Kampo Japanese Herbal Medicine Research Articles

Association between complementary use of Goreisan (a Japanese herbal Kampo medicine) and heart failure readmission: A nationwide propensity score-matched study

BackgroundGoreisan, a Japanese herbal medicine, possesses aquaretic properties to regulate body fluid homeostasis and may therefore be effective as a complement to standard therapy in improving outcomes in patients with heart failure (HF). MethodsWe retrospectively identified 431,393 patients (mean age 79.2 ± 12.6 years; male 52.3 %) who were admitted for HF for the first time and were discharged alive with standard HF medications between April 2016 and March 2022, using the Japanese Diagnosis Procedure Combination database. We divided patients into two groups according to the prescription of Goreisan at discharge: patients who received standard HF medications plus Goreisan and those who received standard medications alone. We compared the incidence of HF readmission within 1 year after discharge between the groups using propensity score matching. ResultsOverall, Goreisan was prescribed in 1957 (0.45 %) patients at discharge. Patients who received Goreisan were older and received diuretics more frequently than those who did not. One-to-four propensity score matching created a cohort of 1957 and 7828 patients treated with and without Goreisan, respectively. No significant difference was found in the incidence of 1-year HF readmission between the groups [22.1 % vs. 21.7 %; hazard ratio (HR) = 1.02, 95 % confidence interval (CI) = 0.92–1.13]. This result was consistent with that from competing risk analysis (subdistribution HR = 1.02, 95 % CI = 0.92–1.13) and across clinically relevant subgroups except for renal disease. Goreisan use was associated with a lower incidence of HF readmission among patients with renal disease (HR = 0.77, 95 % CI = 0.60–0.97), but not among those without (HR = 1.09, 95 % CI = 0.97–1.23; p for interaction = 0.009). ConclusionsThis nationwide propensity score-matched analysis did not demonstrate that complementary Goreisan use at discharge was associated with a lower incidence of 1-year HF readmission in patients with HF receiving standard medications. An ongoing randomized trial is awaited to establish the effectiveness of Goreisan use in patients with HF.

Use of Japanese Herbal Kampo Medicine in Patients With Acute Cardiovascular Disease - A 12-Year Nationwide Cohort Analysis.

Kampo, a Japanese herbal medicine, is approved for the treatment of various symptoms/conditions under national medical insurance coverage in Japan. However, the contemporary nationwide status of Kampo use among patients with acute cardiovascular diseases remains unknown.Methods and Results: Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified 2,547,559 patients hospitalized for acute cardiovascular disease (acute myocardial infarction, heart failure, pulmonary embolism, or aortic dissection) at 1,798 hospitals during the fiscal years 2010-2021. Kampo medicines were used in 227,008 (8.9%) patients, with a 3-fold increase from 2010 (4.3%) to 2021 (12.4%), regardless of age, sex, disease severity, and primary diagnosis. The top 5 medicines used were Daikenchuto (29.4%), Yokukansan (26.1%), Shakuyakukanzoto (15.8%), Rikkunshito (7.3%), and Goreisan (5.5%). From 2010 to 2021, Kampo medicines were initiated earlier during hospitalization (from a median of Day 7 to Day 3), and were used on a greater proportion of hospital days (median 16.7% vs. 21.4%). However, the percentage of patients continuing Kampo medicines after discharge declined from 57.9% in 2010 to 39.4% in 2021, indicating their temporary use. The frequency of Kampo use varied across hospitals, with the median percentage of patients prescribed Kampo medications increasing from 7.7% in 2010 to 11.5% in 2021. This nationwide study demonstrates increasing Kampo use in the management of acute cardiovascular diseases, warranting further pharmacoepidemiological studies on its effectiveness.

Antiemetic Effect of Rikkunshito, a Japanese Kampo Herbal Medicine, on Cisplatin-induced Nausea and Vomiting: A Nationwide Database Study in Japan.

