Regional Disparities in Transvenous Lead Extraction for Cardiac Implantable Electronic Device Infection in Japan　- A Descriptive Study Using the National Database Open Data.

BACKGROUND: Because the penetration of transvenous lead extraction (TLE) for cardiac implantable electronic device (CIED) infection has not been investigated in Japan, we conducted a population-based, retrospective, descriptive study to evaluate regional disparities in the use of TLE for CIED infection and the potential undertreatment of CIED infection using a nationwide insurance claims database.Methods and Results: Patients who underwent CIED implantation or generator exchange and TLE between April 2018 and March 2020 were identified. Moreover, the penetration ratio of TLE for CIED infection in each prefecture was estimated. CIED implantation and TLE were most prevalent in the age categories of 80-89 years (40.3%) and 80-89 years (36.9%), respectively. There was no correlation between the number of CIED implantations and that of TLE (rho=-0.087, 95% confidence interval -0.374 to 0.211, P=0.56). The median penetration ratio was 0.00 (interquartile range 0.00-1.29). Of the 47 prefectures, 6, comprising Okinawa, Miyagi, Okayama, Fukuoka, Tokyo, and Osaka, showed a penetration ratio ≥2.00. CONCLUSIONS: Our study data indicated great regional disparities in the penetration of TLE and potential undertreatment of CIED infection in Japan. Additional measures are needed to address these issues.

Zone Formation of Lymphocyte Infiltration at Invasive Front as a Biomarker of Prognosis in Endometrial Carcinomas.

OBJECTIVE: The clinical significance of lymphocyte infiltration (LI) at the invasive front in endometrial carcinomas (EC) has not been determined. The aim of the current study was to evaluate the association between zone formation of LI at the invasive front of the tumor margin and prognoses of the patients with EC. METHODS: All available pathological slides of the enrolled cases were reviewed, and the degree of LI at the invasive front was categorized into 2 groups: strong LI and weak LI. Clinical significance of LI was evaluated retrospectively. RESULTS: A total of 333 cases with EC were enrolled in the study: 225 cases with weak LI and 108 cases with strong LI. Weak LI was more frequently observed in the patients with grade1/2 endometrioid EC. Multivariate analyses for progression-free survival (PFS) and overall survival (OS) revealed that weak LI was identified as an independent worse prognostic factor for OS (p = 0.004) in addition to PFS (p = 0.022). CONCLUSION: Weak LI at the invasive front of the tumor margin was associated with worse prognoses in EC. Although further studies are needed, it is suggested that LI could be a biomarker of prognoses in EC.

Pretreatment Neutrophil-to-Lymphocyte Ratio Was a Predictor of Lymph Node Metastasis in Endometrial Cancer Patients.

OBJECTIVE: The pretreatment neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) have been reported to be useful as markers for prognostic factors and metastasis in several cancers. The aim of this study was to identify the predictor of lymph node (LN) metastasis by pretreatment NLR and PLR in patients with endometrial cancer. METHODS: Medical charts of the patients with endometrial cancers that received primary surgery at our hospital between 2007 and 2013 were retrospectively analyzed. The cutoff value was calculated from the receiver operating characteristics (ROC) curve. Clinicopathological parameters including inflammatory markers were evaluated for LN metastasis using multiple logistic regression analysis. RESULTS: Among 197 patients enrolled in the study, LN metastasis was observed in 25 patients (13%). ROC curves demonstrated that the best cutoff value of NLR for predicting LN metastasis was 2.18 and that of PLR was 206. In univariate analysis, several pathological factors, NLR, and PLR were identified as predictors of LN metastasis. In multiple logistic regression analysis, lymphovascular invasion and NLR were found to be significantly correlated with LN metastasis (p = 0.002, 0.039). CONCLUSION: A higher pretreatment NLR was identified as a predictor of LN metastasis in endometrial cancers. Although further study is needed to confirm the results, NLR could be a candidate clinical marker for detection of LN metastasis.

Thrombotic events induce the worse prognosis in ovarian carcinomas and frequently develop in ovarian clear cell carcinoma.

