Predictive ability of pulse oximetry-derived indices for hypotension after spinal anaesthesia for caesarean section: protocol for a systematic review and meta-analysis.

INTRODUCTION: In general, caesarean sections are performed under spinal anaesthesia. Hypotension after spinal anaesthesia adversely affects both the mother and fetus. Although several studies have used pulse oximetry-derived indices, such as pulse perfusion index (PI) and Pleth variability index (PVI), to predict hypotension after spinal anaesthesia, the predictive ability of the PI and PVI remain controversial. METHODS AND ANALYSIS: We prepared this protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. We will conduct searches of MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Clinicaltrial.gov, European Union Clinical Trials Register (EU-CTR), WHO International Clinical Trials Registry Platform (ICTRP) and University Hospital Medical Information Network Clinical Trials Registry (UMIN) from inception until 8 October 2022. We will include retrospective and prospective observational studies and randomised controlled trials that evaluated the predictive ability of PI and PVI for hypotension after spinal anaesthesia for caesarean section, published in any language. We will exclude case reports, case series and animal studies. Two authors will independently scan and select eligible studies and perform data extraction and assessment of risk of bias. We will estimate predictive ability of PI and PVI as indices of hypotension after spinal anaesthesia for caesarean section using the Reitsma-type bivariate random-effects synthesis model and the hierarchical summary receiver operating characteristic curve. We will assess the quality of evidence using the Grading of Recommendation Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION: Ethics approval is not required as the systematic review will use existing published data. The results will be submitted for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022362596.

Comparative retrospective study on the validity of point-of-care testing device for massive obstetrical hemorrhage: dry hematology vs thromboelastography.

BACKGROUND: Early recognition of hypofibrinogenemia and prompt initiation of transfusion therapy in patients with massive obstetrical hemorrhage can improve prognosis. There are reports on the usefulness of point-of-care testing, which provides quicker test results compared with fibrinogen measurements using the conventional Clauss method. OBJECTIVE: This study aimed to compare and investigate the diagnostic accuracy of dry hematology and thromboelastography in point-of-care testing for the diagnosis of hypofibrinogenemia. STUDY DESIGN: A single-center, retrospective study of 126 massive obstetrical hemorrhage cases with point-of-care testing before treatment was initiated. The correlation of fibrinogen values with the Clauss method and the diagnostic accuracy for hypofibrinogenemia were compared between dry hematology and thromboelastography. RESULTS: Fibrinogen value in dry hematology showed a strong positive correlation with values measured by the Clauss method, and the diagnostic accuracy for hypofibrinogenemia was high, but there were many residuals above 100 mg/dL, and the distribution of these residuals was not uniform. Although thromboelastography cannot be used to directly measure fibrinogen values, maximum amplitude citrated functional fibrinogen, amplitude-10 citrated rapid thromboelastography, and amplitude-10 citrated functional fibrinogen showed a strong positive correlation with fibrinogen values using the Clauss method, and no significant difference in correlation or diagnostic accuracy was observed relative to dry hematology. CONCLUSION: Dry hematology and thromboelastography were equally accurate in diagnosing hypofibrinogenemia, with results correlating well with fibrinogen values measured by the Clauss method.

Maternal cardiopulmonary resuscitation.

The perinatal resuscitation history in Japan is short, with the earliest efforts in the field of neonatology. In contrast, the standardization and dissemination of maternal resuscitation is lagging. With the establishment of the Maternal Death Reporting Project and the Maternal Death Case Review and Evaluation Committee in 2010, with the aim of reducing maternal deaths, the true situation of maternal deaths came to light. Subsequently, in 2015, the Japan Council for the Dissemination of Maternal Emergency Life Support Systems (J-CIMELS) was established to educate and disseminate simulations in maternal emergency care; training sessions on maternal resuscitation are now conducted in all prefectures. Since the launch of the project and council, the maternal mortality rate in Japan (especially due to obstetric critical hemorrhage) has gradually decreased. This has been probably achieved due to the tireless efforts of medical personnel involved in perinatal care, as well as the various activities conducted so far. However, there are no standardized guidelines for maternal resuscitation yet. Therefore, a committee was set up within the Japan Resuscitation Council to develop a maternal resuscitation protocol, and the Guidelines for Maternal Resuscitation 2020 was created in 2021. These guidelines are expected to make the use of high-quality resuscitation methods more widespread than ever before. This presentation will provide an overview of the Guidelines for Maternal Resuscitation 2020.

