Therapeutic effect of dose-dense paclitaxel plus carboplatin with or without bevacizumab for Japanese patients with epithelial ovarian cancer.

BACKGROUND: Evidence regarding chemosensitivity to different therapeutic regimens in epithelial ovarian cancer (EOC) remains limited. This study aimed to investigate EOC implementation in daily clinical practice and reveal favorable regimens for EOC among Japanese patients. METHODS: We retrospectively collected clinical data of patients newly diagnosed with EOC from 2012 to 2021 at our affiliated institutions. We evaluated overall survival (OS) and progression-free survival (PFS) of conventional paclitaxel plus carboplatin (TC) vs. dose-dense TC (ddTC) according to the eligibility of GOG262 and JGOG3016 and those with bevacizumab (BEV) vs. without BEV based on GOG218. Further, we evaluated OS and PFS of ddTC and ddTC + BEV to TC + BEV among patients with stage III/IV. RESULTS: The ddTC group (n = 402) demonstrated longer PFS and OS than the TC group (n = 165) (adjusted hazard ratios [aHRs] [95% confidential intervals (CIs)]: 0.69 [0.55-0.88] and 0.67 [0.50-0.90], respectively). The group with BEV (n = 158) demonstrated a longer PFS than those without BEV (n = 296) (0.74 [0.57-0.95]), but not for OS (0.84 [0.60-1.17]). The ddTC and ddTC + BEV groups (n = 259 and 117) demonstrated no statistically significant differences in PFS and OS than the TC + BEV group (n = 75) (1.09 [0.79-1.50] and 0.74 [0.52-1.08] for PFS and 0.89 [0.59-1.34] and 0.73 [0.50-1.05] for OS, respectively). CONCLUSION: Our study may indicate ddTC, BEV, and their combination regimen as the promising first-line chemotherapy option among Japanese patients with advanced EOC.

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine.

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490.

Prolongation of the Menstrual Cycle After Receipt of the Primary Series and Booster Doses of mRNA Coronavirus Disease 2019 (COVID-19) Vaccination.

OBJECTIVE: To quantitatively evaluate the effect of a booster vaccination dose against coronavirus disease 2019 (COVID-19) on menstrual cycle in a large-scale retrospective cohort study using a menstrual cycle tracking smartphone application (app). METHODS: Prospectively or retrospectively recorded data, including the start and finish dates of menstrual cycles, were collected with the app. Detailed data on vaccinations, side effects, and participants' characteristics were retrospectively collected from a questionnaire on the app. For each COVID-19 vaccination shot (first, second, and third), within-individual changes in menstrual cycle length up to the fourth postvaccination cycle were evaluated. RESULTS: Among the 7,376 and 6,873 participants who had the first and second COVID-19 vaccine doses in different menstrual cycles, respectively, menstrual cycles immediately after the vaccination (first postvaccination cycles) were an average of 0.22 days (95% CI, 0.06-0.39) and 0.37 days (95% CI, 0.20-0.54) longer than the prevaccination cycle. In contrast, among the 1,672 participants who received the first and second doses in the same cycle, the first postvaccination cycle was an average of 4.21 days (95% CI, 3.69-4.72) longer. The second to fourth postvaccination cycles returned to the level of the prevaccination cycle. However, among the 4,768 participants who had the third COVID-19 vaccine dose, the menstrual cycle immediately after the vaccination was an average of 1.20 days (95% CI, 1.00-1.40) longer, with prolongation of cycles of 0.27 days (95% CI, 0.10-0.44) to 0.41 days (95% CI, 0.22-0.59) persisting from the second to the fourth postvaccination cycle. CONCLUSION: The booster shot against COVID-19 may have a greater and longer-lasting effect on menstrual cycles than the primary-series shots. Although the effect size was small, evidence on the side effects of immunization on menstruation should be accumulated.

Novel therapeutic strategies for injured endometrium: intrauterine transplantation of menstrual blood­derived cells from infertile patients.

