Controlled Sequential Doping of Metal Nanocluster.

Atomically precise doping of metal nanoclusters provides excellent opportunities not only for subtly tailoring their properties but also for in-depth understanding of composition (structure)-property correlation of metal nanoclusters and has attracted increasing interest partly due to its significance for fundamental research and practical applications. Although single and multiple metal atom doping of metal nanoclusters (NCs) has been achieved, sequential single-to-multiple metal atom doping is still a big challenge and has not yet been reported. Herein, by introducing a second ligand, a novel multistep synthesis method was developed, controlled sequential single-to-multiple metal atom doping was successfully achieved for the first time, and three doped NCs Au25Cd1(p-MBT)17(PPh3)2, Au18Cd2(p-MBT)14(PPh3)2, and [Au19Cd3(p-MBT)18]- (p-MBTH: para-methylbenzenethiol) were obtained, including two novel NCs that were precisely characterized via mass spectrometry, single-crystal X-ray crystallography, and so forth. Furthermore, sequential doping-induced evolutions in the atomic and crystallographic structures and optical and catalytic properties of NCs were revealed.

Twin pregnancy and postpartum haemorrhage: a systematic review and meta-analysis.

BACKGROUND: Postpartum haemorrhage (PPH) continues to stand as the primary cause of maternal morbidity and mortality post-delivery, with twin pregnancies carrying a heightened risk of PPH compared to singleton deliveries. OBJECTIVES: To investigate the incidence of primary PPH among twin pregnancies and report on maternal and peripartum characteristics within this population. METHODS: A literature search was conducted using data from PubMed, EMBASE, Cochrane, Scopus, and Web of Science. The search aimed to identify studies concerning mothers with twin pregnancies and postpartum haemorrhage (PPH) from the inception of each respective database to June 8th, 2023. Pooled means and proportions were analyzed using the generic inverse variance method. This review was registered prospectively with PROSPERO (CRD42023427192). RESULTS: A total of 21 studies involving 23,330 twin pregnant patients were included. Incidence of PPH for vaginal delivery and Caesarean delivery (CS) was found to be 10.9% (95% CI: -0.017, 0.235, I2 = 96%) and 27.0% (95% CI: 0.180, 0.359, I2 = 99%) respectively. In vitro fertilization (IVF) was the most common conception method at 62.0% (95% CI: 0.448, 0.792, I2 = 100%) with 81.1% (95% CI: 0.708, 0.915, I2 = 100%) of twins being dichorionic diamniotic. CONCLUSION: This meta-analysis demonstrated more than one in ten vaginal deliveries and over one in four cesarean sections result in PPH for twin pregnancies. IVF is the predominant method of conception in this patient group and seems to contribute to subsequent PPH risk in specific mothers. While preliminary, these findings underscore the necessity for further well-designed and high-quality studies to validate these results.

Machine learning approach to predict postpancreatectomy hemorrhage following pancreaticoduodenectomy: a retrospective study.

BACKGROUND: Postpancreatectomy hemorrhage (PPH) is a rare yet dreaded complication following pancreaticoduodenectomy (PD). This retrospective study aimed to explore a machine learning (ML) model for predicting PPH in PD patients. METHODS: A total of 284 patients who underwent open PD at our institute were included in the analysis. To address the issue of imbalanced data, the adaptive synthetic sampling (ADASYN) technique was employed. The best-performing ML model was selected using the PyCaret library in Python and evaluated based on recall, precision, and F1 score metrics. In addition to assessing the model's performance on the test data, bootstrap validation (n = 1000) with the original dataset was conducted. RESULTS: PPH occurred in 11 patients (3.9%), with a median onset time of 22 days postoperatively. These minority cases were oversampled to 85 using ADASYN. The extra trees classifier demonstrated superior performance with recall, precision, and F1 score of 0.967, 0.914, and 0.937, respectively. Both validation using the test data and bootstrap resampling consistently demonstrated recall, precision, and F1 score exceeding 0.9. The model identified the peak value of C-reactive protein during the first 7 postoperative days as the most significant feature, followed by the preoperative neutrophil-to-lymphocyte ratio. CONCLUSIONS: This study highlights the potential of the ML approach to predict PPH occurrence following PD. Vigilance and early interventions guided by such model predictions could positively impact outcomes for high-risk patients.

