Prognostic Significance of Serum Interleukin-6 Levels in Oral Squamous Cell Carcinoma.

Introduction The prognosis of oral squamous cell carcinoma (OSCC) is often poor despite standard treatments. Additionally, no useful prognostic markers are available. Therefore, we aimed to investigate the relationship between serum Interleukin-6 (IL-6) levels and prognosis and explore its local and systemic effects in patients with OSCC. Methods Ninety-five new cases of OSCC were included, and the prognosis was compared between high and low serum IL-6 groups. The localization of IL-6 in OSCC tissues was examined. Furthermore, a comprehensive gene expression analysis was performed in OSCC tissues and compared between the two groups. Results A significant difference in overall survival and disease-free survival was observed. Furthermore, a substantial expression of IL-6 was localized in the stroma. Comprehensive gene expression analysis of tumor localization showed increased expression of genes related to oxidoreductase and lipid metabolism in the primary tissues of the group with high serum IL-6 levels. Regarding the correlation between blood tests and serum IL-6 levels, a strong positive correlation was observed between inflammatory responses and nutritional factors. Conclusion These results suggest that serum IL-6 may be a prognostic factor for metabolic abnormalities in patients with OSCC and that aggressive nutritional interventions may contribute to prognosis.

Changes in use and outcomes after fibrinogen concentrate insurance coverage for critical obstetrical hemorrhage: a nationwide questionnaire survey in Japan.

Fibrinogen concentrate (FC) for acquired hypofibrinogenemia associated with critical obstetrical hemorrhage (COH) was covered by public medical insurance in September 2021 in Japan. We aimed to investigate changes in the policy of FC use and its effect on COH after insurance coverage. A primary survey covering September 2020 to August 2021 and a secondary survey covering September 2021 to August 2022 were conducted at 428 higher-level medical facilities. We investigated the policy of FC use in transfusion strategy and the maternal outcomes in COH. Among the hospitals that responded to both surveys, the number of facilities that use FC increased from 51.5 (101/196) to 78.6% (154/196) (P < 0.0001). The number of COH cases treated using FC increased from 14.3 to 24.3% (P < 0.0001) and that transfused with ≥ 10 units of red blood cells (RBCs) decreased from 36.8 to 29.8% (P = 0.001). The incidence of pulmonary edema reduced by 3.7-2.0% (P = 0.021), and transfusion-induced allergy by 1.9-0.7% (P = 0.008). No changes were observed in the incidence of thromboembolism, arterial embolization, or hysterectomy. The increased use of FC after insurance coverage led to changes in the transfusion strategy, which may be associated with decreases in transfusions of RBCs, pulmonary edema, and transfusion-induced allergies.

KRT13 and UPK1B for differential diagnosis between metastatic lung carcinoma from oral squamous cell carcinoma and lung squamous cell carcinoma.

Oral squamous cell carcinomas unusually show distant metastasis to the lung after primary treatment, which can be difficult to differentiate from primary squamous cell carcinoma of the lung. While the location and number of tumor nodules is helpful in diagnosing cases, differential diagnosis may be difficult even with histopathological examination. Therefore, we attempted to identify molecules that can facilitate accurate differential diagnosis. First, we performed a comprehensive gene expression analysis using microarray data for OSCC-LM and LSCC, and searched for genes showing significantly different expression levels. We then identified KRT13, UPK1B, and nuclear receptor subfamily 0, group B, member 1 (NR0B1) as genes that were significantly upregulated in LSCC and quantified the expression levels of these genes by real-time quantitative RT-PCR. The expression of KRT13 and UPK1B proteins were then examined by immunohistochemical staining. While OSCC-LM showed no KRT13 and UPK1B expression, some tumor cells of LSCC showed KRT13 and UPK1B expression in 10 of 12 cases (83.3%). All LSCC cases were positive for at least one of these markers. Thus, KRT13 and UPK1B might contribute in differentiating OSCC-LM from LSCC.

Differences in the prevention and incidence of maternal venous thromboembolism according to the type of institution in Japan in 2018: A sub-analysis of national questionnaire surveillance.

