Antiplatelet drugs may increase the risk for checkpoint inhibitor-related pneumonitis in advanced cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients. PATIENTS AND METHODS: This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk. RESULTS: Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n = 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86). CONCLUSIONS: An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management.

Changes in cerebrovascular disease-related deaths and their location during the COVID-19 pandemic in Japan.

OBJECTIVE: The COVID-19 pandemic placed an enormous strain on healthcare systems and raised concerns for delays in the management of patients with acute cerebrovascular events. In this study, we investigated cerebrovascular excess deaths in Japan. STUDY DESIGN: Vital mortality statistics from January 2012 to May 2022 were obtained from the Japanese Ministry of Health, Labour and Welfare. METHODS: Using quasi-Poisson regression models, we estimated the expected weekly number of cerebrovascular deaths in Japan from January 2020 through May 2022 by place of death. Estimates were calculated for deaths in all locations, as well as for deaths in hospitals, in geriatric health service facilities, and at home. The age subgroups of ≥75 and <75 years were also considered. Weeks with a statistically significant excess of cerebrovascular deaths were determined when the weekly number of observed deaths exceeded the upper bound of 97.5% prediction interval. RESULTS: Excess deaths were noted in June 2021 and became more pronounced from February 2022 onward. The trend was notable among those aged ≥75 years and for those who died in hospitals. With respect to the location of deaths, the excess was significant in geriatric health services facilities from April 2020 to June 2021, whereas no evidence of excess hospital deaths was observed during the same period. CONCLUSIONS: Beginning in the late 2021, excess cerebrovascular deaths coincided with the spread of the Omicron variant and may be associated with increased healthcare burden. In 2020, COVID-19 altered the geography of cerebrovascular deaths, with fewer people dying in hospitals and more dying in geriatric health service facilities and at home.

Impact of near-infrared fluorescence imaging with indocyanine green on structural sequelae of anastomotic leakage after laparoscopic intersphincteric resection of malignant rectal tumors.

BACKGROUND: Recent studies have indicated the potential benefit of intraoperative near-infrared fluorescence imaging (NIR-FI) with indocyanine green in reducing early anastomotic leakage in colorectal surgery. Nonetheless, whether NIR-FI is effective in reducing structural sequelae of anastomotic leakage (SSAL) remains unclear. The aim of the present study was to investigate the impact of NIR-FI on SSAL after laparoscopic intersphincteric resection (ISR) of malignant rectal tumors. METHODS: This study was a retrospective single-center cohort study. A total of 293 consecutive patients who underwent elective laparoscopic ISR from May 2010 to August 2017 were included. Patients were divided into 2 groups; those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors using NIR-F (NIR-FI group) and those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors without using NIR-FI (control group). Thirty were excluded from the analyses (13 died, 7 had pelvic recurrence, and 10 were lost to follow-up). The primary endpoint was the rate of SSAL within 2 years after the primary resection, whereas the secondary endpoint was the rate of natural defecation via the anus at 2 years after the primary resection. Using various statistical analyses, such as propensity score matching, the rate of SSAL was compared between groups. RESULTS: A total of 263 patients were analyzed [177 males and 86 females, median age 61 (27-84) years]. Prior to propensity score matching (n = 263), NIR-FI was performed in 70 patients (26.6%) The rates of SSAL were 1.4% (1/70) in the NIR-FI group and 10.4% (20/193) in the control group (p = 0.02). After propensity score matching (n = 163), the rates of SSAL were 1.5% (1/66) in the NIR-FI group and 11.7% (12/103) in the control group (p = 0.02). Propensity score analyses, as well as simple regression analyses, revealed that NIR-FI was associated with a significantly lower risk of SSAL (OR 0.10-0.13; p = 0.03-0.05). CONCLUSIONS: NIR-FI is useful in reducing the rate of SSAL after laparoscopic ISR.

Excess deaths from COVID-19 in Japan and 47 prefectures from January through June 2021.

OBJECTIVES: In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27. STUDY DESIGN: Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021. METHODS: A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval. RESULTS: Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12-18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31-June 6 (excess deaths: 1431-2587; excess percentage: 5.95-10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures. CONCLUSIONS: For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.

The relationship between fever rate and telework implementation as a social distancing measure against the COVID-19 pandemic in Japan.