Prenatal anaemia and risk of postpartum haemorrhage: a cohort analysis of data from the Predict-PPH study.

BACKGROUND: Most previous clinical studies investigating the connection between prenatal anaemia and postpartum haemorrhage (PPH) have reported conflicting results. OBJECTIVES: We examined the association between maternal prenatal anaemia and the risk of PPH in a large cohort of healthy pregnant women in five health institutions in Lagos, Southwest Nigeria. METHODS: This was a prospective cohort analysis of data from the Predict-PPH study that was conducted between January and June 2023. The study enrolled n = 1222 healthy pregnant women giving birth in five hospitals in Lagos, Nigeria. The study outcome, WHO-defined PPH, is postpartum blood loss of at least 500 milliliters. We used a multivariable logistic regression model with a backward stepwise conditional approach to examine the association between prenatal anaemia of increasing severity and PPH while adjusting for confounding factors. RESULTS: Of the 1222 women recruited to the Predict-PPH study between January and June 2023, 1189 (97·3%) had complete outcome data. Up to 570 (46.6%) of the enrolled women had prenatal anaemia while 442 (37.2%) of those with complete follow-up data had WHO-defined PPH. After controlling for potential confounding factors, maternal prenatal anaemia was independently associated with PPH (adjusted odds ratio = 1.37, 95% confidence interval: 1.05-1.79). However, on the elimination of interaction effects of coexisting uterine fibroids and mode of delivery on this association, a sensitivity analysis yielded a lack of significant association between prenatal anaemia and PPH (adjusted odds ratio = 1.27, 95% confidence interval: 0.99-1.64). We also recorded no statistically significant difference in the median postpartum blood loss in women across the different categories of anaemia (P = 0.131). CONCLUSION: Our study revealed that prenatal anaemia was not significantly associated with PPH. These findings challenge the previously held belief of a suspected link between maternal anaemia and PPH. This unique evidence contrary to most previous studies suggests that other factors beyond prenatal anaemia may contribute more significantly to the occurrence of PPH. This highlights the importance of comprehensive assessment and consideration of various maternal health factors in predicting and preventing this life-threatening obstetric complication.

Educational results of the Japan Maternal Emergency Life-Saving (J-MELS) simulation training organized by Japan Council for the Implementation of the Maternal Emergency Life-Saving System (J-CIMELS): a 12-month longitudinal follow-up study in Japan.

AIMS: This study aimed to evaluate the long-term results of Japan Maternal Emergency Life-Saving (J-MELS) simulation training on obstetric healthcare providers, over a 12-month follow-up period. METHODS: A total of 273 trainees from 17 J-MELS Basic courses conducted between August 2021 and October 2023 were included. The trainees' responses to the pre- and post-tests, questionnaires, and self-reports on the usefulness of the J-MELS scenarios in actual clinical settings at 1, 6, and 12 months after the training were analyzed. Multivariate logistic regression analysis was also conducted to identify the factors influencing knowledge retention. RESULTS: We found an overall improvement in clinical knowledge acquisition after J-MELS training and a significant retention of this improvement at least until 12 months later. However, these scores gradually declined over. Trainees reported increased usefulness of J-MELS scenarios in actual clinical practice at 1, 6, and 12 months after training, particularly in managing obstetric emergencies such as atonic postpartum hemorrhage. Knowledge retention was influenced by several specific factors, such as years of clinical experience, affiliated institutions, qualifications, and especially pre-test scores. CONCLUSION: Our longitudinal follow-up study demonstrated, for the first time, the long-term results of J-MELS simulation training using post-tests and self-report data. Our findings provide valuable insight into the impact of J-MELS simulation training on maternal emergency care. By elucidating the factors influencing knowledge retention and practical utility, the findings offer actionable recommendations for optimizing training strategies and improving maternal outcomes in actual clinical practice.

