Breast milk concentrations of acetaminophen and diclofenac - unexpectedly high mammary transfer of the general-purpose drug acetaminophen.

BACKGROUND: Breastfeeding is considered to be the most effective way of ensuring the health and survival of newborns. However, mammary transfer of drugs administered to mothers to breastfeeding infants remains a pressing concern. Acetaminophen and diclofenac sodium are widely prescribed analgesics for postpartum pain relief, but there have been few recent reports on the mammary transfer of these drugs, despite advances in analytic techniques. METHODS: We conducted a study on 20 postpartum mothers from August 2019-March 2020. Blood and milk samples from participants were analyzed using liquid chromatography-electrospray ionization tandem mass spectrometry within 24 hours after oral administration of acetaminophen and diclofenac sodium. The area under the concentration-time curve (AUC) was calculated from the concentration curve obtained by a naive pooled-data approach. RESULTS: For acetaminophen, AUC was 36,053 ng/mL.h and 37,768 ng/mL.h in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 1.048. For diclofenac, the AUC was 0.227 ng/mL.h and 0.021 ng/mL.h, in plasma and breast milk, respectively, with a milk-to-plasma drug concentration ratio of 0.093. CONCLUSIONS: While diclofenac sodium showed low mammary transfer, acetaminophen showed a relatively high milk-to-plasma drug concentration ratio. Given recent studies suggesting potential connections between acetaminophen use during pregnancy and risks to developmental prognosis in children, we believe that adequate information regarding the fact that acetaminophen is easily transferred to breast milk should be provided to mothers.

Efficacy and safety of atrial fibrillation ablation in heart failure patients with left ventricular ejection fraction less than 50.

INTRODUCTION: The efficacy of catheter ablation in patients with low cardiac function has been previously reported; however, only a few studies have included mid-range ejection fraction (mrEF). This study aimed to evaluate the efficacy and safety of atrial fibrillation (AF) ablation in patients with left ventricular ejection fraction (LVEF) < 50%. METHODS: This study retrospectively analyzed 79 patients (reduced ejection fraction [rEF]/mrEF, 38/41; paroxysmal/persistent, 37/42; heart failure hospitalizations within one year before ablation, 36 [45.6%]) who underwent the first ablation procedure at our hospital from April 2017 to December 2021. Radiofrequency ablation and cryoablation were performed for 69 and 10 patients, respectively. RESULTS: Complications included pacemaker implantation for postoperative sick sinus syndrome in one patient and inguinal hematoma in one patient. Regarding efficacy, there were significant postoperative improvements in echocardiographic data, blood test values, and diuretic use. After a mean follow-up of 60 months, 86.1% patients had no AF recurrence. There were 9 heart failure hospitalizations (11.4%) and 5 all-cause deaths (6.3%); no significant differences were found between the rEF and mrEF groups. No significant predictors of AF recurrence were found in preoperative patient characteristics. CONCLUSION: AF ablation in patients with LVEF <50% significantly improved cardiac and renal functions with few complications, resulting in a high non-recurrence rate and reduced heart failure.

The prognosis of endometrial cancers stratified with conventional risk factors and modified molecular classification.

This study aimed to validate the Proactive Molecular Risk Classifier for Endometrial Cancer, a modified version of The Cancer Genome Atlas, using data from 184 patients with endometrial cancer (median age: 57.5 years; median follow-up period: 109 months) who had undergone radical surgery (including systemic lymphadenectomy) and subsequent adjuvant chemotherapy (patients with intermediate or high recurrence risk) from 2003 to 2015. Tissue microarrays were prepared from surgical specimens and classified using the conventional clinical risk classifier. Immunohistochemistry was used to detect mismatch repair proteins, L1 cell adhesion molecule, and p53. Direct sequencing was used to identify hotspot mutations in the polymerase-epsilon gene. Forty-five patients were identified as having high L1 cell adhesion molecule expression, 41 as low risk, 34 as mismatch repair-deficient, 13 as polymerase-epsilon gene-mutated, five as having abnormal p53, and 46 as other. Patients were stratified into significantly different prognostic groups (p < 0.0001): favorable (low risk and polymerase-epsilon gene-mutated), intermediate (mismatch repair-deficient and other), and unfavorable (high L1 cell adhesion molecule expression and abnormal p53) with 5-year disease-specific survival rates of 100%, 93.8%, and 75.1%, respectively (Kaplan-Meier method). The combination of conventional recurrent risk classification, sequencing for polymerase-epsilon gene mutations and immunohistochemistry for L1 cell adhesion molecule, p53, and mismatch repair proteins can be used to determine the prognoses of patients with endometrial cancer.

