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Objective: Perspectives of women aged 18–45 years with chronic rheumatic diseases (CRD), and clinicians, in the Asia-Pacific (APAC) region are reported. Methods: Online surveys were completed by women, pregnant in the past 2–5 years, with moderate to severe rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and rheumatologists, obstetricians, orthopaedic surgeons who medically manage CRDs. Results: Among 210 (RA 122, PsA 48, axSpA 40) patients, 52% (n = 109/210) delayed their decision to have children, most commonly due to concerns of passing on disease to offspring. 33% (n = 70/210) discussed family planning with a healthcare professional at diagnosis. Patients most often initiated discussions. 94% (n = 193/205) stopped treatment around pregnancy due to fear of fetal harm. 66% (n = 139/210) of patients felt they did not receive all relevant information on the impact of CRDs and treatment on pregnancy. Among 335 clinicians who participated, 82% (n = 143/174) of rheumatologists, 86% (n = 72/84) of obstetricians and 43% (n = 33/77) of orthopaedic surgeons agreed good disease control during pregnancy was their primary goal. 69% (n = 120/174) of rheumatologists were 'very comfortable' with prescribing tumour necrosis factor inhibitors (TNFi) for women aged 18–45 years. Comfort levels generally decreased with the onset of family planning. More obstetricians and orthopaedic surgeons supported avoiding TNFi during pregnancy than rheumatologists (40% [n = 34/84]/38% [n = 29/77] versus 16% [n = 28/174]). Access to more TNFi safety data during pregnancy was considered paramount for increasing clinician comfort. Conclusions: Patients and physicians need current information and multidisciplinary discussions for improved management of CRD in women in APAC. [ABSTRACT FROM AUTHOR]

Background: Additional evidence regarding the effectiveness of self-management programs for patients awaiting total knee arthroplasty is required. Objective: The study aimed to determine if self-reported physical activity was related to muscle strength and walking ability in patients with knee osteoarthritis awaiting total knee arthroplasty. Methods: The study included subjects with knee osteoarthritis awaiting total knee arthroplasty (n = 767). Walking ability and bilateral knee muscle strength were measured as dependent variables. Self-report physical activity was assessed based on the guidelines from the Japanese Ministry of Health, Labor and Welfare. Multiple regression models determined if self-reported physical activity was significantly related to dependent variables, after accounting for other related factors. Results: Physical activity was associated with both higher knee flexion (β = −0.09, p =.013) and higher extension (β = −0.09, p =.007) muscle strength on the unaffected side only. In addition, physical inactivity was associated with a lower walking ability level (TUG: β = 0.08, p =.015; 5mWT: β = 0.10, p =.005). Conclusions: These results can help health-services providers develop educational and/or self-management programs to maintain muscle strength on the unaffected side and walking ability in patients awaiting total knee arthroplasty. [ABSTRACT FROM AUTHOR]

Background : The prevalence of magnesium imbalance in critically ill children is very high. However, its significance in the development of acute kidney injury (AKI) and mortality remains unknown. Methods: In this retrospective observational study from 2010 to 2018, the pediatric-specific intensive care database was analyzed. We included critically ill children aged > 3 months and those without chronic kidney disease. Patients were diagnosed with AKI, according to the Kidney Disease Improving Global Outcomes (KDIGO) study. We calculated the initial corrected magnesium levels (cMg) within 24 h and used a spline regression model to evaluate the cut-off values for cMg. We analyzed 28-day mortality and its association with AKI. The interaction between AKI and magnesium imbalance was evaluated. Results: The study included 3,669 children, of whom 105 died within 28 days, while 1,823 were diagnosed with AKI. The cut-off values for cMg were 0.72 and 0.94 mmol/L. Both hypermagnesemia and hypomagnesemia were associated with 28-day mortality (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.89–4.71, p < 0.001; OR = 2.80, 95% CI = 1.60–4.89, p < 0.001). Hypermagnesemia was associated with AKI (OR = 1.52, 95% CI = 1.27–1.82, p < 0.001), while neither hypermagnesemia nor hypomagnesemia interacted with the AKI stage on the 28-day mortality. Conclusions: Abnormal magnesium levels were associated with 28-day mortality in critically ill children. AKI and hypermagnesemia had a strong association. "A higher resolution version of the Graphical abstract is available as Supplementary information". [ABSTRACT FROM AUTHOR]

Background: Modified thoracoabdominal nerves block through perichondrial approach (M-TAPA) was first described as a peripheral nerve block by Tulgar in 2019. This technique provides an analgesic effective range from Th7–11 with a single puncture per side. Although the efficacy and effective duration of M-TAPA have been reported, further examination is required. Therefore, this study aimed to evaluate the analgesic range and effective duration of M-TAPA in open gynecologic surgery. Methods: Following approval, 10 adult female patients scheduled for open radical hysterectomy via a vertical incision or laparotomy using a midline incision from under the xiphoid process to the symphysis pubis were enrolled. The primary outcome was the number of anesthetized dermatomes at 2 and 24 h postoperatively. Secondary outcomes included numerical rating scale scores and the total amount of fentanyl used. Cadaveric evaluation was performed to assess the spread of the dye. Results: The median numbers (interquartile range) of anesthetized dermatomes at 2 and 24 h postoperatively were 6 (5–7) and 6.5 (5–7) in the anterior cutaneous branch area and 5 (4–7) and 7 (5–7) in the lateral cutaneous branch area, respectively. There was an 85% chance of simultaneously acquiring analgesia in areas innervated by Th8–11, including complete block in areas innervated by the anterior cutaneous branches of Th9–10. Cadaveric evaluation showed the spread of the dye in Th8–11. Conclusions: M-TAPA may have analgesic effects in the areas supplied by the anterior cutaneous branches of Th8–11. Trail registration: IRB approval (No.2700; registered on July 10, 2020) and registration (UMIN Clinical Trials Registry: UMIN000041137; registered on July 17, 2020). [ABSTRACT FROM AUTHOR]

Objective: Rheumatoid arthritis (RA) is a chronic condition characterized by articular and non-articular features. Patients with RA have an increased risk of developing cardiovascular disease. This study aimed to ascertain what patients with RA know about their numbers (biomedical data, including blood pressure, cholesterol, disease activity score-28 joints [DAS28], and body mass index [BMI]) and to understand the barriers to patients knowing these health indicators and how their knowledge can be improved. Methods: A total of 50 consecutive patients from a clinic were approached to complete an anonymous survey in a nurse-led clinic. The questionnaire included 10 questions that assessed the demographic data, knowledge of biomedical data, importance of these data, and how their awareness could be increased. Results: A total of 40 patients responded to the questionnaire; the estimated mean age was 58.1±13.4 (mean±standard deviation) years. Most respondents were females (87%). The highest disease category duration was 2-5 years (40% patients). Moreover, 30% of respondents were aware of the "know your numbers" concept; 90% did not know their BMI, and 75% did not know about their DAS28 score. Furthermore, 40% reported that they were not informed about their biomedical data; 95% of patients revealed that they would like to know their numbers; 27.5% suggested that a regularly updated and explained written record would be appropriate, and 35% proposed that a multidisciplinary input would be useful in regularly informing them of the numbers. Conclusion: This study has shown that although patients are not very familiar with all of their biomedical data, they are interested in knowing them. Knowing their biomedical data may encourage them to be more concerned about their health and even lead to improved RA self-management and health outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Esophageal cancer patients may simultaneously have resectable esophageal cancer and undiagnosable incidental minute solid pulmonary nodules. While the latter is rarely metastatic, only a few studies have reported on the outcomes of such nodules after surgery. In this retrospective study, we assessed the incidence of such nodules, the probability that they are ultimately metastatic nodules, and the prognosis of patients after esophagectomy according to the metastatic status of the nodules. Methods: Data of 398 patients who underwent esophagectomy for resectable esophageal cancer between January 2012 and December 2016 were collected. We reviewed computed tomography (CT) images from the first visit and searched for incidental minute pulmonary nodules <10 mm in size. We followed the outcomes of these nodules and compared the characteristics of metastatic and nonmetastatic nodules. We also assessed the prognosis of patients whose minute pulmonary nodules were metastatic. Results: Among the patients who underwent esophagectomy, 149 (37.4%) had one or more minute pulmonary nodules, with a total of 285 nodules. Thirteen (4.6%) of these nodules in 12 (8.1%) patients were ultimately diagnosed as being metastatic. Thirteen (8.7%) patients experienced recurrence at a different location from where the nodules were originally identified. Characteristics of the metastatic nodules were not unique in terms of size, SUVmax, or location in the lungs. Two-year and 5-year overall survival rates of patients whose nodules were metastatic were 64.2 and 32.1%, respectively. Conclusion: The rate of minute pulmonary nodules which were ultimately metastatic was 4.6%. Our findings suggest that esophagectomy followed by the identification of minute pulmonary nodules is an acceptable strategy even if the nodules cannot be diagnosed as being metastatic on the first visit CT due to their small size. [ABSTRACT FROM AUTHOR]

