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Monitoring is recommended to prevent severe adverse drug events, but such examinations are often missed. To increase the number of monitoring that should be ordered for high-risk medications, we introduced a clinical decision support system (CDSS) that alerts and orders the monitoring for high-risk medications in an outpatient setting. We conducted a 2-year prospective cohort study at a tertiary care teaching hospital before (phase 1) and after (phase 2) the activation of a CDSS. The CDSS automatically provided alerts for liver function tests for vildagliptin, thyroid function tests for immune checkpoint inhibitors (ICIs) and multikinase inhibitors (MKIs), and a slit-lamp examination of the eyes for oral amiodarone when outpatients were prescribed the medications but not examined for a fixed period. The order of laboratory tests automatically appeared if alert was accepted. The alerts were hidden and did not appear on the display before activation of the CDSS. The outcomes were the number of prescriptions with alerts and examinations. During the study period, 330 patients in phase 1 and 307 patients in phase 2 were prescribed vildagliptin, 20 patients in phase 1 and 19 patients in phase 2 were prescribed ICIs or MKIs, and 72 patients in phase 1 and 66 patients in phase 2 were prescribed oral amiodarone. The baseline characteristics were similar between the phases. In patients prescribed vildagliptin, the proportion of alerts decreased significantly (38% vs 27%, P  < 0.0001), and the proportion of examinations increased significantly (0.9% vs 4.0%, P  < 0.0001) after activation of the CDSS. In patients prescribed ICIs or MKIs, the proportion of alerts decreased significantly (43% vs 11%, P  < 0.0001), and the proportion of examinations increased numerically, but not significantly (2.6% vs 7.0%, P  = 0.13). In patients prescribed oral amiodarone, the proportion of alerts decreased (86% vs 81%, P  = 0.055), and the proportion of examinations increased (2.2% and 3.0%, P  = 0.47); neither was significant. The CDSS has potential to increase the monitoring for high-risk medications. Our study also highlighted the limited acceptance rate of monitoring by CDSS. Further studies are needed to explore the generalizability to other medications and the cause of the limited acceptance rates among physicians. [ABSTRACT FROM AUTHOR]

Background: It is shown that the postoperative adjuvant chemotherapy for non-small cell lung cancer (NSCLC) was associated with survival benefit in an elderly population. We aimed to analyze the feasibility and efficacy of alternate-day S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in elderly patients with completely resected pathological stage IA (tumor diameter > 2 cm) to IIIA (UICC TNM Classification of Malignant Tumours, 7th edition) NSCLC. Methods: Elderly patients were randomly assigned to receive adjuvant chemotherapy for one year consisting of either alternate-day oral administration of S-1 (80 mg/m2/day) for 4 days a week (Arm A) or a daily oral administration of S-1 (80 mg/m2/day) for 14 consecutive days followed by 7-day rest (Arm B). The primary endpoint was feasibility (treatment completion rate), which was defined as the proportion of patients who completed the allocated intervention for 6 months with a relative dose intensity (RDI) of 70% or more. Results: We enrolled 101 patients in which 97 patients received S-1 treatment. The treatment completion rate at 6 months was 69.4% in Arm A and 64.6% in Arm B (p = 0.67). Treatment completion rate in Arm B tended to be lower compared to Arm A, as the treatment period becomes longer (at 9 and 12 months). RDI of S-1 at 12 months and completion of S-1 administration without dose reduction or postponement at 12 months was significantly better in Arm A than in Arm B (p = 0.026 and p < 0.001, respectively). Among adverse events, anorexia, skin symptoms and lacrimation of any grade were significantly more frequent in Arm B compared with Arm A (p = 0.0036, 0.023 and 0.031, respectively). The 5-year recurrence-free survival rates were 56.9% and 65.7% for Arm A and B, respectively (p = 0.22). The 5-year overall survival rates were 68.6% and 82.0% for Arm A and B, respectively (p = 0.11). Conclusion: Although several adverse effects were less frequent in Arm A, both alternate-day and daily oral administrations of S-1 were demonstrated to be feasible in elderly patients with completely resected NSCLC. Trial registration: Unique ID issued by UMIN: UMIN000007819 (Date of registration: Apr 25, 2012) https://center6.umin.ac.jp/cgi-open-bin/ctr%5fe/ctr%5fview.cgi?recptno=R000009128. Trial ID issued by jRCT: jRCTs061180089 (Date of registration: Mar 22, 2019, for a shift toward a "specified clinical trial" based on Clinical Trials Act in Japan) https://jrct.niph.go.jp/en-latest-detail/jRCTs061180089. [ABSTRACT FROM AUTHOR]