OBJECTIVES: On March 28, the Japanese government decided on the "Basic Policies for Novel Coronavirus Disease Control" and called on the public to thoroughly implement social distancing measures (i.e., behavioral restrictions to limit the frequency and intensity of human contact), especially telework. METHODS: We used population-level questionnaire data from a social networking service (SNS), with 275,560 respondents from March 5 to April 6, to evaluate the relationship between telework implementation and the presence of a fever (body temperature higher than 37.5 °C) within 1 month as a surrogate indicator of COVID-19 infection, by occupation type and age-group. RESULTS: Among company employees, statistical significance was identified in the 15- to 29-year and 30- to 59-year age-groups, showing higher fever rates in the non-teleworker group (for the 15- to 29-year age-group, non-teleworkers: 7.64%; teleworkers: 6.45%; P = 0.02; for the 30- to 59-year age-group, non-teleworkers: 3.46%; teleworkers: 3.14%; P = 0.02). CONCLUSIONS: Telework remains a controversial topic in Japan as the government called for emergency measures. Although caution is warranted in interpreting our findings because our data are limited to the voluntary SNS users, they will be essential to push forward with more measures to promote social distancing measures in the midst of Japan's current tense political climate.

Human papillomavirus vaccine effectiveness within a cervical cancer screening programme: cohort study.

OBJECTIVE: To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. DESIGN: Retrospective cohort study using administrative health data. SETTING: General population of Ferrara Province, Italy. POPULATION: Female residents born in 1986-1993 and participating in the organized cervical screening programme in 2011-2018, who were eligible for HPV vaccination in catch-up cohorts. METHODS: Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. MAIN OUTCOME MEASURES: Cervical abnormalities, as predicted by low-grade or high-grade cytology, by number of vaccine doses, stratified by age. RESULTS: The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34-0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). CONCLUSIONS: In the context of an organised cervical screening programme in Italy, catch-up HPV vaccination almost halved the risk of cytological abnormalities. TWEETABLE ABSTRACT: Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.

Trend change of the transmission route of COVID-19-related symptoms in Japan.

OBJECTIVES: The Japanese prime minister declared a state of emergency on April 7 2020 to combat the outbreak of coronavirus disease 2019 (COVID-19). This declaration was unique in the sense that it was essentially driven by the voluntary restraint of the residents. We examined the change of the infection route by investigating contact experiences with COVID-19-positive cases. STUDY DESIGN: This study is a population-level questionnaire-based study using a social networking service (SNS). METHODS: To assess the impact of the declaration, this study used population-level questionnaire data collected from an SNS with 121,375 respondents (between March 27 and May 5) to assess the change in transmission routes over the study period, which was measured by investigating the association between COVID-19-related symptoms and (self-reported) contact with COVID-19-infected individuals. RESULTS: The results of this study show that the declaration prevented infections in the workplace, but increased domestic infections as people stayed at home. However, after April 24, workplace infections started to increase again, driven by the increase in community-acquired infections. CONCLUSIONS: While careful interpretation is necessary because our data are self-reported from voluntary SNS users, these findings indicate the impact of the declaration on the change in transmission routes of COVID-19 over time in Japan.

Serum high-mobility group box 1 is correlated with interferon-α and may predict disease activity in patients with systemic lupus erythematosus.

Sensing self-nucleic acids through toll-like receptors in plasmacytoid dendritic cells (pDCs), and the dysregulated type I IFN production, represent pathogenic events in the development of the autoimmune responses in systemic lupus erythematosus (SLE). Production of high-mobility group box-1 protein (HMGB1) promotes type I IFN response in pDCs. To better understand the active pathogenic mechanism of SLE, we measured serum levels of HMGB1, thrombomodulin, and cytokines (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, IFNα, IFNγ, TNFα) in 35 patients with SLE. Serum HMGB1 and IFNα were significantly higher in patients with active SLE (SLE Disease Activity Index (SLEDAI) score ≥ 6) compared with healthy donors or patients with inactive SLE. Furthermore, the HMGB1 levels were significantly correlated with IFNα levels. By qualitative analysis, the detection of serum IFNα or HMGB1 suggests active SLE and the presence of SLE-related arthritis, fever, and urinary abnormality out of SLEDAI manifestations. Collectively, HMGB1 and IFNα levels are biomarkers reflecting disease activity, and qualitative analysis of IFNα or HMGB1 is a useful screening test to estimate SLE severity and manifestations. Our results suggest the clinical significance of type I IFNs and HMGB1 as key molecules promoting the autoimmune process in SLE.