Correlation of factor XIII subunit A with factor XIII activity in a population of parturient women.

BACKGROUND: The role of factor XIII in acute bleeding situations is gaining more and more importance. It has previously been shown that prepartum factor XIII activity has a significant impact on postpartum blood loss. Whether factor XIII antigen behaves in a similar manner is unknown. As postpartum hemorrhage is one of the leading causes of maternal morbidity and mortality worldwide and factor XIII antigen determination might be available more readily in some centers as compared to factor XIII activity, this is an important question to answer, especially in the emergency situation of a postpartum hemorrhage. OBJECTIVE: To assess the correlation of prepartum factor XIII antigen with prepartum factor XIII activity and to evaluate the correlation between prepartum factor XIII antigen on measured postpartum blood loss. METHODS: This is a secondary analysis of a prospective cohort study which analyzed the impact of prepartum blood coagulation factor XIII activity on postpartum blood loss in 1300 women at the University Hospital Zurich, Switzerland between October 2015 and November 2016 ("PPH-1300 study"). Blood loss was quantified using a previously validated technique. The association of factor XIII activity and factor XIII antigen was assessed by means of a Spearman rank correlation and differences were displayed using Bland-Altman plot and Passing-Bablok regression. The effect of the prepartum factor XIII antigen on blood loss was estimated by continuous outcome logistic regression. RESULTS: Prepartum factor XIII activity significantly correlated with prepartum factor XIII antigen (Spearman rank correlation coefficient for prepartum values 0.89, p < 0.001 and postpartum values 0.902, p < 0.001). Elevated values of prepartum factor XIII antigen showed a trend toward lower measured postpartum blood loss. CONCLUSION: The correlation of factor XIII activity with factor XIII antigen (subunit A) in a large real-world sample as well as an association of prepartum factor XIII antigen and postpartum blood loss is observed. Factor XIII antigen determination, a highly automatable test, could be useful in emergency situations such as a PPH (as well as other bleeding situations) if the determination of factor XIII activity is not possible. To evaluate whether FXIII replenishment reduces blood loss is the focus of ongoing studies.

Preeclampsia complicated with hypofibrinogenemia: 2 case reports and review of the literature.

BACKGROUND: Preeclampsia complicated with hypofibrinogenemia is a rare disorder. We report two cases of severe preeclampsia complicated with hypofibrinogenemia followed by postpartum haemorrhage (PPH). CASE: Two women diagnosed as preeclampsia and hypofibrinogenemia developed severe PPH after undergoing Cesarean sections. Besides supplement with fibrinogen concentrate and supportive treatment, the second patient got administration of heparin after delivery and bleeding was stopped. The haemorrhage in case 1 didn't disappear until an hysterectomy. The two patients both recovered and were discharged soon. CONCLUSIONS: Severe preeclampsia patients with hypofibrinogenemia could suffer PPH. It's necessary to detect and master coagulation function. Heparin could be considered to balance hypercoagulation and hypocoagulation to avoid catastrophic haemorrhage and hysterectomy.

Cost-effectiveness and budget impact of adding tranexamic acid for management of post-partum hemorrhage in the Indian public health system.

