Incidence of sodium-glucose cotransporter-2 inhibitor-associated perioperative ketoacidosis in surgical patients: a prospective cohort study.

PURPOSE: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are commonly prescribed anti-diabetic medications with various beneficial effects; however, they have also been associated with ketoacidosis. The aim of this study was to determine the incidence of SGLT2i-associated perioperative ketoacidosis (SAPKA) in surgical patients. METHODS: We conducted a multicenter, prospective cohort study across 16 centers in Japan, enrolling surgical patients with diabetes who were prescribed SGLT2is between January 2021 and August 2022. Patients were monitored until the third postoperative day to screen for SAPKA, defined as urine ketone positivity with a blood pH of < 7.30 and HCO3 level ≤ 18.0 mEq/L, excluding cases of respiratory acidosis. RESULTS: In total, 759 of the 762 evaluated patients were included in the final analysis. Among these, three patients (0.40%) had urine ketones with a blood pH of < 7.30; however, blood gas analysis revealed respiratory acidosis in all three, and none of them was considered to have SAPKA. The estimated incidence of SGLT2i-associated postoperative ketoacidosis was 0% (95% confidence interval, 0%-0.4%). CONCLUSIONS: The observed incidence of SAPKA in our general surgical population was lower than expected. However, given that the study was observational in nature, interpretation of study results warrants careful considerations for biases.

Workflow Optimization for Identification of Female Germline or Oogonial Stem Cells in Human Ovarian Cortex Using Single-Cell RNA Sequence Analysis.

In 2004, the identification of female germline or oogonial stem cells (OSCs) that can support post-natal oogenesis in ovaries of adult mice sparked a major paradigm shift in reproductive biology. Although these findings have been independently verified, and further extended to include identification of OSCs in adult ovaries of many species ranging from pigs and cows to non-human primates and humans, a recent study rooted in single-cell RNA sequence analysis (scRNA-seq) of adult human ovarian cortical tissue claimed that OSCs do not exist, and that other groups working with OSCs following isolation by magnetic-assisted or fluorescence-activated cell sorting have mistaken perivascular cells (PVCs) for germ cells. Here we report that rare germ lineage cells with a gene expression profile matched to OSCs but distinct from that of other cells, including oocytes and PVCs, can be identified in adult human ovarian cortical tissue by scRNA-seq after optimization of analytical workflow parameters. Deeper cell-by-cell expression profiling also uncovered evidence of germ cells undergoing meiosis-I in adult human ovaries. Lastly, we show that, if not properly controlled for, PVCs can be inadvertently isolated during flow cytometry protocols designed to sort OSCs because of inherently high cellular autofluorescence. However, human PVCs and human germ cells segregate into distinct clusters following scRNA-seq due to non-overlapping gene expression profiles, which would preclude the mistaken identification and use of PVCs as OSCs during functional characterization studies.

The influence of temperature on the metabolic activity of CYP2C9, CYP2C19, and CYP3A4 genetic variants in vitro.

1. Temperature is considered to affect the activity of drug-metabolizing enzymes; however, no previous studies have compared temperature dependency among cytochrome P450 genetic variants. This study aimed to analyse warfarin 7-hydroxylation by CYP2C9 variants; omeprazole 5-hydroxylation by CYP2C19 variants; and midazolam 1-hydroxylation by CYP3A4 variants at 34 °C, 37 °C, and 40 °C.2. Compared with that seen at 37 °C, the intrinsic clearance rates (Vmax/Km) of CYP2C9.1 and .2 were decreased (76 ∼ 82%), while that of CYP2C9.3 was unchanged at 34 °C. At 40 °C, CYP2C9.1, .2, and .3 exhibited increased (121%), unchanged and decreased (87%) intrinsic clearance rates, respectively. At 34 °C, the clearance rates of CYP2C19.1A and .10 were decreased (71 ∼ 86%), that of CYP2C19.1B was unchanged, and those of CYP2C19.8 and .23 were increased (130 ∼ 134%). At 40 °C, the clearance rates of CYP2C19.1A, .1B, .10, and .23 remained unaffected, while that of CYP2C19.8 was decreased (74%). At 34 °C, the clearance rates of CYP3A4.1 and .16 were decreased (79 ∼ 84%), those of CYP3A4.2 and .7 were unchanged, and that of CYP3A4.18 was slightly increased (112%). At 40 °C, the clearance rate of CYP3A4.1 remained unaffected, while those of CYP3A4.2, .7, .16, and .18 were decreased (58 ∼ 82%).3. These findings may be clinically useful for dose optimisation in patients with hypothermia or hyperthermia.