Objective The effect of Rikkunshito, a Japanese herbal Kampo medicine, on chemotherapy-induced nausea and vomiting (CINV) has been evaluated in several small prospective studies, with mixed results. We retrospectively evaluated the antiemetic effects of Rikkunshito in patients undergoing cisplatin-based chemotherapy using a large-scale database in Japan. Methods The Diagnosis Procedure Combination inpatient database from July 2010 to March 2019 was used to compare adult patients with malignant tumors who had received Rikkunshito on or before the day of cisplatin administration (Rikkunshito group) and those who had not (control group). Antiemetics on days 2 and 3 and days 4 and beyond following cisplatin administration were used as surrogate outcomes for CINV. Patient backgrounds were adjusted using the stabilized inverse probability of treatment weighting, and outcomes were compared using univariable regression models. Results We identified 669 and 123,378 patients in the Rikkunshito and control groups, respectively. There were significantly fewer patients using intravenous 5-HT3-receptor antagonists in the Rikkunshito group (odds ratio, 0.38; 95% confidence interval, 0.16-0.87; p=0.023) on days 2 and 3 of cisplatin-based chemotherapy. Conclusion The reduced use of antiemetics on day 2 and beyond of cisplatin administration suggested a beneficial effect of Rikkunshito in palliating the symptoms of CINV.

Association of the Japanese herbal kampo medicine kakkonto with antibiotic use and surgical drainage for noninfectious mastitis: A nationwide database study.

Kakkonto, a Japanese herbal kampo medicine, is empirically prescribed to improve milk stasis and ameliorate breast inflammation in patients with noninfectious mastitis. We investigated whether early use of kakkonto is associated with a reduction in antibiotic use and surgical drainage in patients with noninfectious mastitis. We identified 34 074 patients with an initial diagnosis of noninfectious mastitis within 1 year of childbirth between April 2012 and December 2022 using the nationwide administrative JMDC Claims Database. Patients were divided into the kakkonto (n = 9593) and control (n = 9648) groups if they received and did not receive kakkonto on the day of the initial diagnosis of noninfectious mastitis, respectively. Antibiotic administration and surgical drainage within 30 days after the initial diagnosis of noninfectious mastitis in the two groups were compared using propensity score-stabilized inverse probability of treatment weighting analysis. The frequency of antibiotic administration within 30 days after the initial diagnosis of noninfectious mastitis was significantly lower in the kakkonto group than in the control group (10% vs. 12%; odds ratio, 0.88 [95% confidence interval, 0.80-0.96]). The frequency of antibiotic administration during 1-3 and 4-7 days after the initial diagnosis were also significantly lower in the kakkonto group than in the control group. The frequency of surgical drainage did not differ significantly between the two groups. Kakkonto was associated with reduced administration of antibiotics for noninfectious mastitis, making it a potential treatment option for relieving breast inflammation and promoting antimicrobial stewardship.

Japanese herbal kampo medicine individually contributes to alleviating side effects of cancer patients

Cancer patients suffer from physical pain due to cancer itself and side effects by anticancer drugs, as well as social pain such as employment problems, psychological and spiritual pain. It is important to overcome these total pains with multidisciplinary medical care. Regarding drug treatment, if there is no drug effective in alleviating the patients' symptoms, it is necessary to develop a novel drug or drug repositioning to apply existing drugs. Among them, "Japanese herbal kampo medicine", introduced from China and developed in Japan, has come to occupy an important position as a complementary and alternative medicine to Western drugs.

The Efficacy of Japanese Herbal Kampo Medicine as an Acute and Prophylactic Medication to Treat Chronic Daily Headache and Medication Overuse Headache:-Single Arm Retrospective Study.

IntroductionA chronic daily headache (CDH) comprises a group of headaches occurring at least 15 days per month for three or more consecutive months. We retrospectively investigated the effectiveness of the hybrid treatment strategy for CDH using Kampo medicine combined with Western medication.MethodsWe retrospectively investigated 43 consecutive first-visit CDH patients. In addition to Western acute and prophylactic medications, we prescribed three types of Kampo medicines: goreisan, goshuyuto, and kakkonto depending on the patients’ symptoms. Headache impact test-6 (HIT-6), monthly headache days (MHD), monthly migraine days (MMD), and monthly acute medication intake days (AMD) before, 1- and 3-months after starting the hybrid medications were assessed as outcomes.ResultsThirty-six women and seven men were included. The median age was 51 years old. Nine were chronic migraine (CM), 22 were episodic migraine and tension-type headaches (EM+TTH), and 12 were chronic TTH. Twenty-seven patients also had medication overuse headaches (MOH). The medians of HIT-6 before, one and three months after treatment were 63, 48, and 40, respectively. Those of MHD were 20, 5, and 2. Those of MMD were 2, 0, and 0. Those of AMD were 15, 0, and 0. Significant reductions in HIT-6, MDH, MMD, and AMD were observed one and three months after starting Kampo treatment. Similar trends were observed in the EM+TTH and MOH patients as subgroup analyses.ConclusionThe hybrid medication strategy of Kampo and Western medicines for CDH is safe and effective in terms of both acute and prophylactic medications with rapid efficacy.