Objectives: To analyze the proportion of successful biological disease-modifying antirheumatic drugs (bDMARDs) discontinuation and related factors in patients with rheumatoid arthritis (RA) in clinical settings. Methods: Among 1775 RA patients who started bDMARDs between 2003 and 2012, 43 patients with DAS28-ESR <3.2 at the time of bDMARD discontinuation were extracted. Patients were divided into two groups (bio-free success: BS and bio-free failure: BF groups) based on bDMARD usage and disease activity 1 year after discontinuation. We evaluated the proportion of bio-free success and assessed factors related to bio-free success. Results: Twenty-five patients (58.1%: BS group) maintained discontinuation of bDMARDs and DAS28- ESR <3.2 at 1 year after discontinuation. The median DAS28-ESR at bDMARD initiation was lower in the BS group than in the BF group (3.95 vs 5.04; p=.04). The BS group experienced a larger decrease in average glucocorticoid (GC) dose during bDMARD use than the BF group (-3.0 mg/day vs 0 mg/ day; p=.01). Conclusion: bDMARDs were discontinued without flare up of RA in 58.1% of patients with RA in clinical settings. A lower DAS28-ESR at initiation and reduction of GC dose before discontinuation of bDMARD were important factors associated with bio-free success. [ABSTRACT FROM AUTHOR]

BACKGROUND: Previous studies have examined when activities of daily living (ADL) recovery more than six months after surgery can be predicted, and how much accuracy the predictors have. OBJECTIVE: The purpose of this study was to determine the predictors of ADL decline and evaluate their accuracies one year post-operation for hip-fracture patients. METHODS: We studied patients who underwent hip fracture surgery and were able to walk independently pre-operatively. The predictors of ADL declined one year post-operation, as analyzed using data of the basic medical attributes of the patients, including pain, 30-s chair-stand test, dementia [using the Revised Hasegawa Dementia Scale (HDS-R)], and walking/mobility style [using Barthel Index (BI)]. Using a receiver operating curve (ROC) curve, the cut-off value for each significant predictor was determined in the logistic regression analysis. To calculate the cut-off values and diagnostic performances of each of the extraction factors. RESULTS: The data of 36 patients were collected over a period of one year. The prior probability of ADL decline at one year post-operation was 44.4%. The results of logistic regression analyses showed that the score of HDS-R at admission and the walking/mobility BI score at three weeks post-operation were significant predictors of the one year post-operative decline in ADL. The results of the ROC analyses showed that the cut-off value of the HDS-R score at admission was < 23 points. The posterior probability increased to 62.0%. In contrast, the cut-off value of the walking/mobility BI score was 0 points. The posterior probability increased to 91.0%. CONCLUSION: The ADL decline of the patients who underwent hip fracture surgery at one year after surgery can be predicted at three weeks post-operation. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is one of the leading causes of end stage renal disease. Despite recent therapies, mortality due to DKD and resources spent on healthcare are important problems. Thus, appropriate markers are needed to predict renal outcomes. Therefore, we investigated the role of peripheral perfusion as an indicator for renal events in patients with type 2 diabetes mellitus. This retrospective cohort study included 566 patients who were admitted to Matsushita Memorial Hospital in Osaka, Japan for type 2 diabetes mellitus. Peripheral perfusion was assessed using perfusion index (PI), which represents the level of circulation through peripheral tissues and was measured on each toe using a Masimo SET Radical-7 (Masimo Corporation, Irvine, CA, USA) instrument. The duration of follow up was 3.0 years. The median age of patients was 70 years (IQR range: 61–77 years) and median PI value was 2.9% (IQR range: 1.8–4.8%). Multiple logistic regression analyses showed that PI (per 1% increase) was associated with an odds ratio of composite of end-stage renal disease (ESRD) and/or doubling of serum creatinine level; n = 40 (odds ratio 0.823 [95% CI: 0.680–0.970]), and composite of ESRD, doubling of serum creatinine level, and renal death and/or cardiovascular death; n = 44 (odds ratio 0.803 [95% CI: 0.665–0.944]). The factors which were statistically significant in univariate analysis and those known to be related factors for renal event were considered simultaneously as independent variables for multiple logistic regression analysis. PI can be a novel indicator for renal events in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Oral nutritional supplements (ONS) are multi-nutrient products used to increase the energy and nutrient intakes of patients. The aim of this study was to examine whether or not the adherence of patients varies according to their receiving prescription or over-the-counter ONS. Data were obtained from an online cross-sectional survey conducted with patients in Japan. A total of 107 patients who matched the inclusion criteria for the prescription ONS group and 148 who matched the criteria for the over-the-counter ONS group were further analyzed. In the prescription and over-the-counter ONS groups, the main medical reason for ONS consumption were “malnutrition” (48 patients [44.9%] vs. 63 patients [42.6%] p = 0.798], “frailty” (29 patients [27.1%] vs. 36 patients [24.3%] p = 0.663) and “aging” (25 patients [23.4%] vs. 30 patients [20.3%] p = 0.644). The proportion of “No particular disease” for prescription ONS consumption was significantly lower than that for over-the-counter ONS (6 patients [5.6%] vs. 24 patients [16.2%] p = 0.001). The body mass index of the prescription ONS group was significantly higher than that of the over-the-counter ONS group (21.1±4.38 kg/m2 vs. 19.9±3.75 kg/m2, p = 0.0161). In the prescription ONS group, all patients were given medical advice by doctors or registered dietitians. In contrast, in the over-the-counter ONS group, only 46 patients (31.1%) were given advice by doctors or registered dietitians (p<0.001). In the prescription ONS group, ONS was taken significantly more times and for a longer duration than in the over-the-counter ONS group (p<0.0001). However, among patients given advice by doctors or registered dietitians, there were no significant differences between the groups. Greater support by the medical team is still needed in order to maximize adherence to supplementation, especially concerning the calories, timing and period, so that benefits can be achieved and sustained. [ABSTRACT FROM AUTHOR]

Summary: We conduct a longitudinal study to examine how new VCF alter spinal sagittal balance. New VCF increased SVA by an average of 2.8 cm. Sagittal balance deteriorates as a VCF develops in the lower lumbar spine. A new fracture below L1 increased the relative risk of a deterioration of sagittal balance 2.9-fold compared to one above Th12. Purpose: Studies on the relationship between osteoporotic vertebral fractures and spinal sagittal balance have all been limited to cross-sectional studies. The aim of this study is to conduct a longitudinal study to examine how new vertebral compression fracture (VCF) alter spinal sagittal balance. Methods: Subjects were patients undergoing periodic examinations after treatment of a vertebral fracture or lumbar spinal canal stenosis. Forty patients who developed a new VCF were included in this study. Full-spine standing radiographs were compared before and after the fracture to examine changes in spinopelvic parameters and factors determining the changes in sagittal balance. Results: The mean age of the patients was 79.0 years. The mean interval between pre- and post-fracture radiographs was 22.7 months, and the mean time between development of a fracture and post-fracture radiographs was 4.6 months. After a fracture, sagittal vertical axis (SVA) increased an average of 2.78 cm and spino-sacral angle (SSA) decreased an average of 5.3°. Both ⊿SVA and ⊿SSA were not related to pre-fracture parameters. The wedge angle of the fractured vertebra was not related to changes in sagittal balance. ⊿SVA increased markedly in patients with a fracture of the lower lumbar vertebrae. receiver operating characteristic analysis revealed that the relative risk of a deterioration of sagittal balance was 2.9 times higher for a new fracture below L1 than for a fracture above Th12. Conclusion: New VCF increased SVA by an average of 2.8 cm. Sagittal balance deteriorates as a new fracture develops in the lower lumbar spine. Early intervention in osteoporosis is vital for the elderly. [ABSTRACT FROM AUTHOR]

Objectives: To determine the influence of serum uric acid (UA) levels on renal impairment in patients with UA stone. Materials and methods: We retrospectively analyzed 463 patients with calcium oxalate and/or calcium phosphate stones (CaOx/CaP), and 139 patients with UA stones. The subjects were divided into the serum UA-high (UA ≥ 7.0 mg/dL) or the UA-low group (UA < 7.0 mg/dL). The control group comprised 3082 community-dwelling individuals that were pair-matched according to age, sex, body mass index, comorbidities, hemoglobin, serum albumin, and serum UA using propensity score matching. We compared renal function between controls and patients with UA stone (analysis 1), and between patients with CaOx/CaP and with UA stone (analysis 2). Logistic regression analysis was used to evaluate the impact of the hyperuricemia on the development of stage 3 and 3B chronic kidney disease (CKD) (analysis 3). Results: The renal function was significantly associated with serum UA levels in the controls and patients with CaOx/CaP and UA stones. In pair-matched subgroups, patients with UA stone had significantly lower renal function than the control subjects (analysis 1) and patients with CaOx/CaP stones (analysis 2) regardless of hyperuricemia. Multivariate logistic regression analysis revealed that patients with UA stone, CaOx/CaP, hyperuricemia, presence of cardiovascular disease, higher body mass index, older age and lower hemoglobin had significantly higher risk of stage 3 and 3B CKD (analysis 3). Conclusion: Patients with UA stones had significantly worse renal function than controls and CaOx/CaP patients regardless of hyperuricemia. Urolithiasis (CaOx/CaP and UA stone) and hyperuricemia had an association with impaired renal function. Our findings encourage clinicians to initiate intensive treatment and education approaches in patients with urolithiasis and/or hyperuricemia in order to prevent the progression of renal impairment. [ABSTRACT FROM AUTHOR]