Sodium-glucose cotransporter 2 inhibitor-associated perioperative ketoacidosis: a systematic review of case reports.

Although the recommended preoperative cessation period for sodium-glucose cotransporter 2 inhibitors (SGLT2is) changed in 2020 (from 24 h to 3-4 days preoperatively) to reduce the risk of SGLT2i-associated perioperative ketoacidosis (SAPKA), the validity of the new recommendation has not been verified. Using case reports, we assessed the new recommendation effectiveness and extrapolated precipitating factors for SAPKA. We searched electronic databases up to June 1, 2022 to assess SAPKA (blood pH < 7.3 and blood or urine ketone positivity within 30 days postoperatively in patients taking SGLT2i). We included 76 publications with 99 cases. The preoperative SGLT2i cessation duration was reported for 59 patients (59.6%). In all cases with available cessation periods, the SGLT2is were interrupted < 3 days preoperatively. No SAPKA cases with > 2-day preoperative cessation periods were found. Many case reports lack important information for estimating precipitating factors, including preoperative SGLT2i cessation period, body mass index, baseline hemoglobin A1c level, details of perioperative fluid management, and type of anesthesia. Our study suggested that preoperative SGLT2i cessation for at least 3 days could prevent SAPKA. Large prospective epidemiologic studies are needed to identify risk factors for SAPKA.

Feasibility of a mobile cardiotocogram device for fetal heart rate self-monitoring in low-risk singleton pregnant women.

AIM: This study aimed to clarify the feasibility of a mobile cardiotocogram (CTG) device for self-monitoring fetal heart rate (FHR) in low-risk singleton pregnant women. METHODS: This study was conducted at six university hospitals and seven maternity clinics in Japan. Using a mobile cardiotocogram device (iCTG, Melody International Ltd., Kagawa, Japan), participants of more than 34 gestational weeks measured the FHR by themselves at least once a week until hospitalization for delivery. We evaluated the acquisition rate of evaluable FHR recordings and the frequency of abnormal FHR patterns according to the CTG classification system of the Japan Society of Obstetrics and Gynecology (JSOG). The participants also underwent a questionnaire survey after delivery to evaluate their satisfaction level of self-monitoring FHR using the mobile CTG device. RESULTS: A total of 1278 FHR recordings from 101 women were analyzed. Among them, 1276 (99.8%) were readable for more than 10 min continuously, and the median percentage of the total readable period in each recording was 98.9% (range, 51.4-100). According to the JSOG classification system, 1245 (97.6%), 9 (0.7%), 18 (1.4%), and four (0.3%) FHR patterns were classified as levels 1, 2, 3, and 4, respectively. The questionnaire survey revealed high participant satisfaction with FHR self-monitoring using the iCTG. CONCLUSION: The mobile CTG device is a feasible tool for self-monitoring FHR, with a high participant satisfaction level.

Prevalence and molecular characteristics of DNA mismatch repair deficient endometrial cancer in a Japanese hospital-based population.

BACKGROUND: The prevalence and molecular characteristics of defective DNA mismatch repair endometrial cancers in the Japanese population have been underexplored. Data supporting clinical management of patients with Lynch-like syndrome and germline variant of uncertain significance of mismatch repair genes are still lacking. METHODS: Immunohistochemistry of mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed on formalin-fixed paraffin-embedded sections prepared from resected primary endometrial cancers in 395 women with a median age of 59 years. Genetic and/or epigenetic alterations of the mismatch repair genes were also investigated. RESULTS: Loss of expression of one or more mismatch repair proteins was observed in 68 patients (17.2%). A total of 17 out of 68 patients (25%, 4.3% of all cases) were identified as candidates for genetic testing for Lynch syndrome after excluding 51 patients with MLH1 hypermethylated cancer. Fourteen of these 17 patients subjected to genetic testing were found to have Lynch syndrome (n = 5), germline variant of uncertain significance (n = 2) or Lynch-like syndrome (n = 7). Compared with patients with Lynch syndrome, those with germline variant of uncertain significance and Lynch-like syndrome tended to demonstrate an older age at the time of endometrial cancer diagnosis (P = 0.07), less fulfillment of the revised Bethesda guidelines (P = 0.09) and lower prevalence of Lynch syndrome-associated tumors in their first-degree relatives (P = 0.01). CONCLUSIONS: This study provides useful information for management in patients with DNA mismatch repair endometrial cancer. Specifically, cancer surveillance as recommended in patients with Lynch syndrome might not be necessary in patients with germline variant of uncertain significance and Lynch-like syndrome and their relatives.

