The overall efficacy and safety of anti-interleukin (IL)-13 therapies remain to be fully characterized. We conducted a meta-analysis of randomized controlled trials (RCTs) on the efficacy and safety of anti-IL-13 therapies compared with placebo in patients with uncontrolled asthma. This meta-analysis complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary efficacy outcome was pulmonary function, and the primary safety outcome was the incidence rate of all adverse events (AAEs). Secondary outcomes included asthma exacerbation, asthma control, and asthma-related quality of life (QoL). Pooled estimates are presented as mean differences (MDs), hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). Five RCTs of anti-IL-13 therapies, including tralokinumab, GSK679586, or lebrikizumab, met the criteria for study inclusion. The overall MD for change in forced expiratory volume in 1 second was 0.08 (95% CI 0.02, 0.15). The RR for the incidence of AAEs compared with placebo was 1.03 (95% CI 0.86, 1.25). The time to first exacerbation improved significantly in the anti-IL-13 compared with placebo group (HR 0.69; 95% CI 0.55, 0.87). Analysis of asthma control and asthma-related QoL revealed significant improvements in the Asthma Control Questionnaire-6 and Asthma Quality of Life Questionnaire scores among anti-IL-13-compared with placebo-treated patients, with MDs of −0.17 (95% CI −0.29, −0.04) and 0.19 (95% CI 0.08, 0.31), respectively. These results strongly indicate that anti-IL-13 therapies are effective and generally well tolerated in patients with uncontrolled asthma.

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In recent years, various adhesion molecules have been discovered. Very late antigen-4 (VLA-4), an adhesion molecule belonging to the integrin family, plays an important role in lymphocyte migration and infiltration into sites of inflammation. In the present study, we investigated whether administration of anti-VLA-4 monoclonal antibody (mAb) reduces inflammation in ischemia-reperfusion injury using a skin flap model in Sprague-Dawley rats. A superficial epigastric arteriovenous pedicle flap, sized 45×30mm, was elevated in the right inguinal area. The vessel was clamped to induce ischemia and the clamp was removed after 9hours. Fifteen minutes prior to clamp release, the rats were administered anti-VLA-4 mAb (0.2mg/kg i.v., n=10) or saline (n=10). At the same time, a sham group (n=5) was established with a similar operation but the vessel was only clamped to induce ischemia for 5minutes. Anti-VLA-4 mAb significantly improved the survival area of the skin flap to 92.4% (median), when compared to 12.5% (median) in the control group. Severe inflammatory cell infiltration and edema was consistently observed in the skin flaps of the control group, while anti-VLA-4 reduced these parameters to a level similar to the sham group. These results indicate that anti-VLA-4 mAb may be used as an anti-inflammation agent, however the underlying mechanism still remains to be elucidated.

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In emergency cases, the family members must decide whether or not to donate the patient's organs. This study sought to identify factors that could help medical staff support family members during the decision-making process. Surveys about organ donation and emergency patients were distributed to family members of patients at the tertiary emergency outpatient clinic of a university hospital for one year, from October 2014. Family members completed the forms immediately after arrival at the clinic. Nursing records from the same clinic were also examined during the study period using qualitative and inductive analyses. The survey results were analyzed by statistical analysis to determine attitudes towards organ donation. In total, 1,548 survey forms were collected. Only 59 respondents (3.8%) were aware that patients had indicated their wish to donate their organs on their donor cards, driver's licenses, or other means. Family members who recognized that patients were willing to donate their organs were more likely to request an interview with the organ transport coordinator (P<0.01). Qualitative consideration of the nursing records showed that family members were more likely to agree to donate patients' organs if they were aware that “the patients themselves had clearly indicated their wishes”. Overall, we found that a family's decision to donate a patient's organs is influenced by whether they recognized the patient's wishes.

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Evaluation of masticatory performance is an important objective of orthognathic surgery. The purpose of this study was to examine masticatory performance including masticatory efficiency using chewing gum containing spherical resinous microparticles before and after orthognathic surgery. We evaluated 18 patients who underwent orthognathic surgery for masticatory efficiency (gum chewing), occlusal contact area (silicone bite) and occlusal pressure (pressure-sensitive sheet recording), and masticatory muscle activity (electromyographic evaluation of the masticatory muscles). Examinations were performed immediately before surgery, and 3, 6, and 12 months after surgery. No significant difference in masticatory efficiency as a standard degree of comminution was found among any of the chewing sites or examination time points, and the patients showed a variety of changes in masticatory efficiency. Masticatory performance excluding masticatory efficiency was apparent after surgical recovery. These results suggest that masticatory efficiency as a standard degree of comminution varies before and after orthognathic surgery on a patient-to-patient basis.