What Is Known and Objective: In this study, changes in patient outcomes were analysed to evaluate the effects of prospective audit and feedback (PAF), which was promoted under a new system of antimicrobial stewardship (AS), in patients with gram‐negative rod (GNR)‐positive blood cultures. Methods: This study included patients with positive blood cultures treated at Kagawa University Hospital between 2019 and 2020. The effects of PAF, as promoted in 2020 and performed within a few days of treatment initiation, were examined in terms of patient prognosis and estimated cost of extra hospital stay associated with GNR infection. Results and Discussion: As AS activities under the new system, proposals were made for targeted therapy based on susceptibility results and for the duration of antimicrobial therapy, escalation and dose increases, and imaging evaluation. Between 2019 and 2020, there was no difference in the rate of de‐escalation in the form of switching to a narrower‐spectrum intravenous antimicrobial, the rate of image inspection, but the rate of switching to oral therapy after receiving culture results increased from 19.7% to 31.3%, the rate of sensitivity‐based treatment increased from 76.4% to 92.2%. Regarding patient outcomes, the 90‐day mortality rate and the duration of hospital stay were similar between the groups. The rate of recurrent bloodstream infections decreased from 8.7% to 0.9%. What Is New and Conclusion: Most of the changes in the indicators related to patient outcomes analysed in this study suggest that the increased use of PAF in AS activities improved patient outcomes. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES The short-term efficacy of virtual-assisted lung mapping (VAL-MAP), a preoperative bronchoscopic multi-spot lung-marking technique, has been confirmed in 2 prospective multicentre studies. The objectives of this study were to analyse the local recurrence and survival of patients enrolled in these studies, long-term. METHODS Of the 663 patients enrolled in the 2 studies, 559 patients' follow-up data were collected. After excluding those who did not undergo VAL-MAP, whose resection was not for curative intent, who underwent concurrent resection without VAL-MAP, or who eventually underwent lobectomy instead of sublobar resection (i.e. wedge resection or segmentectomy), 422 patients were further analysed. RESULTS Among 264 patients with primary lung cancer, the 5-year local recurrence-free rate was 98.4%, and the 5-year overall survival (OS) rate was 94.5%. Limited to stage IA2 or less (≤2 cm in diameter; n  = 238, 90.1%), the 5-year local recurrence-free and OS rates were 98.7% and 94.8%, respectively. Among 102 patients with metastatic lung tumours, the 5-year local recurrence-free rate was 93.8% and the 5-year OS rate was 81.8%. Limited to the most common (colorectal) cancer (n  = 53), the 5-year local recurrence-free and OS rates were 94.9% and 82.3%, respectively. CONCLUSIONS VAL-MAP, which is beneficial in localizing small barely palpable pulmonary lesions and determining the appropriate resection lines, was associated with reasonable long-term outcomes. Subj collection 152, 1542 [ABSTRACT FROM AUTHOR]

What is known and objective: Our objective is to report on a case of posterior reversible encephalopathy syndrome associated with pazopanib. Case description: A 64‐year‐old patient with uterine sarcoma developed PRES 3 days after pazopanib was initiated. After the discontinuation of pazopanib, the symptoms of PRES improved. What is new and Conclusion: The first report worldwide to describe a patient with uterine sarcoma experiencing PRES caused by pazopanib. Patients with uterine sarcoma may experience PRES, even in the early phase of pazopanib therapy. [ABSTRACT FROM AUTHOR]

Abstract: The ternary BaO–TiO2–B2O3 glasses containing a large amount of TiO2 (20–40mol%) are prepared, and their optical basicities (), the formation, structural features and second-order optical nonlinearities of BaTi(BO3)2 and Ba3Ti3O6(BO3)2 crystals are examined to develop new nonlinear optical materials. It is found that the glasses with high TiO2 contents of 30–40mol% show large optical basicities of , suggesting the high polarizabity of TiO n polyhedra () in the glasses. BaTi(BO3)2 and Ba3Ti3O6(BO3)2 crystals are found to be formed as main crystalline phases in the glasses. It is found that BaTi(BO3)2 crystals tend to orient at the surface of crystallized glasses. The new XRD pattern for the Ba3Ti3O6(BO3)2 phase is proposed through Rietvelt analysis. The second harmonic intensities of crystallized glasses were found to be 0.8 times as large as α-quartz powders, i.e., , for the sample with BaTi(BO3)2 crystals and to be for the sample with Ba3Ti3O6(BO3)2 crystals. The Raman scattering spectra for these two crystalline phases are measured for the first time and their structural features are discussed. [Copyright &y& Elsevier]