Japan health system review

The Asia Pacific Observatory on Health Systems and Policies (the APO) is a collaborative partnership of interested governments, international agencies, foundations, and researchers that promotes evidence-informed health systems policy regionally and in all countries in the Asia Pacific region. The APO collaboratively identifies priority health system issues across the Asia Pacific region; develops and synthesizes relevant research to support and inform countries' evidence-based policy development; and builds country and regional health systems research and evidence-informed policy capacity.

Comparison of postoperative biomechanical function between anatomic double-bundle and single-bundle ACL reconstructions using calcium phosphate-hybridized tendon grafts in goats.

BACKGROUND: Calcium phosphate (CaP)-hybridized tendon grafts improved biomechanical function compared with untreated grafts after single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the biomechanical function between anatomic double-bundle (DB) and single-bundle (SB) ACL reconstructions using CaP-hybridized tendon grafts at 6 months postoperatively in goats. HYPOTHESIS: We hypothesized that the postoperative biomechanical function in the DB group will be better than that in the SB group. MATERIALS AND METHODS: Knee kinematics and in situ forces in the grafts under applied anterior tibial load (ATL) of 50N and internal tibial torque (ITT) of 2.0 Nm at full extension, and 60° and 90° of knee flexion, and the histology of the tendon-bone interface were compared between the DB group (n=6) and SB group (n=6). RESULTS: The in situ forces under ATL in the DB group at full extension and 90°of knee flexion were greater than those in the SB group. The in situ forces under ITT in the DB group at full extension and 60°of knee flexion were greater than those in the SB group. The in situ forces on the posterolateral bundle of the grafts under ATL and ITT in the DB group at full knee extension were greater than those on the posterior half of the grafts in the SB group. The histology did not differ significantly between the groups. CONCLUSIONS: Although CaP-hybridized tendon grafts were used in both groups, the in situ forces under ATL and ITT in the DB group were greater than those in the SB group at 6 months postoperatively. The posterolateral bundle of the grafts in the DB group acted effectively against both ATL and ITT at full extension. The tendon-to-bone healing was similar in both groups. STUDY DESIGN: Controlled laboratory study. Level 2.

Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.

In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm3 /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

The longitudinal mental health impact of Fukushima nuclear disaster exposures and public criticism among power plant workers: the Fukushima NEWS Project study.

BACKGROUND: The Fukushima Daiichi and Daini Nuclear Power Plant workers experienced multiple stressors as both victims and onsite workers after the 2011 Great East Japan Earthquake and subsequent nuclear accidents. Previous studies found that disaster-related exposures, including discrimination/slurs, were associated with their mental health. Their long-term impact has yet to be investigated. METHOD: A total of 968 plant workers (Daiichi, n = 571; Daini, n = 397) completed self-written questionnaires 2-3 months (time 1) and 14-15 months (time 2) after the disaster (response rate 55.0%). Sociodemographics, disaster-related experiences, and peritraumatic distress were assessed at time 1. At time 1 and time 2, general psychological distress (GPD) and post-traumatic stress response (PTSR) were measured, respectively, using the K6 scale and Impact of Event Scale Revised. We examined multivariate covariates of time 2 GPD and PTSR, adjusting for autocorrelations in the hierarchical multiple regression analyses. RESULTS: Higher GPD at time 2 was predicted by higher GPD at time 1 (ß = 0.491, p < 0.001) and discrimination/slurs experiences at time 1 (ß = 0.065, p = 0.025, adjusted R 2 = 0.24). Higher PTSR at time 2 was predicted with higher PTSR at time 1 (ß = 0.548, p < 0.001), higher age (ß = 0.085, p = 0.005), and discrimination/slurs experiences at time 1 (ß = 0.079, p = 0.003, adjusted R 2 = 0.36). CONCLUSIONS: Higher GPD at time 2 was predicted by higher GPD and discrimination/slurs experience at time 1. Higher PTSR at time 2 was predicted by higher PTSR, higher age, and discrimination/slurs experience at time 1.

