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The New England Journal of Medicine Jul 2023Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle.
METHODS
We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle.
RESULTS
A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was detected in 93.1% of the patients in the intervention group and in 51.1% of those in the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28).
CONCLUSIONS
Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).
Topics: Female; Humans; Pregnancy; Early Diagnosis; Oxytocics; Postpartum Hemorrhage; Risk; Tranexamic Acid
PubMed: 37158447
DOI: 10.1056/NEJMoa2303966 -
American Journal of Obstetrics and... Mar 2024Oxytocin is a peptide hormone that plays a key role in regulating the female reproductive system, including during labor and lactation. It is produced primarily in the... (Review)
Review
Oxytocin is a peptide hormone that plays a key role in regulating the female reproductive system, including during labor and lactation. It is produced primarily in the hypothalamus and secreted by the posterior pituitary gland. Oxytocin can also be administered as a medication to initiate or augment uterine contractions. To study the effectiveness and safety of oxytocin, previous studies have randomized patients to low- and high-dose oxytocin infusion protocols either alone or as part of an active management of labor strategy along with other interventions. These randomized trials demonstrated that active management of labor and high-dose oxytocin regimens can shorten the length of labor and reduce the incidence of clinical chorioamnionitis. The safety of high-dose oxytocin regimens is also supported by no associated differences in fetal heart rate abnormalities, postpartum hemorrhage, low Apgar scores, neonatal intensive care unit admissions, and umbilical artery acidemia. Most studies reported no differences in the cesarean delivery rates with active management of labor or high-dose oxytocin regimens, thereby further validating its safety. Oxytocin does not have a predictable dose response, thus the pharmacologic effects and the amplitude and frequency of uterine contractions are used as physiological parameters for oxytocin infusion titration to achieve adequate contractions at appropriate intervals. Used in error, oxytocin can cause patient harm, highlighting the importance of precise administration using infusion pumps, institutional safety checklists, and trained nursing staff to closely monitor uterine activity and fetal heart rate changes. In this review, we summarize the physiology, pharmacology, infusion regimens, and associated risks of oxytocin.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Oxytocin; Oxytocics; Labor, Induced; Labor, Obstetric; Cesarean Section
PubMed: 37460365
DOI: 10.1016/j.ajog.2023.06.041 -
Anasthesiologie, Intensivmedizin,... Oct 2023Postpartum hemorrhage (PPH) affects about 4% of all deliveries in high-income countries and continues to rise, a trend attributable to the increase in caesarean section... (Review)
Review
Postpartum hemorrhage (PPH) affects about 4% of all deliveries in high-income countries and continues to rise, a trend attributable to the increase in caesarean section rates and maternal morbidity. Preventive measures such as the precautionary administration of uterotonics effectively reduce the risk of severe bleeding irrespective of birth mode. As a time-critical condition and a significant contributor to adverse maternal outcomes, PPH needs to be diagnosed early by measuring, not estimating, blood losses. Institutional treatment algorithms should be available to guide stage-based interdisciplinary management without delay. The main therapy goals are to identify the etiology and stop the bleeding by using uterotonics and mechanical and surgical interventions, to restore hemodynamic stability by volume and transfusion therapy and to optimize hemostasis by laboratory- and viscoelastic assay-guided factor replacement. This review highlights current recommendations for prevention, diagnosis and treatment of PPH.
Topics: Pregnancy; Female; Humans; Postpartum Hemorrhage; Oxytocics; Cesarean Section; Blood Transfusion
PubMed: 37832561
DOI: 10.1055/a-2043-4451 -
Journal of Biomedical Science Aug 2023Excess polymorphonuclear neutrophil (PMN) recruitment or excessive neutrophil extracellular trap (NET) formation can lead to the development of multiple organ...
BACKGROUND
Excess polymorphonuclear neutrophil (PMN) recruitment or excessive neutrophil extracellular trap (NET) formation can lead to the development of multiple organ dysfunction during sepsis. M2 macrophage-derived exosomes (M2-Exos) have exhibited anti-inflammatory activities in some inflammatory diseases to mediate organ functional protection, but their role in treating sepsis-related acute lung injury (ALI) remains unclear. In this study, we sought to investigate whether M2-Exos could prevent potentially deleterious inflammatory effects during sepsis-related ALI by modulating abnormal PMN behaviours.
METHODS
C57BL/6 wild-type mice were subjected to a caecal ligation and puncture (CLP) mouse model to mimic sepsis in vivo, and M2-Exos were administered intraperitoneally 1 h after CLP. H&E staining, immunofluorescence and immunohistochemistry were conducted to investigate lung tissue injury, PMN infiltration and NET formation in the lung. We further demonstrated the role of M2-Exos on PMN function and explored the potential mechanisms through an in vitro coculture experiment using PMNs isolated from both healthy volunteers and septic patients.