BACKGROUND: This study aimed to examine the clinical significance and risk factors of thromboembolic events (TEEs) in patients with ovarian carcinoma. METHODS: Patients with ovarian carcinoma treated at our hospital between 2000 and 2017 were identified. The risk factors of TEEs, including venous TEEs and arterial TEEs, and the association between TEEs and prognosis were investigated. Patients with TEEs were classified into two groups: those with severe TEEs, defined as patients who required urgent treatment for deep vein thrombosis, massive pulmonary embolism, acute myocardial infarction, and symptomatic cerebral infarction, and those with mild TEEs. The risk factors of severe TEEs and the association between severe TEEs and prognosis were investigated. RESULTS: A total of 369 patients were enrolled. Among them, 53 patients (14.4%) were complicated with TEEs. Clear cell carcinoma (CCC) was a greater risk factor of TEEs than serous carcinoma (hazard ratio [HR] = 2.81, p = 0.03). In multivariate analysis for survival, TEEs were a prognostic factor of poor progression-free survival (PFS; HR = 2.90, p < 0.01) and overall survival (OS; HR = 2.89, p < 0.01). Among 53 patients with TEEs, 17 (32.1%) developed severe TEEs. CCC was strongly associated with severe TEEs (HR = 42.6, p = 0.02). Multivariate analysis for survival demonstrated that severe TEEs were a risk factor of worse PFS (HR = 4.34, p < 0.01) and OS (HR = 3.30, p = 0.03). CONCLUSION: TEEs induced poor prognosis and was associated with CCC. A standard treatment for CCC should be included in the strategy of TEEs.

Measurement of blood-oxygen saturation using a photoacoustic technique in the rabbit hypoxemia model.

The golden standard method to obtain accurate blood oxygen saturation is blood gas analysis that needs invasive procedure of blood sampling. Photoacoustic technique enables us to measure real-time blood oxygen saturation without invasive procedure. The aim of this study is to use the photoacoustic technique, an optical method, for accurately determining oxygen saturation in vivo. We measured induced photoacoustic signals of arterial blood in the rabbit model of stable hypoxemia after irradiation at 750 and 800 nm. Oxygen saturation was calculated from the photoacoustic signals using two calibration curves. Calibration curve 1 is a conventional curve derived from the absorbance coefficient of hemoglobin, whereas calibration curve 2 is derived from the photoacoustic signals obtained from the original blood vessel model. Simultaneously, blood-gas analysis was performed to obtain the reference standard of oxygen saturation. Regression analysis and Bland-Altman analysis were performed to assess the accuracy of oxygen saturation obtained using the two methods. The oxygen saturation calculated using calibration curves 1 and 2 showed strong correlations with the reference standard in regression analysis (R = 0.965, 0.964, respectively). The Bland-Altman analysis revealed better agreement and precision with calibration curve 2, whereas there was significant underestimation of values obtained using calibration curve 1. Photoacoustic measurement of oxygen saturation using calibration curve 2 provided an accurate estimate of oxygen saturation, which was similar to that obtained using a portable blood-gas analyzer.

Small Foci of Serous Component as a Predictor of Recurrence and Prognosis for Stage IA Endometrial Carcinomas.

OBJECTIVE: Most of the endometrial carcinomas are detected in early stages and have a better prognosis; however, predictive factors for recurrence have not been determined. METHODS: Patients with grade 1 endometrioid carcinoma (EG1) according to the 2014 WHO criteria at FIGO 2009 stage IA that were identified through scanning medical charts were included, and we assessed whether the presence of uterine serous carcinoma (SC) component which comprised less than 5% of the total volume using the ovarian two-tiered grading system could be a recurrent risk factor in these patients. RESULTS: Among 126 cases which met inclusion criteria, 12 cases had SC. SC tumors were divided into 2 groups: SC resembling high-grade serous carcinoma (HGSC) and SC resembling low-grade serous carcinoma (LGSC). Five (3.9%) cases had HGSC and 7 (5.6%) cases had LGSC. Recurrence was observed in 3 of all cases (2.3%): 2 cases with HGSC, and 1 case with LGSC. Regarding several clinicopathological factors, only the presence of SC was associated with recurrence. The sensitivity and specificity to predict recurrence using this system were 100 and 93%, respectively. CONCLUSION: The identification of SC using the ovarian two-tiered grading system could be an accurate predictor of recurrence in stage IA EG1.

Multiple placental surface cysts with intracystic hemorrhaging: A case report and review of the literature.

