Long-term outcomes of indocyanine green fluorescence imaging-guided laparoscopic lateral pelvic lymph node dissection for clinical stage II/III middle-lower rectal cancer: a propensity score-matched cohort study.

BACKGROUND: We previously reported that indocyanine green fluorescence imaging (ICG-FI)-guided laparoscopic lateral pelvic lymph node dissection (LPLND) was able to increase the total number of harvested lateral pelvic lymph nodes without impairing functional preservation. However, the long-term outcomes of ICG-FI-guided laparoscopic LPLND have not been evaluated. The aim of the present study was to compare the long-term outcomes of ICG-FI-guided laparoscopic LPLND to conventional laparoscopic LPLND without ICG-FI. METHODS: This was a retrospective, multi-institutional study with propensity score matching. The study population included consecutive patients with middle-low rectal cancer (clinical stage II to III) who underwent laparoscopic LPLND between January 2013 and February 2018. The main evaluation items in this study were the 3-year overall survival, relapse-free survival (RFS), local recurrence rate, and lateral local recurrence (LLR) rate. RESULTS: A total of 172 patients with middle-lower rectal cancer who had undergone laparoscopic LPLND were included in this study. After propensity score matching, 58 patients were matched in each of the ICG-FI and non-ICG-FI groups. There were no substantial differences in the baseline characteristics between the two groups. The ICG-FI group and non-ICG-FI group included 40 and 38 women and had a median age of 65 (IQR 60-72) and 66 (IQR 60-73) years, respectively. The median follow-up for all patients was 63.7 (IQR 51.3-76.8) months. The estimated respective 3-year overall survival, RFS, and local recurrence rates were 93.1%, 70.7%, and 5.2% in the ICG-FI group and 85.9%, 71.7%, and 12.8% in the non-ICG-FI group (p = 0.201, 0.653, 0.391). The 3-year cumulative LLR rate was 0% in the ICG-FI group and 9.3% in the non-ICG-FI group (p = 0.048). CONCLUSIONS: This study revealed that laparoscopic LPLND combined with ICG-FI was able to decrease the LLR rate. It appears that ICG-FI could contribute to improving the quality of laparoscopic LPLND and strengthening local control of the lateral pelvis. TRIALS REGISTRATION: This study was registered with the Japanese Clinical Trials Registry as UMIN000041372 ( http://www.umin.ac.jp/ctr/index.htm ).

Initial experience with the transanal approach for lateral pelvic lymph node dissection in rectal cancer.

BACKGROUND: The efficacy and safety of transanal lateral pelvic lymph node dissection (TaLPLND) in rectal cancer has not yet been clarified. The aim of the present study was to evaluate the short-term results as an initial experience of TaLPLND. METHODS: This retrospective study included patients with middle to lower rectal cancer who underwent TaLPLND from July 2018 to July 2021. Our institutions targeted lymph nodes in the internal iliac area and the obturator area for lateral pelvic lymph node dissection (LPLND). RESULTS: A total of 30 consecutive patients with rectal cancer were included in this analysis. The median age was 60 years (range, 36-83 years), and the male-female ratio was 2:1. The median operative time was 362 min (IQR, 283-661 min), and the median intraoperative blood loss was 74 ml (IQR, 5-500 ml). Intraoperative blood transfusion was required in one case. No cases required conversion to laparotomy. TaLPLND was performed bilaterally in 13 patients (43.3%). Five patients (16.7%) underwent LPLND with combined resection of the internal iliac vessels. The median distance of the distal margin from the anal verge was 20 mm. The pathological radial margin (pRM) was positive in one case, and the negative pRM rate was 96.7%. Short-term postoperative complications (Clavien-Dindo classification grade ≥ II) were observed in nine cases (30.0%). There were no cases of reoperation or mortality. The median number of harvested lateral pelvic lymph nodes was 11 (range, 3-28). On pathological examination, lateral pelvic lymph nodes were positive for metastasis in seven cases (23.3%). CONCLUSIONS: TaLPLND appeared to be beneficial from an oncological point of view because it was close to the upstream lymphatic drainage from the tumor. The short-term outcomes of this initial experience indicate that this novel approach is feasible.

TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer.