C-reactive protein level predicts need for medical intervention in pregnant women with SARS-CoV2 infection: A retrospective study.

AIM: To make effective use of the limited available hospital space during the Coronavirus disease 2019 (COVID-19) pandemic, we conducted this study to investigate the laboratory indices that identify pregnant women with SARS-CoV2 infection who require medical intervention. METHODS: We carried out a retrospective analysis of pregnant women positive for COVID-19 who were admitted to Hokkaido University Hospital from September 2020 to June 2021. Medical interventions included oxygen supplementation, systemic corticosteroids, or supplemental liquids to treat infection-related symptoms. RESULTS: Forty-two infected pregnant patients were admitted to the hospital, half of whom required medical intervention (n = 21). Fever, C-reactive protein (CRP), and platelet count are all associated with need for medical intervention. Of the 32 patients with a fever of ≥37.5°C on days 0-3 after onset of syndromes, 22 (69%) continued to have a fever on days 4-6, of which 19 (86.4%) required medical intervention. CRP level on days 4-6 predicted the presence or absence of medical intervention (area under the receiver operating characteristic curve = 0.913), with a sensitivity of 81% and specificity of 100% at a CRP cutoff of 1.28 mg/dL. CONCLUSIONS: The need for medical intervention in pregnant patients can be predicted with high accuracy using a CRP cutoff of 1.28 mg/dL on days 4-6 after onset of syndromes. The presence of fever also may be an easy marker for selecting subjects who need or will need therapeutic intervention. These could be an effective triage method to determine appropriate indications for the hospitalization of pregnant women in future outbreaks.

Interleukin-34 expression in ovarian cancer: a possible correlation with disease progression.

Ovarian cancer is the second-most lethal gynecological malignancy and the seventh-commonest cause of cancer-related death in women around the world. Most of the ovarian cancer patients are diagnosed at advanced stages and suffer from recurrence after primary cytoreductive surgery and standard first-line chemotherapy. Thus, the successful management of ovarian cancer patients requires the identification of factors that contribute to progression and relapse. Interleukin-34 (IL-34) is a novel cytokine that acts as a tissue-specific ligand of colony-stimulating factor-1 receptor (CSF-1R). In cancer, IL-34 exerts pro-tumorigenic functions that promote tumor growth, metastasis, angiogenesis, immune suppression and therapeutic resistance. In this study, we evaluate the impact of IL-34 on progression and survival of ovarian cancer patients. First, IL-34 was found to be expressed in several human ovarian cancer cell lines and cancer tissues from patients. The expression of IL-34 was enhanced by cytotoxic chemotherapy in ovarian cancer cell lines and cancer tissues from chemotherapy-treated ovarian cancer patients. Importantly, high IL-34 expression correlated with worse progression-free survival (PFS) and overall survival in different cohorts. The assessment of PFS based on a combination between IL34 expression and other related genes such as CSF1R and CD163 helped further to reach more statistical significance compared with IL34 alone. Furthermore, in the murine ovarian cancer cell HM-1 in vivo model, it was suggested that IL-34-derived tumor cells was correlated with tumor progression and survival by modulating the immune environment. Collectively, these findings indicate a possible correlation between IL-34 expression and disease progression in ovarian cancer patients and the mouse model.

Clinical Outcomes Following Emergent Percutaneous Coronary Intervention for Acute Total/Subtotal Occlusion of the Left Main Coronary Artery.

BACKGROUND: Data regarding the clinical features, outcomes and prognostic factors in patients presenting with acute total/subtotal occlusion of the unprotected left main coronary artery (LMCA) remain limited.Methods and Results:From a multi-center registry, 134 patients due to acute total/subtotal occlusion of the unprotected LMCA were reviewed. Emergency room (ER) status classification was defined according to the presence of cardiogenic shock and cardiopulmonary arrest (CPA) in the ER (class 1=no cardiogenic shock; class 2= cardiogenic shock but not CPA; and class 3=CPA). In-hospital mortality and cerebral performance category (CPC) as the endpoints were evaluated. One-half (67/134) of the enrolled patients presented with total occlusion of the unprotected LMCA. Regarding ER status classification, class 1, 2, and 3 were observed in 30.6%, 45.5%, and 23.9% of the patients, respectively. In-hospital mortality occurred in 73 (54.5%) patients; of the remaining patients, 52 (85.3%) could be discharged with a CPC 1 or 2. ER status classification (odds ratio 4.4 [95% confidence interval: 2.33-10.67]; P<0.001) and total occlusion of the unprotected LMCA (odds ratio 8.29 [95% confidence interval 2.93-23.46]; P<0.001) were strong predictors of in-hospital mortality. CONCLUSIONS: Acute total/subtotal occlusion involving the unprotected LMCA appeared to be associated with high in-hospital mortality. ER status classification and initial flow in the unprotected LMCA were significant predictive factors of in-hospital mortality.