AIM: To clarify the relation between institutions capacity to manage venous thromboembolism (VTE) and its incidence in pregnant women throughout Japan. METHODS: Among the 2299 institutions that received the surveillance questionnaire, 666 (29.0%) responded, after which data from 295 961 women who gave birth at those institutions in 2018 were analyzed. Incidences and characteristics of antepartum and postpartum VTE in perinatal medical centers (PMCs), general hospital with obstetric facilities (GHs), and maternal clinic with beds (MCs) were then determined. RESULTS: The frequencies at which routine antepartum and postpartum thromboprophylaxis for high-risk women and routine transport to the more advanced medical institutions upon antepartum and postpartum pulmonary thromboembolism (PE) onset were performed differed significantly according to types of institution (PMCs: 92.4%, 96.2%, 23.8%, and 21.2%; GHs: 76.5%, 80.6%, 58.8%, and 54.1%; MCs: 29.2%, 41.7%, 96.5%, and 96.2%, respectively). Among the 295 961 women analyzed, 243 (0.082%) developed VTE. Incidences of antepartum VTE differed significantly according to institution types (PMCs: 106.4, GHs: 51.6, and MCs: 11.6 per 100 000 women). PMCs and GHs had significantly higher incidences of postpartum VTE compared to MCs (43.3 and 26.6 vs. 10.7 per 100 000 women, respectively), although PMCs and GHs had similar incidences. Among the four women (1.4%) who died due to VTE, three and one developed a PE in a PMC and MC, respectively. CONCLUSIONS: PMCs had higher incidences of VTE despite their more frequent performance of thromboprophylaxis. Several pregnant women with higher risk of VTE transported to PMCs.

Factors Related to Sleeping Disorder Due to Pruritus in Patients with Chronic Liver Disease.

Objective This study evaluated cases of pruritus, which is known to be associated with sleep disorder, in chronic liver disease (CLD) patients. Methods Questionnaires were given to 339 enrolled CLD outpatients in winter (November 2019 to March 2020) and again in summer (April to October 2020) (median interval: 104 days). Relative changes in symptoms shown by a visual analogue scale (VAS) and Kawashima's pruritus score between winter and summer were evaluated in Study 1 (n=199), while Study 2 examined the clinical features of patients with sleep disorder based on the results of the second questionnaire (n=235, median age 70 years old; 141 men, liver cirrhosis 37%). Results Study 1. There was a significant relationship in VAS between daytime and nighttime for each season, as well as between winter and summer for each time period (p<0.001). A comparison of Kawashima's pruritus scores for the daytime and nighttime showed no significant seasonal differences (p=0.436 and 0.828, respectively). When Kawashima's score increased, so did the average VAS for both daytime (0:1:2:3:4=0.4±0.2:1.4±0.9:3.0±1.8:5.9±2.1:6.2±2.3) and nighttime (0:1:2:3:4=0.3±0.1:1.4±1.5:3.5±2.3:6.7±2.6:6.9±1.8) (p<0.001 for both). Study 2. Twenty subjects (8.5%) complained of sleep disorder. An elevated FIB-4 index (≥3.07) showed a good predictive value for sleep disorder (p<0.01). The cut-off for the daytime and nighttime VAS values for existing sleep disorder were 1.6 [area under the curve (AUC) 0.901] and 3.4 (AUC 0.931). The respective sensitivity, specificity, and positive and negative predictive values for sleep disorder based on Kawashima's score (≥2) were 0.85, 0.28, 0.10, and 0.95 for the daytime and 1.00, 0.29, 0.12, and 1.00 for the nighttime. Conclusion Intervention against pruritus is recommended in CLD patients with a high Kawashima's score (≥2) in any season, especially with an elevated FIB-4 index.

Identifying the associated factors with onset of preterm PROM compared with term PROM - A retrospective cross-sectional study.