Guidance on the need for contraception related to use of pharmaceuticals: the Japan Agency for Medical Research and Development Study Group for providing information on the proper use of pharmaceuticals in patients with reproductive potential.

BACKGROUND: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) have published guidelines on the use of cancer treatments in young people of reproductive potential. However, no such guideline is available in Japan. Therefore, this project aimed to gather relevant data and draft a respective guidance paper. METHODS: From April 2019 to March 2021, the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential at the Japan Agency for Medical Research and Development gathered opinions from experts in reproductive medicine, toxicology, and drug safety measures. The group considered these opinions, the FDA and EMA guidelines, and relevant Japanese guidelines and prepared a guidance paper, which they sent to 19 related organizations for comment. RESULTS: By November 2020, the draft guidance paper was completed and sent to the related organizations, 17 of which provided a total of 156 comments. The study group finalized the guidance paper in March 2021. CONCLUSIONS: The "Guidance on the Need for Contraception Related to Use of Pharmaceuticals" (The report of the Study Group for Providing Information on the Proper Use of Pharmaceuticals in Patients with Reproductive Potential, Research on Regulatory Science of Pharmaceuticals and Medical Devices, Japan Agency for Medical Research and Development: JP20mk0101139) is expected to help Japanese healthcare professionals provide fertility-related care and advice to adolescents, and young adults with cancer and their families.

Intravenous infusion route in maternal resuscitation: a scoping review.

BACKGROUND: The concept that upper extremities can be used as an infusion route during cardiopulmonary resuscitation in pregnant women is a reasonable recommendation considering the characteristic circulation of pregnant women; however, this method is not based on scientific evidence. OBJECTIVE OF THE REVIEW: We conducted a scoping review to determine whether the infusion route should be established above the diaphragm during cardiopulmonary resuscitation in a pregnant woman. DISCUSSION: We included randomized controlled trials (RCTs) and non-RCTs on the infusion of fluids in pregnant women after 20 weeks of gestation requiring establishment of an infusion route due to cardiac arrest, massive bleeding, intra-abdominal bleeding, cesarean section, severe infection, or thrombosis. In total, 3150 articles from electronic database were extracted, respectively. After title and abstract review, 265 articles were extracted, and 116 articles were extracted by full-text screening, which were included in the final analysis. The 116 articles included 78 studies on infusion for pregnant women. The location of the intravenous infusion route could be confirmed in only 17 studies, all of which used the upper extremity to secure the venous route. CONCLUSION: Pregnant women undergo significant physiological changes that differ from those of normal adults, because of pressure and drainage of the inferior vena cava and pelvic veins by the enlarged uterus. Therefore, despite a lack of evidence, it seems logical to secure the infusion route above the diaphragm when resuscitating a pregnant woman.

Survey on spontaneous miscarriage and induced abortion surgery safety at less than 12 weeks of gestation in Japan.

AIM: In Japan, dilatation and curettage (D&C) is a common procedure for spontaneous miscarriage and induced abortion, and its safety has long been an issue. Electric vacuum aspiration (EVA) is also common, but manual vacuum aspiration (MVA) was introduced recently, with medical abortions using mifepristone or misoprostol which are not yet legally accepted. This nationwide retrospective study surveyed the surgical methods and complications associated with spontaneous miscarriage and induced abortion at less than 12 weeks of gestation in Japan to assess their safety, in comparison with a similar survey for induced abortions in 2012. METHODS: Questionnaires were sent to 4176 facilities with a license for induced abortion surgeries in 2019. The questions included were the methods used, number of spontaneous miscarriages and induced abortions, and number of complications (uterine perforation, incomplete abortion, and gross bleeding requiring blood transfusion). RESULTS: Responses were received from 1706 facilities (40.9%). Although EVA with sharp curettage was the most common surgical method, which was used for 11 953 spontaneous miscarriages (28.9%) and 24 045 induced abortions (37.3%), the most common surgical method per facility was D&C, and the rates of D&C for spontaneous miscarriages (38.4%) and induced abortions (44.7%) performed in general hospitals were significantly higher than those in clinics (24.1% and 22.0%, respectively). There was no significant difference in the complication incidence rate among surgical methods for spontaneous miscarriages. However, in induced abortion surgery, the total complication and incomplete abortion incidence rates for D&C were significantly higher than those for EVA without sharp curettage (47/15 162 [0.31%] vs. 29/18 693 [0.16%], p = 0.00362, 45/15 162 [0.30%] vs. 27/18 693 [0.14%], p = 0.00285, respectively). There was no significant difference in the complication incidence rate between MVA and other surgical methods for each abortion surgery. CONCLUSION: In Japan, especially in general hospitals, D&C is still widely used for miscarriage and induced abortion surgery. Its complication-incidence rates significantly decreased compared with that of the nationwide survey in 2012, but were still significantly higher than EVA without sharp curettage. Few facilities used MVA, but its complication rate was comparable with those of other surgical methods.