BACKGROUND: Postpartum hemorrhage (PPH) is the global leading cause of maternal mortality, affecting nearly 3 to 6 percent of all women giving birth in India. The World Health Organization (WHO) has updated its guidelines to recommend the early use of intravenous (IV) tranexamic acid (TXA) in addition to standard care for all diagnosed PPH cases. This study aimed to assess the cost-effectiveness of introducing TXA for PPH management in the Indian public health system. METHODS: A decision analytic model was built using a decision tree to determine the cost-effectiveness of administering IV TXA to women experiencing PPH within 3 h of birth to existing management with uterotonics and supportive care. Using a disaggregated societal perspective, the costs and consequences for a hypothetical cohort of women experiencing PPH in public health facilities was estimated. The model was populated using probabilities, clinical parameters, and utilities from published literature, while cost parameters were largely derived from a primary economic costing study. The primary outcome of interest was the incremental cost-utility ratio (ICUR). Associated clinical events and net benefits were estimated. One-way and probabilistic sensitivity analysis (PSA) was undertaken. The budget impact was estimated for a national-level introduction. RESULTS: For an estimated annual cohort of 510,915 PPH cases in India, the addition of IV TXA would result in a per-patient disaggregated societal cost of INR 6607 (USD 95.15) with a discounted gain of 20.25 QALYs, as compared to a cost of INR 6486 (USD 93.41) with a discounted gain of 20.17 QALYs with standard care PPH management. At an ICUR value of INR 1470 per QALY gained (USD 21), the addition of IV TXA is cost-effective in Indian public health settings. The intervention is likely to prevent 389 maternal deaths, 177 surgeries, and 128 ICU admissions per 100,000 PPH cases. The findings are robust under uncertainty, with 94.5% of PSA simulations remaining cost-effective. A cumulative increase of 2.3% financial allocation for PPH management over five years will be incurred for TXA introduction. CONCLUSIONS: Addition of tranexamic acid for primary PPH management, as recommended by WHO, is cost-effective in Indian public health settings. Policy guidelines, training manuals, and facility checklists should be updated to reflect this recommendation.

A five year descriptive analysis of potentially preventable hospitalisations for Ear, Nose, and Throat conditions in regional Victoria, Australia, from 2015 to 2020.

BACKGROUND: Potentially preventable hospitalisations of ear, nose, and throat conditions in the Murray Primary Health Network region have been found to be higher than the state average of Victoria, Australia. This study aimed to examine the association between selected patient-level characteristics and the likelihood of residing in a Murray PHN postcode with higher than expected numbers of potentially preventable ENT hospitalisations. METHODS: Unit record hospital separation data were obtained from the Victorian Admitted Episodes Dataset. Postcodes were classified as having higher than expected numbers of potentially preventable hospitalisations across three subgroups of ENT using indirect standardisation techniques. Differences between patients from 'higher than expected' postcodes and 'other' postcodes with respect to the distribution of demographic and other patient characteristics were determined using chi-squared tests for each ENT subgroup. The results were confirmed by logistic regression analyses using resident of a postcode with higher than expected hospitalisations as the outcome variable. RESULTS: Of the 169 postcodes located in the catchment area, 15 were identified as having higher than expected numbers of upper respiratory tract infection hospitalisations, 14 were identified for acute tonsillitis, and 12 were identified for otitis media. Patients from postcodes with 'higher than expected' hospitalisations for these conditions were more likely than others to be aged between 0 and 9 years, Indigenous, or from a culturally and linguistically diverse background. CONCLUSION: Further investigation of the identified postcodes is warranted to determine access to and utilisation of primary healthcare services in the management of PPH ENT conditions in the region.

Functional analysis of a novel de novo variant in PPP5C associated with microcephaly, seizures, and developmental delay.

We describe a proband evaluated through the Undiagnosed Diseases Network (UDN) who presented with microcephaly, developmental delay, and refractory epilepsy with a de novo p.Ala47Thr missense variant in the protein phosphatase gene, PPP5C. This gene has not previously been associated with a Mendelian disease, and based on the population database, gnomAD, the gene has a low tolerance for loss-of-function variants (pLI = 1, o/e = 0.07). We functionally evaluated the PPP5C variant in C. elegans by knocking the variant into the orthologous gene, pph-5, at the corresponding residue, Ala48Thr. We employed assays in three different biological processes where pph-5 was known to function through opposing the activity of genes, mec-15 and sep-1. We demonstrated that, in contrast to control animals, the pph-5 Ala48Thr variant suppresses the neurite growth phenotype and the GABA signaling defects of mec-15 mutants, and the embryonic lethality of sep-1 mutants. The Ala48Thr variant did not display dominance and behaved similarly to the reference pph-5 null, indicating that the variant is likely a strong hypomorph or complete loss-of-function. We conclude that pph-5 Ala48Thr is damaging in C. elegans. By extension in the proband, PPP5C p.Ala47Thr is likely damaging, the de novo dominant presentation is consistent with haplo-insufficiency, and the PPP5C variant is likely responsible for one or more of the proband's phenotypes.