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This study evaluated the urinary metabolism of ursodeoxycholic acid (UDCA) by measuring 7β-N-acetylglucosaminide and 3α-sulfate composition in neonates to adolescents using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). We obtained urine from 13 babies, corrected gestational age (CGA) 37–70 weeks, receiving UDCA to treat cholestasis due to total parenteral nutrition (TPN) and 8 patients, aged from 9 months to 15 years, who were treated with oral UDCA administration. The ratios of each UDCA conjugate to total UDCA were as follows: at CGA 37–42 weeks: non-amidated and glycine- or taurine- amidated ursodeoxycholic acid (UDCAs): 44.0±8.0% (mean±SD), UDCAs 3α-sulfate (UDCAs-3S): 37.8±10.1%, UDCAs 7β-N-acetylglucosaminide (UDCAs-7NAG): 18.1±14.9%; at 9 months-3years: UDCAs: 15.7±23.2%, UDCAs-3S: 37.2±8.8%, UDCAs-7NAG: 47.0±22.1%. The ratios of UDCAs-3S and UDCAs-7NAG increased gradually between the ages of 5 and 15 years, as follows: UDCAs, 2.2±1.3%; UDCAs-3S, 51.2±22.9%; and, UDCAs-7NAG, 46.6±22.6%. The ratio of 3-sulfooxy-7-N-acetylglucosaminyl-UDCAs (UDCAs-3S-7NAG) lowered by 0.2% per each age group. Urinary UDCAs-7NAG was not detectable in 2 of 21 patients, who were thus considered to have 7β-hydroxy bile acid N-acetylglucosaminyl transferase (UGT3A1) deficiency. The enzyme activity of N-acetylglucosaminyl transferase to UDCAs was at the same degree as sulfotransferase to UDCAs in early neonates, but reached the adult values by 3–5 years.

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Biomarkers of atherothrombosis can predict the risk of cardiovascular events. However, it is difficult to predict second adverse events using these biomarkers at the point in time when the first cardiovascular event occurs. Therefore, we evaluated atherothrombosis-related biomarkers to determine their associations with prognosis after percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) patients. A total of 309 AMI patients were enrolled in this study. The patients had undergone successful coronary interventions and the levels of various atherothrombosis-related biomarkers were assessed within the first postoperative hour. Biomarkers other than those assessed by routine biochemical tests were analyzed, including defined endothelial cell damage markers such as thrombomodulin (TM), inflammatory markers such as C-reactive protein (CRP), and coagulation and fibrinolysis system markers such as D-dimer, prothrombin fragment F1+2 (F1+2) and plasminogen activator inhibitor-1 (PAI-1). Major adverse cardiac events (MACEs) occurred in 98 patients during the follow-up period (872.6±579.8 days). Multivariate analysis revealed that clinical parameters such as decreased levels of left ventricular ejection fraction and elevated levels of brain natriuretic peptide, hemoglobin A1c and TM were significantly associated with MACEs. The association between TM and MACEs was especially high (OR: 3.65, 95% CI; 1.75–7.68). Neither dyslipidemia, hypertension, smoking, advanced age, a history of cardiac events nor the type of AMI were associated with MACEs. TM is independently associated with MACEs and may be predictive of second events following PCI in patients with AMI.