Early endoscopic management for early bowel obstruction after gastrectomy: a case report.

BACKGROUND: Early bowel obstruction is not a rare complication of gastrectomy, and it may require re-operation in some cases. CASE PRESENTATION: We report the case of a 71-year-old woman who underwent a total gastrectomy with Roux-en-Y reconstruction for a massive gastrointestinal stromal tumor. Postoperatively, she was making good progress and started consuming meals on postoperative day 3. However, on postoperative day 10, she complained of upper abdominal discomfort and nausea. Blood tests showed a mild inflammatory reaction. An upper gastrointestinal series showed obstruction of the elevated jejunum. An abdominal computed tomography scan suggested upper bowel obstruction. Endoscopic observation and repositioning was selected as an effective approach for treatment considering the patient's clinical condition and background. Upper gastrointestinal endoscopy showed kinking of the elevated jejunum, easy passage through to the anal intestine, and no evidence of mucosal edema, stenosis of the Roux-en-Y anastomosis, bowel ischemia, or necrosis. After endoscopic repositioning, upper gastrointestinal series showed good passage of the jejunum and no evidence of bowel obstruction. At the 6-month follow-up examination, the patient was in good condition and had no complaints. CONCLUSION: We concluded that early endoscopic management should be the effective procedure considered for diagnosis and treatment of early bowel obstruction after gastrectomy in some cases.

Short-term outcomes of robotic radical esophagectomy for esophageal cancer by a nontransthoracic approach compared with conventional transthoracic surgery.

Transthoracic esophagectomy (TTE) is believed to have advantages for mediastinal lymphadenectomy in the treatment of resectable esophageal cancer despite its association with a greater incidence of pulmonary complications and postoperative mortality. Transhiatal esophagectomy is regarded as less invasive, though insufficient in terms of lymph node dissection. With the aim of achieving lymph dissection equivalent to that of TTE, we have developed a nontransthoracic esophagectomy (NTTE) procedure combining a video-assisted cervical approach for the upper mediastinum and a robot-assisted transhiatal approach for the middle and lower mediastinum. We prospectively studied 22 accumulated cases of NTTE and verified feasibility by analyzing perioperative and histopathological outcomes. We compared this group's short-term outcomes with outcomes of 139 equivalent esophageal cancer cases operated on at our institution by conventional TTE (TTE group). In the NTTE group, there were no procedure-related events and no midway conversions to the conventional surgery; the mean operation time was longer (median, 524 vs. 428 minutes); estimated blood loss did not differ significantly between the two groups (median, 385 mL vs. 490 mL); in the NTTE group, the postoperative hospital stay was shorter (median, 18 days vs. 24 days). No postoperative pneumonia occurred in the NTTE group. The frequencies of other major postoperative complications did not differ significantly, nor were there differences in the numbers of harvested mediastinal lymph nodes (median, 30 vs. 29) or in other histopathology findings. NTTE offers a new radical procedure for resection of esophageal cancer combining a cervical video-assisted approach and a transhiatal robotic approach. Although further accumulation of surgical cases is needed to corroborate these results, NTTE promises better prevention of pulmonary complications in the management of esophageal cancer.

Cyclic mechanical pressure-loading alters epithelial homeostasis in a three-dimensional in vitro oral mucosa model: clinical implications for denture-wearers.

Denture-wearing affects the quality and quantity of epithelial cells in the underlying healthy oral mucosa. The physiologic mechanisms, however, are poorly understood. This study aimed to compare histologic changes and cellular responses of an epithelial cell layer to cyclic mechanical pressure-loading mimicking denture-wearing using an organotypic culture system to develop a three-dimensional in vitro oral mucosa model (3DOMM). Primary human oral keratinocytes and fibroblasts were serially grown in a monolayer culture, and cell viability was measured under continuous cyclic mechanical pressure (50 kPa) for 7 days (cycles of 60 min on, 20 s off to degas and inject air). Upon initiation of an air-liquid interface culture for epithelial stratification, the cyclic pressure, set to the mode above mentioned, was applied to the 3DOMMs for 7 days. Paraffin-embedded 3DOMMs were examined histologically and immunohistochemically. In the monolayer culture, the pressure did not affect the viability of oral keratinocytes or fibroblasts. Few histologic changes were observed in the epithelial layer of the control and pressure-loaded 3DOMMs. Immunohistochemical examination, however, revealed a significant decrease in Ki-67 labelling and an increase in filaggrin and involucrin expression in the suprabasal layer of the pressure-loaded 3DOMMs. Pressure-loading attenuated integrin ß1 expression and increased matrix metalloproteinase-9 activity. Incomplete deposition of laminin and type IV collagen beneath the basal cells was observed only in the pressure-loaded 3DOMM. Cyclic pressure-loading appeared to disrupt multiple functions of the basal cells in the 3DOMM, resulting in a predisposition towards terminal differentiation. Thus, denture-wearing could compromise oral epithelial homeostasis.