OBJECTIVE: To determine the risk factors associated with the preterm premature rupture of membranes (p-PROM). MATERIALS AND METHODS: This retrospective cross-sectional study assessed 110 p-PROM cases from among 6642 deliveries at a Japanese perinatal medical center, from June 2016 to September 2018. The control group comprised 220 term PROM (t-PROM) cases. We excluded cases with artificial PROM or rupture of membranes after labor, those with multiple pregnancies, those with p-PROM at 36 weeks and those with t-PROM at 37 weeks. In order to compare p-PROM with t-PROM, univariate and multivariate analysis were performed using several clinical factors at the time of PROM onset. RESULTS: The p-PROM group included 110 cases with 14-35 weeks PROM, and the t-PROM group included 220 cases with 38-41 weeks PROM. Eleven factors were identified as significant factors on the univariate analysis. A history of cervical conization (OR 37.5, 95% CI: 2.31-607.1), cervical length <25 mm at 28 weeks (OR 9.31, 95% CI: 1.76-49.3), negative Lactobacillus (OR 4.01, 95% CI: 1.18-13.7), and bleeding during the second trimester (OR 3.35, 95% CI: 1.18-9.53) were identified as significant factors by the multivariate analysis. Based on the risk factors identified during the multivariate analysis, we divided the 330 cases in the following three groups: 0 group (n = 244), 1 group (n = 60), and 2-4 group (n = 26). The ratio of p-PROM:t-PROM was calculated and compared for each group. The ratios were 21% (0 group), 57% (1 group), and 100% (2-4 group), indicating statistically significant differences between the groups (p < 0.001). CONCLUSION: We found that the following four factors were associated with p-PROM: history of cervical conization, cervical length <25 mm at 28 weeks, negative Lactobacillus, and bleeding during the second trimester. Our results suggest that we can identify patients who are at increased risk for p-PROM, based on these factors. Further research is necessary to determine the optimal treatment approach for these patients to prevent p-PROM.

A retrospective cohort study using a national surveillance questionnaire to investigate the characteristics of maternal venous thromboembolism in Japan in 2018.

BACKGROUND: In Japan, the numbers of deliveries by women of older maternal age and women with overweight or obesity have recently increased. Since 2008, the guidelines and practices to prevent the maternal venous thromboembolism (VTE) have been recommended antepartum and postpartum thromboprophylaxis for each risk level of VTE. This study aimed to clarify the incidence and characteristics (type of VTE and thromboprophylaxis) of VTE in pregnant women in Japan to reduce the rate of mortality from VTE METHODS: Of 2299 institutions sent the surveillance questionnaire, 666 (29.0%) responded, and data from 295,961 women who gave birth in those institutions in 2018 were analyzed. We calculated the incidence and characteristics of VTE before and after the deliveries. RESULTS: At the responding institutions, 243 women (0.082%) had VTE in 2018. In 2018, deep vein thrombosis was significantly more common (0.0053%) than pulmonary thromboembolism (0.0019%; p < 0.0001). The incidence of antepartum VTE (0.0055%) was significantly higher than that of postpartum VTE (0.0026%; p < 0.0001). The incidence of VTE after cesarean Sect. (0.0074%) was significantly higher than that after vaginal delivery (0.0012%; p < 0.0001). Of the women with VTE, 4 (1.6%) died. CONCLUSIONS: Among the women thought to have a low risk of VTE during the antepartum period, and especially women who had a vaginal delivery, the actual incidence of VTE might have increased in Japan.

Capacity of Japanese institutions to manage obstetrical disseminated intravascular coagulation in 2018: A national surveillance questionnaire and retrospective cohort study.

AIM: To investigate the management of obstetrical disseminated intravascular coagulation (DIC) in Japan. METHODS: We sent a surveillance questionnaire to 2299 institutions to collect details about the deliveries they performed in 2018. We investigated differences in the management of obstetrical DIC among three types of institutions: perinatal medical centers (PMCs), general hospitals with obstetrical facilities (GHs), and maternal clinics with beds (MCs). RESULTS: We received responses from 703 institutions (30.6% of the total mailed) with results of 306 799 women who gave birth in 2018. In Japan, the potential to treat postpartum hemorrhage and obstetrical DIC was high in the PMC group, moderate in the GH group, and low in the MC group. The incidence of obstetrical DIC in the PMC group (0.44%) was significantly higher than that in the GH (0.21%) and MC (0.06%) groups. The mortality of women with obstetrical DIC in PMCs (1.3%) was similar to that in GHs (0.6%) and MCs (0.0%). The percentages of PMCs that always or sometimes transfused fresh frozen plasma or fibrinogen concentrates (100% and 42.2%, respectively) were significantly higher than those in the GH (88.2% and 29.5%, respectively) and MC groups (29.4% and 5.3%, respectively). Furthermore, institutions whose internal protocols mandated that replacement therapy be always administered in women with obstetrical DIC scores of ≥8 had similar protocols to those for women with fibrinogen levels of ≤1.5 g/L. CONCLUSIONS: The capacity to provide therapy for postpartum hemorrhage and obstetrical DIC varied widely among the three groups of institutions.