We investigated the effects of esaxerenone, a novel, nonsteroidal, and selective mineralocorticoid receptor blocker, on cardiac function in Dahl salt-sensitive (DSS) rats. We provided 6-week-old DSS rats a high-salt diet (HSD, 8% NaCl). Following six weeks of HSD feeding (establishment of cardiac hypertrophy), we divided the animals into the following two groups: HSD or HSD + esaxerenone (0.001%, w/w). In survival study, all HSD-fed animals died by 24 weeks of age, whereas the esaxerenone-treated HSD-fed animals showed significantly improved survival. We used the same protocol with a separate set of animals to evaluate the cardiac function by echocardiography after four weeks of treatment. The results showed that HSD-fed animals developed cardiac dysfunction as evidenced by reduced stroke volume, ejection fraction, and cardiac output. Importantly, esaxerenone treatment decreased the worsening of cardiac dysfunction concomitant with a significantly reduced level of systolic blood pressure. In addition, treatment with esaxerenone in HSD-fed DSS rats caused a reduced level of cardiac remodeling as well as fibrosis. Furthermore, inflammation and oxidative stress were significantly reduced. These data indicate that esaxerenone has the potential to mitigate cardiac dysfunction in salt-induced myocardial injury in rats. [ABSTRACT FROM AUTHOR]

We describe a simple palliative mediastinal tracheostomy procedure in 3 patients with respiratory deficiency resulting from cervical tracheal stenosis caused by unresectable advanced tumors. A hole in the "apron" skin flap was anastomosed to the tracheostomy in the unaffected upper mediastinal trachea after partial resection of the manubrium and clavicle head. Simple palliative mediastinal tracheostomy helps to improve performance status by relieving respiratory deficiency or prolonged oroendotracheal intubation in patients with cervical tracheal stenosis caused by advanced tumors. [ABSTRACT FROM AUTHOR]

Abstract Objective Virtual-assisted lung mapping is a preoperative bronchoscopic multi-spot dye-marking technique. This study aimed to examine the efficacy of virtual-assisted lung mapping for obtaining sufficient surgical margins in sublobar lung resection. Methods The multicenter, prospective, single-arm study was conducted from September 2016 to July 2017 in 19 registered centers. Patients who required sublobar lung resection and careful determination of resection margins underwent virtual-assisted lung mapping followed by thoracoscopic surgery. Successful resection was defined as resection of the lesion with margins greater than the lesion diameter or 2 cm using the preoperatively planned resection without additional resection. We defined the primary goal of the study as achieving successful resection in 95% of lesions. Results The resection of 203 lesions (average diameter, 9.6 ± 5.3 mm) was intended in 153 patients. The lesions included pure and mixed ground-glass nodules (75 [35.9%] and 36 [17.2%], respectively), solid nodules (91 [43.5%]), and others (7 [3.3%]). Surgical procedures included wedge resection (131, 71.2%), segmentectomy (51, 27.7%), and others (2, 1.1%). Successful resection was achieved in 178 lesions (87.8% [95% confidence interval, 82.4-91.9%]), and virtual-assisted lung mapping markings successfully aided in the identification of 190 lesions (93.6% [95% confidence interval, 89.3-96.5%]). Multivariable analysis showed that the most significant factor affecting resection success was the depth of the necessary resection margin (P =.0072). Conclusions This study showed that virtual-assisted lung mapping has reasonable efficacy, although the successful resection rate did not reach the primary goal. The depth of the required margin was the most significant factor leading to resection failure. Graphical abstract [ABSTRACT FROM AUTHOR]

Chronic expanding hematomas occur at various locations in the body; however, their occurrence in the sternum has not been reported yet. We report a patient with chronic expanding hematoma in the sternum 5 years after undergoing a median sternotomy for cardiac surgery. Although preoperative biopsy specimens did not lead to a definitive diagnosis, we could not rule out the possibility of a malignant tumor because of the expanding and infiltrative behavior of the hematoma. We performed a sternectomy and reconstructed the chest wall using artificial materials. [Copyright &y& Elsevier]