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The purpose of this study was to clarify the validity of measuring the signal intensities of cortical bone (CB) and temporomandibular joint (TMJ) discs on magnetic resonance (MR) images for the diagnosis of TMJ disease. Two investigations were performed. In the first investigation, MR images of 13 TMJs of volunteers were obtained using a multi spin-echo sequence. Echo time (TE) was increased from 10msec to 200msec in steps of 10msec. The signal intensities of the CB of the condylar head, and the anterior (AD) and posterior (PD) bands of the TMJ disc were measured, and their attenuation patterns were compared. In the second investigation, clinical MR images of 30 TMJs from patients with suspected TMJ disorders were selected. Proton density-weighted images (PDWIs) and T2-weighted images (T2WIs) were obtained at TEs of 14 and 85msec, respectively, using a double-echo fast spin-echo sequence. The signal intensities of CB, AD, and PD were measured and compared with that of the external auditory meatus (air) using a Bonferroni test. AD and PD showed nearly identical signal intensity attenuation patterns. The signal intensities of AD and PD were lower than CB at TEs longer than 20msec although they were higher at TEs shorter than 20msec. Clinical PDWIs and T2WIs showed similar results. The signal intensities of CB, AD, and PD were significantly higher than the external auditory meatus (air) in both PDWIs and T2WIs. CB and TMJ discs show characteristic signal intensities, suggesting that the signal intensity measurement of these structures is valid.

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Bone augmentation is required for cases of highly absorbed alveolar ridge in the placement of dental implants. Various biomaterials and/or growth factors have been used to induce new bone formation; however, it remains difficult to obtain the required bone shape. In this study, we used cylindrical silicone molds coupled with recombinant human bone morphogenetic protein (rhBMP) to induce a specifically shaped bone. The cylindrical mold was made of silicone rubber impression material with a 10mm outer diameter, 5mm inner diameter, and 5mm height. RhBMP-2 was applied using an atelocollagen sponge placed into the silicone mold; it was then implanted into the parietal subperiosteal region of 8-week-old male Wistar rats. Histological and micro-computed tomography (micro-CT) analyses were performed to detect new bone formation at 2, 4, and 8 weeks after the surgery. Micro-CT analysis indicated a disc-shaped bone formation adjacent to the periosteum at 2 weeks after surgery. Newly formed bone was also detected near the parietal bone at 4 weeks. At 8 weeks, an almost cylindrical bone was formed in the silicone mold, and histological observation confirmed that the newly formed bone completely adhered to the host parietal bone. Hematopoietic bone marrow was also detected in the newly formed bone. A specifically made silicone mold might provide the scaffold required to induce a specific shape of newly formed bone under the combined induction of rhBMP.

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We comparatively assessed the overall efficacies of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and chemotherapy for previously untreated, EGFR mutation-positive, advanced non-small cell lung cancer in Asians through a meta-analysis of relevant phase-3 trials. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. Pooled estimates were calculated as hazard ratios (HRs) with 95% confidence intervals (CIs). Seven studies on EGFR-TKIs met the inclusion criteria for this study. The HRs and 95% CIs for OS and PFS for EGFR-TKIs, relative to chemotherapy, were 0.98 (0.77–1.24) and 0.32 (0.24–0.43), respectively. We found no difference in overall efficacy between EGFR-TKIs and chemotherapy in terms of OS, although the median PFS with EGFR-TKI was superior to that with chemotherapy among Asians with previously untreated, EGFR mutation-positive, advanced non-small cell lung cancer (UMIN ID: UMIN28424).

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Sialolithiasis most commonly affects the submandibular glands, followed by the parotid and sublingual glands. Sialolithiasis is a condition characterized by the obstruction of a salivary gland or its excretory duct due to calculi. Herein we describe a case of a 72-year-old male patient with a painful swelling of the parotid gland region. Parotitis due to sialolithiasis in the parotid gland duct was diagnosed based on computed tomography findings of a calculus (12×6×5mm) in the parotid gland duct. The calculus was spontaneously discharged from the parotid gland duct with viscous pus into the oral cavity after the inflammation had decreased. Thereafter, the parotitis quickly decreased more markedly. This case indicates that a calculus may be discharged spontaneously into the mouth, even if its diameter is>5mm.

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True left-sided gallbladder (sinistroposition) is a rare anatomic anomaly in which the gallbladder is found to the left of the falciform ligament under the left lobe of the liver. Though uncommon, it is important for the surgeon to identify this anomaly because the ductal anatomy is unique and the surgery is technically challenging. Multiple case reports have documented safe management of sinistroposition encountered during conventional laparoscopic cholecystectomy. We present a case of sinistroposition encountered during a single-incision laparoscopic cholecystectomy. We conclude that this single-site laparoscopic technique is not only safe when sinistroposition is encountered, but it may actually provide certain ergonomic benefits for surgeons.

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