Clinical guidance for peripartum management of patients with hereditary thrombophilia.

Hereditary thrombophilia is a condition in which individuals are susceptible to the formation of thrombi due to a hereditary deficiency in anticoagulant factors, antithrombin (AT), protein C (PC), or protein S (PS). Many Japanese thrombophilia patients have PS deficiency, especially PS p.K196E (also called as PS Tokushima), which is exclusive to the Japanese population, and thrombosis sometimes occurs during pregnancy. At present, no management guidelines for pregnancy and delivery in thrombophilia patients have been developed. The Study Group for Hereditary Thrombophilia, one of the research groups of blood coagulation abnormalities in the Research Program on Rare and Intractable Diseases supported with the Research Grants of the Ministry of Health, Labour and Welfare Science, has therefore developed this clinical guidance to provide healthcare workers with necessary information on safe pregnancy, parturition and neonatal management, adopting a format of responses to seven clinical questions (CQ). At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

A randomized phase 3 trial evaluating antithrombin gamma treatment in Japanese patients with early-onset severe preeclampsia (KOUNO-TORI study): Study protocol.

INTRODUCTION: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Several studies have demonstrated the beneficial effects of antithrombin replacement in patients with preeclampsia. Here, we describe the study protocol of KOUNO-TORI (KW-3357 randOmized, mUlti-center, double-bliNd, placebO-controlled phase 3 sTudy in patients with early Onset pReeclampsIa) to evaluate recombinant human antithrombin gamma (rhAT-gamma) for the treatment of early-onset severe de novo preeclampsia. MATERIAL AND METHODS: Patients with early-onset severe de novo preeclampsia who are ≥24 to <32 weeks pregnant at the time of registration and have an antithrombin activity of ≤100% at screening are included. The target population is selected based on a reanalysis of the data of a previous plasma-derived antithrombin phase 3 study. Primary endpoint is the prolongation of pregnancy from the initiation of rhAT-gamma treatment to the pregnancy termination. Secondary endpoints include gestational age in terms of achievement of 32- and 34-weeks'gestation, and gestational age in terms of achievement of 28 weeks' gestation for patients enrolled at <28 weeks' gestation. Maternal, fetal, and neonatal outcomes will be assessed. DISCUSSION: As we have selected a specifically defined target population based on reanalysis of data of a previous plasma-derived antithrombin phase 3 study, the results of our study are expected to provide efficacy and safety data concerning rhAT-gamma treatment in Japanese patients. This study could help identify an effective novel treatment for such patients with early-onset severe preeclampsia for whom appropriate treatment is unavailable.

Easy clinical predictor for low BCAA to tyrosine ratio in chronic liver disease patients with hepatocellular carcinoma: Usefulness of ALBI score as nutritional prognostic marker.

BACKGROUND/AIM: Low branched-chain amino acid (BCAA) to tyrosine ratio (BTR) is known as an indicator of amino acid imbalance. We elucidated usefulness of newly developed albumin-bilirubin (ALBI) score as alternative methods of BTR in patients with naïve hepatocellular carcinoma (HCC) retrospectively. MATERIALS/METHODS: In 842 patients with HCC and without BCAA supplementation (71 years, male 614, Child-Pugh A:B:C = 689:116:37), relationships among BTR and clinical features were evaluated. Of those, 438 patients, with Milan criteria HCC, treated curatively were divided into the high-BTR (>4.4) (n = 293) and low-BTR (≤4.4) (n = 145) groups. The prognostic value of BTR was evaluated using inverse probability weighting (IPW) with propensity score. RESULTS: The low-BTR group showed worse prognosis than the other (3-, 5-, 10-year overall survival rates: 88.9% vs. 86.3%/70.5% vs. 78.1%/38.1% vs. 52.3%, respectively; p < 0.001). Multivariate Cox-hazard analysis adjusted for IPW showed elderly (≥65 years) HR 2.314, p = 0.001), female gender (HR 0.422, p < 0.001), ECOG PS ≥2 (HR 3.032, p = 0.002), low platelet count (HR 1.757, p = 0.010), and low BTR (≤4.4) (HR 1.852, p = 0.005) to be significant prognostic factors. Both serum albumin level (r = 0.370, p < 0.001) and ALBI score (r = -0.389, p < 0.001) showed a significant relationship with BTR. Child-Pugh class B, modified ALBI grade (mALBI) 2a, and mALBI 2b predictive values for BTR were 3.589, 4.509, and 4.155 (AUC range: 0.735-0.770), respectively, while the predictive value of ALBI score for low-BTR (≤4.4) was -2.588 (AUC 0.790). CONCLUSION: ALBI score -2.588 was a predictor for low-BTR (≤4.4), which was prognostic factors for early HCC patients, and at least patients with mALBI 2b might have an amino acid imbalance.