Long-term renal outcomes after elective percutaneous coronary intervention in patients with advanced renal dysfunction.

The aim of the present study was to evaluate the renal outcomes, including the time course of renal function, after elective PCI in patients with advanced renal dysfunction and to assess the predictors of renal dysfunction progression. This is a subanalysis of a previous observational multicenter study that investigated long-term clinical outcomes in patients with advanced renal dysfunction (eGFR < 30 mL/min/1.73 m2), focusing on 151 patients who underwent elective PCI and their long-term renal outcomes. Renal dysfunction progression was defined as a 20% relative decrease in eGFR at 1 year from baseline or the initiation of permanent dialysis within 1 year. Progression of renal dysfunction at 1 year occurred in 42 patients (34.1%). Among patients with renal dysfunction progression, the decrease of renal function from baseline was not observed at 1 month but after 6 months of the index PCI. Baseline eGFR and serum albumin level were significant predictors of renal dysfunction progression at 1 year. Among 111 patients who had not been initiated on dialysis within 1 year, those with renal dysfunction progression had a significantly higher incidence of dialysis initiation more than 1 year after the index PCI than those with preserved renal function (p < 0.001). Among patients with advanced renal dysfunction who underwent elective PCI, 34.1% showed renal dysfunction progression at 1 year. The decrease in renal function was not observed at 1 month but after 6 months of the index PCI in patients with renal dysfunction progression. Furthermore, patients with renal dysfunction progression had poorer long-term renal outcomes.

L1CAM Predicts Adverse Outcomes in Patients with Endometrial Cancer Undergoing Full Lymphadenectomy and Adjuvant Chemotherapy.

BACKGROUND: L1 cell adhesion molecule (L1CAM) has been established as an important predictor of poor survival of early-stage endometrial cancer patients. We investigated whether L1CAM remains a significant predictor of poor survival of patients with advanced-stage endometrial cancer undergoing extensive surgical staging and adjuvant chemotherapy. METHODS: We prepared tissue microarray (TMA) from surgical tissue specimens of 161 endometrial cancer patients who underwent full lymphadenectomy combined with adjuvant chemotherapy for patients at risk for recurrence, and evaluated expression of L1CAM using immunohistochemistry. The correlation between L1CAM positivity and clinicopathological factors and the prognostic significance of L1CAM expression was investigated. RESULTS: Among 161 cases who had a follow-up duration of over 3 years, 48 cases (29.8%) showed positive staining for L1CAM. L1CAM positivity was significantly correlated with non-endometrioid histology (p < 0.0001), vascular invasion (p = 0.0157), and positive cytology (p = 0.005), and was a significant predictor of poor survival among advanced-stage patients, but not early-stage patients in our cohort. L1CAM-positive patients showed a higher recurrence rate and frequency of distant failure than L1CAM-negative patients. Multivariate analysis revealed that para-aortic lymph node metastasis (PANM) and L1CAM positivity were independent predictors of poor survival. Overall survival can be stratified into three groups by the combination of PANM and L1CAM positivity. CONCLUSION: L1CAM is an independent predictor of poor survival in endometrial cancer patients undergoing full lymphadenectomy and adjuvant chemotherapy, thus indicating that L1CAM can be clinically used as a biomarker to identify those patients at increased risk of recurrence.