Objectives: This real-world study assessed the effectiveness and safety outcomes of initiating adalimumab and methotrexate (≥12 mg/week) with adjustable dosing in Japanese patients with early rheumatoid arthritis (RA). Methods: This single-arm, prospective postmarketing observational study (conducted from September 2012 to March 2017 at 119 sites) enrolled biologic-naïve patients with early RA (≤2 years duration) and a Disease Activity Score in 28 joints using C-reactive protein (DAS28-CRP) >3.2 who were treated with methotrexate for ≥3 months and had initiated treatment with adalimumab and methotrexate (≥12 mg/week). This report presents 52-week data. The primary outcome was the proportion of patients who achieved DAS28-CRP scores <2.6 at week 52. Results: Overall, 293 of 346 enrolled patients were included in the effectiveness population: women, 73%; mean (standard deviation) age, 54.3 (13.9) years; DAS28-CRP score, 4.51 (0.90); and modified total Sharp score (mTSS), 7.69 (9.98). At week 52, 77% of patients achieved clinical remission (DAS28-CRP <2.6), 92.3% achieved low disease activity (DAS28-CRP ≤3.2), and 86% of evaluable patients experienced structural remission (ΔmTSS ≤0.5). Conclusion: Adalimumab plus methotrexate (≥12 mg/week) with adjustable dosing was well tolerated, and could be a beneficial treatment option for Japanese patients with early RA. [ABSTRACT FROM AUTHOR]

Background: Adverse events (AEs) are unintended consequences of healthcare management that result in temporary or permanent disability, death or prolonged hospital stay. The incidence of AEs has been reported to be higher in surgical specialties compared to medical specialties but information on the incidence of AEs in gynaecology is sparse. Aims: To collect evidence on the incidence, preventability and mortality of AEs in gynaecological hospital admissions by conducting a systematic review and meta‐analysis. Materials and methods: A systematic search of the PubMed, EMBASE, and CINAHL electronic medical databases was performed. Identified articles were screened and a full‐text review was conducted by two independent reviewers. Results: Of the 49 studies assessed for eligibility, three studies were included in this systematic review. Meta‐analysis showed that the incidence of AEs in gynaecological hospital admissions was 10.8% (95% CI 9.4–12.1%), preventability was 52.5% (95% CI 47.3–57.7%) and mortality was 1.2% (95% CI 0–2.5%). Conclusions: Evidence on AEs in gynaecological hospital admissions is limited. Available evidence suggests that approximately one in ten gynaecological inpatients suffer at least one AE and half of AEs are considered preventable. Further research is needed to determine strategies regarding how the incidence of preventable AEs can be reduced. [ABSTRACT FROM AUTHOR]

Purpose: Development of new treatment strategies for endometrial cancer that has become refractory or resistant to taxane/platinum is a critical need. The present study was a phase I/II study of gemcitabine, levofolinate, irinotecan, and 5-fluorouracil (5-FU) (GLIF) combination chemotherapy to determine optimal dosages, safety, and efficacy.Methods: Taxane/platinum-resistant or -refractory endometrial disease was defined as tumor progression within 6 months after a taxane/platinum-based regimen. Maximum tolerated dose was investigated by a 3 + 3-designed phase I study. The phase II study was conducted using the recommended doses determined in the phase I study.Results: The dosages recommended for the phase II trial were determined, in the phase I trial, to be: gemcitabine 800 mg/m2, levofolinate 100 mg/m2, irinotecan 80 mg/m2, and 5-FU 1000 mg/m2. Thirty patients were enrolled, including the three patients who received GLIF therapy at the same dose as the recommended phase II dose in the phase I study. Two patients were excluded at this point due to study protocol violations, and the remaining 28 patients were included for analysis. Phase II revealed that the response and disease control rates were 7.1% (2/28) and 39.3% (11/28), respectively, and that the median PFS and OS were 3 months [95% confidence interval (CI) 3-7] and 12 months (95% CI 9-17), respectively. Febrile or grade 4 neutropenia was observed in 14% (4/28) of the cases. Grade 3 or 4 thrombocytopenia was not observed.Conclusion: We found that GLIF combination chemotherapy is potentially a useful treatment option for endometrial cancers refractory or resistant to taxane/platinum-based chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Aims/Introduction: The present multicenter, cross‐sectional survey was initiated to evaluate self‐monitoring of blood glucose (SMBG)‐associated mental distress among patients with diabetes. Materials and Methods: The survey was carried out in patients with type 1 diabetes and type 2 diabetes using SMBG recruited from 42 medical institutions. Profiles of Mood States 2 and diabetes therapy‐related quality of life questionnaires were used to evaluate mood status and health‐related quality of life. Two original questionnaires were also developed to evaluate SMBG ‘importance,’ ‘painfulness’ and ‘confidence’ among patients, and to evaluate physician attitudes to SMBG use. Results: Questionnaires from 517 type 1 diabetes and 1,648 type 2 diabetes patients showed that 46.0% of type 1 diabetes and 37.5% of type 2 diabetes patients reported ‘painfulness,’ and that these patients reporting ‘painfulness’ showed significantly higher Profiles of Mood States 2 scores, lower diabetes therapy‐related quality of life scores and higher glycated hemoglobin compared with those not reporting ‘painfulness,’ whereas the number of their daily SMBG tests were comparable. Patients reporting ‘painfulness’ also reported that SMBG use was significantly less important. Whether or not patients recognized the importance of SMBG use was well correlated with the frequency of physicians checking patient diaries. Conclusions: Type 1 diabetes and type 2 diabetes patients reporting ‘painfulness’ in SMBG use had more mental distress, lower health‐related quality of life and higher glycated hemoglobin regardless of their number of daily SMBG tests. The importance of SMBG use was recognized less by patients experiencing pain, and the importance of SMBG use was recognized more in medical institutions in which physicians regularly checked SMBG diaries to provide meaningful feedback to patients in clinical settings. [ABSTRACT FROM AUTHOR]

There is no proven therapy for heart failure with preserved ejection fraction (HFpEF). Research has shown beneficial responses to cardiac rehabilitation (CR) among HF patients. To date, there are no reports comparing those responses between patients with HFpEF and those with reduced ejection fraction (HFrEF). The purpose of this study was to compare responses to CR in patients with HFpEF versus those with HFrEF. We included 78 consecutive patients (mean age 69 ± 15 years; 80% male) with HF in our CR unit who underwent cardiopulmonary exercise testing and brachial artery flow-mediated dilation (FMD) testing pre- and 5 months post-CR. Patients were judged as HFpEF (n = 40) or HFrEF (n = 38) using a left ventricular ejection fraction (LVEF) cut-off of 50%, and endothelial dysfunction was defined as FMD ≤ 5.0%. Following 155 ± 11 days and 44 ± 8 sessions, peak oxygen uptake (VO2) and plasma B-type natriuretic peptide concentrations improved significantly in both groups. The percentage change in peak VO2 of HFrEF patients was significantly greater than compared with the HFpEF patients (P < 0.01). To further investigate whether a combination of LVEF and FMD values predicts the effect of CR, we divided patients into four groups according to LVEF of 50% and FMD of 50%. Post hoc analysis showed a significant difference between HFrEF patients without endothelial dysfunction and HFpEF patients with endothelial dysfunction (P = 0.01). In conclusion, although CR improves prognosis in HF patients, a larger effect can be expected in HFrEF patients than in HFpEF patients, and endothelial function may enhance the effect. [ABSTRACT FROM AUTHOR]

Aim: As primary biliary cholangitis (PBC) is a heterogeneous disease, we hypothesized that there is a population of patients with early PBC who do not require prompt treatment with ursodeoxycholic acid (UDCA). In this study, we analyzed data from a large‐scale PBC cohort in Japan, and retrospectively investigated whether outcomes of early PBC patients were affected with prompt or deferred/no UDCA treatment. Methods: We defined early PBC as asymptomatic, serum alkaline phosphatase <1.67‐fold the upper limit of normal, normal bilirubin, and histological stages I–II at presentation. We compared the outcomes of early PBC patients between the treatment regimens; prompt treatment group (UDCA was initiated within 1 year after diagnosis) and deferred/no treatment group (UDCA initiated >1 year after diagnosis or never initiated). Furthermore, we examined the outcomes of early PBC patients alternatively defined only with symptomatology and biochemistry. Results: We identified 562 early PBC patients (prompt: n = 509; deferred/no treatment: n = 53). Incidence rates (per 1000 patient‐years) for liver‐related mortality or liver transplantation and decompensating events were 0.5 and 5.4, respectively, in the prompt treatment group, and 0 and 8.7, respectively, in the deferred/no treatment group. Multivariate analyses showed that age and bilirubin were significantly associated with developing decompensating events, whereas the prompt and deferred/no treatments were not. We obtained similar results in early PBC patients defined without histological examination. Conclusions: We showed that deferred/no treatment for early PBC patients did not affect the outcomes. This study provides a rationale for a future prospective, randomized study. [ABSTRACT FROM AUTHOR]