Effect of hypofibrinogenemia on obstetrical disseminated intravascular coagulation in Japan in 2018: a multicenter retrospective cohort study.

Japanese obstetrical hemorrhage recommendations state that not only pregnant women with an obstetrical disseminated intravascular coagulation (DIC) score ≥ 8 points but also those with fibrinogen levels ≤ 1.5 g/L have a high risk of maternal death and warrant blood transfusion. Our aim was to demonstrate the potential of fibrinogen levels ≤ 1.5 g/L as predictors of a Japanese obstetrical DIC score of ≥ 8. We included 595 participants with blood loss ≥ 1000 mL during vaginal delivery or ≥ 2000 mL during cesarean delivery. The frequency and volume of red blood cell (RBC), fresh-frozen plasma, platelet concentrate (PC), and fibrinogen administration in women with a DIC score of ≥ 8 and fibrinogen levels of ≤ 1.5 g/L were significantly higher than controls (P < 0.0001). Multivariate analysis demonstrated that a score of ≥ 3 was associated with RBC or fibrinogen administration and a score of ≥ 5 was associated with PC transfusion. Fibrinogen levels ≤ 1.89 g/L and ≤ 2.44 g/L were associated with PC transfusion and fibrinogen administration, respectively. Fibrinogen levels ≤ 1.5 g/L may have similar potential to a DIC score of ≥ 8 points for detecting obstetrical DIC in Japan.

Comparative evaluation of reagents for measuring protein S activity: possibility of harmonization.

Patients with congenital protein S (PS) deficiency show a hereditary predisposition for thrombosis, and PS deficiency is prevalent among Japanese populations. Diagnosis is based on symptoms of thrombosis and reduced PS activity. Three reagents that use different measurement principles for determining PS activity are available in Japan. This study aimed to confirm the possibility of harmonization of these three reagents to establish a universal standard for PS activity in Japanese populations. Commercial normal plasma and plasma samples obtained from healthy individuals and healthy pregnant women were tested at three facilities using three reagents for measuring PS: STA-Staclot Protein S (STA-PS), HemosIL Protein S (Clotting) (IL-PS), and a total PS assay (SNT-PS). The within-run precision of each reagent was good, as each had a coefficient of variation of ≤ 3.8%. The dilution linearity for each reagent was also good. The correlation coefficient was 0.94 for STA-PS vs. IL-PS, 0.93 for SNT-PS vs. STA-PS, and 0.90 for SNT-PS vs. IL-PS, indicating a good correlation. Although the three reagents available in Japan for measuring PS activity use different measurement methods, each showed good performance, and large differences were not observed between the obtained values. Harmonization among them appears possible.

Hypertensive disorders of pregnancy by oocyte donation pregnancy in Japanese women aged 40 years or older: a single-center retrospective cohort study.

This study aimed to examine the incidence of hypertensive disorders of pregnancy (HDP) among Japanese women with oocyte donation pregnancy (ODP) aged 40 years or older and estimate whether the women with ODP were more likely to develop HDP than those with autologous oocyte pregnancy (AOP) and spontaneous pregnancy (SP). In our study (N = 1361), the proportions of women who developed HDP were 20.5%, 12.8%, and 7.6% for ODP, AOP, and SP, respectively. After adjustment of covariables, the women with ODP were more likely to develop HDP than those with AOP or SP.

Low antithrombin levels accompanied by high urine protein/creatinine ratios are predictive of acute kidney injury among CS patients with preeclampsia.