Residual paralysis caused by 50 mg rocuronium after reversal with 4 mg/kg sugammadex: a case report.

BACKGROUND: Rocuronium-induced neuromuscular blockade can be quickly and completely reversed by administration of an optimal dose of sugammadex. Sugammadex antagonizes rocuronium-induced neuromuscular blockade by encapsulating rocuronium. Herein, we report a case of residual neuromuscular paralysis in which the recommended dose of sugammadex (4 mg·kg- 1) failed to antagonize a rocuronium-induced blockade. CASE PRESENTATION: A 71-year-old man (body mass index: 26.7 kg·m- 2) underwent endoscopic submucosal dissection of early-stage gastric cancer. He had no known factors that may have affected the effects of rocuronium and sugammadex. He received rocuronium (50 mg; 0.7 mg·kg- 1) for anesthesia induction. No additional rocuronium was administered during the 71-min procedure. Ninety-four minutes after rocuronium administration, neuromuscular monitoring showed 20 twitches in response to post-tetanic count stimulation. The train-of-four (TOF) ratio was not measurable despite sugammadex (280 mg; 4 mg/kg) administration, although four weak twitches in response to TOF stimulation appeared in 3 min. The TOF ratio became detectable following administration of an additional dose of sugammadex (120 mg; 1.7 mg·kg- 1), and it recovered to 107% 8 min after the second dose. The patient opened his eyes; moved his neck, arms, and limbs; and regained consciousness. The trachea was extubated and the patient was transferred to the ward. CONCLUSIONS: Neuromuscular monitoring should be used if a neuromuscular blockage agent is administered, even if the recommended dose of sugammadex is administered.

Differences in laboratory reporting standards leading to a difficult prenatal diagnosis for a patient with suspected 4p duplication.

Not all obstetric care facilities offer sufficient genetic counseling in Japan. When necessary, patients are referred to tertiary perinatal care centers for genetic counseling and further testing. Because each facility typically has an exclusive contract with a laboratory, the additional testing required may be performed at a different laboratory. With no reporting standards for normal chromosomal variants, differences between laboratories impede result interpretation, and clinical errors may occur. We present a case of a patient diagnosed with 46,XX,?dup (4)(p12p12) variant over two pregnancies. During the first pregnancy, the variant was determined to be a de novo, leading the parents to terminate the pregnancy. During the second pregnancy, further analysis revealed no 4p duplication, and we diagnosed as a normal variant, 4cenh+, inherited from the mother. Differences in reporting standards for a normal variant made evaluation of this patient difficult. Medical staff should be aware of this issue, and reporting standards should be standardized.

Effects of intrathecal opioids on cesarean section: a systematic review and Bayesian network meta-analysis of randomized controlled trials.

PURPOSE: We aimed to compare the beneficial and harmful effects of opioids used as adjuncts to local anesthetics in patients undergoing cesarean section under spinal anesthesia. METHODS: We searched electronic databases and ClinicalTrials.gov from their inception until March, 2021 without language restrictions. The primary outcome was the complete analgesia duration (Time to VAS > 0). Data were synthesized using the Bayesian random-effects model. Evidence confidence was evaluated using the Confidence In Network Meta-Analysis. RESULTS: We identified 66 placebo-controlled randomized controlled trials (RCTs) comprising 4400 patients undergoing elective cesarean section. Compared with the placebo, intrathecal opioids (fentanyl, sufentanil, and morphine) significantly prolonged the analgesia duration by 96, 96, and 190 min, respectively (mean difference). Despite morphine ranking first, opioid efficacy was similar; the results were inconsistent with respect to other analgesic outcomes. Except for diamorphine, all opioids were associated with significant increases in the pruritus incidence. Sufentanil and morphine were associated with increases in the respiratory depression incidence. CONCLUSIONS: We confirmed that intrathecal opioids benefit postoperative analgesia. Although morphine seems to be the most appropriate agent, some results were inconsistent, and the evidence confidence was often moderate or low, especially for adverse outcomes. Well-designed RCTs with an evidence-based approach are imperative for determining the most appropriate opioid for cesarean sections.