A placental surface cyst is a cystic mass arising from the surface of the placenta. It is seldom complicated by intracystic hemorrhaging and the clinical importance of this kind of case is unclear. Therefore, we present a case of a placental surface cyst with intracystic hemorrhaging. A 29-year-old multiparous woman was diagnosed with multiple placental surface cysts with threatened preterm birth and fetal growth restriction on ultrasonography at 26 gestational weeks (GW). At 31 GW, the hemorrhage was identified inside the cyst. At 32 GW, she presented with placental abruption, and emergency cesarean section was performed. Both the mother and her baby survived. Placental surface cysts up to 77 × 65 mm in diameter containing old hemorrhages were discovered, and pathological examination revealed hemosiderin and fibrin deposition. Pregnancy with a placental surface cyst with intracystic hemorrhaging may have the potential for severe obstetric complications.

Effect of routine rapid insertion of Bakri balloon tamponade on reducing hemorrhage from placenta previa during and after cesarean section.

PURPOSE: To evaluate the effectiveness of routine rapid insertion of a Bakri balloon during cesarean section for placenta previa based on a retrospective control study. METHODS: Women with singleton pregnancies who underwent cesarean section for placenta previa at our institution between 2003 and 2016 were enrolled. Between 2015 and 2016, women who routinely underwent balloon tamponade during cesarean section were defined as the balloon group. Between 2003 and 2014, women who underwent no hemostatic procedures except balloon tamponade were defined as the non-balloon group. The clinical outcomes of the two groups were retrospectively analyzed. RESULTS: Of the 266 women with placenta previa, 50 were in the balloon group and 216 were in the non-balloon group. The bleeding amounts were significantly smaller in the balloon group than in the non-balloon group: intraoperative bleeding (991 vs. 1250 g, p < 0.01), postoperative bleeding (62 vs. 150 g, p < 0.01), and total bleeding (1066 vs. 1451 g, p < 0.01). Furthermore, the mean surgical duration was shorter in the balloon group than the non-balloon group (30 vs. 50 min, p < 0.01). In the balloon group, five patients suffered from increasing hemorrhage due to prolapse of the balloon from the uterus after the operation, but the hemorrhage was controlled by balloon re-insertion without additional hemostatic procedures. CONCLUSIONS: This study demonstrated that the routine rapid insertion of Bakri balloon tamponade during cesarean section significantly decreased intra- and postoperative hemorrhage and shortened the surgical duration in women with placenta previa.

Cervical varicosities may predict placenta accreta in posterior placenta previa: a magnetic resonance imaging study.

PURPOSE: The aim of this study was to prenatally predict placenta accreta in posterior placenta previa using magnetic resonance imaging (MRI). METHODS: This retrospective study was approved by the Institutional Review Board of our hospital. We identified 81 patients with singleton pregnancy who had undergone cesarean section due to posterior placenta previa at our hospital between January 2012 and December 2016. We calculated the sensitivity and specificity of several well-known findings, and of cervical varicosities quantified using magnetic resonance imaging, in predicting placenta accreta in posterior placenta previa. To quantify cervical varicosities, we calculated the A/B ratio, where "A" was the minimum distance from the most dorsal cervical varicosity to the deciduous placenta, and "B" was the minimum distance from the most dorsal cervical varicosity to the amniotic placenta. The appropriate cut-off value of the A/B ratio was determined using a receiver operating characteristic (ROC) curve. RESULTS: Three patients (3.7%) were diagnosed as having placenta accreta. The sensitivity and specificity of the well-known findings were 0 and 97.4%, respectively. Furthermore, the A/B ratio ranged from 0.02 to 0.79. ROC curve analysis revealed that the area under the combined placenta accreta and A/B ratio curve was 0.96. When the cutoff value of the A/B ratio was set 0.18, the sensitivity and specificity were 100 and 91%, respectively. CONCLUSION: It was difficult to diagnose placenta accreta in the posterior placenta previa using the well-known findings. The quantification of cervical varicosities could effectively predict placenta accreta.

High Expression of p62 Protein Is Associated with Poor Prognosis and Aggressive Phenotypes in Endometrial Cancer.

High expression of SQSTM1/p62 (p62) protein, which functions as a hub of oncogenic signaling pathways, has been detected in several human cancers. However, the clinicopathological and functional contribution of p62 expression is largely unknown in endometrial cancers (ECs). In this study, we assessed the expression status of p62 in primary ECs (n = 194) by immunohistochemistry and analyzed its clinical significance. Although p62 was expressed in the cytoplasm and/or nucleus in primary ECs, we observed that an expression subtype, high expression of cytoplasmic p62 but low expression of nuclear p62 (cytoplasm(High)/nucleus(Low)), significantly correlated with nonendometrioid types (P = 0.002), high grade (P < 0.001), deep myometrial invasion (P = 0.025), vascular invasion (P = 0.012), and poor prognosis (P < 0.001), and may be an independent prognostic marker of ECs (P = 0.011). Furthermore, RNA interference-mediated inhibition of p62 expression in the HEC-1A EC cell line led to the reduction of invasiveness and resistance to oxidative stress in vitro, as well as the suppression of in vivo tumor growth in an orthotopic mouse model of ECs. High expression of cytoplasmic p62 is a novel prognostic biomarker of ECs, and excess p62 expression may functionally contribute to the acquirement of malignant phenotypes in EC cells.