Objective: The current guideline recommends lowering low-density lipoprotein cholesterol (LDL-C) for the primary management of dyslipidemia in patients at high-risk of cardiovascular events. Patients who have achieved LDL-C levels below the recommended targets may still experience cardiovascular events, suggesting additional therapeutic targets beyond LDL-C. The aim of this study was to investigate whether high-density lipoprotein cholesterol (HDL-C) levels had an impact on plaque stabilization in patients with acute coronary syndrome (ACS). Methods: This study consisted of 90 ACS patients with untreated dyslipidemia. In optical coherence tomography (OCT) analysis, a plaque with fibrous cap thickness ≦160 μm was defined as a high-risk plaque. We registered one high-risk plaque per one patient by baseline OCT imaging, and then administrated high-intensity statin. Based on the follow-up OCT results, patients whose registered plaque was no longer high-risk plaque were classified into a responder group and the remains into a non-responder group. Results: No differences were observed in the baseline LDL-C and HDL-C levels between the two groups. Reduction of LDL-C levels (δ LDL-C: −53 ± 21 mg/dL vs. −42 ± 29 mg/dL, p = 0.036) and increase of HDL-C levels (δ HDL-C: 2.5 ± 5.9 mg/dL vs. −0.3 ± 6.7 mg/dL, p = 0.039) were greater in the responder group. On multivariate logistic regression analysis, δ LDL-C levels (OR: 0.956, 95% CI: 0.921–0.993; p = 0.020) and δ HDL-C levels (OR: 1.143; 95% CI: 1.005–1.300, p = 0.041) were independent contributors for plaque stabilization. Conclusions: Increase of HDL-C levels is associated with plaque stabilization in patients with ACS. HDL-C could be a therapeutic target for residual risk management. [ABSTRACT FROM AUTHOR]

Background: Large scale data on preoperative risk stratification for gastrointestinal bleeding (GIB) following continuous-flow left ventricular assist device (CF-LVAD) implantation are scarce.Aims: To identify independent predictors for GIB following CF-LVAD implantation.Methods: We conducted a retrospective cohort study of consecutive 243 patients who underwent CF-LVAD implantation (HeartMateII) from January 2009 to March 2015 at the University of Chicago Medical Center. GIB was defined as the presence of overt bleeding or occult GIB with ≥ 2 g/dl drop in hemoglobin (Hgb) from recorded baseline values and hemoccult-positive stool. The preoperative and postoperative data were reviewed.Results: Within a median follow-up duration of 408 (IQR 113-954) days, 83 (34%) patients developed GIB after a median of 149 (IQR 27-615) days after implantation of CF-LVAD. There were no significant differences between the groups of GIB and non-GIB with respect to preoperative demographics and comorbidity except for ethnicity. The source of bleeding was identified in 39 (47%) patients and arteriovenous malformation or submucosal streaming vessel was the most frequent cause of bleeding (18/39, 46%). Multivariate-adjusted analysis demonstrated preoperative central venous pressure (CVP) ≥ 18 mmHg (HR 3.56; 95% CI 1.16-10.9; p = 0.026), mean pulmonary artery pressure (mPA) ≥ 36 mmHg (HR 4.14; 95% CI 1.35-12.7; p = 0.013), and the presence of moderate/severe tricuspid valve disease (HR 1.01; 95% CI 1.01-3.86; p = 0.046) were associated with the risk of GIB.Conclusions: In this study, preoperative right-sided cardiac congestion (i.e., increased CVP, mPA and the presence of moderate/severe tricuspid valve disease) was associated with GIB in patients with CF-LVAD. [ABSTRACT FROM AUTHOR]

Binocular vision may be compromised in children after unilateral cataract surgery because the distances at which clear vision is present are different for the two eyes. We believe that wearing progressive additional lenses can be effective in improving the binocular vision in children with pseudophakia. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular glycol that regulates cell proliferation, tissue repair, and tumorigenesis. Despite evidence linking SPARC to inflammation, the mechanisms are unclear. Accordingly, the role of SPARC in intestinal inflammation was investigated. Methods: Colitis was induced in wild‐type (WT) and SPARC knockout (KO) mice using trinitrobenzene sulfonic acid (TNBS). Colons were assessed for damage; leukocyte infiltration; Tnf, Ifng, Il17a, and Il10 mRNA expression; and histology. Cytokine profiling of colonic lamina propria mononuclear cells (LPMCs) was performed by flow cytometry. Naïve CD4+ T cells were isolated from WT and SPARC KO mouse spleens, and the effect of SPARC on Th17 cell differentiation was examined. Recombination activating gene 1 knockout (RAG1 KO) mice reconstituted with T cells from either WT or SPARC KO mice were investigated. Results: Trinitrobenzene sulfonic acid exposure significantly reduced bodyweight and increased mucosal inflammation, leukocyte infiltration, and Il17a mRNA expression in WT relative to SPARC KO mice. The percentage of IL17A‐producing CD4+ T cells among LPMCs from KO mice was lower than that in WT mice when both groups were exposed to TNBS. Th17 cell differentiation was suppressed in cells from SPARC KO mice. In the T cell transfer colitis model, RAG1 KO mice receiving T cells from WT mice were more severely affected than those reconstituted with cells from SPARC KO mice. Conclusions: Secreted protein acidic and rich in cysteine accelerates colonic mucosal inflammation via modulation of IL17A‐producing CD4+ T cells. SPARC is a potential therapeutic target for conditions involving intestinal inflammation. [ABSTRACT FROM AUTHOR]

Highly active antiretroviral therapy (HAART) has successfully reduced the mortality rate of patients with human immune deficiency virus (HIV) and HIV protease inhibitors (HIV PIs) are key components of HAART. Complications of HAART, particularly those associated with HIV PIs including lipodystrophy and metabolic disturbance, have emerged as an important public health issue. No specific treatment is available to prevent and/or treat HIV PI-associated lipodystrophy and metabolic syndrome. The present study demonstrated that a relatively low-dose of farnesyltransferase inhibitor (FTI), tipifarnib (3 mg/kg/day, subcutaneous injection) and lonafarnib (5 mg/kg/day, subcutaneous injection), prevented the onset of lipodystrophy and metabolic syndrome induced by the combination of two HIV PIs, lopinavir (50 mg/kg/day, intraperitoneal injection) and ritonavir (12.5 mg/kg/day, intraperitoneal injection), in mice. Consistent with previous studies, treatment with lopinavir/ritonavir for 2 weeks decreased body weight, adipose tissue mass, levels of plasma adiponectin and leptin, and increased plasma levels of triglycerides, total cholesterol and insulin. Tipifarnib and lonafarnb prevented or ameliorated all of these alterations in the HIV PI-treated mice. These data identify FTIs as a novel potential strategy to prevent or treat HIV PI-associated lipodystrophy and metabolic syndrome in HIV-infected patients on HAART. [ABSTRACT FROM AUTHOR]

Objectives Rovalpituzumab tesirine (Rova-T), an antibody-drug conjugate directed against Delta-like protein 3 (DLL3), is under development for patients with small cell lung cancer (SCLC) positive for this protein. However, the prevalence of DLL3 expression and its association with patient ethnicity and other characteristics have remained unclear. Materiais and methods Tumor samples from 63 patients with SCLC were subjected to immunohistochemical staining for DLL3. The relation of patient characteristics including sex, age, disease stage, and smoking history to DLL3 expression status was analyzed. Results and conlusions Fifty-two patients (83%) were positive for DLL3 expression, with 20 patients (32%) being positive in at least 50% of cancer cells (DLL3-high). DLL3 expression was not associated with any of the patient characteristics examined. In addition, overall survival did not differ between DLL3-high and DLL3-low patients. Our results reveal that DLL3 is expressed in tumor specimens from most patients with SCLC, and they should inform the undertaking of clinical trials of Rova-T including an ongoing phase I study (NCT03086239) in Japan as well as global phase III trials (NCT03061812 and NCT03033511). [ABSTRACT FROM AUTHOR]

Objective Detection of epidermal growth factor receptor (EGFR) gene mutations is essential in deciding therapeutic strategy in non-small cell lung cancer (NSCLC) patients at initial diagnosis. Moreover, in EGFR mutation-positive ( EGFR m) NSCLC patients, re-biopsy at disease progression to clarify resistance mechanisms is also important. However, collecting histology samples is often difficult because of inaccessibility and invasiveness. In some cases, only cytology samples can be collected, and studies have reported that cytology samples are appropriate for EGFR gene mutation testing. The cobas ® EGFR Mutation Test (Roche Molecular Systems Inc., Branchburg, New Jersey, USA) is approved as a companion diagnostic for osimertinib, a third-generation EGFR-tyrosine kinase inhibitor approved in Japan. However, it is not clear whether the EGFR T790M mutation can be detected in cytology samples using this test. The primary objective of this study was to assess concordance of EGFR T790M gene mutation detection between histology and matched cytology samples using the cobas ® EGFR Mutation Test. Materials and methods We conducted a multicenter, observational study in Japan. Overall, 41 EGFR m NSCLC patients who had both histology and cytology samples collected at the same time at re-biopsy and with the results of EGFR mutation test using histology samples were enrolled. The EGFR mutation status of both sample types was tested using the cobas ® EGFR Mutation Test and the concordance rates were calculated. Results The EGFR T790M mutation detection rate in histology and cytology samples was 42.5% and 37.5%, respectively. The overall percent agreement between the histology and cytology samples was 91.7%. Conclusions These data demonstrate that the cobas ® EGFR Mutation Test can detect the EGFR T790M mutation in both cytology and histology samples. [ABSTRACT FROM AUTHOR]