A 73-year-old woman presented with left anterior chest pain and back pain. Computed tomography (CT) scan showed an anterior mediastinal tumor. It also showed partial anomalous pulmonary venous drainage (left superior pulmonary vein draining into the left brachiocephalic vein), and the tumor was located near the left brachiocephalic vein. The operation was performed through a median sternotomy to resect the thymus and tumor with partial resection of the left upper lobe due to the tumor's adhesion to the left upper lobe. One of the vascular anomalies encountered in adult thoracic surgery is partial anomalous pulmonary venous drainage. It is important to recognize the presence of such an anomaly on imaging and to anticipate the surgical procedure with a preoperative surgical technique.

Background: Pulmonary epithelioid hemangioendothelioma is a rare malignant disease, and most cases are found as multiple lung nodules, rarely as a single nodule., Case: Computed tomography( CT) in a 71-year-old man revealed a growing 3-mm lung nodule in the left S6 after rectal cancer operation. Wedge resection was performed. A pathological examination resulted in a diagnosis of pulmonary epithelioid hemangioendothelioma based on CD31 and CD34 positivity in immunohistochemistry., Conclusion: When new nodules are noted on routine CT scans of other malignancies, it is essencial to make a pathological diagnosis, bearing in mind that pulmonary nodules can arise from a variety of causes.

The patient was a 66-year-old male. Computed tomography( CT) scan revealed a tumor of the posterior mediastinum 2 years before and grew slowly 49.0 to 51.4 mm in the longest diameter of the coronal slice. Thoracoscopic surgery was performed to resect it. The pathological examination revealed a predominantly mature adipose tissue with hematopoietic tissue in hematoxylin and eosin( HE) staining and the hematopoietic tissue was comprised of mature erythroblasts, megakaryocytes, and granulocytes in immune staining, which diagnosed it as myelolipoma. Incidence of myelolipoma which originates from besides adrenal glands is reported 0.08 to 0.2%. As far as we can search, 40 cases of myelolipoma of the posterior mediastinum are in the literatures.

This study aimed to evaluate the effects on the medical economy of the use of tracing reports by pharmacy-based pharmacists for pharmaceutical interventions, including to reduce leftover medicines. These effects were estimated by analyzing 267 tracing reports issued by pharmacy pharmacists over a period of 1 year, 2020-2021. We estimate that these interventions created cost savings of USD108170.02/year (USD104800 via pharmaceutical interventions, USD3370.02 via interventions to reduce leftover medicines). The cost savings from pharmaceutical interventions prompted by patient follow-up was estimated to be USD47650. The medical economic effect per tracing report was estimated to be USD392.51 from pharmaceutical interventions, USD12.62 from reducing leftover medicines, and USD445.33 from pharmaceutical intervention prompted by patient follow-up. Overall, therefore, pharmaceutical interventions by pharmacy pharmacists using tracing reports, including those designed to reduce leftover medicines, may benefit the medical economy.

We report a haemodialysis patient with end-stage renal failure whom a pharmacist aided in the management of acyclovir (ACV) encephalopathy, which may have been related to valacyclovir hydrochloride (VACV) administered without sufficient dose reduction. The patient 78 years was admitted with a tentative diagnosis of varicella zoster viral meningitis. A pharmacist suspected ACV encephalopathy related to excessive VACV administration and raised a query with the attending physician. According to the pharmacist's proposal, ACV administration was discontinued and continuous hemodiafiltration (CHDF) was performed. On day 5 of hospitalisation, the consciousness disorder was improved. In this report, we showed the detailed CHDF conditions of the present case, and the contribution of a pharmacist to treating and avoiding ACV encephalopathy was discussed.