Is Modified Radical Hysterectomy Needed for Patients with Clinical Stage I/II Endometrial Cancers? A Historical Control Study.

OBJECTIVE: The aim of the present study was to assess whether hysterectomy with wider resection could improve survival by preventing local recurrence. METHODS: Medical charts of the patients with clinical stage I/II endometrial cancers treated at our hospital between 1990 and 2009 were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse effects according to the type of hysterectomy. RESULTS: A total of 247 patients were identified: 46 patients treated with total abdominal hysterectomy (TAH group) and 201 patients with modified radical hysterectomy (mRH group). No significant differences were observed in OS (p = 0.52) and PFS (p = 0.67) between the two groups. Also, there was no significant difference in the distribution of recurrent sites between the two groups. The patients treated with mRH had a longer operation time and more frequently developed severe adverse events, such as blood loss and lymphedema. CONCLUSION: In our cohorts, there were no significant differences in both PFS and OS according to surgical procedures, and the mRH group more frequently developed severe adverse events. Overall, clinical benefit was not obtained by mRH in patients with clinical stage I/II endometrial carcinomas.

Appropriate timing of blood sampling for blood gas analysis in the ventilated rabbit.

BACKGROUND: Arterial and venous blood gas analyses (BGAs) are essential to evaluate devices that measure biological oxygenation. The appropriate timing of blood sampling for BGA after respiratory rate (RR) change in animal experiments has not been reported. This study investigated the appropriate timing of blood sampling for BGA in ventilated rabbits and whether venous samples are an alternative to arterial samples. MATERIALS AND METHODS: Under general anesthesia, 14 rabbits (body weight, 3.02 ± 0.09 kg) were ventilated and their RR was changed (40/min, 30/min, and 20/min). Blood was sampled through cervical arterial and venous catheters. Experiment 1: in seven rabbits, arterial BGA was measured at 0, 0.5, 1, 2, 3, 5, 10, 15, and 20 min after the RR change. Experiment 2: in seven different rabbits, simultaneous arterial and venous BGA were measured at 0, 2, 5, 10, 15, and 20 min after the RR change. RESULTS: Oxygen partial pressure (PO2) and saturation (SO2) of the arterial blood stabilized 0.5 min after the RR changed. In venous BGA, no index stabilized during observation. The arterial and venous values of the carbon dioxide partial pressure (PCO2) and pH had significant correlations (arterial PCO2 = 0.9316 × venous PCO2-4.4425 [r = 0.9178]; arterial pH = 1.0835 × venous pH-0.5795 [r = 0.9453]). CONCLUSIONS: In ventilated rabbits, arterial PO2 and SO2 stabilized in 0.5 min. No venous value stabilized after the RR change. Only the PCO2 and pH of venous samples may be an alternative to arterial samples under the defined formula.

Analytical approach to transforming filter design for sound field recording and reproduction using circular arrays with a spherical baffle.

A sound field recording and reproduction method using circular arrays of microphones and loudspeakers with a spherical baffle is proposed. The spherical baffle is an acoustically rigid object on which the microphone array is mounted. The driving signals of the loudspeakers must be obtained from the signals received by the microphones. A transform filter for this signal conversion is analytically derived, which is referred to as the wave field reconstruction filter. The proposed method using a spherical baffle is compared with methods using an array of directional microphones and a microphone array mounted on a cylindrical baffle. Numerical simulations indicated that the proposed method is advantageous for sound field recording and reproduction compared with the other two methods. The results of measurement experiments in a real environment are also demonstrated.

Efficacy and safety of triple therapy with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy for gynecological cancer: KCOG-G1003 phase II trial.

PURPOSE: Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥ 50 mg/m(2)). METHODS: Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy). RESULTS: Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each). CONCLUSIONS: Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.

Can measurement of maternal anti-cytomegalovirus immunoglobulin-M antibody levels be used to screen for cytomegalovirus infection in embryos and fetuses?