[Current Status and Issues in Providing Information about Contraception and Fertility Preservation in the Pharmaceutical Treatments for Female Cancer Patients].

Many of oncology pharmaceuticals have ovotoxicity and/or genotoxicity. Ovarian reserve, numbers of healthy oocytes in the ovary, gradually decreases in aging, but abruptly decreases when young female cancer patients are exposed to ovotoxic pharmaceuticals. Therefore increasing number of young patients undergo fertility preservation in which oocytes or ovarian tissue are retrieved and cryopreserved before chemotherapy. The deterioration of the quality of oocytes in aging is called "oocyte aging", and the function of DNA repair in the oocytes are known to be deteriorated in aging. Similar to those from U. S. Food and Drug Administration and European Medicines Agency, labeling guidance in Japan recommends"5×T1/2 plus 6 months"of contraception period after the cessation of genotoxic pharmaceuticals, based on mouse model experiments. However, the teratogenicity of pharmaceuticals has been generally found when administered during the 4th to 10th weeks of pregnancy, and healthy children were born even when they originated from the oocytes or ovarian tissue which had been retrieved immediately after chemotherapy. We caregivers should carefully provide information to the female patients and their partners who get unexpectedly pregnant during the above‒mentioned contraception period.

Risk factors for neonatal bronchopulmonary dysplasia in extremely preterm premature rupture of membranes: a retrospective study.

BACKGROUND: Determination of the optimal timing for termination of pregnancy in cases of preterm premature rupture of membranes (pPROM) during the extremely preterm period is still difficult. Bronchopulmonary dysplasia (BPD) is a major disease widely taken into account when determining the prognosis of respiratory disorders in a neonate. Many aspects of this disease remain unclear. With the aim of further improving the prognosis of neonates born to mothers with pPROM, this study examined cases who were diagnosed with pPROM before 28 weeks of gestation. The study analysed risk factors for neonatal BPD. METHODS: This study included 73 subjects with singleton pregnancy, diagnosed with pPROM during the gestational period from 22 weeks and 0 days to 27 weeks and 6 days. The following factors were retrospectively examined: the gestational week at which pPROM was diagnosed, the gestational week at which delivery occurred, the period for which the volume of amniotic fluid was maintained, and neonatal BPD as a complication. Receiver operating characteristic (ROC) curve analyses were conducted to analyse the relationship of the onset of BPD with the duration of oligohydramnios and the gestational weeks of delivery. RESULTS: The mean gestational week at which a diagnosis of amniorrhexis was made was 24.5 ± 1.9 weeks (mean ± SD), and that at which delivery occurred was 27.0 ± 3.0 weeks. Fifty-seven cases (78.1%) were diagnosed with oligohydramnios, the mean duration of which was 17.4 ± 20.5 days. The mean birth weight of neonates was 1000 ± 455 g, of which 49 (67.1%) were diagnosed with BPD following birth. No neonates died in this study. The ROC curve indicated that the cut-off values for the duration of oligohydramnios and gestational age at delivery were 4 days and 24.1 weeks, respectively. Multivariate analysis indicated that the duration of oligohydramnios for more than 4 days before delivery and preterm delivery at less than 24.1 weeks were risk factors for the onset of BPD. CONCLUSIONS: Our findings suggest that duration of oligohydramnios for more than 4 days before delivery and preterm delivery less than 24.1 weeks are risk factors for BPD in cases who are diagnosed with pPROM before 28 weeks of gestation.

Optimal preoperative autologous blood storage volume required in surgeries for placenta previas and low-lying placentas.