Efficacy of isoproterenol in the evaluation of dormant conduction and arrhythmogenic foci identification in atrial fibrillation ablation.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) is an established therapy. However, postoperative recurrence is a serious issue caused by the reconduction of the isolated pulmonary veins (PV) and the onset of non-PV foci. The objectives of this study were to elucidate dormant conduction, confirm PV arrhythmia substrate, induce non-PV foci after PV isolation, and assess the acute efficacy of high dose isoproterenol (ISP) when administered in addition to adenosine. METHODS: The study consisted of 100 patients with drug-refractory AF (paroxysmal and persistent) who underwent ablation therapy (either radio-frequency or cryoballoon ablation) as the first-line of therapy at our hospital. All patients first underwent PV isolation (PVI) and were administered adenosine followed by ISP (6 µg × 5 min). The effects were observed, and the therapeutic strategy was evaluated. RESULTS: Persistent dormant conduction due to ISP administration was observed in 13 patients. In over half of the patients, arrhythmia substrates were identified in the PV. Ten patients presented with persistent PV firing. The ablation of non-PV foci was additionally performed in 23 patients. CONCLUSIONS: We found that dormant conduction, as a result of ISP administration, is persistent and ISP is useful when performing an ablation. In addition, ISP administration is useful for the identification of PV arrhythmia substrates and induction of non-PV foci. However, the effectiveness of ISP may be partially due to the complementary effect of adenosine, and, therefore, a combination of the two drugs seems preferable.

Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study.

OBJECTIVE: This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. METHODS: A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient's background differences were assessed with inverse probability of treatment weighting using propensity score. RESULTS: Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3-4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51-10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. CONCLUSION: This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

Clinical outcomes after percutaneous coronary intervention in non-dialysis patients with acute coronary syndrome and advanced renal dysfunction.

BACKGROUND: Data about the clinical outcomes of ACS patients with advanced renal dysfunction (estimated glomerular filtration rate < 30 mL/min/1.73 m2) following percutaneous coronary intervention (PCI) are limited. METHODS: We examined the data obtained from 194 ACS patients with non-dialysis advanced renal dysfunction who underwent PCI at five hospitals. The primary composite endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE: all-cause death, myocardial infarction, and ischemic stroke). RESULTS: Eighty patients (41.2%) were diagnosed with ST-elevation myocardial infarction (STEMI), and 117 patients (58.8%) with non-ST-elevation ACS (NSTE-ACS). Overall patients were followed for a median of 657.5 days. Cumulative incidence of MACCE at median follow-up was 32.3% (45.4% for STEMI and 23.4% for NSTE-ACS). Kaplan-Meier analysis demonstrated that patients in the STEMI group had significantly higher incidence of MACCE than those in the non-STEMI and unstable angina group (Log-rank p < 0.001). In-hospital MACCE rate was higher in the STEMI group than in the NSTE-ACS group, whereas post-discharge MACCE rate was comparable between the two groups. In the multivariate analysis, STEMI and Killip classification ≥ 2 were associated with in-hospital MACCE. On the other hand, body mass index and serum albumin at admission were independent predictors of post-discharge MACCE. CONCLUSIONS: Short- and long-term prognoses following PCI in non-dialysis patients with ACS and advanced renal dysfunction is still unfavorable. STEMI and Killip classification ≥ 2 were independent predictors for in-hospital MACCE, and body mass index and serum albumin were for post-discharge MACCE.

Treatment outcomes of Kugel repair for obturator hernias: a retrospective study.

BACKGROUND: We examined the validity and applicability of the Kugel repair approach for obturator hernias, whereby we placed a Kugel patch through the preperitoneal space after placing a short 5-cm skin incision just medial to the anterior iliac spine and 2 cm cranial to the expected origin of the internal inguinal ring. METHODS: We studied patients who underwent surgical Kugel repair for obturator hernias at the Department of General Surgery, Saitama Medical University between 2007 and 2017. We examined the operating time, length of hospital stay, postoperative complications, and mortality rate. RESULTS: Fifty-eight patients with obturator hernias presented with symptoms of small bowel obstruction. A Kugel approach was used in 53 patients and a midline approach was used in 5 patients with preoperative peritonitis. Of the 53 patients managed using the Kugel approach, 39 did not require intestinal resection; a mesh was used in all these patients. In the remaining 14 patients, intestinal resection was required and performed using the same approach; subsequently, a mesh was used successfully in 6 of these 14 patients. The overall median operating time was 47 min; the corresponding values for procedures with and without intestinal resection were 39 and 68 min, respectively. In terms of postoperative complications, operative mortality was not noted among patients without intestinal perforation; however, superficial surgical site infection developed in 2 patients. Among the 5 patients with preoperative peritonitis who underwent exploratory laparotomy via a midline incision, intestinal perforation was detected during surgery, and all patients required intestinal resection; none of the patients had received a mesh, and 2 patients died after surgery. CONCLUSIONS: The Kugel repair approach was possible even in patients with obturator hernia requiring intestinal resection. However, for patients with perforations, open surgery should be performed after securing the surgical field through a midline incision.