BACKGROUND: Menstrual blood-derived cells show regenerative potential as a mesenchymal stem cell and may therefore be a novel stem cell source of treatment for refractory infertility with injured endometrium. However, there have been few pre-clinical studies using cells from infertile patients, which need to be addressed before establishing an autologous transplantation. Herein, we aimed to investigate the therapeutic capacity of menstrual blood-derived cells from infertile patients on endometrial infertility. METHODS: We collected menstrual blood-derived cells from volunteers and infertile patients and confirmed their mesenchymal stem cell phenotype by flow cytometry and induction of tri-lineage differentiation. We compared the proliferative and paracrine capacities of these cells. Furthermore, we also investigated the regenerative potential and safety concerns of the intrauterine transplantation of infertile patient-derived cells using a mouse model with mechanically injured endometrium. RESULTS: Menstrual blood-derived cells from both infertile patients and volunteers showed phenotypic characteristics of mesenchymal stem cells. In vitro proliferative and paracrine capacities for wound healing and angiogenesis were equal for both samples. Furthermore, the transplantation of infertile patient-derived cells into uterine horns of the mouse model ameliorated endometrial thickness, prevented fibrosis, and improved fertility outcomes without any apparent complications. CONCLUSIONS: In our pre-clinical study, intrauterine transplantation of menstrual blood-derived cells may be a novel and attractive stem cell source for the curative and prophylactic therapy for injured endometrium. Further studies will be warranted for future clinical application.

Analysis of the Factors That Affect the Detection Duration of SARS-CoV-2 in Loop Mediated Isothermal Amplification among COVID-19 Inpatients.

In COVID-19 patients who are immunocompromised or have severe COVID-19, the duration of infectious viral shedding may be longer, and a longer isolation duration is recommended. At the National Sagamihara Hospital, a decline in the viral load to end the isolation of hospitalized patients with COVID-19 was confirmed using loop-mediated isothermal amplification (LAMP). However, a subset of patients displayed LAMP positivity for more than 20 days after symptom onset. Therefore, we conducted a retrospective observational study to investigate the factors that affect the persistence of LAMP positivity. This study included a total of 102 participants. The severity of COVID-19 was mild (25.5%), moderate (67.6%), or severe (6.9%). The median number (interquartile range) of days until negative LAMP results from symptom onset were 16 (14-19) days. Multivariate logistic regression analysis showed that patients ≥55 years and/or those with the delta variant were correlated with persistent LAMP positivity for more than 20 days after symptom onset. This study identified age, the delta variant, and oxygen requirement as factors that contribute to persistently positive LAMP results. Therefore, it is posited that in these patients, the implementation of LAMP for deisolation would result in a prolonged isolation duration.

Predictive factors for vaginal delivery by induction of labor in uncomplicated pregnancies at 40-41 gestational weeks: A Japanese prospective single-center cohort study.

AIM: We investigated cervical parameters predictive of vaginal delivery in elective labor induction among women at 40-41 gestational weeks. METHODS: This Japanese prospective single-center cohort study was conducted between July 2019 and June 2020. We enrolled women with an uncomplicated singleton pregnancy who underwent labor induction at 40-41 gestational weeks. We analyzed background characteristics and cervical parameters, including Bishop score, cervical length, posterior cervical angle, and changes in cervical parameters before and after cervical dilatation. The endpoint was the rate of vaginal delivery. RESULTS: Of 142 eligible participants, all 24 multiparous women underwent vaginal delivery. Among the nulliparous women (n = 118), the following categories showed significantly higher rates of vaginal delivery: Bishop scores of ≥6 before and after dilatation, compared with Bishop score <6 (adjusted prevalence ratio (aPR) [95% confidence interval (CI)]; 1.58 [1.17-2.13] and 1.56 [1.13-2.14], respectively) and cervical length of <10 and 10-20 mm before dilation, compared with cervical length of >30 mm (aPR [95% CI]; 1.47 [1.00-2.15] and 2.13 [1.42-3.18], respectively). The posterior cervical angle and other background characteristics showed no significant associations. Furthermore, women with cervical lengths of ≥20 mm before and <20 mm after dilatation showed a higher rate of vaginal delivery, compared to cervical length of ≥20 mm even after dilatation (aPR [95% CI]; 1.95 [1.19-3.20]). CONCLUSIONS: High Bishop score, short cervical length, and changes in cervical length with dilatation are potential independent predictors of vaginal delivery following elective labor induction in nulliparous women at 40-41 gestational weeks.

Association between fetal sex and pregnancy outcomes among women with twin pregnancies: a multicenter cross-sectional study.