Preventing postpartum hemorrhage after cesarean delivery: a network meta-analysis of available pharmacologic agents.

BACKGROUND: Postpartum hemorrhage causes a quarter of global maternal deaths. The World Health Organization recommends oxytocin as the first line agent to prevent hemorrhage during cesarean delivery. However, some randomized controlled trials suggest that other uterotonics are superior. OBJECTIVE: We conducted a network meta-analysis comparing the ability of pharmacologic agents to reduce blood loss and minimize the need for additional uterotonics during cesarean delivery. DATA SOURCES: We searched the Cochrane Central Register of Controlled Trials, Embase, and MEDLINE databases from inception to May 2020. STUDY ELIGIBILITY CRITERIA: We included randomized controlled trials that compared oxytocin, carbetocin, misoprostol, ergometrine, carboprost, or combinations of these in the prevention of postpartum hemorrhage during cesarean delivery. METHODS: We performed a systematic review followed by an NMA in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Quality of the evidence was assessed with the Confidence in Network Meta-Analysis approach and Grading of Recommendations, Assessment, Development and Evaluations tool within the summary of findings table. Our primary outcomes were the estimated blood loss and need for additional uterotonics. Secondary outcomes included nausea and postpartum hemorrhage of >1000 mL. We performed sensitivity analyses to explore the influence of surgical context and oxytocin administration strategy. RESULTS: A total of 46 studies with 7368 participants were included. Of those, 21 trials (6 agents and 3665 participants) formed the "estimated blood loss" network and, considering the treatment effects, certainty in the evidence, and surface under the cumulative ranking curve scores, carbetocin was assessed to probably be superior to oxytocin, but only in reducing the estimated blood loss by a clinically insignificant volume (54.83 mL; 95% confidence interval, 26.48-143.78). Misoprostol, ergometrine, and the combination of oxytocin and ergometrine were assessed to probably be inferior, whereas the combination of oxytocin and misoprostol was assessed to definitely be inferior to oxytocin. A total of 37 trials (8 agents and 6193 participants) formed the "additional uterotonic" network and, again, carbetocin was assessed to probably be superior to oxytocin, requiring additional uterotonics 185 (95% confidence interval, 130-218) fewer times per 1000 cases. Oxytocin plus misoprostol, oxytocin plus ergometrine, and misoprostol were assessed to probably be inferior, whereas carboprost, ergometrine, and the placebo were definitely inferior to oxytocin. For both primary outcomes, oxytocin administration strategies had a higher probability of being the best uterotonic, if initiated as a bolus. CONCLUSION: Carbetocin is probably the most effective agent in reducing blood loss and the need for additional uterotonics. Oxytocin appears to be more effective when initiated as a bolus.

Risk of postpartum haemorrhage is associated with ethnicity: A cohort study of 981 801 births in England.

OBJECTIVE: To determine the association between ethnic group and risk of postpartum haemorrhage in women giving birth. DESIGN: Cohort study. SETTING: Maternity units in England. SAMPLE: A total of 981 801 records of births between 1 April 2015 and 31 March 2017 in a national clinical database. METHODS: Multivariable logistic regression analyses with multiple imputation to account for missing data and robust standard errors to account for clustering within hospitals. MAIN OUTCOME MEASURE: Postpartum haemorrhage of ≥1500 ml (PPH). RESULTS: A total of 28 268 (2.9%) births were complicated by PPH. Risks were higher in women from black (3.9%) and other (3.5%) ethnic backgrounds. Following adjustment for maternal and fetal characteristics, and care at birth, there was evidence of an increased risk of PPH in women from all ethnic minority groups, with the largest increase seen in black women (adjusted OR 1.54, 95% CI 1.45-1.63). The increase in risk was robust to sensitivity analyses, which included changing the outcome to PPH of ≥3000 ml. CONCLUSIONS: In England, women from ethnic minority backgrounds have an increased risk of PPH, when maternal, fetal and birth characteristics are taken into account. Factors contributing to this increased risk need further investigation. Perinatal care for women from ethnic minority backgrounds should focus on preventative measures to optimise maternal outcomes. TWEETABLE ABSTRACT: Women with an ethnic minority background giving birth in England have an increased risk of postpartum haemorrhage, even when characteristics of the mother, the baby and the care received are taken into account.