Objectives: To explore the awareness and practice of clinical research integrity among Japanese physicians., Design: A nationwide cross-sectional study conducted in March 2020., Setting: All hospitals in Japan., Participants: Physicians aged <65 years who work at hospitals participated in clinical research over the past 5 years. The sample was stratified according to geographical location and subspecialty, and 1100 physicians were proportionally selected., Primary and Secondary Outcome Measures: Knowledge and awareness of research integrity., Results: Among the 1100 participants, 587 (53%) had the experience of being the first author, 299 (27%) had been co-authors only and 214 (19%) had no authorship. A total of 1021 (93%) had experienced learning research integrity, and 555 (54%) became aware of research integrity. The experience of learning about research integrity was highest among those with first authorship (95%) and lowest among those without authorship (89%) (p=0.003). The majority of participants learnt about research integrity for passive reasons such as it being 'required by the institution' (57%) or it being 'required to obtain approval of institutional review board (IRB)' (30%). Potentially inappropriate research behaviours were observed in participants, with 11% indulging in copying and pasting for writing the paper, 11% for gifted authorship and 5.8% for the omission of IRB approval. Factors significantly associated with copying and pasting were being below 40 years old (OR: 1.84; 95% CI: 1.05 to 3.26), being the first presenter (OR: 1.64; 95% CI: 1.05 to 2.57) or having passive reasons for learning research integrity (OR: 2.96; 95% CI: 1.57 to 5.59). Furthermore, gifted authorship was significantly associated with being a co-author only (OR: 1.84; 95% CI: 1.18 to 2.87) and having passive reasons for learning about research integrity (OR: 1.79; 95% CI: 1.03 to 3.12)., Conclusions: Most physicians conducting clinical research have learnt about research integrity, but potentially inappropriate research behaviours are associated with passive reasons for learning., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors such as afatinib are used for non-small cell lung cancer (NSCLC) and show varying efficacy depending on EGFR gene mutation. Few studies have examined the relationship between EGFR gene mutations and the adverse events of afatinib in NSCLC. This retrospective study included 32 Japanese patients with NSCLC with EGFR gene mutation who were treated with afatinib between May 2014 and August 2018 at Kagawa University Hospital. Among the 32 Japanese patients with NSCLC treated with afatinib, 19 patients were positive for exon 19 deletion mutation (Del 19) and 13 patients were negative for Del 19. The incidence of grade ≥ 2 skin rash was slightly higher in patients positive for Del 19 (42.1% vs. 7.7%, P = 0.050). No significant differences were detected in other adverse events between the two patient groups. Patients positive for Del 19 also showed significantly longer median progression-free survival (288 vs. 84 days, P = 0.049). Our study indicates a higher incidence of skin rash associated with afatinib treatment in Japanese patients with NSCLC positive for Del 19 compared with patients without Del 19. The Del 19 positive patient group also showed better progression-free survival. J. Med. Invest. 68 : 125-128, February, 2021.

Tazobactam / piperacillin (TAZ / PIPC) is an injectable combination drug consisting of a broad-spectrum penicillin and a β-lactamase inhibitor. This antimicrobial has a wide spectrum of efficacy against both Gram-positive bacteria and anaerobes. Adverse events usually present as diarrhea or liver dysfunction ; agranulocytosis has not been reported in Japanese patients with puerperal disorders. However, we report a 32-year-old Japanese woman who received TAZ / PIPC to treat an intraperitoneal infection that developed after complications related to transvaginal delivery. Within 14 days of beginning TAZ / PIPC therapy, the patient developed agranulocytosis, indicated by a white blood cell count of 1900 cells / µL and a neutrophil count of 475 cells / µL. We discontinued TAZ / PIPC at this point and changed the antimicrobial to meropenem. Seven days later, her white blood cell count increased to 3700 cells / µL (neutrophil count : 1684 cells / µL), and the intraperitoneal infection resolved. Patients receiving TAZ / PIPC should be monitored periodically for agranulocytosis as well as for diarrhea and liver dysfunction. J. Med. Invest. 68 : 368-371, August, 2021.