PURPOSE: To examine the frequency and to what extent fetal sex is associated with pregnancy outcomes among twin pregnancies, stratified by chorionicity. METHODS: This registry-based multicenter cross-sectional study was conducted using the Japan Society of Obstetrics and Gynecology perinatal database between 2007 and 2016. The sample population was restricted to women with twin pregnancies. The main pregnancy-related outcomes included preterm birth, very preterm birth, extremely preterm birth, preeclampsia, twin-to-twin transfusion syndrome (TTTS), and selective intrauterine growth restriction (s-IUGR). Birth weight, small for gestational age (SGA), and fetal death were also investigated. RESULTS: The primary analysis was performed based on 37,953 women, including 23,804 women with dichorionic diamniotic (DD) twins and 14,149 women with monochorionic diamniotic (MD) twins. Women with male/male DD twins had a significantly higher risk of preterm birth (adjusted risk ratio [aRR]: 1.07, 95% confidence interval [CI]: 1.03-1.10) and a lower risk of preeclampsia (aRR: 0.74, 95% CI: 0.62-0.88) than women with female/female DD twins. Women with male/male MD twins also had a significantly higher risk of preterm birth (aRR: 1.06, 95% CI: 1.04-1.09) than women with female/female MD twins. Risks of preeclampsia, TTTS, and s-IUGR did not differ by sex among MD pregnancies. Male SGA risk was significantly higher among male/male twins than among male/female DD twins. Among MD twins, risks of SGA and fetal death were significantly higher in male/male fetuses. CONCLUSIONS: This study demonstrated significant associations between fetal sex and several pregnancy outcomes in twin pregnancies, some of which differed by chorionicity.

Gestational glycosuria, proteinuria, and borderline hypertension in pregnancy are predictors for the later onset of maternal chronic disease.

AIM: Although hypertensive disorders of pregnancy and gestational diabetes mellitus (DM) are risk factors for hypertension, DM, and kidney disease in later life, the association of gestational glycosuria, proteinuria, and borderline hypertension with these chronic diseases has been unclear. METHODS: This cross-sectional study was conducted between April 2017 and November 2020 at a Japanese tertiary hospital. Three variables listed in the Maternal and Child Health Handbook were analyzed: glycosuria, proteinuria, and systolic blood pressure (<130, 130-139, and ≥ 140 mmHg) during pregnancy. The incidences of DM, kidney disease, and hypertension self-reported by mothers of pregnant women on a questionnaire were assessed with logistic regression analysis. RESULTS: The 312 women completed the questionnaires an average of 35.8 ± 4.2 years after delivering their daughters. Risk for DM was significantly increased among women with glycosuria (adjusted odds ratio [aOR], 3.62; 95% confidence interval [CI], 1.21-10.9), and risk for kidney disease was significantly increased among women with proteinuria (aOR, 4.07; 95% CI, 1.29-12.9). Risk for hypertension was significant in women whose blood pressures were ≥ 140 mmHg (aOR, 4.26; 95% CI, 1.96-9.24), but the association between blood pressures of 130-139 mmHg and hypertension was not significant (aOR, 1.72; 95% CI, 0.95-3.11); however, a significant positive trend (p < 0.001) between increasing blood pressure and hypertension was observed. CONCLUSIONS: Gestational glycosuria, proteinuria, and increased blood pressure were associated with the development of maternal chronic diseases. These standard and inexpensive assessments may improve lifelong health management in women.

Quantitative assessment of coat-hanger ribs detected on three-dimensional ultrasound for prenatal diagnosis of Kagami-Ogata syndrome.

Kagami-Ogata syndrome (KOS14) is a rare disease characterized by omphalocele, polyhydramnios and a bell-shaped thorax. Although the coat-hanger appearance of the ribs on postnatal X-rays is a key diagnostic finding of KOS14, its prenatal diagnosis remains challenging. We encountered a case of KOS14 diagnosed prenatally that showed omphalocele, polyhydramnios, and a bell-shaped narrow thorax. The coat-hanger angle (CHA) measured at the sixth thoracic vertebrae and the ribs using three-dimensional (3D) ultrasonography was 39°, reflecting the coat-hanger appearance of the ribs. Segmental uniparental disomy chromosome 14 (UPD(14)pat) was confirmed by a methylation analysis and microsatellite analysis after birth. The median CHA (minimum, maximum) in 25 normal fetuses was 19 (9, 26) degrees, and a sonographic CHA of 30° may be a border value for diagnosing KOS14. When the combination of omphalocele and polyhydramnios is found prenatally, 3D ultrasonography for CHA might aid in the differential diagnosis of KOS14.

Scoring Systems of Peritoneal Dissemination for the Prediction of Operative Completeness in Advanced Ovarian Cancer.

BACKGROUND/AIM: We investigated the predictive value of scoring systems of peritoneal disseminations for complete surgery (CS) at primary debulking surgery (PDS) in advanced ovarian cancer. PATIENTS AND METHODS: We retrospectively enrolled eligible patients with clinical stages III or IVA selected for PDS from January 2015 to December 2019. Concern variables were predictive index value (PIV) and peritoneal cancer index (PCI) from operative and pathological reports. Primary endpoints were cutoffs to predict operative completeness using the receiver operating characteristic curve. RESULTS: Among 111 patients, PIV ≥8 and PCI ≥13 were the best predictors of incomplete PDS, including optimal and suboptimal surgeries (AUC=0.821 and 0.855, respectively). CS rates in PIV ≤6 and PCI ≤12 were significantly higher than in PIV ≥8 (89.3% vs. 47.2%; p<0.05) and PCI ≥13 (90.9% vs. 41.2%: p<0.05). CONCLUSION: PIV and PCI are potential predictors for CS at PDS.