RESULTS
Here, we report that M2-Exos inhibited PMN migration and NET formation, alleviated lung injury and reduced mortality in a sepsis mouse model. In vitro, M2-Exos significantly decreased PMN migration and NET formation capacity, leading to lipid mediator class switching from proinflammatory leukotriene B4 (LTB4) to anti-inflammatory lipoxin A4 (LXA4) by upregulating 15-lipoxygenase (15-LO) expression in PMNs. Treatment with LXA4 receptor antagonist attenuated the effect of M2-Exos on PMNs and lung injury. Mechanistically, prostaglandin E2 (PGE2) enriched in M2-Exos was necessary to increase 15-LO expression in PMNs by functioning on the EP4 receptor, upregulate LXA4 production to downregulate chemokine (C-X-C motif) receptor 2 (CXCR2) and reactive oxygen species (ROS) expressions, and finally inhibit PMN function.
CONCLUSIONS
Our findings reveal a previously unknown role of M2-Exos in regulating PMN migration and NET formation through lipid mediator class switching, thus highlighting the potential application of M2-Exos in controlling PMN-mediated tissue injury in patients with sepsis.
Topics: Mice; Animals; Dinoprostone; Neutrophils; Neutrophil Infiltration; Extracellular Traps; Lung Injury; Immunoglobulin Class Switching; Mice, Inbred C57BL; Sepsis; Macrophages; Platelet Activating Factor
PubMed: 37533081
DOI: 10.1186/s12929-023-00957-9 -
Nature Jan 2024Oxytocin (OXT), a nine-amino-acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation and...
Oxytocin (OXT), a nine-amino-acid peptide produced in the hypothalamus and released by the posterior pituitary, has well-known actions in parturition, lactation and social behaviour, and has become an intriguing therapeutic target for conditions such as autism and schizophrenia. Exogenous OXT has also been shown to have effects on body weight, lipid levels and glucose homeostasis, suggesting that it may also have therapeutic potential for metabolic disease. It is unclear, however, whether endogenous OXT participates in metabolic homeostasis. Here we show that OXT is a critical regulator of adipose tissue lipolysis in both mice and humans. In addition, OXT serves to facilitate the ability of β-adrenergic agonists to fully promote lipolysis. Most surprisingly, the relevant source of OXT in these metabolic actions is a previously unidentified subpopulation of tyrosine hydroxylase-positive sympathetic neurons. Our data reveal that OXT from the peripheral nervous system is an endogenous regulator of adipose and systemic metabolism.
Topics: Animals; Humans; Mice; Adipose Tissue; Adrenergic beta-Agonists; Lipolysis; Neurons; Oxytocin; Tyrosine 3-Monooxygenase
PubMed: 38093006
DOI: 10.1038/s41586-023-06830-x -
Physiological Reviews Jul 2024Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this... (Review)
Review
Parturition is a complex physiological process that must occur in a reliable manner and at an appropriate gestation stage to ensure a healthy newborn and mother. To this end, hormones that affect the function of the gravid uterus, especially progesterone (P4), 17β-estradiol (E), oxytocin (OT), and prostaglandins (PGs), play pivotal roles. P4 via the nuclear P4 receptor (PR) promotes uterine quiescence and for most of pregnancy exerts a dominant block to labor. Loss of the P4 block to parturition in association with a gain in prolabor actions of E are key transitions in the hormonal cascade leading to parturition. P4 withdrawal can occur through various mechanisms depending on species and physiological context. Parturition in most species involves inflammation within the uterine tissues and especially at the maternal-fetal interface. Local PGs and other inflammatory mediators may initiate parturition by inducing P4 withdrawal. Withdrawal of the P4 block is coordinated with increased E actions to enhance uterotonic signals mediated by OT and PGs to promote uterine contractions, cervix softening, and membrane rupture, i.e., labor. This review examines recent advances in research to understand the hormonal control of parturition, with focus on the roles of P4, E, PGs, OT, inflammatory cytokines, and placental peptide hormones together with evolutionary biology of and implications for clinical management of human parturition.
Topics: Parturition; Humans; Female; Pregnancy; Animals; Progesterone; Oxytocin; Uterus; Prostaglandins; Estradiol
PubMed: 38329421
DOI: 10.1152/physrev.00019.2023 -
Psychoneuroendocrinology Dec 2023Oxytocin (OT) has been detected in various body fluids, including blood, urine, saliva, breastmilk, and spinal fluid. Consistent with models that regard skin as a social...
BACKGROUND
Oxytocin (OT) has been detected in various body fluids, including blood, urine, saliva, breastmilk, and spinal fluid. Consistent with models that regard skin as a social organ and in line with studies demonstrating that skin cells express both OT and its receptor, our study sought to examine the presence of OT in human sweat.