How to boost an obstetrician's confidence in vaginal delivery after high-intensity focused ultrasound: a comparison study on delivery outcomes.

OBJECTIVE: To assess the feasibility of vaginal delivery after HIFU. METHODS: A total of 37 women who met the trial of labor after HIFU (TOLAH) inclusion criteria and 368 women who met the trial of labor after cesarean delivery (TOLAC) inclusion criteria gave birth at Shanghai First Maternity and Infant Hospital between 14th June 2018 and 24th September 2021. The delivery outcomes of the two groups were compared. Multivariable logistic regression analysis was used to estimate the adjusted risk of postpartum hemorrhage (PPH). RESULTS: In the Qualified Candidates for TOLAH group, vaginal delivery is substantially less common (p = 0.000). The prevalence of PPH in the Qualified Candidates for TOLAH group is lower than in the Candidates for TOLAC group (8.82% vs 10.51%, p = 0.534; 0% vs 2.51%, p = 0.418). Hemoglobin drop in the Qualified Candidates for TOLAH group is also lower (7.03 ± 7.39vs 12.11 ± 12.62, p = 0.001). The rate of using more than two types of uterotonic medications to promote contraction is significantly lower in the Qualified Candidates for TOLAH group (54.05% vs 69.84%, p = 0.04), and the percentage of abnormal uterine contraction is lower in the Qualified Candidates for TOLAH group (35.14% vs 49.18%, p = 0.072). PPH is strongly predicted by abnormal uterine contraction (aOR: 17.177, 95% CI:5.046 ∼ 58.472, p = 0.000), but not by HIFU (aOR:1.105; 95% CI:0.240 ∼ 5.087, p = 0.898). No uterine rupture occurred in the cases after HIFU. CONCLUSIONS: No uterine rupture occurred in our study group after HIFU. HIFU is not a risk for PPH. It is promising for those after HIFU to choose vaginal delivery.

Does the use of chitosan covered gauze for postpartum hemorrhage reduce the need for surgical therapy including hysterectomy? A databased historical cohort study.

OBJECTIVES: Postpartum hemorrhage (PPH) is still one of the leading causes of maternal mortality worldwide. Recently effective PPH therapy with uterine packing with the chitosan-covered gauze was shown. This databased retrospective case-control study compares the therapy success of the chitosan tamponade with that of the balloon tamponade and medical therapy only. METHODS: All women who delivered at a university hospital between May 2016 and May 2019 with PPH were included. Based on the applied therapy, women were divided into three groups: medical therapy only, balloon tamponade and chitosan tamponade. The groups were compared in terms of therapy success, side-effects and reasons for PPH. Primary outcome was the need for surgical/radiological measures including hysterectomy, secondary outcomes were differences in hemoglobin levels, duration of inpatient stay, admission to intensive care unit, number of administered blood products and inflammation parameters. RESULTS: A total of 666 women were included in the study. 530 received medical therapy only, 51 the balloon tamponade and 85 the chitosan tamponade. There were no significant differences in the need for surgical therapy, but a significantly lower number of hysterectomies in the chitosan tamponade group than in the balloon tamponade group. There were no relevant differences in secondary outcomes and no adverse events related to the chitosan tamponade. Since the introduction of chitosan tamponade, the number of PPH related hysterectomies dropped significantly by 77.8%. CONCLUSIONS: The chitosan tamponade is a promising treatment option for PPH. It reduces the postpartum hysterectomy rate without increased side effects compared to the balloon tamponade.

Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report.