BACKGROUND: Osimertinib is a potent, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). The multi-arm phase Ib TATTON study (NCT02143466) was designed to assess the safety and tolerability of osimertinib in combination with other targeted therapies: selumetinib (MEK1/2 inhibitor), savolitinib (MET-TKI), or durvalumab [anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody]. PATIENTS AND METHODS: Patients with advanced EGFR-mutant non-small-cell lung cancer and disease progression on a prior EGFR-TKI were enrolled and allocated to dose-escalating cohorts combining osimertinib 80 mg orally (p.o.) once a day with selumetinib (25-75 mg p.o. twice a day; continuous or intermittent), savolitinib (600-800 mg p.o. once a day), or durvalumab (3-10 mg/kg intravenous every 2 weeks). RESULTS: At data cut-off (28 February 2018), 77 patients were enrolled and received osimertinib plus selumetinib (n = 36), savolitinib (n = 18), or durvalumab (n = 23). Most common adverse events (any grade), occurring in ≥20% of patients across dose groups, were: selumetinib arm-diarrhea (75%), rash (58%), nausea (47%); savolitinib arm-nausea (67%), rash (56%), vomiting (50%); durvalumab arm-rash (48%), vomiting (43%), diarrhea (39%). Dose-limiting toxicities were reported in the selumetinib 25 mg (n = 1), 50 mg (n = 1), and 75 mg (n = 4) continuous-dose groups, savolitinib 600 mg (n = 1) and 800 mg dose groups (n = 2), and durvalumab 10 mg/kg (n = 1) dose group. The objective response rate was 42% (95% confidence interval 26% to 59%), 44% (22% to 69%), and 43% (23% to 66%) in the selumetinib, savolitinib, and durvalumab arms, respectively. CONCLUSION: Our results demonstrate the feasibility of combining osimertinib 80 mg with selumetinib or savolitinib at identified tolerable, active doses. A combination of osimertinib with durvalumab was not feasible due to increased reporting of interstitial lung disease. Osimertinib-based combination therapies represent a compelling approach now being further investigated. CLINICAL TRIALS NUMBER: NCT02143466.

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients.

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

Sagittal alignment and mobility of the thoracolumbar spine are associated with radiographic progression of secondary hip osteoarthritis.

OBJECTIVE: To identify predictors of radiographic progression of hip osteoarthritis (OA) over 12 months among functional hip impairments and spinal alignment and mobility. DESIGN: Fifty female patients with secondary hip OA, excluding those with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA over 12 months (>0.5 mm in JSW) as dependent variable, logistic regression analyses were performed to identify predictors for hip OA progression among functional impairments of the hip and spine with and without adjustment for age, body mass index (BMI), and minimum JSW at baseline. The independent variables were hip pain, Harris hip score (HHS), hip morphological parameters, hip passive range of motion (ROM) and muscle strength, and alignment and mobility of the thoracolumbar spine at baseline. RESULTS: Twenty-one (42.0%) patients demonstrated radiographic progression of hip OA. Multivariable logistic regression analysis showed that larger anterior inclination of the spine in standing position (adjusted OR [95% CI], 1.37 [1.04-1.80]; P = 0.028) and less thoracolumbar spine mobility (adjusted OR [95% CI], 0.96 [0.92-0.99]; P = 0.037) at baseline were statistically significantly associated with radiographic progression of hip OA, even after adjustment for age, BMI, and minimum JSW. CONCLUSIONS: The findings suggest that spinal alignment and mobility should be considered when assessing risk and designing preventive intervention for radiographic progression of secondary hip OA.

Monitoring of somatic mutations in circulating cell-free DNA by digital PCR and next-generation sequencing during afatinib treatment in patients with lung adenocarcinoma positive for EGFR activating mutations.

Background: Analysis of circulating cell-free DNA (cfDNA) is under intensive investigation for its potential to identify tumor somatic mutations. We have now explored the usefulness of such liquid biopsy testing with both the digital polymerase chain reaction (dPCR) and next-generation sequencing (NGS) during treatment of patients with the epidermal growth factor receptor (EGFR) inhibitor afatinib. Patients and methods: Eligible patients had advanced lung adenocarcinoma with EGFR activating mutations and were treated with afatinib. Plasma samples were collected before and during (4 and 24 weeks) afatinib treatment as well as at disease progression. Tumor and plasma DNA were analyzed by dPCR and NGS. Results: Thirty-five patients were enrolled. The objective response rate and median progression-free survival (PFS) were 77.1% and 13.8 months, respectively. Tumor and plasma DNA were available for 32 patients. dPCR and NGS detected EGFR activating mutations in 81.3% and 71.9% of baseline cfDNA samples, respectively. In 19 patients treated with afatinib for ≥24 weeks, the number of EGFR mutant alleles detected in cfDNA by dPCR declined rapidly and markedly after treatment onset, becoming undetectable or detectable at only a low copy number (<10 copies per milliliter) at 4 weeks. Median PFS was slightly longer for patients with undetectable EGFR mutant alleles in cfDNA at 4 weeks than for those in whom such alleles were detectable (14.3 versus 10.0 months). A total of 45 somatic mutations was identified in baseline tumor DNA, and 30 (66.7%) of these mutations were identified in cfDNA by NGS. Allele frequency for somatic mutations in cfDNA determined by NGS changed concordantly during afatinib treatment with the number of EGFR mutant alleles determined by dPCR. Conclusions: Monitoring of cfDNA by dPCR is informative for prediction of afatinib efficacy, whereas that by NGS is reliable and has the potential to identify mechanisms of treatment resistance.