Preoperative drainage using a transanal tube enables elective laparoscopic colectomy for obstructive distal colorectal cancer.

BACKGROUND AND STUDY AIMS: Acute colorectal obstruction (ACO) often accompanies colorectal cancer (CRC) and requires urgent treatment, but achieving elective laparoscopy-assisted colectomy (LAC) is difficult in this setting. The aim of the current study was to assess the clinical outcomes of a transanal tube (Dennis colorectal tube [DCT]) for CRC with ACO, focusing in particular on the impact of the DCT on subsequent elective LAC. PATIENTS AND METHODS: Among 1142 patients who underwent surgery for CRC between January 2007 and December 2011, 92 patients with ACO were identified retrospectively. Of these 92 patients, the DCT procedure was performed in 66 patients who fulfilled the indications for DCT, and these patients were included in the study. RESULTS: All 66 patients presented with complete obstruction. Technical and clinical success rates for DCT were 93.9 % and 86.4 %, respectively. Perforation after DCT occurred in 4.5 % and the mortality rate was 1.5 %. The rate of LAC was 48.5 %, and the rate of primary stoma was 13.6 %. For curative stage II/III CRC with ACO, DCT resulted in a primary stoma rate of 13.6 %, a one-stage surgery rate of 90.9 %, a LAC rate of 50.0 %, and a 3-year survival rate of 73.1 %. For stage II/III CRC cases with clinical success by DCT, the one-stage surgery rate was 97.4 % and the LAC rate was 56.4 %. CONCLUSIONS: DCT achieved a high rate of clinical success and enabled safe one-stage surgery and LAC for CRC with ACO. DCT followed by LAC is proposed as a promising non-invasive strategy for CRC with ACO.

A lower starting dose of eltrombopag is efficacious in Japanese patients with previously treated chronic immune thrombocytopenia.

BACKGROUND: Eltrombopag is an oral, non-peptide thrombopoietin receptor agonist that has shown efficacy and safety in chronic immune thrombocytopenia (ITP). However, ethnic differences in eltrombopag exposure have been reported: area under the curve exposure to eltrombopag was 87% greater among ITP patients of East Asian descent than among ITP patients of non-East Asian ITP descent. OBJECTIVES: To evaluate the efficacy and safety of eltrombopag by using, in Japanese ITP patients, lower starting (12.5 mg) and maximum (50 mg) doses of eltrombopag than the standard starting (50 mg) and maximum (75 mg) doses approved in the USA and Europe. PATIENTS: We examined 23 Japanese patients with previously treated chronic ITP with a platelet count of < 30,000 µL(-1) in a multicenter study comprising a randomized, double-blind, placebo-controlled phase for 6-week evaluation (15 eltrombopag, and eight placebo) and an open-label phase for 6-month evaluation (23 eltrombopag). RESULTS AND CONCLUSIONS: The response rate (platelet count of ≥ 50,000 µL(-1) ) at week 6 of the 6-week double-blind phase was 60% in eltrombopag-treated patients and 0% in placebo-treated patients. Ten of 23 patients (43.5%) responded for ≥ 75% of predefined assessment visits during the 6-month open-label phase. Notably, 22% (5/23) of patients responded to 12.5 mg of eltrombopag, which was administered within the first 3 weeks of eltrombopag treatment. Bleeding decreased with eltrombopag treatment as compared with baseline. Eltrombopag was generally well tolerated; one patient experienced a transient ischemic attack on day 9. Eltrombopag (12.5-50 mg) is effective for the management of Japanese patients with chronic ITP (NCT00540423).