BACKGROUND: Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. CASE PRESENTATION: A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. CONCLUSIONS: We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

The Safety and Feasibility of a Family First Aid Approach for the Management of Postpartum Hemorrhage in Home Births: A Pre-post Intervention Study in Rural Pakistan.

OBJECTIVE: To evaluate the safety and feasibility of a Family First Aid approach whereby women and their families are provided misoprostol in advance to manage postpartum hemorrhage (PPH) in home births. METHODS: A 12-month prospective, pre-post intervention study was conducted from February 2017 to February 2018. Women in their second and third trimesters were enrolled at home visits. Participants and their families received educational materials and were counseled on how to diagnose excessive bleeding and the importance of seeking care at a facility if PPH occurs. In the intervention phase, participants were also given misoprostol and counselled on how to administer the four 200 mcg tablets for first aid in case of PPH. Participants were followed-up postpartum to collect data on use of misoprostol for Family First Aid at home deliveries (primary outcome) and record maternal and perinatal outcomes. RESULTS: Of the 4008 participants enrolled, 97% were successfully followed-up postpartum. Half of the participants in each phase delivered at home. Among home deliveries, the odds of reporting PPH almost doubled among in the intervention phase (OR 1.98; CI 1.43, 2.76). Among those reporting PPH, women in the intervention phase were significantly more likely to have received PPH treatment (OR 10.49; CI 3.37, 32.71) and 90% administered the dose correctly. No maternal deaths, invasive procedures or surgery were reported in either phase after home deliveries. CONCLUSIONS: The Family First Aid approach is a safe and feasible model of care that provides timely PPH treatment to women delivering at home in rural communities.

Cost of hospital care of women with postpartum haemorrhage in India, Kenya, Nigeria and Uganda: a financial case for improved prevention.

OBJECTIVE: Access to quality, effective lifesaving uterotonics in low and middle-income countries (LMICs) remains a major barrier to reducing maternal deaths from postpartum haemorrhage (PPH). Our objective was to assess the costs of care for women who receive different preventative uterotonics, and with PPH and no-PPH so that the differences, if significant, can inform better resource allocation for maternal health care. METHODS: The costs of direct hospital care of women who received oxytocin or heat-stable carbetocin for prevention of PPH in selected tertiary care facilities in India, Kenya, Nigeria, and Uganda were assessed. We collected data from all women who had PPH, as well as a random sample of women without PPH. Cost data was collected for the cost of stay, PPH interventions, transfusions and medications for 2966 women. We analyzed the difference in cost of care at a facility level between women who experienced a PPH event and those who did not. Key findings The mean cost of care of a woman experiencing PPH in the study sites in India, Kenya, Nigeria, and Uganda exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries. CONCLUSION: Our results quantify the increased cost of PPH of up to 4.1 times that for a birth without PPH. PPH cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization's recommendations on uterotonics for the prevention of PPH or other interventions used to treat PPH. Trial registration HRP Trial A65870; UTN U1111-1162-8519; ACTRN12614000870651; CTRI/2016/05/006969, EUDRACT 2014-004445-26. Date of registration 14 August 2014 Access to quality, effective lifesaving medicines in low and middle-income countries remains a major barrier to reducing maternal deaths from bleeding after childbirth. Information on to what extent treatments for bleeding increases the cost of care of women after childbirth is important for informed resource allocation. We collected data from all women who had bleeding after childbirth, as well as a random sample of women without bleeding in selected hospitals in India, Kenya, Nigeria, and Uganda. Cost data was collected for the cost of stay and interventions to manage bleeding for 2966 women. We compared the difference in cost of care between women who experienced a bleeding event and those who did not. The mean cost of care of a woman with bleeding in the study sites exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries. Our results indicate an increased cost of bleeding of up to 4.1 times that for birth without bleeding. Effective prevention reduces the cost of care. Cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization's recommendations on medications for the prevention of bleeding after childbirth or other interventions used to treat bleeding.

Polyphosphorhydrazone-Based Radical Dendrimers.