AIM: The high rate of stored preoperative autologous blood wastage is concerning. This study analyzed patients who provided preoperative autologous blood donations (PABDs) for massive bleeding during surgery for placenta previas and low-lying placentas, and investigated the optimal PABD storage volume required to avoid allogeneic transfusion. METHODS: Of 386 patients who provided PABDs at our hospital from 2008 to 2013, 269 patients with placenta previas or low-lying placentas were retrospectively analyzed. The PABD storage volumes were stratified into four groups based on the amounts stored, and the allogeneic transfusion usage frequencies were compared. RESULTS: A total of 124 patients (46.1%) received PABDs and 12 patients (4.5%) received allogeneic transfusions. The average PABD volume wasted was 23 940 mL/year. The allogeneic transfusion utilization rate was significantly higher in the 1- to 300-mL group (17.2%) than in the 301- to 600-mL (1.69%), 601- to 900-mL (3.82%), and 901- to 1200-mL (0%) groups (P < 0.05). The PABD cut-off volume for avoiding allogeneic blood transfusion was 300 mL, and the odds ratio for ≤300-mL PABD in a multivariate analysis was 14.3 (95% confidence interval 1.3-149.3; P = 0.03). The maximum surgical blood order schedule was 2.16 units (432 mL), and the surgical blood order equation was 2.15 units (430 mL). CONCLUSION: The allogeneic transfusion utilization rate did not differ between the 600-mL group and the groups with higher PABD storage volumes; hence, storing 600 mL of PABD was appropriate for surgery for placenta previas and low-lying placentas.

Retrospective study of umbilical cord ulceration related to congenital intestinal atresia: A single-center report.

AIM: Umbilical cord ulceration (UCU) is a disease in which an ulcer forms in the umbilical cord in the pregnant uterus and is accompanied by hemorrhaging from the same site. UCU occurs in fetuses with congenital upper-intestinal atresia (CUIA); however, its onset mechanism remains unclear. Here, we report our investigation of cases of UCU in our hospital. METHODS: Among the 9825 deliveries performed between 2007 and 2016 at this hospital, 20 fetuses were diagnosed with CUIA, 4 (20%) of which had UCU. There was no difference in the backgrounds of the fetuses with UCU (UCU group: 4 fetuses) and those without (non-UCU group: 16 fetuses). RESULTS: There was no intergroup difference in gestational age at delivery. Four cases in the UCU group had maternal age 35 weeks (26-39), weeks of delivery 35 weeks (35-36) and weight 2178.5 g (1600-2640); three out of four fetuses were female; and the location of gastrointestinal obstruction was in the duodenum in one case and in the jejunum in three cases. Death occurred in three of four fetuses in the UCU group versus none in the non-UCU group. CONCLUSION: We performed a retrospective statistical investigation on the risk of UCU onset in cases from this hospital; however, we could not identify any prognostic factors for its onset. We investigated a total of 27 past reported UCU cases and the 4 cases in this study. Mean gestational age at onset was 33.3 ± 2.7 for all 27 cases. Various methods for the early discovery of UCU have been reported in the past; however, there is currently no gold standard. Based on this report and a review of past papers, for CUIA, it is desirable to perform in-hospital management from gestational week 30 onward and decide proper delivery timing on a case-by-case basis.

The Clinical Efficacy of Fibrinogen Concentrate in Massive Obstetric Haemorrhage with Hypofibrinogenaemia.

Massive obstetric haemorrhage remains a major cause of maternal death attributable to hypofibrinogenaemia. Transfusion of large volumes of fresh frozen plasma (FFP) is required to normalise fibrinogen levels. We compared the efficacy of FFP (F group) with that of FFP plus fibrinogen concentrate (F + F group) in massive obstetric haemorrhage. In this retrospective study, we compared the medical charts (2004-2016) of 137 patients with <150 mg/dl fibrinogen treated with F + F (n = 47; after August 2009) or F (n = 56; before August 2009). Although fibrinogen concentrate was only administered in severe cases, the FFP/red blood cell concentrate (RCC) ratio was significantly lower in the F + F group than in the F group. A sub-group analysis of cases requiring ≥18 RCC units showed that the F + F group received significantly less FFP than the F group (40.2 ± 19.6 versus 53.4 ± 18.5 units; P = 0.047) and showed significantly less pulmonary oedema (24.0% vs 57.1%; P < 0.05) in the absence of any significant differences in pre-transfusion coagulation, estimated blood loss, or RCC transfusion volume. Administration of fibrinogen concentrate increased the rate of fibrinogen supplementation five-fold and reduced FFP dosage, the FFP/RCC ratio, and the incidence of pulmonary oedema.

