal and cardiac dysfunctions. The use of low-dose vasopressin has been found to be beneficial in adult cardiac surgeries. OBJECTIVE To assess the hemodynamic and renal effects of patients undergoing on-pump pediatric cardiac surgery under general anesthesia (GA) with low-dose vasopressin infusion. DESIGN Prospective randomized controlled study. SETTING Operation room and ICU, tertiary care teaching hospital. PATIENTS Fifty-five pediatric cardiac patients undergoing repair for congenital heart diseases (CHD). INTERVENTIONS Low-dose vasopressin infusion in the study group and placebo in the control group. MEASUREMENTS AND MAIN RESULTS Renal near-infrared spectroscopy (NIRS), serum NGAL, and inflammatory mediators-IL6 and IL8 along with other renal and hemodynamic parameters in the perioperative period were recorded. Diastolic blood pressure (DBP) and cardiac index were significantly higher in the vasopressin group. Inflammatory markers were significantly high in the immediate postoperative period in all patients which later stabilized in the next 48 h but showed similar trends in both groups. Low-dose vasopressin infusion did not improve either renal perfusion or function. The duration of mechanical ventilation and length of hospital stay, the incidence of AKI development, and transfusion requirements were marginally lower in the vasopressin group, although not significant. CONCLUSION Low-dose vasopressin infusion improved hemodynamics and showed a decreased incidence of complications. However, it failed to show any benefit of renal function and overall outcome in pediatric cardiac surgery.
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10.
Proton pump inhibitor has no effect in the prevention of post-endoscopic sphincterotomy delayed bleeding: a prospective randomized controlled trial
Yu, Z., He, J., Cao, R., Yang, Z., Li, B., Hong, J., Chen, Y., Zhu, L.
Frontiers in medicine. 2023;10:1179512
Abstract
BACKGROUND AND AIMS Bleeding is one of the common adverse events of endoscopic retrograde cholangiopancreatography (ERCP), which is mainly caused by endoscopic sphincterotomy (EST). At present, it remains unclear whether proton pump inhibitor (PPI) should be used to prevent post-EST bleeding. Therefore, we performed a randomized controlled trial to investigate whether PPI is effective in the prevention of post-EST delayed bleeding. METHODS Consecutive eligible patients were randomly assigned (1:1) to experimental group (PPI group) or control group (normal saline, NS group). The patients in PPI group received intravenous esomeprazole 40 mg and normal saline 100 mL every 12 h for 2 days after ERCP immediately, and followed by oral esomeprazole (Nexium) 20 mg once a day for 7 days. Correspondingly, patients in the control group received intravenous normal saline 100 mL and did not take PPIs or any acid-suppressing drugs during hospitalization and after discharge. All patients were followed up for 30 days after ERCP. The primary endpoint was the incidence and severity of post-EST delayed bleeding. RESULTS Between July 2020 and July 2022, 290 patients were randomly assigned to PPI group (n = 146) or NS group (n = 144). 5 patients from each group were excluded from the final analysis. There were 6 patients with post-EST delayed bleeding, with an incidence rate of 2.14%. The median time of delayed bleeding was 2.5 days after ERCP. 3 cases (2.12%, 3/141) occurred in the PPI group, with 1 case of mild and 2 cases of moderate bleeding. 3 cases (2.16%, 3/139) occurred in the NS group, with 2 cases of mild and 1 case of moderate bleeding. There was no significant difference in the incidence and the severity of post-EST delayed bleeding between the two groups (p = 1.000). CONCLUSION Prophylactic use of PPI after EST does not reduce the incidence and severity of post-EST delayed bleeding in patients. CLINICAL TRIAL REGISTRATION https://www.chictr.org.cn/searchproj.aspx, identifier ChiCTR2000034697.