The search for new biomedical applications of dendrimers has promoted the synthesis of new radical-based molecules. Specifically, obtaining radical dendrimers has opened the door to their use in various fields such as magnetic resonance imaging, as anti-tumor or antioxidant agents, or the possibility of developing new types of devices based on the paramagnetic properties of organic radicals. Herein, we present a mini review of radical dendrimers based on polyphosphorhydrazone, a new type of macromolecule with which, thanks to their versatility, new metal-free contrast agents are being obtained, among other possible applications.

A new non-invasive procedure for refractory PPH after vaginal delivery and caesarean section.

Worldwide, the incidence of postpartum haemorrhage (PPH) is ∼6% and it is the leading cause of maternal mortality. The present study introduces a non-invasive procedure called bilateral cervix apex clamping (BCAC) as a new treatment for refractory PPH. A total of 13 vaginal deliveries and 5 caesarean section patients received the BCAC procedure to stop bleeding. During the procedure, the anterior and posterior walls of the cervical apex were clamped using toothless ovum forceps from the left and right side. The procedure was terminated when the bleeding had nearly stopped without clamping. The success rate of the procedure was 94.4% (17/18) overall, and 92.3% for vaginal delivery and 100% in caesarean section patients. Only one case of vaginal delivery did we resort to exploratory laparotomy and hysterectomy as amniotic fluid embolism occurred. The time spent on the procedure was 2-4 min for vaginal delivery cases and 5-7 min for caesarean section patients. The blood loss reduced significantly after the procedure, before the BCAC and after it was 875(450) ml versus 100(80)ml (p < .0001). There was a reduction in the need for UAE (uterine artery embolisation) from 13 in 22,817 deliveries (2013-2015) to 0 in 18,212 deliveries (2016-2017 (p < .001). But no change in the rate of hysterectomy (5/22817 versus 5/18212) (p = .76). BCAC is a simple, easy, safe, effective and non-invasive procedure that can decrease bleeding in patients with PPH.Impact statementWhat is already known on this subject? The BCAC clamping procedure was first described in Russia 80 years ago as the Genkel-Tikanadze method. But a PUBMED search did not identify and previous studies published on use of the technique.What do the results of this study add? The results of this study show that the BCAC clamping procedure can reduce bleeding significantly in refractory postpartum haemorrhage, when the uterine body is well contracted. The procedure can be performed after both in vaginal delivery and caesarean section. It can also reduce the necessity for UAE and balloon tamponade.What are the implications of these findings for clinical practice and/or further research? BCAC can be used after the failure of regular first line therapy for postpartum haemorrhage.

Stapled Hemorrhoidopexy: Technique and Long Term Results.

Background: Stapled hemorrhoidopexy (Longo operation) is a infrequent technique in our area. A different concept from hemorrhoidectomy, a proportionally important raise in cost and a special training may have contributed to it. We report our long-term results with the standard technique. Methods: The data of 35 patients with symptomatic second- and third-degree hemorrhoids who had stapled hemorrhoidopexy using a PPH03 stapler, from 01 January 2012 to 04 December 2020, were retrospectively collected. The sex ratio male: female was 3:4 and the mean age 45 (range 28-60) years. The follow-up consisted in a rectal exam and evaluated anatomical recurrence or prolapse. Results: The mean operative time was 42 (30-70) min. The mean parenteral analgesic doses during the first 24 h were 1,52. The mean postoperative hospital stay was 1.55 (1-2) days. A single patient needed reoperation for a staple line bleeding, two patients had a thrombosis of internal hemorrhoids and in one patient a small prolapse was diagnosed at 3 months follow-up. No hematoma, anastomotic stenosis, persistent anal pain, tenesmus, or impaired anal continence was recorded. One patient mentioned discomfort related to the presence of staples. Patients were followed-up for 6 (1-9) years. Global satisfaction rate was 94%. Conclusion: Stapled hemorrhoidopexy procedure is a safe and feasible procedure, which necessitates few analgesics and allows an early discharge. A rigorous selection of cases and a correct surgical technique allow to obtain good long-term results and offer a high level of patients satisfaction.