Randomized controlled trial of S-1 versus docetaxel in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy (East Asia S-1 Trial in Lung Cancer).

BACKGROUND: Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC. PATIENTS AND METHODS: Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60 mg/m2 in Japan, 75 mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80-120 mg/day, depending on body surface area; days 1-28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2. RESULTS: A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms, respectively [HR 0.945; 95% confidence interval (CI) 0.833-1.073; P = 0.3818]. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913-1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm. CONCLUSION: S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC. CLINICAL TRIAL NUMBER: Japan Pharmaceutical Information Center, JapicCTI-101155.

Daily cumulative hip moment is associated with radiographic progression of secondary hip osteoarthritis.

OBJECTIVE: To investigate whether higher daily cumulative hip moment at baseline is associated with subsequent radiographic progression of hip osteoarthritis (OA) over 12 months. DESIGN: Fifty patients with secondary hip OA, excluding patients with end-stage hip OA, participated in this prospective cohort study. Joint space width (JSW) of the hip was measured at baseline and 12 months later. With radiographic progression of hip OA (>0.5 mm/year in JSW) as dependent variable (yes/no), univariable and multivariable logistic regression analyses were performed to assess the association between load-related parameters during gait (i.e., peak hip moment, hip moment impulse, and daily cumulative hip moment [product of hip moment impulse and mean steps/day]) and hip OA progression with and without adjustment for age, body weight, and minimum JSW. RESULTS: Of the 50 patients (47.4 ± 10.7 years old), 21 (42.0%) were classified into the progression group. The higher daily cumulative hip moment in the frontal plane at baseline was statistically significantly associated with radiographic progression of hip OA (adjusted odds ratio (OR) [95% confidence interval (CI)], 1.34 [1.06-1.70]; P = 0.013). The higher daily cumulative hip moment in the sagittal plane was also approaching significance in its association with hip OA progression (adjusted OR, 1.80 [0.99-3.26]; P = 0.052). CONCLUSIONS: In the female patients with secondary hip OA, higher daily cumulative hip moment, particularly in the frontal plane, was a predictor of radiographic progression of hip OA over 12 months. Reduction in daily cumulative hip moment by modification in gait and physical activity may potentially slow hip OA progression.

C3435T polymorphism of the MDR1 gene is not associated with blood levels of hypothalamus-pituitary-adrenal axis hormones in healthy male subjects.

In vitro studies have shown that multidrug resistance protein 1 (MDR1) has an affinity for cortisol; however, in vivo association studies on the relationship between MDR1 gene polymorphisms and blood cortisol levels have produced inconsistent results. Therefore, we examined the effects of the C3435T polymorphism of the MDR1 gene on blood levels of hypothalamus-pituitary-adrenal (HPA) axis hormones such as cortisol and adrenocorticotropic hormone (ACTH) in healthy subjects. The subjects comprised 30 healthy Japanese males. Ten subjects were recruited for each of the C3435T MDR1 genotypes: C/C, C/T, and T/T. Blood samples were taken at 6:00 pm on two occasions with an interval of 2 weeks. Blood levels of cortisol and ACTH were determined by an electrochemiluminescence immunoassay. There were no significant differences in the blood levels of the HPA axis hormones among the MDR1 genotypes. The present study suggests that the C3435T MDR1 polymorphism does not affect blood levels of HPA axis hormones in healthy Japanese males.

Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.

BACKGROUND: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea). RESULTS: Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369). CONCLUSION: The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point. CLINICAL TRIAL REGISTRY IDENTIFIER: UMIN000004863.

Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study.

BACKGROUND: The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle. RESULTS: As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively. CONCLUSIONS: Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC. CLINICAL TRIALS NUMBER: Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071.