Sudden hearing loss may occur in rare cases of relapsing-remitting multiple sclerosis (RRMS). There have also been reports of idiopathic sudden sensorineural hearing loss (SNHL) in patients with neuromyelitis optica spectrum disorders (NMOSD), but the frequency of such cases is unclear. We conducted a retrospective analysis of the medical records of 173 consecutive patients with multiple sclerosis (MS) and 101 consecutive patients with NMOSD who tested positive for anti-aquaporin-4 antibodies in addition to 37 consecutive patients with clinically isolated syndromes (CIS) to investigate the frequency and onset timing of SNHL. SNHL was observed in six (3.5%) of the RRMS cases, one (1.0%) of the seropositive NMOSD cases, and three (8.1%) of the CIS cases. SNHL occurred ahead of onset in 4/6 MS patients and in all of 3 CIS patients. Patient with NMOSD exhibited SNHL 6 years after the onset of NMOSD. Although SNHL is rare, these results suggest the risk of developing demyelinating lesions in the central nervous system and further conversion to MS in the future. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We aimed to explore the association between abnormal glucose metabolism such as diabetes, prediabetes, and short-term prognosis in patients with acute ischemic stroke. Methods: Of 242 consecutive acute ischemic stroke patients, a 75-g oral glucose tolerance test was administered to 116 patients without previously diagnosed diabetes. One hundred forty patients were classified into diabetes, 52 patients were prediabetes (impaired glucose tolerance or impaired fasting glucose or both), and 50 patients were normal glucose tolerance (NGT). The association between each glycemic status and early neurological deterioration (END; increase in the NIH Stroke Scale (NIHSS) of ≥2 points during the first 14days after admission) or poor short-term outcome (30-day modified Ranking Scale [mRS] score 2–6) was evaluated. Results: In multivariable analysis, the risk of END was significantly higher in the diabetes group than in the NGT group (ORs=11.354; 95% CI, 1.492–86.415; p=0.019), even after adjustment for possible confounding factors (ORs=12.769; 95% CI, 1.361–119.763; p=0.026). Similar but insignificant associations were observed between prediabetes and NGT groups (ORs=6.369; 95% CI, 0.735–55.177; p=0.093). The risk of poor outcome (30-day mRS 2–6) was significantly higher in the diabetes group (ORs=3.667; 95% CI, 1.834–7.334; p<0.001) than in the NGT group, even after adjusting for confounding factors (ORs=3.340; 95% CI, 1.361–8.195; p=0.008). Similar but insignificant associations were observed between prediabetes and NGT groups (ORs=2.058; 95% CI, 0.916–4.623; p=0.08). Conclusion: In our patient population, both diabetes and prediabetes were associated with a poor early prognosis after acute ischemic stroke. [Copyright &y& Elsevier]

The t(3;21)(q26.2;q22) translocation is a rare chromosomal abnormality exhibited almost exclusively in therapy‑related myelodysplastic syndrome/acute myeloid leukemia (t‑MDS/AML) or in the blastic crisis phase of chronic myelogenous leukemia, which results in the fusion of the runt related transcription factor 1 (RUNX1, also called AML1) gene at 21q22 to the myelodysplasia syndrome 1 (MDS1)‑ecotropic virus integration site 1 (EVI1) complex locus (MECOM) at 3q26.2, generating various fusion transcripts, including AML1/MDS1/EVI1 (AME). The present study examined the case of an 84‑year‑old Japanese woman who developed t‑MDS/AML with t(3;21)(q26.2;q22) subsequent to receiving low‑dose methotrexate (MTX) treatment for rheumatoid arthritis. Following treatment with MTX for 6 years, the patient developed anemia and neutropenia, and MTX was discontinued. A total of 3 years later, the patient was diagnosed with MDS with t(3;21)(q26.2;q22) and del (5q), which progressed rapidly to AML within 3 months. The patients was subsequently treated with azacitidine and cytarabine chemotherapy, but succumbed to the disease 6 months after diagnosis. Sequencing analysis of the nested reverse transcription‑PCR products from the leukemic cells revealed the expression of two types of alternatively‑spliced AME transcripts with or without RUNX1 exon 6 sequences. Western blot analysis of the leukemic cells of the patient additionally revealed that the corresponding AME fusion protein products were expressed at high levels, and that these cells also prominently expressed CCAAT/enhancer‑binding protein α, the repression of which has been reported to be involved in leukemogenesis mediated by AME. To the best of our knowledge, the case discussed in the present study represents the first report of MDS/AML with t(3;21)(q26.2;q22) developing following low‑dose MTX therapy for rheumatoid arthritis. Nonetheless, the clinical and molecular features of the patient in the present study were representative of those patients who typically develop this disease following exposure to chemotherapy or radiotherapy for primary malignancy, which implicates MTX in the pathogenesis of t‑MDS/AML. Moreover, we confirmed the expression of two AME fusion proteins for the first time in primary leukemic cells and analyzed several cellular factors implicated in AME‑mediated leukemogenesis to gain some insight into its molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background Although male gender, aging, hypertension, dyslipidemia, and smoking are common risk factors for abdominal aortic aneurysm, diabetes mellitus is an independent negative risk factor. In aneurysm tissue, matrix metalloproteinases (MMPs) expressed by activated macrophages degrades extracellular matrix proteins. In our previous experimental study, we demonstrated that the aneurysmal formation and macrophage activity were suppressed by inhibiting mimicking hyperglycemia (HG) through upregulation of glucose-sensing nuclear receptor, Nr1h2. Here in this study, we focused on the role of HG-induced altered glucose uptake on macrophage activation. Methods RAW264.7 murine macrophage cells were pretreated in cultures containing HG (HG group, 15.5 mM) or normal glucose (NG) concentrations (NG group, 5.5 mM) for 7 d. The culture medium was then changed in both groups to NG conditions, and the cells were stimulated with recombinant murine soluble receptor activator of NF-κB ligand (sRANKL). Macrophage activation was confirmed by tartrate-resistant acid phosphatase (TRAP) staining. Results Compared with the NG group, MMP-9 expression in the HG group was significantly suppressed. Glucose uptake was increased in the NG group but not in the HG group during macrophage activation. To determine the mechanism of activation, we studied the expression and distribution of glucose transporters (Gluts) in the macrophages. Although Glut expression was unaffected by glucose pretreatment, membrane translocation of Glut-1 was significantly enhanced in macrophages in the NG group but not in the HG group during activation. Insulin receptor and insulin receptor substrate-1 (IRS-1) messenger RNA, known stimulate to membrane translocation of Gluts, were both decreased by the HG condition but not by the NG condition. Conclusions HG pretreatment suppressed the macrophage activation. sRANKL increased macrophage glucose uptake at NG concentrations, which was impaired by HG pretreatment through the inhibition of Glut1 membrane translocation and the insulin receptor and IRS-1 gene transcription. These data suggest that HG suppressed macrophage activation, through attenuation of glucose uptake via the suppression of the membrane translocation of Glut1 and insulin signaling. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is an established independent risk factor for progression to end-stage renal disease (ESRD) and incidence of cardiovascular disease (CVD). The onset and progression of CKD are associated with both genetic predisposition and various lifestyle-related factors, but little is known about the influence of genetic-environmental interactions on the incidence of ESRD or CVD in patients with CKD. Methods: The Fukuoka Kidney disease Registry (FKR) Study is designed as one of the largest prospective, multicenter, observational cohort studies in non-dialysis dependent CKD patients. The FKR Study aims to enroll approximately 5000 individuals at multiple clinical centers and follow them for up to at least 5 years. At baseline, subjects enrolled in the FKR Study will fill out extensive lifestyle-related questionnaires. Further, their health status and treatments will be monitored annually through a research network of nephrology centers. Blood and urine samples, including DNA/RNA, will be collected at the time of enrolment and every 5-years follow-up. Conclusions: The FKR Study will provide many insights into the onset and progression of CKD, which will suggest hypothesis-driven interventional clinical trials aimed at reducing the burden of CKD. The features of the FKR Study may also facilitate innovative research to identify and validate novel risk factors, including genetic susceptibility and biomarkers, using biomaterials by high-throughput omics technologies. [ABSTRACT FROM AUTHOR]