Comparison of anticoagulants and risk factors for bleeding following endoscopic sphincterotomy among anticoagulant users: Results from a large multicenter retrospective study.

BACKGROUND AND AIM: Bleeding is an inevitable and often severe complication after endoscopic sphincterotomy (EST). We aimed to investigate the factors associated with post-EST bleeding in patients treated with anticoagulants. METHODS: The data of patients who underwent EST at 15 hospitals between July 2015 and June 2017 were extracted. We investigated the incidence of post-EST bleeding and risk factors for bleeding in patients treated with anticoagulants. RESULTS: One hundred forty-nine patients undergoing EST who met the inclusion criteria were included in this study. The total-EST bleeding (bleeding occurring during or after EST) rate did not differ between the heparin replacement (8.0%, 6/75) and continuation (16.6%, 2/12; P = 0.37) groups of warfarin users. The total-EST-bleeding rate in the heparin replacement group (12.9%, 4/31) was significantly higher than that in the continuation group (0%, 0/31; P = 0.016) in direct oral anticoagulant (DOAC) users. The rate of total-EST bleeding with continuation of DOAC (0%, 0/31) was significantly lower with continuation of warfarin (16.6%, 2/12; P = 0.021). During-EST bleeding (bleeding occurring during EST) (P = 0.0083) and precut (P = 0.033) were significant risk factors for post-EST bleeding in all 149 patients. Heparin replacement was only a significant risk factor for total-EST bleeding (P = 0.033) in DOAC users. CONCLUSION: Heparin replacement was a significant risk factor for post-EST bleeding in DOAC users; however, there was no significant difference between the bleeding rate of heparin replacement and that of continuation groups in patients taking warfarin. During EST and precut were significant risk factors for post-EST bleeding in all patients treated with anticoagulants.

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.

How could we suspect life-threatening perinatal group A streptococcal infection?

AIM: Perinatal group A streptococcal infection is a rare but life-threatening condition. Few reports have focused on its clinical characteristics and how to prevent deterioration. We report our experience with two antenatal fatal cases and reviewed 96 cases in the literature to assess the clinical characteristics of group A streptococcal infection. METHODS: English-language clinical reports of antenatal and postnatal group A streptococcal infection in 1974-2019 were retrieved and examined. Relationships between clinical characteristics and maternal outcomes were assessed. RESULTS: Univariate analysis revealed that antenatal group A streptococcal infection was significantly associated with an age of ≤19 or ≥ 35 years, cesarean section, sore throat as an initial symptom, positive throat culture, maternal death and fetal death. Multivariate analysis revealed that antenatal onset (odds ratio = 7.922, 95% confidence interval = 1.297-48.374; P = 0.025) and a quick sepsis-related organ-failure assessment score (qSOFA; low blood pressure, high respiratory rate or altered mental status) of ≥2 (odds ratio = 6.166, 95% confidence interval = 1.066-35.670; P = 0.042) were significantly related to maternal death. CONCLUSION: Per our findings, antenatal group A streptococcal infection was significantly associated with maternal and fetal death. Further, the antenatal infection was revealed as a more critical risk factor. We suggest that the presence of any sign related to the qSOFA is a potential clue suspecting perinatal group A streptococcal infection in primary obstetric facilities.

Robotic rehabilitation of the paralyzed upper limb for a stroke patient using the single-joint hybrid assistive limb: a case study assessed by accelerometer on the wrist.

[Purpose] Recent studies have reported the effectiveness of robotic rehabilitation of paralyzed upper limbs in stroke patients. For example, the Single-Joint Hybrid Assistive Limb has been shown to improve upper limb impairments. However, limited data are available on the effectiveness of robotic rehabilitation of the upper limb with regards to daily living. In this case study, an accelerometer was adopted to examine whether rehabilitation using the Single-Joint Hybrid Assistive Limb improved upper limb activity during daily living in a stroke patient. [Participant and Methods] The participant was a 69-year-old male diagnosed with stroke and left hemiparesis. The Single-Joint Hybrid Assistive Limb was applied to the participant's elbow on the paralyzed side. The participant wore an accelerometer on each wrist to measure the activities of the upper limbs. Clinical tests of the paralyzed upper limb were also performed. [Results] The activity of the paralytic limb was significantly higher after Single-Joint Hybrid Assistive Limb intervention than before the intervention. On the other hand, none of the results of the clinical tests changed beyond a clinically important difference. [Conclusion] The Single-Joint Hybrid Assistive Limb could be useful for promoting active use of a paralyzed upper limb in daily living. In addition, an accelerometer could be especially useful for evaluating the effects of robotic rehabilitation.