Wearing Compression Garment after Endurance Exercise Promotes Recovery of Exercise Performance.

The present study examined the effects of wearing a lower-body compression garment (CG) after endurance exercise on recovery of physiological function. 18 males were divided into 2 experiments, the downhill running (n=10, DHR) experiments and the level running (n=8, LR) experiments. Subjects performed 30 min of DHR (gradient: - 10%) or LR (gradient: 0%) at 70% of ˙VO2max with either wearing a CG (CG trial) or normal garment (CON trial) for 24 h after running. Changes in jump performance (counter movement jump; CMJ, rebound jump; RJ, drop jump; DJ), subjective feelings, circumferences of leg, and blood variables (creatine kinase, myoglobin, interleukin-6, high-sensitivity C-reactive protein) were evaluated before exercise, immediately after exercise, 1, 3 and 24 h following exercise. Running economy was evaluated at 24 h following exercise. CMJ height and RJ index were significantly higher in the CG trial than in the CON trial 24 h after running (P<0.05). Although changes in muscle soreness and blood variables were significantly greater in the DHR experiment than in the LR experiment, there was no significant difference between the trials in either experiment. Wearing a CG following endurance exercise facilitated recovery of jump performance under situations with severe exercise-induced muscle damage.

Macrophage deficiency in osteopetrotic (op/op) mice inhibits activation of satellite cells and prevents hypertrophy in single soleus fibers.

Effects of macrophage on the responses of soleus fiber size to hind limb unloading and reloading were studied in osteopetrotic homozygous (op/op) mice with inactivated mutation of macrophage colony-stimulating factor (M-CSF) gene and in wild-type (+/+) and heterozygous (+/op) mice. The basal levels of mitotically active and quiescent satellite cell (-46 and -39% vs. +/+, and -40 and -30% vs. +/op) and myonuclear number (-29% vs. +/+ and -28% vs. +/op) in fibers of op/op mice were significantly less than controls. Fiber length and sarcomere number in op/op were also less than +/+ (-22%) and +/op (-21%) mice. Similar trend was noted in fiber cross-sectional area (CSA, -15% vs. +/+, P = 0.06, and -14% vs. +/op, P = 0.07). The sizes of myonuclear domain, cytoplasmic volume per myonucleus, were identical in all types of mice. The CSA, length, and the whole number of sarcomeres, myonuclei, and mitotically active and quiescent satellite cells, as well as myonuclear domain, in single muscle fibers were decreased after 10 days of unloading in all types of mice, although all of these parameters in +/+ and +/op mice were increased toward the control values after 10 days of reloading. However, none of these levels in op/op mice were recovered. Data suggest that M-CSF and/or macrophages are important to activate satellite cells, which cause increase of myonuclear number during fiber hypertrophy. However, it is unclear why their responses to general growth and reloading after unloading are different.

Ipragliflozin in combination with metformin for the treatment of Japanese patients with type 2 diabetes: ILLUMINATE, a randomized, double-blind, placebo-controlled study.

This multicenter, double-blind, placebo-controlled study examined the efficacy and safety of ipragliflozin, a sodium-glucose co-transporter 2 inhibitor, in combination with metformin in Japanese patients with type 2 diabetes mellitus (T2DM). Patients were randomized in a 2 : 1 ratio to 50 mg ipragliflozin (n = 112) or placebo (n = 56) once daily for 24 weeks, followed by a 28-week open-label extension in which all patients received 50 or 100 mg ipragliflozin, while continuing metformin. The primary outcome was the change in glycated haemoglobin (HbA1c) from baseline to week 24. HbA1c decreased significantly in the ipragliflozin group (-0.87%; adjusted mean difference from placebo: -1.30%; p < 0.001). The overall incidence of treatment-emergent adverse events was similar in both groups, although pollakiuria and constipation were more common in the ipragliflozin group; thus, ipragliflozin significantly improved glycaemic control and reduced body weight without major safety issues in Japanese patients with T2DM.

Planned Overreaching and Subsequent Short-term Detraining Enhance Cycle Sprint Performance.