METHODS
Overall, 553 individuals participated in a pilot study and three experiments. Firstly, 50 participants provided sweat after engaging in various sports for different durations. Secondly, 26 participants provided sweat from forehead, upper-chest, forearm, and underarm, including 11 in natural setting and 15 following OT administration and a 30-minute exercise. Thirdly, of 435 volunteers, 97 provided sufficient axillary sweat for assaying. Of these, 84 participated in a naturalistic experiment that involved saliva and sweat collection in response to physical activity in either solitary or social settings. OT and testosterone (TS) were assayed in sweat and saliva.
RESULTS
Intense activity for at least 25 min was required to produce sufficient sweat for OT analysis. Highest OT levels were found in axillary sweat compared to sweat from the forehead, upper-chest, and forearm. Salivary OT and TS increased after both solitary and social physical activity; however, higher sweat OT was found after solitary sports. Post-hoc preliminary findings indicate that highly extroverted individuals exercising in solitary environments showed the highest sweat OT levels.
CONCLUSIONS
Findings demonstrate, for the first time, the presence of OT in human sweat and show the feasibility of its measurement. Much further research is required to illuminate how sweat OT is impacted by personality and social context and to uncover the role of the skin in OT production.
Topics: Humans; Oxytocin; Sweat; Pilot Projects; Saliva; Social Behavior; Testosterone
PubMed: 37797406
DOI: 10.1016/j.psyneuen.2023.106407 -
International Journal of Molecular... Aug 2023The involvement of prostaglandins in cancer was first observed in human esophageal carcinoma cells, whose invasive and metastatic potential in nude mice was found to be...
The involvement of prostaglandins in cancer was first observed in human esophageal carcinoma cells, whose invasive and metastatic potential in nude mice was found to be related to PGE and PGF production [...].
Topics: Animals; Mice; Humans; Mice, Nude; Prostaglandins; Dinoprostone; Cyclooxygenase 2; Cyclooxygenase 1; Esophageal Neoplasms
PubMed: 37569718
DOI: 10.3390/ijms241512342 -
Frontiers in Endocrinology 2023Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the or gene lead... (Review)
Review
Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the or gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels. The identification of the causative genes has provided a better understanding of the underlying mechanisms. PHO can be divided into three subtypes according to its pathogenic gene and inheritance patterns. The onset age, sex ratio and clinical features differ among subtypes. The synthesis and signaling pathways of PGE2 are outlined in this review. Cyclooxygenase-2 (COX-2) is the key enzyme that acts as the rate-limiting step for prostaglandin production, thus COX-2 inhibitors have been used to treat this disease. Although this treatment showed effective results, it has side effects that restrain its use. Here, we reviewed the genetics, clinical features, differential diagnosis and current treatment options of PHO according to our many years of clinical research on the disease. We also discussed probable treatment that may be an option in the future.
Topics: Humans; Dinoprostone; Osteoarthropathy, Primary Hypertrophic; Cyclooxygenase 2; Diagnosis, Differential; Drug-Related Side Effects and Adverse Reactions; Organic Anion Transporters
PubMed: 37705574
DOI: 10.3389/fendo.2023.1235040 -
Obstetrical & Gynecological Survey Jan 2024Induction of labor (IOL) is a common obstetric intervention. Augmentation of labor and active management of the second stage is frequently required in obstetric...
IMPORTANCE
Induction of labor (IOL) is a common obstetric intervention. Augmentation of labor and active management of the second stage is frequently required in obstetric practice. However, techniques around labor and induction management vary widely. Evidence-based practice regarding induction and labor management can reduce birth complications such as infection and hemorrhage and decrease rates of cesarean delivery.
OBJECTIVE
To review existing evidence on IOL and labor management strategies with respect to preparing for induction, cervical ripening, induction and augmentation, and second stage of labor techniques.
EVIDENCE ACQUISITION
Review of recent original research, review articles, and guidelines on IOL using PubMed (2000-2022).
RESULTS
Preinduction, pelvic floor training and perineal massage reduce postpartum urinary incontinence and perineal trauma, respectively. Timely membrane sweeping (38 weeks) can promote spontaneous labor and prevent postterm inductions. Outpatient Foley bulb placement in low-risk nulliparous patients with planned IOL reduces time to delivery. Inpatient Foley bulb use beyond 6 to 12 hours shows no benefit. When synthetic prostaglandins are indicated, vaginal misoprostol should be preferred. For nulliparous patients and those with obesity, oxytocin should be titrated using a high-dose protocol. Once cervical dilation is complete, pushing should begin immediately. Warm compresses and perineal massage decrease risk of perineal trauma.
CONCLUSION AND RELEVANCE
Several strategies exist to assist in successful IOL and promote vaginal delivery. Evidence-based strategies should be used to improve outcomes and decrease risk of complications and cesarean delivery. Recommendations should be shared across interdisciplinary team members, creating a model that promotes safe patient care.
Topics: Pregnancy; Female; Humans; Misoprostol; Delivery, Obstetric; Labor, Induced; Cesarean Section; Cervical Ripening; Oxytocics
PubMed: 38306291
DOI: 10.1097/OGX.0000000000001225