Background: Medication dose adjustment is crucial for patients with renal dysfunction (RD). The assessment of renal function is generally mandatory; however, the renal function may change during the hospital stay and the manual assessment is sometimes challenging., Objective: We developed the clinical decision support system (CDSS) that provided a recommended dose based on automated calculated renal function., Methods: We conducted a prospective cohort study in a single teaching hospital in Japan. All hospitalized patients were included except for obstetrics/gynecology and pediatric wards between September 2013 and February 2015. The CDSS was implemented on December 2013. Renal and hepatic dysfunction (HD) were defined as changes in the estimated glomerular filtration rate (eGFR) and alanine aminotransferase or alkaline phosphatase levels based on these measurements during hospital stay. These measurements were obtained before (phase I), after (phase II), and 1 year after (phase III) the CDSS implementation., Results: We included 6,767 patients (phase I: 2,205; phase II: 2,279; phase III: 2,283). The patients' characteristics were similar among phases. Changes in eGFR were similar among phases, but the incidence of RD increased in phase III (phase I: 228 [10.3%]; phase II: 260 [11.4%]; phase III: 296 [13.0%], p  = 0.02). However, the differences in incidences of RD were not statistically significant after adjusting for eGFR at baseline and age. The incidences of HD were also similar among phases (phase I: 175 [13.2%]; phase II: 171 [12.9%]; phase III: 167 [12.2%], p  = 0.72)., Conclusion: The CDSS implementation did not affect the incidence of renal and HD and changes in renal and hepatic function among hospitalized patients. The effectiveness of the CDSS with renal-guided doses should be investigated with respect to other endpoints., Competing Interests: R.W. is an employee of Novartis Pharma KK. All other authors do not have any conflict of interest., (Thieme. All rights reserved.)

Several reports have investigated relationships between epidermal growth factor receptor ( EGFR ) mutations and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer; however, there have been insufficient analyses of relationships between EGFR mutations and adverse reactions. This study investigated the relationships between EGFR mutations and skin rash. We first compared skin rash grades between different mutations, then tested factors possibly affecting skin rash by multivariate analysis. The main outcome measure was the significant difference in incidence of skin rash between each group with different mutations. Our study suggested that the risk of skin rash is low in patients with exon 19 deletion mutations who are taking EGFR-TKIs, whereas it is high in those with exon 21 point mutations. These results will be useful indicators for instructions regarding daily examinations, skin care, and use of oral antibiotics or topical steroids in patients taking EGFR-TKIs with skin rash.

Background: Virtual-assisted lung mapping (VAL-MAP), a bronchoscopic multi-spot dye-marking technique, was tested for its ability to resect ground glass nodules (GGNs) in sublobar lung resections., Methods: All patients were prospectively registered in the multi-institutional lung mapping (MIL-MAP) study using VAL-MAP. The data were retrospectively analyzed, focusing on GGNs. GGN characteristics, pathological findings, operation type, and the surgical contribution of VAL-MAP were evaluated., Results: The 370 GGNs in 299 patients included 257 pure and 113 mixed GGNs. There were 146 wedge resections (43.6%), 99 simple segmentectomies (29.6%), and 60 complex segmentectomies (18.0%). The largest number of marks were used in complex segmentectomy (4.05±0.74), followed by simple segmentectomy (3.35±0.97) and wedge resection (2.96±0.80). The overall successful resection rate was 98.6%. Multiple [2-5] GGNs were concurrently targeted by VAL-MAP in 53 patients (17.7%) with 123 GGNs. Two concurrent resections were conducted in 36 patients (12.1%), most commonly wedge resection and segmentectomies (21 patients). Among 190 sub-centimeter GGNs, 24 out of 51 GGNs ≤5 mm in diameter (47.1%) and 113 of 139 GGNs >5 mm in diameter (81.3%) were primary lung cancer (P<0.0001). Regarding the contribution of VAL-MAP to successful resection, wedge resection and pure GGNs were graded higher than both other resection types and mixed GGNs., Conclusions: VAL-MAP enabled thoracoscopic limited resection of GGNs. Its multiple marks facilitated resections of multi-centric GGNs. Resected suspicious GGNs >5 mm in diameter are likely to be lung cancer. VAL-MAP may impact decision-making regarding the indications and type of surgery for suspicious small GGNs., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Bevacizumab (BV), an inhibitor of vascular endothelial growth factor, is used in combination with paclitaxel (PTX) to treat advanced breast cancer. Hypertension and proteinuria are characteristic adverse events of BV therapy. We assessed the potential of these adverse events as predictors of BV treatment responses. Our results revealed that groups that developed hypertension and proteinuria early (by day 56) had a stronger antitumor response (Fisher's exact test p<0.05). However, no significant difference was observed in progression-free survival (the Kaplan-Meier method and Log-rank test). As a reference, age, the treatment line, subtypes, liver and renal function, diabetes mellitus and hyperlipidemia history, body mass index, influencing concomitant medicine, average relative dose intensity and hematotoxicity did not significantly differ between groups with or without hypertension and with or without proteinuria. These results indicate the potential of the development of hypertension and proteinuria as predictors of improved outcomes with PTX plus BV therapy in patients with breast cancer. However, since both adverse events may preclude the continuation of treatment, their earlier management may be required.