[Report Based on Fiscal 2015 Diagnostic X-ray Equipment Questionnaire Survey].

We have conducted a questionnaire survey every 5 years from 1974 to grasp the existing status of X-ray equipment. This time, we will report on the results of the fiscal 2015 diagnostic X-ray equipment questionnaire survey. Compared to the previous survey on X-ray equipment, there has been a progress in the introduction of inverter type X-ray generators and image receptor systems in digital systems. We think that this transition will be occurred when the X-ray equipment are updated. In addition, there has been an increase in digital breast tomosynthesis (DBT) and the use of tungsten anodes in the X-ray tubes of mammography apparatuses. X-ray equipment management was performed in many facilities. It seems that the importance of quality control of X-ray equipment is being realized. Constancy tests corresponding to digital systems were conducted at each facility. Maintenance by manufacturers has also increased. This is considered to be because the equipment management of digital systems has become difficult. We believe that it is necessary to continue the survey on the status of diagnostic X-ray equipment.

[Effect of Interspaces of Anti-scatter Grid on the Image Improvement Factor].

The standard general purpose of anti-scatter girds: JIS Z 4910: 2015 (IEC 60627: 2013) has been revised, with the new addition of an image improvement factor (Q) to the physical characteristic. Using aluminum (Al) and fiber-interspaced anti-scatter grids; we studied the meaning of Q by calculating each of the physical characteristics and assessing the image. The experimental method was based on JIS Z 4910: 2015. The two anti-scatter grids had a grid ratio of 12: 1 and a strip frequency of 40 cm-1. Assessment items consisted of grid exposure factor (B), grid selectivity (Σ), contrast improvement ratio (K), and Q. In addition, the contrast to noise ratio (CNR) and contrast-detail curve (CD-curve) were determined from the contrast-detail phantom image, and the inverse image quality figure (IQF) was then calculated from the CD-curve. Compared to the Al-interspaced anti-scatter grid, the fiber-interspaced anti-scatter grid had B at 0.87, Σ at 0.95, K at 0.99, and Q at 1.14. In the assessment of the contrast-detail phantom image, the fiber-interspaced anti-scatter grid had an IQF of 1.02 times and a CNR of approximately 1.24 times when compared to the Al interspaced anti-scatter grid. The fiber-interspaced anti-scatter grid was superior with respect to the B and Q of the physical characteristics and to the CNR of image quality assessment.

Postoperative recurrence and risk factors of colorectal cancer perforation.

PURPOSE: The common causes of colorectal perforation are benign. However, perforated colorectal cancer confers a risk of recurrence in the long term because of the malignant nature of the disease. In addition, the recurrence rate can also increase because of dissemination of cancer cells, reduced extent of lymph node dissection to prioritize saving life, and other reasons. METHODS: We evaluated the clinical features and postoperative recurrence in patients with perforated colorectal cancer who developed general peritonitis and underwent emergency surgery during a 7-year period between April 2007 and March 2014. RESULTS: During the study period, 44 patients had colorectal cancer perforation. The cancer sites were the ascending colon in 6 patients, transverse colon in 1, descending colon in 4, sigmoid colon in 15, and rectum in 18. The disease stage was stage II in 18 patients, stage III in 15, and stage IV in 7. Among 22 patients who could be followed up, 8 had postoperative recurrence. The recurrence rates were 18.2% for stage II cancer and 54.5% for stage III. Postoperative recurrence was more likely to occur in the patients positive for lymph node metastasis, those with poorly differentiated adenocarcinoma, those with T4 cancer, and those who did not receive postoperative adjuvant chemotherapy. CONCLUSION: The recurrence rate was higher in the patients with perforated colorectal cancer than in those who underwent surgery for common colorectal cancer. The prognosis can be expected to improve by performing standard surgical procedures, to the maximum extent possible, followed by postoperative adjuvant chemotherapy.

Distribution of Anti-Factor Xa Activity in Patients on Edoxaban Therapy for Non-Valvular Atrial Fibrillation.