The effects of skin cold stimulation on quadriceps muscle activity during walking in older adults.

Purpose: Given that walking speed declines with ageing and decreasing walking speed restricts activities of daily living (ADL), it is important for the old to maintain walking speed in order to prevent affecting ADL. Although skin cold stimulation (SCS) facilitates instantaneous muscle activity, which occurs during walking, the effects of SCS on muscle activity during walking remain unclear. Thus, the present study aimed to investigate the effect of SCS during walking in older adults.Methods: Seventeen community-dwelling healthy older adults (73 ± 6 years old) participated in this study. Walking speed at a comfortable pace and the electromyographic (EMG) activity of the vastus lateralis (VL) and biceps femoris (BF) were measured. SCS, which maintains the skin temperature at 25 °C, was applied to the front of the thigh during the procedures. Walking speed, root mean square EMG (rmsEMG) and mean power frequency (MPF) were compared under SCS and control conditions.Results: SCS significantly increased the walking speed (p < 0.01) and the rmsEMG of the vastus lateralis (p = 0.032). No change in the rmsEMG of the BF was observed, and SCS had no effect on MPF of both the VL and BF. Furthermore, a significant relationship was observed between these changes (r = 0.619, p = 0.042).Conclusion: SCS increased the EMG activity of the VL while increasing walking speed. Our results suggest that SCS is an effective strategy that can be included in daily life in order to improve walking ability of older adults.

Fibrinogen for the management of critical obstetric hemorrhage.

AIM: In cases of critical obstetric hemorrhage leading to extreme hypofibrinogenemia, fibrinogen is the marker that indicates the critical severity, and early fibrinogen supplementation centering on hemostatic resuscitation is a vital treatment to stabilize a catastrophic condition. In this review, we investigated the effect of fibrinogen level on hemostasis and what we can do to treat hypofibrinogenemia efficiently and improve patients' outcome. METHODS: We reviewed numerous articles related to hypofibrinogenemia in critical obstetric hemorrhage. Especially, we performed a systematic review on target value of fibrinogen for hemostasis and effectiveness of fibrinogen concentrate. We also reviewed the articles about the methods for early normalization of fibrinogen level such as tranexamic acid, massive transfusion protocol, and point-of-care testing. RESULTS: The target value of fibrinogen calculated by needs for massive transfusion was 200 mg/dL or 10 mm of A5FIBTEM . Although fibrinogen concentrate worked poorly on fibrinogen levels within the normal range, it improved the blood fibrinogen levels rapidly when it was administered to critical obstetric hemorrhage patients with serious hypofibrinogenemia. Hence, the volume of FFP transfused could be reduced along with a reduction in the frequency of pulmonary edema due to volume overload. CONCLUSION: The patient group for which fibrinogen concentrate works most effectively is cases with severe hypofibrinogenemia. Further research is required in the light of evidence. The essence of the transfusion algorithm in critical obstetric hemorrhage is to approach the target value for obtaining hemostasis, ensure an accurate and prompt grasp of the severity using point-of-care testing, introduce a massive transfusion protocol and use tranexamic acid.

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.

[Perinatal bone and calcium metabolism in the patient complicated with renal dysfunction.]

The incidence of pregnancy complicated with renal dysfunction has tended to increase due to aging and progress in the treatment methods. Generally, pregnancy is allowed only in women with normal renal function and in patients with mild renal insufficiency; therefore, the incidence of osteoporosis and the resulting fragile fracture is rare during pregnancy complicated with renal dysfunction. In recent years, the incidence of pregnancy in dialysis patients and in patients who have undergone kidney transplantation has been increasing due to the progress in treatment methods. Eventually, it has become possible for patients with renal dysfunction to give birth as long as they fulfill certain conditions for pregnancy; however, the rate of preterm births has remained high. The incidence of femoral neck fracture has been about 5 times more in dialysis patients than in healthy individuals; however, the prevention and treatment of osteoporosis in pregnant dialysis patients have been difficult, since many osteoporosis medications are contraindicated in pregnant women and also their pregnancy period is not long due to the higher rate of preterm births.

Prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancer in a Japanese hospital-based population.

BACKGROUND: The prevalence and molecular characteristics of defective mismatch repair epithelial ovarian cancers in the Japanese population have scarcely been investigated. METHODS: Immunohistochemistry for mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) was performed in formalin-fixed paraffin-embedded sections prepared from resected primary epithelial ovarian cancers in patients who underwent oophorectomy at our institution between April 2005 and September 2014. Genetic and/or epigenetic alterations of the mismatch repair genes were investigated in patients with loss of any mismatch repair proteins in the tumor. RESULTS: There were 305 patients with a median age of 54 years (range, 18-83 years). Loss of expression in the ovarian tumor of one or more mismatch repair proteins was observed in 3 of the 305 patients (0.98%): 2 patients MLH1/PMS2 loss and 1 patient showed MSH2/MSH6 loss. Genetic testing of these three patients failed to reveal any pathogenic germline mutations of MLH1 or MSH2. One patient with MLH1/PMS2 loss showed hypermethylation of the promoter region of MLH1. Somatic mutations were found in each of the alleles of MLH1 (c.545dupG and deletion of exons 2-19) in the other patient with MLH1/PMS2 loss. In the patient with MSH2/MSH6 loss, two somatic mutations were detected in MSH2 (c.229_230delAG and c.1861C>T), although we could not determine whether these mutations were biallelic or not. CONCLUSIONS: The prevalence of defective mismatch repair epithelial ovarian cancer in the Japanese hospital-based population was extremely low. Molecular mechanism involved in such defective mismatch repair ovarian cancers seems to be epigenetic events through MLH1 promotor hypermethylation or somatically mutated mismatch repair genes without germline mismatch repair mutation.

Complications with vacuum delivery from a forceps-delivery perspective: Progress toward safe vacuum delivery.

AIM: To examine the rates of medical malpractice and cerebral palsy after vacuum delivery in comparison with forceps delivery and establish approaches for enabling safe vacuum delivery from the perspective of forceps delivery. METHODS: This study reviewed the Japan Obstetric Compensation System report data, which contains data from studies involving 188 cases through May 2013, including cases of emergency delivery. These cases included 118 cases of cesarean section (62.8%) and 70 cases of vaginal delivery (37.2%). Of the 188 patients, 145 required emergency delivery (77.1%), of which cesarean sections were performed in 117 patients (80.7%), vacuum delivery in 24 patients (16.6%) and forceps delivery in 4 patients (2.8%). RESULTS: In evaluating the contents of the report with a focus on vacuum delivery, it was found that vacuum delivery was attempted in 35 patients, and delivery was successful in 24 of these patients (68.6%); however, in 11 patients (31.4%), delivery was unsuccessful and cesarean section was required. Thus, vacuum delivery was unsuccessful in approximately one third of the cases. CONCLUSION: For delivery to be completed as successfully and quickly as possible, it is essential for obstetricians to have a good understanding of the process of vacuum delivery, and to have expertise in the relevant techniques. However, it is also necessary to modify the indications under which vacuum delivery is considered safe to perform, from fetal station ±0, that is, engagement of the fetal head, to station +2, or descent of the fetal head.

Maternal peripartum septic shock caused by intrauterine infection with Edwardsiella tarda: A case report and review of the literature.

Edwardsiella tarda (E. tarda) is a rare pathogen in humans, especially during the peripartum period. Only a few cases of fatal neonatal infection with E. tarda have been reported. Herein, we describe a case of maternal septicemia caused by E. tarda following peripartum chorioamnionitis. The mother developed septic shock, disseminated intravascular coagulation and a post-cesarean wound hematoma with abscess. Her condition improved with multidisciplinary therapy including blood transfusion, antimicrobial agents, recombinant thrombomodulin and surgical debridement. E. tarda was isolated from the maternal blood, cesarean wound and neonatal skin, pharynx and gastric fluid. This case demonstrates that peripartum infection with E. tarda is a rare but life-threatening condition, not only for the neonate but also for the mother.