AIMS: Our study aims to estimate whether measurement of maternal anti-cytomegalovirus immunoglobulin-M antibody (CMV-IgM) levels are useful as a screening method for achieving early detection of congenital CMV infection. MATERIAL AND METHODS: Levels of maternal CMV-IgM were measured by enzyme immunoassay in all (n =2865) pregnant women who visited our hospital in the first trimester during the period from January 2005 to December 2009. RESULTS: Among them, 21 individuals (0.73%) had a CMV-IgM titer of ≥0.08 and were judged to be CMV-IgM-positive. Informed consent was obtained from all 21 individuals to perform the confirmation test that quantifies the levels of cytomegalovirus DNA (CMV-DNA) in amniotic fluid by real-time polymerase chain reaction. However, only one (0.03%) of the 21 individuals was CMV-DNA-positive (CMV-DNA concentration, 1.0 × 10(4) copies/ml). CONCLUSION: In order to detect congenital CMV infection in early pregnancy, it is considered appropriate to use ultrasound for close examination of embryo or fetal symptoms indicative of CMV instead of performing serological screening based on CMV-IgM.

Feasibility study of paclitaxel plus carboplatin in patients with endometrial cancer: a Japan Kanto Tumor Board study (JKTB trial).

AIM: The optimal chemotherapy regimen for patients with endometrial cancer has not been established. We assessed the feasibility of paclitaxel plus carboplatin (TC) for postoperative chemotherapy in patients with endometrial cancer. MATERIAL AND METHODS: Patients with newly diagnosed endometrial cancer received TC (paclitaxel 180 mg/m(2) , carboplatin AUC6 mg/mL/min) every three weeks. Treatment was continued until disease progression or completion of six cycles. Toxicities were evaluated every cycle according to NCI-CTCAE version 3.0. RESULTS: Sixty patients were registered from December 2005 through November 2006. Forty-four of 60 (73.3%) cases completed all of the planned six cycles. Grades 3 and 4 hematologic toxicities were observed as follows: leukopenia (61.7%), neutropenia (95.0%), anemia (21.7%), and thrombocytopenia (5.0%). There were six patients who dropped out from the protocol by neutropenia. Grade 3 non-hematologic toxicities were observed as follows: nausea (3.3%), vomiting (1.7%), neuropathy (5.0%), myalgia (6.7%) and constipation (1.7%). No grade 4 non-hematologic toxicity was observed. CONCLUSION: This TC regimen is feasible for endometrial cancer patients.

Analysis about the influence on the fetus infected with parvovirus B19 using amniotic erythropoietin and troponin-T.

OBJECTIVE: We tried to identify the influence on the fetus infected with parvovirus B19 (PB19) and retrospectively analyze the severity of fetal infection. METHODS: Twenty pregnant women who developed maternal PB19 infection were included in this study. A total of 20 amniotic fluid samples were collected for measurement of PB19-DNA, erythropoietin (Epo) and troponin-T (TnT). RESULTS: Of the 5 fetuses with hydrops, 2 were rescued by fetal therapy. Significant differences between groups were found for Epo and TnT: Epo 107.1 ± 45.3 mU/ml and TnT 0.040 ± 0.028 ng/ml (mean ± standard deviation) for the symptomatic fetus group; and Epo 18.9 ± 13.7 mU/ml and TnT 0.008 ± 0.014 ng/ml for the asymptomatic fetus group (p = 0.043 for both variables). Setting Epo ≥50 mU/ml as the predictor of disease onset resulted in an Odds ratio of 56.0, with a 95 % confidence interval of 7.68-1,108.76. CONCLUSION: The study has determined an amniotic Epo level of ≥50 mU/ml as a factor of the influence on the fetus infected with PB19. The measurement of amniotic Epo level combined with amniotic TnT level is effective for determining the severity of fetal hypoxia.

A Heart Failure Smartphone Application That Nudges Patients/Physicians Toward Optimal Medical Therapy　- Development and Usability Study.

Background: The low implementation rate of guideline-directed medical therapy for heart failure (HF) remains a problem worldwide. To address this issue, we hypothesized that a smartphone application (app) based on behavioral economics that nudges physicians and patients towards optimal medical therapy would be a scalable approach. Methods and Results: The app prototype was developed, and its usability was tested with 5 HF patients in the outpatient setting. Adherence to the app was outstanding, with a high usability rating from the patients. Conclusions: It appears feasible to further study our app in a larger cohort to evaluate its efficacy.