BACKGROUND: The distribution of anti-factor Xa activity (AXA) values in non-valvular atrial fibrillation (NVAF) patients on edoxaban therapy has not been fully elucidated. METHODS AND RESULTS: The steady-state trough and peak AXA values were measured in 66 NVAF patients. The trough AXA value did not differ significantly between the 60-mg and the 30-mg OD groups (0.17±0.13 IU/ml vs. 0.12±0.11 IU/ml, respectively; P=0.17). Similarly, the peak AXA value did not differ significantly between the 2 groups (1.45±0.81 IU/ml vs. 1.25±0.48 IU/ml, respectively; P=0.26). CONCLUSIONS: Recommended dosing should be followed for sufficient efficacy of edoxaban. (Circ J 2016; 80: 745-747).

Adjuvant chemotherapy for early-stage cervical cancer.

The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable condition, it is necessary that the therapeutic strategies should be improved with considering adverse events and QOL for long-term survivors.

Measurement of Anti-Factor Xa Activity in Patients on Apixaban for Non-Valvular Atrial Fibrillation.

BACKGROUND: Chromogenic anti-factor Xa activity (AXA) assay is reported to be the most appropriate method to measure the pharmacodynamics of apixaban, but the distribution of AXA in non-valvular atrial fibrillation (NVAF) patients on apixaban therapy has not been fully elucidated. METHODS AND RESULTS: Steady-state trough and peak AXA were measured in 124 NVAF patients taking apixaban. In 25 patients, baseline, first peak, and trough AXA were also examined, and were 0.01±0.02 IU/ml, 0.83±0.43 IU/ml, and 0.34±0.17 IU/ml, respectively. First trough AXA was significantly lower than steady-state trough AXA, although it was significantly higher than baseline (P<0.0001). Similarly, first peak AXA was significantly lower than steady-state peak AXA (P<0.0001). In 124 patients, steady-state peak AXA was significantly higher in the 5-mg b.i.d. group than in the 2.5-mg b.i.d. group (2.05±0.73 IU/ml vs. 1.51±0.65 IU/ml, respectively; P<0.001), although there was no significant difference in trough AXA. Other than dose, age and serum creatinine were significantly related to both trough and peak AXA. CONCLUSIONS: The distribution of AXA in Japanese NVAF patients on apixaban therapy in daily clinical practice both in the acute and steady-state phase was measured. In patients taking apixaban, measurement of AXA clearly showed the pharmacodynamic profile of this drug.

Long-term effects of tolvaptan in patients requiring recurrent hospitalization for heart failure.

Although reports suggest that tolvaptan does not reduce survival or subsequent hospitalization rates in heart failure patients, its continuous use has shown good outcomes in some patients who cannot be effectively managed with high doses of loop diuretics. Therefore, we investigated the association of patient characteristics and continued tolvaptan use in heart failure patients with changes in the frequency and annual duration of patient hospitalization due to heart failure. We carefully reviewed the medical records of patients hospitalized due to heart failure who began tolvaptan therapy and continued with outpatient treatment between December 2010 and November 2013 (tolvaptan group); patients hospitalized for heart failure between May 2008 and March 2009 served as controls. We set the reference dates as the start of tolvaptan therapy (tolvaptan group) or as the date of admission (control group). The changes in hospitalization frequency and total hospitalization time due to heart failure, before and after the reference dates, were not significantly different between the tolvaptan and control groups. In the tolvaptan group, a high estimated glomerular filtration rate was a predictor of decreased hospitalization. Continuous tolvaptan use did not decrease hospitalization duration in all heart failure patients, but good renal function was predictive of a good response.

Genital infection caused by Entamoeba histolytica confirmed by polymerase chain reaction analyses.

Entamoeba histolytica is estimated to infect approximately 1% of the global population. In Japan, the prevalence of amebic dysentery has been increasing, with more than 800 patients newly diagnosed annually. However, genital infection with E. histolytica is uncommon even in endemic areas. We present a case of vaginitis caused by E. histolytica. A 50-year-old Japanese woman without history of overseas travel presented to a nearby clinic with increased vaginal discharge. She had hemorrhagic erosion at the uterine cervix with yellowish vaginal discharge, and was referred to our hospital for exclusion of malignancy. Cervical cytology revealed periodic acid-Schiff-positive protozoa not aggregating around squamous cells, and thus amebic vaginitis was suspected. We performed polymerase chain reaction (PCR) analyses and identified E. histolytica. The vaginitis was treated with metronidazole, and the disappearance of amebic protozoa was confirmed by cytology and PCR. Therefore, it may be important to obtain early diagnosis by cervical cytology and PCR.