Objectives: Virtual-assisted lung mapping (VAL-MAP) is a preoperative bronchoscopic multispot dye-marking technique using virtual images. The purpose of this study was to evaluate the safety, efficacy and reproducibility of VAL-MAP among multiple centres., Methods: Selection criteria included patients with pulmonary lesions anticipated to be difficult to identify at thoracoscopy and/or those undergoing sub-lobar lung resections requiring careful determination of resection margins. Data were collected prospectively and, if needed, compared between the centre that originally developed VAL-MAP and 16 other centres., Results: Five hundred patients underwent VAL-MAP with 1781 markings (3.6 ± 1.2 marks/patient). Complications associated with VAL-MAP necessitating additional management occurred in four patients (0.8%) including pneumonia, fever and temporary exacerbation of pre-existing cerebral ischaemia. Minor complications included pneumothorax (3.6%), pneumomediastinum (1.2%) and alveolar haemorrhage (1.2%), with similar incidences between the original centre and other centres. Marks were identifiable during operation in approximately 90%, whereas the successful resection rate was approximately 99% in both groups, partly due to the mutually complementary marks. The contribution of VAL-MAP to surgical success was highly rated by surgeons resecting pure ground glass nodules ( P  < 0.0001), tumours ≤ 5 mm ( P  = 0.0016), and performing complex segmentectomy and wedge resection ( P  = 0.0072)., Conclusions: VAL-MAP was found to be safe and reproducible among multiple centres with variable settings. Patients with pure ground glass nodules, small tumours and resections beyond conventional anatomical boundaries are considered the best candidates for VAL-MAP., Clinical Trial Registration Number: UMIN 000008031. University Hospital Medical Information Network Clinical Trial Registry ( http://www.umin.ac.jp/ctr/ )., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Tracheobronchial injuries (TBIs) are uncommon but potentially life-threatening. TBIs are mainly classified in 2 category, traumatic and iatrogenic. Most common symptoms are dyspnea, subcutaneous emphysema and pneumomediastinum. Pneumothorax is often found in lower tracheal or bronchial injury. Fiberoptic bronchoscopy is most important examination for TBI to detect injured site and its depth. Iatrogenic TBIs are caused by tracheal intubation, tracheostomy and airway intervention. Injury of iatrogenic TBIs are commonly laceration of membranous part. Surgical repair was performed for treatment of iatrogenic TBI. However, recently there has been reported many successful cases of non-operative treatment. Conservative treatment is a considerable choice of treatment. Approach of surgical repair depends on site of tracheal laceration. For laceration of cervical or upper mediastinal trachea, cervical approach is chosen. Recently transcervical-transtracheal repair were reported. Right posterolateral thoracotomy is suitable for repair of carina or main bronchus. Most of TBI caused by blunt trauma occur around carina. Operative treatment is mandatory in many cases. However morbidity and mortality are considerably high in emergent operation for traumatic TBI. It is necessary to make an appropriate strategy for treatment in an experienced trauma center.

Background/aim: Pleomorphic carcinoma (PC) of the lung is a rare tumor that usually has an aggressive clinical course and a poor prognosis. Clinical and pathological features remain unclear. The aim of this study was to determine whether tumor angiogenesis of PC is up-regulated compared to that in adenocarcinoma (AD)., Materials and Methods: We collected 55 cases of PC and AD in which the patients had undergone either lung resection or autopsy and immunohistochemically examined the expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1α and microvessel density (MVD) in tissue specimens., Results: VEGF was expressed in many cases of both PC and AD with no significant differences between the groups. In contrast, the expression of HIF-1α and MVD were significantly greater in PC than AD. Median survival time of the PC group was 14.7 months and significantly shorter than that of the AD group., Conclusion: MVD and expression of HIF-1α are associated with angiogenesis in PC and confer a poorer prognosis. Tumor angiogenesis provides significant prognostic information regarding clinical outcome in patients with PC., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Bayesian estimation enables the individual pharmacokinetic parameters of the medication administrated to be estimated using only a few blood concentrations. Due to wide inter-individual variability in the pharmacokinetics of methotrexate (MTX), the concentration of MTX needs to be frequently determined during high-dose MTX therapy in order to prevent toxic adverse events. To apply the benefits of Bayesian estimation to cases treated with this therapy, we attempted to develop an estimation method using the Bayesian least-squares method, which is commonly used for therapeutic monitoring in a clinical setting. Because this method hypothesizes independency among population pharmacokinetic parameters, we focused on correlations among population pharmacokinetic parameters used to estimate individual parameters. A two-compartment model adequately described the observed concentration of MTX. The individual pharmacokinetic parameters of MTX were estimated in 57 cases using the maximum likelihood method. Among the available parameters accounting for a 2-compartment model, V1, k10, k12, and k21 were found to be the combination showing the weakest correlations, which indicated that this combination was best suited to the Bayesian least-squares method. Using this combination of population pharmacokinetic parameters, Bayesian estimation provided an accurate estimation of individual parameters. In addition, we demonstrated that the degree of correlation among population pharmacokinetic parameters used in the estimation affected the precision of the estimates. This result highlights the necessity of assessing correlations among the population pharmacokinetic parameters used in the Bayesian least-squares method.