Clinical Availability of Tumour Biopsy Using Diagnostic Laparoscopy for Advanced Ovarian Cancer.

BACKGROUND/AIM: Tumour biopsy using laparoscopy before neoadjuvant chemotherapy for advanced ovarian cancer has been widely accepted. However, there are few reports about its operative outcome compared to biopsy with laparotomy. We investigated the advantage of laparoscopic biopsy for advanced ovarian cancer. PATIENTS AND METHODS: We included 23 patients who underwent laparoscopy and 27 who underwent exploratory laparotomy before neoadjuvant chemotherapy between January 2012 and August 2020. We reviewed their medical records and evaluated their operative outcomes. RESULTS: Blood loss was significantly lower in the laparoscopy group (5 ml vs. 320 ml, p<0.05). The period until the initiation of neoadjuvant chemotherapy was significantly shorter in the laparoscopy group (12 days vs. 16 days, p<0.05). Overall survival did not differ significantly between the two groups (25.4 months vs. 24.7 months, p=0.53). CONCLUSION: Laparoscopic tumour biopsy is useful and safe for histological diagnosis, thereby allowing for early introduction to neoadjuvant chemotherapy.

A rare case of heterotopic pregnancy after a single embryo transfer: A case report and literature review.

Heterotopic pregnancy (HP) is a rare but life-threatening disease. We report a rare case of HP that occurred after single embryo transfer (SET) with spontaneous natural pregnancy possibly due to sexual intercourse (SI) during assisted reproductive technology treatment and reviewed previous reports. A 39-year-old woman at 7 weeks 5 days' gestation with anti-sperm antibody who underwent a single frozen-thawed embryo transfer in her natural cycle presented with lower abdominal pain and vaginal bleeding. She had several SIs before the day of SET. A viable intrauterine fetus and an extrauterine mass at the right adnexa were detected on transvaginal ultrasonography. An emergent laparoscopic surgery showed a swollen right fallopian tube, and right salpingectomy was performed. Unfortunately, intrauterine fetal death was diagnosed at 19 weeks' gestation. In conclusion, the possibility of HP should be considered in patients with SIs around the day of SET.

A case of recurrence of adult-onset Still's disease in the third trimester: a case report and literature review.

BACKGROUND: Adult-onset Still's disease (AOSD) is a self-inflammatory disease showing macrophage and neutrophil activation by inflammatory cytokines such as TNF-α, IL-6, and IL-18. Although some cases with the flare of AOSD during pregnancy have been reported, most had flares in the first or second trimester and few had flares in the third trimester. In this report, we present the case of a patient with recurrent flare of AOSD in the third trimester and discuss the management of AOSD in the third trimester with the review of previous literatures. CASE PRESENTATION: A 38-year-old woman in complete AOSD remission without medication presented with impaired liver function, low platelet count, mild fever, abdominal pain, splenomegaly, and elevated ferritin and IL-18 levels at 30 gestational weeks. Although the laboratory data and physical examination finding suggested HELLP syndrome or acute fatty liver of pregnancy and we considered the termination of her pregnancy, her fetus was in a reactive status. Considering her fetal status, some specific findings of AOSD, and her AOSD history, we and rheumatologists diagnosed her with AOSD recurrence and started systemic steroid therapy. In her clinical course, three flares of AOSD occurred, twice in the third trimester and once in postpartum; twice systemic steroid pulse therapies were then needed. Ultimately, a healthy infant was delivered transvaginally at 36 gestational weeks spontaneously. CONCLUSIONS: Specific findings of the flare of AOSD such as fever, splenomegaly, elevated ferritin and IL-18 levels, and fetal status could be useful findings for differentiation from HELLP syndrome and AFLP in the third trimester. With the careful management supported by rheumatologists, patients complicated with the flare of AOSD may continue their pregnancy longer than we expected.

Leuconostoc lactis and Staphylococcus nepalensis Bacteremia, Japan.

Leuconostoc lactis is a glycopeptide-resistant, gram-positive, facultative anaerobic coccus isolated from dairy products, whereas Staphylococcus nepalensis is coagulase-negative coccus that has not been identified as human pathogen. We report an instructive case of L. lactis and S. nepalensis bacteremia in a 71-year-old man who experienced Boerhaave syndrome after a meal.