In Southeast Asia, particularly in Thailand, β0-thalassemia/hemoglobin E (HbE) disease is a common hereditary hematological disease. It is associated with pathophysiological processes, such as the intramedullary destruction of immature erythroid cells and peripheral hemolysis of mature red blood cells. MicroRNA (miR) sequences, which are short non-coding RNA that regulate gene expression in a suppressive manner, serve a crucial role in human erythropoiesis. In the present study, the plasma levels of the erythroid-expressed miRNAs, miR-451 and miR-155, were analyzed in 23 patients with β0-thalassemia/HbE and 16 control subjects. Reverse transcription-quantitative polymerase chain reaction analysis revealed significantly higher levels of plasma miR-451 and miR-155 in β0-thalassemia/HbE patients when compared to the control subjects. Notably, among the β0-thalassemia/HbE patients, a significant increase in miR-451 levels was detected in severe cases when compared with mild cases. The levels of plasma miR-451 correlated with reticulocyte and platelet counts. The results suggest that increased plasma miR-451 levels may be associated with the degree of hemolysis and accelerated erythropoiesis in β0-thalassemia/HbE patients. In conclusion, miR-451 may represent a relevant biomarker for pathological erythropoiesis associated with β0-thalassemia/HbE. [ABSTRACT FROM AUTHOR]

Background: Evidence related to the effectiveness of combination drug therapy for the treatment of osteoporosis is currently considered insufficient. Therefore, this study was performed to clarify the effects of monotherapy, and combination therapy, with a bisphosphonate (minodronic acid hydrate), a bone resorption inhibitor, and calcitonin (elcatonin), which is effective for the alleviation of pain due to vertebral fractures in osteoporotic patients.Methods: Study participants comprised of 51 female subjects with post-menopausal osteoporosis, whose main complaint was acute lower back pain caused by vertebral fractures. Subjects were randomly allocated into three groups and then administered with either intramuscular injections of elcatonin at a dose of 20 units weekly, minodronic acid hydrate at a dose of 1 mg daily, or a combination of these two drugs. As primary endpoints, time-dependent changes in levels of pain were assessed using a visual analog scale from baseline to 6 months of duration. In addition, we examined the effects of monotherapies, and a combination therapy on bone resorption, with changes in bone mineral density at 4 sites and advanced hip assessment parameters from baseline to 6 months. A two-tailed significance level of 5% was used for hypothesis testing.Results: Elcatonin monotherapy showed some alleviation of pain immediately after any vertebral fractures, which was more than in the minodronic acid hydrate monotherapy group. In addition, the minodronic acid hydrate monotherapy group experienced more effective inhibited bone resorption than the elcatonin monotherapy group. In the combination therapy, the efficacy for alleviating pain and inhibiting bone resorption was equivalent to the effect observed in the elcatonin and minodronic acid hydrate monotherapy groups respectively, with further improved values of bone mineral density observed in the femoral neck and lumbar vertebrae, and in parameters of advanced hip assessment compared with both monotherapy groups.Conclusions: Combination therapy with elcatonin and minodronic acid hydrate appears to be an effective treatment for osteoporosis patients with lower back pain, caused by fresh vertebral fractures. [ABSTRACT FROM AUTHOR]

Background: Thymectomy can effectively cure most thymoma patients; however, patients with advanced thymoma typically require chemotherapy, which is associated with limited efficacy in this context. Here we provide the first report of a patient with recurrent thymoma who achieved complete remission (CR) using cyclosporine therapy. Case presentation: A 63-year-old woman who had undergone resection surgery for recurrent type B1 thymoma developed pure red cell aplasia (PRCA), and CT findings revealed thymoma recurrence. After the initiation of orallyadministered cyclosporine, PRCA quickly resolved, and the thymoma disappeared without the administration of any anti-thymoma therapy. The patient has remained in CR for over 3 years using only cyclosporine. Conclusions: This is the first report describing the curative potential of cyclosporine for the treatment of advanced thymoma. Although the mechanism underlying this effect remains unclear, cyclosporine can become a less toxic and more cost-effective treatment option for thymoma compared with conventional therapy. Clinical trials are needed to confirm the therapeutic potential of cyclosporine as a new treatment option for thymoma. [ABSTRACT FROM AUTHOR]

Objectives: The effects of RBC transfusion on microvascular perfusion are not well documented. We investigated the effect of RBC transfusion on sublingual microcirculation in hemorrhagic shock patients.Design: Prospective, preliminary observational study.Settings: A 28-bed, surgical ICU in a university hospital.Patients: Fifteen hemorrhagic shock patients requiring RBC transfusion.Intervention: Transfusion of one unit of RBCs.Measurements and Main Results: The sublingual microcirculation was assessed with a Sidestream Dark Field imaging device before and after RBC transfusion. After transfusion of one unit of RBC, hemoglobin concentration increased from 8.5 g/dL (7.6-9.5 g/dL) to 9.6 g/dL (9.1-10.3 g/dL) g/dL (p = 0.02) but no effect on macrocirculatory parameters (arterial pressure, cardiac index, heart rate, and pulse pressure variations) was observed. Transfusion of RBC significantly increased microcirculatory flow index (from 2.3 [1.6-2.5] to 2.7 [2.6-2.9]; p < 0.003), the proportion of perfused vessels (from 79% [57-88%] to 92% [88-97%]; p < 0.004), and the functional capillary density (from 21 [19-22] to 24 [22-26] mm/mm; p = 0.003). Transfusion of RBC significantly decreased the flow heterogeneity index (from 0.51 [0.34-0.62] to 0.16 [0.04-0.29]; p < 0.001). No correlations were observed between other macrovascular parameters and microvascular changes after transfusion. The change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion.Conclusions: RBC transfusion improves sublingual microcirculation independently of macrocirculation and the hemoglobin level in hemorrhagic shock patients. The change in microvascular perfusion after transfusion correlated negatively with baseline microvascular perfusion. Evaluation of microcirculation perfusion is critical for optimization of microvascular perfusion and to define which patients can benefit from RBC transfusion during cardiovascular resuscitation. [ABSTRACT FROM AUTHOR]

Objectives To determine the characteristics of testicular germ cell tumors in older patients. Methods A testicular cancer survey was carried out by the Japanese Urological Association in 2011 to register the testicular cancers diagnosed in 2005 and 2008. The survey included age, presenting symptoms, physical examination findings, tumor markers, histopathology, clinical stage, treatment and clinical outcomes. These factors were compared between patients aged ≥50 years and those aged <50 years at diagnosis. Results Of the 1119 cases of primary testicular germ cell tumors, 123 (11.0%) were diagnosed at age ≥50 years. Compared with patients aged <50 years, germ cell tumors in older patients were more frequently seminomas (74.8% vs 61.4%, P = 0.004) and clinical stage I at diagnosis (79.5% vs 70.7%, P = 0.041). Metastatic germ cell tumors in patients aged ≥50 years were more frequently classified into the good prognosis group according to the International Germ Cell Consensus Classification compared with those in younger patients (84.0% vs 53.8%, P = 0.003). Nevertheless, cancer-specific survival of patients aged ≥50 years was not superior to that of younger patients (4-year survival rates; 93.7% vs 97.8%). Conclusions Testicular germ cell tumors in patients aged ≥50 years are more commonly seminomas, and tend to be diagnosed at earlier stages compared with younger patients; however, the prognosis of older patients is not favorable compared with that of younger patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to retrospectively analyze the feasibility of outpatient management without initial assessment for febrile patients undergoing adjuvant chemotherapy for breast cancer. A total of 131 consecutive patients with breast cancer treated with adjuvant or neoadjuvant chemotherapy from 2011 to 2013 at Osaka Medical College Hospital (Osaka, Japan) were retrospectively reviewed. In the case of developing a fever (body temperature, ≥38˚C), the outpatients had been instructed to take previously prescribed oral antibiotics for 3 days without any initial assessment, and if no improvement had occurred by then, they were required to visit the hospital for examination and to undergo treatment based on the results of a risk assessment for complications. The primary aim of the present study was to assess the outcome of febrile episodes, while the secondary aim was to assess the incidence of febrile episodes, hospitalizations, and the type of chemotherapy. The 131 patients received 840 chemotherapy administrations. Fifty‑five patients (42.0%) had a total of 75 febrile episodes after 840 chemotherapy administrations (8.9%). Treatment failure occurred in 12 of the 75 episodes (16.0%) in 11 of the 55 patients (20.0%). Only four episodes required hospitalization. Treatment success was achieved in 63 episodes (84.0%). In conclusion, the feasibility of outpatient management without initial assessment was evaluated in the present study for febrile patients undergoing adjuvant chemotherapy for breast cancer, and the outpatient strategy regimen may be safe and convenient for these patients. [ABSTRACT FROM AUTHOR]