We investigated the effect of a training program consisting of planned overreaching and subsequent short-term detraining on sprint performance. 24 physically active men participated in an 18-day sprint-training program. They were divided into 2 groups: the overreaching-detraining (OR-DT) and the control (CON) groups. Subjects in the OR-DT group performed 12 consecutive days of maximal cycle sprint training followed by 6 days of detraining, whereas a rest day was provided after every 2 successive training days for the CON group. Peak power output during maximal pedaling increased significantly after 6 days of detraining in the OR-DT group compared with the baseline (P<0.05), whereas no change was observed in CON group. Intramuscular phosphocreatine concentration increased significantly after 12 days of daily training in the OR-DT group (69.3±45.8% increase vs. baseline, P<0.05), and it was maintained after the detraining period (46.6±33.6% increase vs. baseline, P<0.05). However, no change was observed in CON group. No significant changes in blood variables were observed after the training period except significant reduction of serum cortisol in the CON group. Daily sprint training and subsequent short-term detraining enhanced peak power output after the detraining period.

ROLES OF TRADITIONAL BIRTH ATTENDANTS AND PERCEPTIONS ON THE POLICY DISCOURAGING HOME DELIVERY IN COASTAL KENYA.

OBJECTIVES: To describe the roles of Traditional Birth Attendants (TBAs), to determine the perceptions of TBAs and Skilled Birth Attendants (SBAs) towards the policy discouraging home delivery by TBAs and to establish the working relationship between TBAs and SBAs in Kwale, Kenya. DESIGN: Community based cross-sectional study. SETTING: Mwaluphamba, Kinango and Golini locations of Kwale County, Kenya. SUBJECTS: Fifty eight participants were involved in the study. Interviews were conducted with 22 TBAs and 8 SBAs as well as 3 FGDs with 28 TBAs were carried out in July 2012. MAIN OUTCOME MEASURES: Roles of TBAs, policy awareness and support as well as the working relationship between TBAs and SBAs. RESULTS: Before delivery, the main role of TBAs was checking position of the baby in the womb (86%) while during delivery, the main role was stomach massage (64%). However, majority (95%) of the TBAs did not provide any after delivery. All SBAs and 59% of TBAs were aware of the policy while 88% SBAs and 36% of TBAs supported it. The working relationship between TBAs and SBAs mainly involved the referral of women to health facilities (HFs). Sometimes, TBAs accompanied women to the HF offering emotional support until after delivery. CONCLUSION: TBAs in Kwale have a big role to play especially during pregnancy and delivery periods. Awareness and support of the policy as well as the collaboration between SBAs and TBAs should be enhanced in Kwale.

Successful lung transplantation in a case with diffuse pulmonary arteriovenous malformations and hereditary hemorrhagic telangiectasia.

Diffuse pulmonary arteriovenous malformations (AVMs) are associated with a poor prognosis and the therapeutic strategy remains controversial. We describe a pediatric patient with diffuse pulmonary AVMs associated with hereditary hemorrhagic telangiectasia (HHT), who presented with two cerebral AVMs in the parietal and occipital lobes as well. Of note, successful bilateral lung transplantation not only improved the hypoxemia but also resulted in size reduction of the cerebral AVMs. Although it is essential to consider involvements other than pulmonary AVMs, especially brain AVMs, to decide the indication, lung transplantation can be a viable therapeutic option for patients with diffuse pulmonary AVMs and HHT.

Medical emergency education using a robot patient in a dental setting.

INTRODUCTION: In an ageing society, the frequency of medical emergencies in a dental setting appears to be increasing because of a growing number of medically compromised patients. However, we currently have no dental-specific simulation environment with advanced reproducibility for medical emergencies. Therefore, we used the robot patient in objective structured clinical examinations (OSCEs) for testing student competence in emergency management. This study aimed to evaluate student responses to medical emergencies in the dental setting. MATERIAL AND METHODS: We used 98 fifth-grade dental students at Showa University as subjects and implemented the OSCE task entitled 'Management of medical emergency using a robot patient'. Candidates were asked to manage an emergency situation immediately after local anaesthesia, with one robot patient configured to develop vasovagal syncope and the other to experience adrenaline hypersensitivity. A questionnaire on the educational value of the robot patient was completed after the examination. RESULTS: Thirty-two per cent of students could not accurately count her pulse because of an inappropriate method. Moreover, 78% could not correctly attach either the tonometer or pulse oximetry to the patient. Accurate diagnoses were given by only 22% of students, with vasovagal syncope diagnosed by 33% and adrenaline hypersensitivity by 8%. From a questionnaire, 78% of students recognised the usefulness of the robot patient in medical emergency training. CONCLUSION: We found that student responses to the emergency situation were poor. The robot patient is useful in dental education for medical emergency training and assessment not only for situation management but also for differential diagnosis.