Zero-field slow relaxation of magnetization in cobalt(ii) single-ion magnets: suppression of quantum tunneling of magnetization by tailoring the intermolecular magnetic coupling.

The correlation between magnetic relaxation dynamics and the alignment of single-ion magnets (SIMs) in a crystal was investigated using four analogous cobalt(ii) complexes with unique hydrogen-bond networks. The hydrogen-bonding interactions in the crystals resulted in a relatively short intermolecular Co⋯Co distance, which led to non-zero intermolecular magnetic coupling. All the complexes with a Co⋯Co distance shorter than 6.5 Å exhibited zero-field slow magnetic relaxation as weak magnetic interactions split the ground ±Ms levels and suppressed quantum tunneling of magnetization (QTM). In particular, antiferromagnetically coupled one-dimensional chain SIM networks effectively suppressed QTM when the two intrachain Co⋯Co distances were non-equivalent. However, when the two distances in a chain were equivalent and each molecular symmetry axis aligned parallell within the chain, QTM suppression was insufficient because magnetic coupling from the adjacent molecules was virtually cancelled. Partial substitution of the CoII ion with the diamagnetic ZnII ion up to 33% for this complex resulted in complete QTM suppression in the absence of an external field. These results show that the manipulation of intermolecular distances and alignments is effective for suppressing undesired QTM events in SIMs.

[A Patient with Breast Cancer Who Achieved Continued Clinical Complete Response after Systemic Therapy Alone].

A 53-year-old woman presented at our hospital because of a mass in the left breast. A mass measuring 2 cm in diameter was palpated in the upper outer region(C region)of the left breast. Mammography showed a mass with calcification. Mammary ultrasonography showed a mass measuring 18×16×14mm and enlarged lymph nodes in the left axillary region. Core needle biopsy revealed Luminal B invasive ductal carcinoma(scirrhous type). The estrogen receptor(ER)positivity was 95%, progesterone receptor(PgR)positivity was 60%, human epidermal growth factor receptor type 2(HER2)score was 2+, fluorescence in situ hybridization(FISH)showed no amplification, and Ki-67 index was 60%. Clinical T1N1M0, StageⅡA cancer was thus diagnosed. As preoperative chemotherapy, the patient received 4 courses of treatment containing epirubicin (100mg/m2), 5-fluorouracil(500mg/m2), and cyclophosphamide(500mg/m2; FEC100), and 4 courses of treatment containing docetaxel and cyclophosphamide(TC). Clinical complete response(cCR)was confirmed on imaging studies. The patient was explained about the need for surgery, but she refused to undergo surgery. The patient is being followed up while receiving endocrine therapy, and there has been no recurrence or metastasis as of 2 years. We described our encounter with a patient with breast cancer who refused surgery after preoperative chemotherapy and has had no recurrence or metastasis during follow-up.

Hydrogen-bonding interactions and magnetic relaxation dynamics in tetracoordinated cobalt(ii) single-ion magnets.

Three tetracoordinated cobalt(ii) complexes with a series of unsymmetrical bidentate ligands were synthesized and crystallographically characterized. Although their static magnetic properties are similar, their dynamic magnetic properties differ drastically depending indirectly on intermolecular hydrogen-bonding interactions.

[Which Should be Treated First - Breast Cancer or Uterine Myoma?]

The patient was a 51-year-old woman with a mass in the left breast.At the first presentation, she had abdominal distension and liver dysfunction.Mammography showed a category 5 mass in the left breast and a category 4, unstructured region in the right breast.Pathological examination revealed bilateral, invasive ductal carcinomas.Stage II B disease(clinical T2N1M0)was diagnosed in the left breast, and Stage I disease(clinical T1N0M0)was diagnosed in the right breast.Computed tomography revealed a massive uterine myoma compressing the inferior vena cava.Liver dysfunction was suspected to be caused by these factors.Preoperative chemotherapy was scheduled to treat breast cancer.A gynecologist stated that "uterine myoma is unlikely to cause liver dysfunction" and refused to perform a hysterectomy.However, we diligently negotiated with him to avoid chemotherapy-induced venous thrombosis and pulmonary infarction; eventually, a hysterectomy(3.6 kg)was performed. After surgery, liver function was normal.Subsequently, breast cancer could be safely and adequately treated.In patients who have benign disease, as well as malignant tumors, treatment of the malignant tumors is generally given the highest priority.However, there are cases when the treatment of benign disease has priority over the treatment of malignant tumors.It is therefore important to intensively discuss such cases with physicians from other departments.