Mycophenolate mofetil (MMF) is used for oral administration to prevent rejection in renal transplant recipients, and is rapidly converted into mycophenolic acid (MPA), the active metabolite, by hydrolysis in vivo. The area under the concentration-time curve (AUC(0-12 h)) of MPA is considered to be an effective pharmacokinetics parameter for predicting acute rejection. However, frequent blood sampling is required to calculate AUC(0-12 h), which imposes a burden on patients and providers. Therefore, we examined a limited sampling strategy (LSS) for estimation of MPA-AUC(0-12 h) using only a trough level (C0) and two points including C0 in Japanese living-related renal transplant recipients with concomitant extended-release tacrolimus (ER-TAC). The present study suggests that better estimation of MPA-AUC(0-12 h) can be obtained by using two points including C0 as compared with only C0 regardless of transplant progress. Furthermore, blood collection points showing the highest estimation of MPA-AUC(0-12 h) by adding to C0 were C4 at pre-transplantation (Tx) and 1 month post-Tx, and C6 at 3 months post-Tx. We conjecture that changes in renal function and serum albumin (Alb) accompanying transplant progress are aggravating factors in terms of estimation, because there was also a significant difference in the reciprocal of serum creatinine (1/Scr) and Alb between pre-Tx and post-Tx in this study. In conclusion, the present study provides useful information for effective and efficient monitoring of MPA levels in Japanese living-related renal transplant recipients.

Background: Pleomorphic carcinoma (PC) of the lung is a rare tumor that usually has an aggressive clinical course and a poor prognosis. In this study, 75 cases of PC were reviewed to identify its clinical features, and we examined the expression of angiogenic factors., Patients and Methods: We immunohistochemically examined the expression of angiogenic factors in tissue specimens of PC., Results: 66 males and 9 females were examined. The median survival time was 16.5 months. The stage and symptomatical diagnosis were significantly associated with the survival. In the immunohistochemical analyses, vascular endothelial growth factor (VEGF) was expressed in many cases of PC. A high score for angiogenesis was significantly related to a poorer prognosis., Conclusion: We conclude that PC should be considered an aggressive disease, and that the stage and symptomatical diagnosis are strong prognostic factors. Furthermore, tumor angiogenesis provides significant prognostic information about the clinical outcome in PC.

We report a case of encephalopathy seemingly caused by tacrolimus (FK506) in spite of blood concentration near the upper limit of therapeutic range. A 26-year-old man received FK506 to prevent acute graft-versus-host disease after hematopoietic stem cell transplantation. He underwent an intravenous injection of FK506 the day before transplantation (day -1). He developed headache, hypertension, nausea and vomiting from day 2 to day 3. A computed tomography scan showed a low density area with unclear border in the bilateral cerebellar hemispheres. Thereafter, these symptoms improved with discontinuation of FK506, which was strongly suggestive of encephalopathy caused by FK506. The blood concentration of FK506 at the onset of encephalopathy was 21.7 ng/mL. Although this value was slightly higher than the standard therapeutic range (10-20 ng/mL), it was within clinically acceptable range in the early stage after stem cell transplantation. This indicates that even if the blood concentration of FK506 is within the therapeutic range, encephalopathy may develop. In summary, although the blood concentration of FK506 is useful as an indicator for prevention of encephalopathy, we propose careful monitoring not only of the blood concentration but also clinical status for the detection of initial symptoms and prevention of aggravation.