OBJECTIVES: Previous acute kidney injury (AKI) is reportedly a risk factor for future preeclampsia (PE), and PE in current pregnancies may trigger the onset of AKI. In this study, we identified risk factors for AKI among Cesarean section (CS) patients with PE. METHODS: We performed a retrospective study at a single center. Among 4602 deliveries between January 2017 and July 2018, 944 women underwent CS. Of these, 90 women had hypertensive disorders during their pregnancies, with 53 diagnoses of PE and 37 diagnoses of gestational hypertension. Medical records of the 90 women were reviewed retrospectively. RESULTS: The rate of AKI was significantly higher in the PE group than in the GH group (17 versus 3%, p < .05). Univariate analyses of the PE group identified low preoperative serum albumin levels, low antithrombin III (ATIII) activities, and urine protein/creatinine ratios (U-P/Cr) as significant predictors of AKI. Cutoff values for these factors were calculated using ROC analyses, and the combination of ATIII and U-P/Cr, which were poorly correlated, was predictive of AKI. Specifically, the proportion of AKI in patients with low ATIII-high U-P/Cr was 50% (7/14), higher than that among patients with high ATIII-low U-P/Cr (0%, 0/19, p < .05), low ATIII-low U-P/Cr (10%, 1/10, p < .05), and high ATIII-high U-P/Cr (10%, 1/10, p < .05). CONCLUSIONS: These data demonstrate that lower preoperative serum albumin levels, ATIII activities, and heavy proteinuria among CS patients with PE are risk factors for AKI.

Uninformed decision-making and regret about delaying childbearing decisions: A cross-sectional study.

Aim: The aim of this study was to examine regret over the timing of the childbearing decision and reasons for its delay. Design: A cross-sectional study. Methods: This cross-sectional study included 219 women and 169 men referred to fertility facilities in Japan from July-December 2018. Participants completed a questionnaire on the reasons for their delay in childbearing decision and the degree of regret regarding their decision. Multiple linear regression was used to analyse the association between degree of regret and the reasons for the delay. Results: The top three reasons for the delay in childbearing decision in women were "Establishing the relationship," "Health problems," and "Financial security." The top three reasons in men were "Establishing the relationship," "Financial security," and "Lack of fertility knowledge." Multiple linear regression showed that lack of fertility knowledge was associated with regret over the timing of childbearing decisions in women and men.

Regret over the delay in childbearing decision negatively associates with life satisfaction among Japanese women and men seeking fertility treatment: a cross-sectional study.

BACKGROUND: Currently, in developed countries, increasing numbers of women and men are delaying childbearing but begin seeking fertility treatment later in life. Some women undergoing infertility treatment develop negative feelings such as depression associated with low life satisfaction and regret over the delay in childbearing. We therefore examine the association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors among Japanese women and men seeking fertility treatment. METHODS: This cross-sectional study included 253 women and 196 men referred to fertility facilities in Japan from July to December 2018. Participants completed a questionnaire on life satisfaction, regret over the delay in childbearing decision, infertility-related factors and sociodemographic characteristics. Life satisfaction was measured using the Satisfaction with Life Scale (SWLS), and the degree of regret over delay in childbearing decision was measured on a 7-point Likert scale. Multiple linear regressions, conducted separately by sex, were used to analyze the association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors. RESULTS: Of the 253 women and 196 men, 102 (40.3%) women and 43 (21.9%) men answered "strongly agree" regarding their regret over the delay in childbearing decision. Among women, life satisfaction was negatively associated with regret (ß = - 0.155, 95% CI [- 0.938, - 0.093], p = 0.017), use of assisted reproduction technology (ART) (ß = - 0.135, 95% CI [- 2.977, - 0.020], p = 0.047). In contrast, previous live birth was positively associated with life satisfaction (ß = 0.134, 95% CI [0.122, 3.739], p = 0.037). In men, we found no significant association of life satisfaction with regret over the delay in childbearing decision and infertility-related factors. CONCLUSIONS: Regret over the delay in childbearing decision is negatively associated with life satisfaction among Japanese women seeking fertility treatment. It may be important for women to make better informed decision regarding the timing of childbearing to not regret later in life. Health professionals should address regret over the delay in childbearing decision during fertility treatment and explore ways to spread information on fertility awareness.

Exacerbation of psoriasis vulgaris by sorafenib treatment for hepatocellular carcinoma.