Managing vulvovaginal hematoma by arterial embolization as first-line hemostatic therapy.

OBJECTIVE: A puerperal vulvovaginal hematoma may continue to grow after a surgical procedure and may require blood transfusion. Thus, we selected arterial embolization for hemostasis as the first-line management in two cases of large vulvovaginal hematoma. MATERIALS AND METHODS: Case 1 was a 32-year-old pregnant woman. After delivery, a 10-cm vulvar hematoma developed. An enhanced computed tomography (CT) scan revealed active bleeding. Arterial embolization was performed and complete hemostasis was obtained. Case 2 was a 34-year-old woman with a recurring hematoma after delivery. An enhanced CT scan revealed extravasation in the hematoma. Gelatin sponges were applied and complete hemostasis was obtained. In both cases, arterial embolization was successful without requiring blood transfusions. RESULTS AND CONCLUSION: We successfully managed two cases of puerperal vulvovaginal hematoma by arterial embolization based on the evaluation of an enhanced CT scan. In conclusion, we suggest arterial embolization to be a viable option for first-line treatment in the management of vulvovaginal hematomas.

A pregnancy-associated nonfamilial case of PAPA (pyogenic sterile arthritis, pyoderma gangrenosum, acne) syndrome.

Little is known about the influence of pregnancy on pyogenic sterile arthritis, pyoderma gangrenosum, acne (PAPA) syndrome. We experienced a rare case of pregnancy complicated with PAPA syndrome. The patient had various histories of skin and joint disorders and experienced subarachnoid hemorrhage during pregnancy; however, her skin lesion was unaffected.

Site and incidence of birth canal lacerations from instrumental delivery with mediolateral episiotomy.

OBJECTIVE: Instrument-assisted vaginal delivery is a significant risk factor for birth canal lacerations. Although many obstetricians recently are recommending restrictive rather than a routine episiotomy, reports have shown restrictive episiotomy to be associated with more extensive anterior birth canal trauma compared with routine episiotomy. MATERIALS AND METHODS: We retrospectively reviewed 110 cases of forceps and vacuum deliveries and investigated the site of birth canal lacerations. Birth canal lacerations were divided into four sites according to direction-anterior, ipsilateral, contralateral, and posterior. RESULTS: The frequency of lacerations were, from most to least, posterior (34%), lateral (21.7%), and anterior (1.9%). Moreover, among the lateral lacerations, they were more frequent in the contralateral side of episiotomy than the ipsilateral side (18.9% vs. 4.7%, p < 0.01). CONCLUSION: Our results indicate that caution is also needed concerning not only the anterior site, but also the contralateral site of an episiotomy to prevent laceration in an instrument-assisted vaginal delivery.

Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates.

Chondroitin 6-sulfotransferase (C6ST) catalyzes the transfer of sulfate to position 6 of the N-acetylgalactosamine residue of chondroitin. To obtain direct evidence regarding the function of C6ST and its product, chondroitin 6-sulfate, in vivo, we isolated the mouse C6ST gene (C6st) and generated mice deficient in this gene (C6st(-/-)) by embryonic stem cell technology. C6st(-/-) mice were born at approximately the expected frequency and were viable through adulthood. In the spleen of C6st(-/-) mice, the level of chondroitin 6-sulfate became almost undetectable. Analyses of these knockout mice provided insights into the biosynthesis of oversulfated chondroitin sulfates in mice; chondroitin sulfate D in the brain of null mice and the cartilage and telencephalon of null embryos disappeared, whereas the chondroitin sulfate E level in the spleen and brain of the null mice was unchanged. Despite the disappearance of chondroitin sulfate D structure, brain development was normal in the C6st(-/-) mice. Further analysis revealed that the number of CD62L(+)CD44(low) T lymphocytes corresponding to naive T lymphocytes in the spleen of 5-6-week-old C6st(-/-) mice was significantly decreased, whereas those in other secondary lymphoid organs were unchanged. This finding suggested that chondroitin 6-sulfate plays a role in the maintenance of naive T lymphocytes in the spleen of young mice.