Objectives To investigate the impact of perioperative plasma fibrinogen level as a biomarker of oncological outcome in localised renal cell carcinoma ( RCC). Patients and methods We consecutively identified 601 patients with localised RCC who underwent curative surgery at a single institution. Subsequent disease recurrence and cancer-specific survival ( CSS) were assessed using the Kaplan-Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, multivariate analysis was performed for these outcomes. Results Using the defined threshold level of preoperative plasma fibrinogen of ≥420 mg/ dL as elevated, we found 56 patients (9.3%) with an elevated plasma fibrinogen level preoperatively. In Kaplan-Meier analysis, there was a significant difference in disease-free survival and CSS rates between patients with and without preoperative plasma fibrinogen levels of ≥420 mg/ dL. Multivariate analysis showed that elevated preoperative plasma fibrinogen level was an independent predictor of subsequent disease recurrence and cancer-specific mortality. In a subgroup analysis of the elevated preoperative plasma fibrinogen level group, postoperative normalisation of plasma fibrinogen level was significantly associated with CSS, showing that patients with non-normalised plasma fibrinogen levels tended to have a higher incidence of cancer-specific mortality after surgery. Conclusion Patients with elevated preoperative plasma fibrinogen levels could be significantly predicted to have subsequent tumour metastasis and cancer-specific mortality, while there was a significant difference in CSS between patients in the normalised and non-normalised postoperative plasma fibrinogen groups. While these are hypothesis generating results, plasma fibrinogen levels may be a useful biomarker due to its low cost and ease of assessment. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim The aim of this study was to identify specific indications for treatment with either yokukansankachimpihange or chotosan, Kampo agents commonly used to treat headache refractory to conventional treatments. Methods On multidimensional contingency table analysis using the Kampo database, specific symptoms associated with positive outcome for each agent were identified according to Akaike information criterion, and logit regression was used to predict outcome for both agents in individual patients. This predictive model was validated in another 157 patients (M/F, 12/145; age, 20-84 years). The Kampo treatment with the higher probability of positive outcome in each patient was then used for that patient for 1 month. Results Specific symptoms identified as indications for yokukansankachimpihange were stiffness in the back (partial regression coefficient, 2.25), painful sensation in the eyes (3.28), and irritability (0.25). Those for chotosan were morning headache (partial regression coefficient 3.68), vasodilatation of sublingual veins (1.62), and stiff shoulder (1.28). Yokukansankachimpihange may mainly relieve triggering factors of headache. In the validation study, the model predicted greater efficacy for yokukansankachimpihange in 79 patients (M/F, 4/75; age, 20-84 years) and for chotosan in 78 patients (M/F, 8/70; age, 22-78 years). After treatment for 1 month, the predictive accuracy was 76%. Conclusions Six symptoms serving as practical indications for selection of either yokukansankachimpihange or chotosan to treat patients with headache, were identified. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Coldness is a common complaint in kampo medicine, and is commonly treated with unkeito, but recommended indications (so-called Kuketsu) are inconsistent. The aim of the present study was therefore to identify a set of self-reported symptoms that would predict a positive outcome of treatment for coldness with unkeito, and that would therefore serve as specific indications for treatment with unkeito. Methods This was a retrospective cohort study of 70 female patients (median age, 33 years; range, 22-71 years) without organic abnormalities who complained of coldness, and who completed a self-report questionnaire about their health using the present kampo questionnaire database system on their first visit. Another 26 female patients (median age, 38 years; range, 22-60 years) were assigned to verify the discriminatory predictive ability of the developed logit model. Patients were treated with two or three packages of unkeito per day for 1 month, and the efficacy of treatment was then recorded as a binary response. Results Unkeito decreased frequency and severity scales (0-4) of coldness from a median of 3.0 (range, 1-4) to 2.0 (range, 0-4; P < 0.001) and from 3.0 (range, 2-4) to 2.0 (range, 0-4; P < 0.001), respectively. Both frequency and severity of coldness were improved in 77.1% of patients. The developed model for prediction of treatment effect consisted of dry lips ( Akaike information criterion ( AIC), −14.10), with coldness in the feet ( AIC, −25.01) but not in the whole body ( AIC, −25.01). Model validation with 26 new patients gave a predictive accuracy of 77%. Conclusion Dry lips, accompanied by coldness in the feet, but not in the whole body, are important indications for treatment with unkeito. [ABSTRACT FROM AUTHOR]

Objectives To prospectively evaluate the persistence of solifenacin treatment in previously untreated Japanese female patients with overactive bladder. Methods A total of 73 previously untreated Japanese female patients diagnosed with overactive bladder were given 5 mg of solifenacin once daily and prospectively followed for 3 years with periodic evaluations. The drug persistence rate was estimated using the Kaplan-Meier method. If solifenacin had to be terminated or a patient did not come to the hospital to receive a prescription, the reason was determined. Results After solifenacin treatment, the overactive bladder symptom score and average voided volume were significantly improved and maintained for 3 years. The 6-month, 1-year, 2-year and 3-year persistence rates were 50.7%, 41.1%, 32.9% and 23.3%, respectively. The major reasons for solifenacin therapy discontinuation were symptom resolution (27.4%) and adverse events (20.5%). Patients with nocturia three times or more at baseline had lower persistence than those with nocturia more than three times. Patients without detrusor overactivity at baseline had lower drug persistence than those with detrusor overactivity. Conclusions Approximately one-quarter of previously untreated Japanese overactive bladder female patients continue solifenacin treatment for 3 years. Many patients discontinue solifenacin for various reasons, including symptom resolution and adverse events. [ABSTRACT FROM AUTHOR]

Purpose: Long-term survivors of biliary atresia (BA) sometimes experience liver dysfunction. We evaluated the prognostic factors for long-term native liver survival (NLS) in BA patients after the Kasai procedure.Methods: This study included 67 patients with jaundice disappearance after the Kasai procedure performed between 1972 and 1995, and NLS for over 10 years. We retrospectively evaluated the clinical parameters, including the type of BA, age at the Kasai procedure, medical conditions, and treatments. The adjusted odds ratios (aOR) were obtained for 20-year NLS using logistic regression analysis.Results: The median age of the patients at the Kasai procedure was 63 days. Of the 67 study patients, 62 patients (92.5 %) had jaundice-free NLS at the age of 20 years, 4 patients died before the age of 20 years from liver failure, and 1 patient underwent living related liver transplantation. The presence of gastro-esophageal varices requiring endoscopic injection sclerotherapy was a significant factor (aOR 33.8; p = 0.0033), while hypersplenism and cholangitis were not identified as significant factors.Conclusions: The existence of symptomatic portal hypertension would influence long-term NLS in BA patients after the Kasai procedure. In such patients, accurate evaluation of hepatic function and adequate treatment for sequelae are needed. [ABSTRACT FROM AUTHOR]

Focal nerve enlargements at sites of conduction blocks can be visualized sonographically in patients with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). However, little is known about association between nerve morphological changes and treatment responses. Here we present a 73-year-old female MADSAM patient whose sonographical multifocal nerve enlargements normalized following a good treatment response. She was admitted to our department with progressive asymmetrical muscle weakness and sensory disturbances for 6 months. Ultrasonography revealed multifocal nerve enlargements at sites of electrophysiological demyelination. Intravenous immunoglobulin improved her symptoms and electrophysiological abnormalities. Six months later, ultrasonography revealed normalization of multifocal nerve enlargements. Contrary to our observations, one previous report described a MADSAM patient with persistent nerve enlargements at the sites of resolved conduction blocks. In this earlier patient, however, the time from onset to remission was approximately 30 months. Morphological changes of nerve enlargements in MADSAM may vary with treatment response. [ABSTRACT FROM AUTHOR]

Objectives We aimed to determine the predictive factors for the ineffectiveness of intravenous methylprednisolone (IVMP) that lead to earlier use of plasmapheresis in patients with relapsing neuromyelitis optica spectrum disorder. Methods A total of 40 patients were investigated retrospectively. The responders were defined as patients who showed IVMP effectiveness within 7 days from IVMP initiation, indicated by an improvement in the Kurtzke Expanded Disability Status Scale (EDSS) ≥0.5, whereas non-responders were defined as those without such an improvement. We analyzed 10 clinical findings and four cerebrospinal fluid (CSF) parameters before IVMP, which included EDSS (baseline before relapse, before IVMP initiation, difference between them: ΔEDSS), CSF-cells, CSF-lactate dehydrogenase, CSF/serum quotient of albumin (Q-ALB) and immunoglobulin G (Q-IgG). Results The 40 patients consisted of 22 responders and 18 non-responders. The levels of ΔEDSS, EDSS before IVMP, CSF-cells, CSF-lactate dehydrogenase, Q-ALB and Q-IgG were significantly higher in non-responders than in responders. Of these, univariate logistic regression analyses showed that the ΔEDSS, EDSS before IVMP, Q-ALB and Q-IgG were significantly related to IVMP ineffectiveness. Because of the significant correlation between ΔEDSS and EDSS before IVMP, and between Q-ALB and Q-IgG, the ΔEDSS and Q-IgG were analyzed as dependent factors for IVMP ineffectiveness in multivariate analysis. The higher Q-IgG level was found to be independently associated with ineffectiveness. The cut-off level for Q-IgG to discriminate non-responders from responders was 4.7 (sensitivity 83, specificity 91%). Conclusions Q-IgG >4.7 before IVMP is a predictive factor for IVMP ineffectiveness. Early use of plasmapheresis should be considered in relapsing neuromyelitis optica spectrum disorder with such high Q-IgG values before IVMP. [ABSTRACT FROM AUTHOR]