We treated a 66-year-old Japanese male with unresectable hepatocellular carcinoma (u-HCC) for multiple (>5) liver tumors (maximum 2.6 cm in size, Child-Pugh B score 7) in September 2018. The patient had a history of psoriasis vulgaris and sorafenib (SOR) was introduced (800 mg/day) because of transcatheter arterial chemoembolization (TACE) refractoriness. However, psoriasis vulgaris exacerbation and a high fever were observed 2 weeks later, and the patient was admitted, after which improvement of psoriasis vulgaris was obtained with external medicine administration and SOR intake discontinuation. Few reports have noted exacerbation of psoriasis vulgaris caused by SOR treatment.

Evaluation of the plasma protein S dynamics during pregnancy using a total protein S assay: Protein S-specific activity decreased from the second trimester.

AIM: The relationship between congenital protein S (PS) deficiency and complications during pregnancy remains unclear, partly due to the difficulty of precisely evaluating the PS level with conventional assays and the physiological decrease of PS during pregnancy. A new PS assay was developed to measure the total PS antigen and activity quantitatively and calculate PS-specific activity. This study aimed to evaluate the plasma PS dynamics during pregnancy using the new PS assay and establish the reference interval for pregnant women. METHODS: A total of 253 pregnant women without a personal or family history of thromboembolism were recruited. Blood samples were obtained in the first, second and third trimesters and at one month post-partum. The total PS antigen, activity, and PS-specific activity were studied. Results were analyzed by the repeated measures single-factor anovas followed by a post-hoc test using Excel Statistics. RESULTS: The mean ± standard deviation (IU/mL) of the total PS antigen levels in the first, second and third trimesters and 1 month post-partum were 0.67 ± 0.12, 0.67 ± 0.09, 0.68 ± 0.11 and 0.92 ± 0.13, respectively. The total PS activity (IU/mL) in the first, second and third trimesters and 1 month post-partum were 0.69 ± 0.14, 0.59 ± 0.10, 0.58 ± 0.12 and 0.87 ± 0.15, respectively. The PS-specific activity was within the normal range of nonpregnant women in the first trimester (1.02 ± 0.10) but decreased in the second and third trimesters (0.88 ± 0.09 and 0.85 ± 0.09, respectively) before increasing in the post-partum period (0.94 ± 0.08). CONCLUSION: The total PS antigen and activity decrease throughout pregnancy, while the PS-specific activity decreases in the second and third trimesters.

SARC-F combined with a simple tool for assessment of muscle abnormalities in outpatients with chronic liver disease.

AIM: An easily performed method for examination of muscle abnormalities is anticipated. We aimed to elucidate the clinical usefulness of simple assessments for muscle abnormality including a simple five-item questionnaire (SARC-F) in chronic liver disease patients. METHODS: From February to July 2019, 383 outpatients (median age 71 years, 259 men; chronic hepatitis (CH) : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B : liver cirrhosis Child-Pugh C = 157:176:39:11) who underwent a computed tomography examination were enrolled. SARC-F, previously reported cut-off values for muscle strength decline (MSD; handgrip), pre-muscle volume loss (pre-MVL), calf circumference and finger-circle test results were used, and these results were analyzed retrospectively. RESULTS: A high SARC-F score (≥4) was observed in 25 patients, and a low score (<4) in 358 patients. The frequency of high SARC-F increased significantly with progression of chronic liver disease (chronic hepatitis : liver cirrhosis Child-Pugh A : liver cirrhosis Child-Pugh B/C = 2.5%:8.0%:14.0%, P=0.010). MSD frequency was 22.4% in men and 41.1% in women. Muscle volume loss and pre-MVL were noted in 22% and 30.5%, respectively, of the male patients, and 9.7% and 32.3%, respectively, of the female patients. In cases with high SARC-F and MSD, calf circumference and finger-circle abnormalities were found in 56% and 40.0% of patients, respectively, whereas those values for patients with low SARC-F and MSD were 14.5% and 10.6%, respectively (P < 0.001, for each; positive/negative predictive values: 0.560/0.855 and 0.400/0.894, respectively). Each SARC-F item showed a good area under the curve for MSD, but not pre-MVL. CONCLUSION: SARC-F score in combination with MSD and calf circumference or finger-circle test results may be an easy and simple method for surveillance of chronic liver disease patients with a high risk of sarcopenia and decline of quality of life.