Introductions Avoidant personality disorder ( AVPD) has excessive and pervasive anxiety and discomfort in social situations. The aims of this study were to explore the relationship between AVPD and physical and psychological stress and psychological tests. Methods We evaluated 93 AVPD patients and 355 nonpatient controls by salivary amylase and cortisol responses during exposure to the Trier Social Stress Test ( TSST) and electrical stimulation stress. Spielberger state-trait anxiety inventory ( STAI), Profile of Mood State ( POMS), Beck Depression Inventory ( BDI), Depression and Anxiety Cognition Scale ( DACS), and Childhood Trauma Questionnaire ( CTQ) were administered. Results Following electrical stimulation, salivary cortisol levels in female AVPD decreased significantly less than that in female's controls, but salivary cortisol levels did not show a difference between male AVPD patients and controls. Salivary alpha-amylase ( sAA) levels did not show a difference between females or male AVPD patients and controls. Following TSST exposure, sAA levels did not show a difference between females or male AVPD patients and controls. Salivary cortisol levels did not show a difference between females or male AVPD patients and controls. In the AVPD patients, POMS scores were significantly higher compared with the controls. STAI, BDI, DACS scores, and CTQ significantly increased in the AVPD patients compared with the controls. LF in heart rate variability in AVPD significantly increased more compared with controls. Conclusions These results suggest that heightened sympathetic reactivity in female AVPD co-occurs with attenuated salivary cortisol responses to electric stimulation stress and there is a significant difference between AVPD and controls in mood, anxiety, social cognition, and automatic nerve systems. [ABSTRACT FROM AUTHOR]

Summary: Purpose: To examine the incidence and clinical features of epileptic seizures in Japanese patients with multiple sclerosis (MS) and neuromyelitis optica (NMO). Methods: We reviewed medical records of all patients who visited the Neurology Clinic in Utano National Hospital between January and December, 2009, and enrolled 63 MS patients who fulfilled the McDonald criteria (2005) (mean age, 41.1 years) and 31 NMO patients who fulfilled the Wingerchuk criteria (2006) (mean age, 44.6 years). Patients with a history of epileptic seizures were selected and their clinical features were obtained. Results: Four MS patients (6.3%; 2 men and 2 women; mean age, 32.5 years) and 4 NMO patients (12.9%; 4 women; mean age, 36.0 years) had epileptic seizures. Disease onset age of MS patients with seizures was significantly younger than those without seizures by 13.1 years, and Expanded Disability Status Scale of NMO patient with seizures was significantly higher than those without seizures by 2.2. All 8 patients showed brain lesions on magnetic resonance imaging and 2 MS patients had tumefactive demyelinating lesions. Electroencephalography showed interictal epileptiform discharges in 5 patients. Seizure types of 6 patients were recognized as partial seizures based on clinical semiology. All patients responded to antiepileptic therapy well. In both MS and NMO, there were both seizures with and without concurrent relapse. Conclusions: Similar to MS, NMO patients possibly have higher risk to develop epileptic seizures than general population. [Copyright &y& Elsevier]

Abstract: Hematopoietic stem cell transplantation (HSCT) has not been indicated for patients with mucopolysaccharidosis II (MPS II, Hunter syndrome), while it is indicated for mucopolysaccharidosis I (MPS I) patients <2years of age and an intelligence quotient (IQ) of ≥70. Even after the approval of enzyme replacement therapy for both of MPS I and II, HSCT is still indicated for patients with MPS I severe form (Hurler syndrome). To evaluate the efficacy and benefit of HSCT in MPS II patients, we carried out a nationwide retrospective study in Japan. Activities of daily living (ADL), IQ, brain magnetic resonance image (MRI) lesions, cardiac valvular regurgitation, and urinary glycosaminoglycan (GAG) were analyzed at baseline and at the most recent visit. We also performed a questionnaire analysis about ADL for an HSCT-treated cohort and an untreated cohort (natural history). Records of 21 patients were collected from eight hospitals. The follow-up period in the retrospective study was 9.6±3.5years. ADL was maintained around baseline levels. Cribriform changes and ventricular dilatation on brain MRI were improved in 9/17 and 4/17 patients, respectively. Stabilization of brain atrophy was shown in 11/17 patients. Cardiac valvular regurgitation was diminished in 20/63 valves. Urinary GAG concentration was remarkably lower in HSCT-treated patients than age-matched untreated patients. In the questionnaire analysis, speech deterioration was observed in 12/19 patients in the untreated cohort and 1/7 patient in HSCT-treated cohort. HSCT showed effectiveness towards brain or heart involvement, when performed before signs of brain atrophy or valvular regurgitation appear. We consider HSCT is worthwhile in early stages of the disease for patients with MPS II. [Copyright &y& Elsevier]

Abstract: This open-label clinical study enrolled 10 adults with attenuated Mucopolysaccharidosis II and advanced disease under the direction of the Japan Society for Research on Mucopolysaccharidosis Disorders prior to regulatory approval of idursulfase in Japan. Ten male patients, ages 21–53years, received weekly intravenous infusions of 0.5mg/kg idursulfase for 12months. Significant reductions in lysosomal storage and several clinical improvements were observed during the study (mean changes below). Urinary glycosaminoglycan excretion decreased rapidly within the first three months of treatment and normalized in all patients by study completion (−79.9%). Liver and spleen volumes also showed rapid reductions that were maintained in all patients through study completion (−33.2% and −31.0%, respectively). Improvements were noted in the 6-Minute Walk Test (54.5m), percent predicted forced vital capacity (3.8 percentage points), left ventricular mass index (−12.4%) and several joint range of motions (8.1–19.0 degrees). Ejection fraction and cardiac valve disease were stable. The sleep study oxygen desaturation index increased by 3.9 events/h, but was stable in 89% (8/9) of patients. Idursulfase was generally well-tolerated. Infusion-related reactions occurred in 50% of patients and were mostly mild with transient skin reactions that did not require medical intervention. Two infusion-related reactions were assessed as serious (urticaria and vasovagal syncope). One patient died of causes unrelated to idursulfase. Anti-idursulfase antibodies developed in 60% (6/10) of patients. In summary, idursulfase treatment appears to be safe and effective in adult Japanese patients with attenuated MPS II. These results are comparable to those of prior studies that enrolled predominantly pediatric, Caucasian, and less ill patients. No new safety risks were identified. [Copyright &y& Elsevier]

Hepatoprotective therapies that include regular glycyrrhizin injections (GIs) are beneficial for chronic hepatitis C patients, but are sometimes insufficient for normalizing serum alanine aminotransferase (ALT) levels. Here, we evaluated whether the addition of minor bloodletting, named petit phlebotomy (PP), prior to each GI could further reduce serum ALT concentrations in such patients. Seventy-six hepatitis C virus (HCV)-infected patients receiving regular GI, with persistently abnormal serum ALT levels, were randomly divided into GI + PP and GI groups and monitored for 12 months. PP was performed before every GI to a total 60 ml of blood a week. The primary PP endpoint was a serum ferritin level of less than 20 ng/ml. PP was suspended upon reaching the endpoint, but was resumed as needed. The efficacy of the addition of PP was evaluated by measuring changes in serum ALT levels. Two patients in each group dropped out because of the appearance of hepatocellular carcinoma. The remainder completed the 12-month treatment with no serious adverse events. Serum ALT and ferritin levels were significantly decreased in the GI + PP group (from 67 ± 34 to 44 ± 14 U/l and from 163 ± 127 to 25 ± 21 ng/ml, respectively, both P < 0.001), but these changes were not seen in the GI group. Although 20 patients in the GI + PP group had compensated cirrhosis, no significant reductions in serum albumin concentrations were observed. The addition of PP is effective and safe for improving serum aminotransferase levels in HCV-infected patients receiving regular GI, even in those with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) in Asian populations is often characterized by the selective involvement of the optic nerve (ON) and spinal cord (SP) (OSMS) in contrast to classic MS (CMS), where frequent lesions are observed in the cerebrum, cerebellum or brainstem. In Western countries, inflammatory demyelinating disease preferentially involving the ON and SP is called neuromyelitis optica (NMO). Recently, Lennon et al. discovered that NMO-IgG, shown to bind to aquaporin 4 (AQP4), could be a specific marker of NMO and also of Japanese OSMS whose clinical features were identical to NMO having long spinal cord lesions extending over three vertebral segments (LCL). To examine this antibody in larger populations of Japanese OSMS patients in order to know its epidemiological and clinical spectra, we established an immunohistochemical detection system for the anti-AQP4 antibody (AQP4-Ab) using the AQP4-transfected human embryonic kidney cell line (HEK-293) and confirmed AQP4-Ab positivity together with the immunohistochemical staining pattern of NMO-IgG in approximately 60% of Japanese OSMS patients with LCL. Patients with OSMS without LCL and those with CMS were negative for this antibody. Our results accorded with those of Lennon et al. suggest that Japanese OSMS with LCL may have an underlying pathogenesis in common with NMO. [ABSTRACT FROM AUTHOR]