Safety of Japanese herbal Kampo medicines for the treatment of depression during pregnancy.

To clarify the fetal safety of herbal Kampo medicines, including Hange-koboku-to, Koso-san, Nyoshin-san, Yokukansan, Yokukansan-kachinpi-hange, Saiko-keishikankyo-to, Keishi-karyukotu-borei-to, and Kanbaku-taisou-to, when administered to pregnant women with depression using a large healthcare administrative database. We extracted data from the JMDC Claims Database (2005-2018) for this retrospective cohort study of pregnant women aged 19 years or older admitted to obstetric clinics or hospitals for delivery. Participants were classified into four groups: those without depression, those diagnosed with depression without medication, those given Kampo medicines for depression, and those given western medicines for depression. Neonatal outcomes (congenital anomalies, low birth weight, and preterm birth) were considered as the safety outcome measures. We identified 179 707 eligible mothers. The adverse outcomes did not differ significantly between participants receiving Kampo medicine and those not diagnosed with depression during pregnancy. The proportion of low-birth-weight neonates did not differ significantly between the Kampo medicine and non-depression groups (adjusted odds ratio [aOR] 1.28; 95% confidence interval [CI] 0.86-1.91), but was significantly higher in the unmedicated depression group (aOR 1.31; 95% CI 1.07-1.61) and western medicine group (aOR 1.47; 95% CI 1.18-1.83). Kampo medicines are safe for treating depression during pregnancy without increasing the incidence of congenital anomalies, low birth weight, or preterm birth.

Japanese herbal kampo medicines exert a comprehensive action through multiple ingredients acting on multiple targets: new prescriptions for Japanese herbal kampo medicines based on the elucidation of their mechanisms of action

Japanese herbal kampo medicines exert a comprehensive action through multiple ingredients acting on multiple targets: new prescriptions for Japanese herbal kampo medicines based on the elucidation of their mechanisms of action

Medication Overuse Headache Successfully Treated by Three Types of Japanese Herbal Kampo Medicine

Medication overuse headache (MOH) usually resolves after the overuse is stopped and starting prophylactic medications. However, it can be challenging to prescribe common prophylactic medications when patients have a history of side effects. As an alternative therapy, traditional Japanese herbal kampo medicine can be used. We herein report a case of a MOH woman with a history of side effects by such common prophylactic medications. A 50-year-old woman presented with a severe migraine attack. She had suffered from migraines for 10 years. She had taken loxoprofen and sumatriptan every day for over eight years. As prophylactic medications, lomerizine, valproic acid, and amitriptyline had been prescribed in the past, but they were discontinued due to side effects. Therefore, she could continue only propranolol as prophylactic medication. She had severe pulsatile headaches and nausea every day. We diagnosed triptan- and non-steroidal anti-inflammatory drug-overuse headache (the International Classification of Headache Disorders 3rd edition code 8.2.2 and 8.2.3.2) and chronic migraine (code 1.3). She was admitted and stopped loxoprofen and sumatriptan. We prescribed three types of Japanese herbal kampo medicines - kakkonto (TJ-1), goreisan (TJ-17), and goshuyuto (TJ-31). Her headache was relieved on day 5, and she was discharged on day 7. In the 40 days after discharge, she had only three times mild headaches with a numeric rating scale (NRS) of 2/10. She did not need any triptans nor anti-inflammatory drugs. We herein presented the MOH woman who was successfully treated using three types of kampo medicine. We should pay attention to their side effects, but kampo medicine may be useful for MOH treatment as acute and prophylactic medications for primary headaches.

Effect of Daikenchuto for Mechanically Ventilated Patients With Enteral Feeding Intolerance: A Propensity Score-Matched Analysis Using a Nationwide Administrative Inpatient Database.

Daikenchuto, a Japanese herbal Kampo medicine, is used to improve gastrointestinal motility in critically ill patients with enteral feeding intolerance (EFI) in Japan. The present study aimed to investigate the effect of Daikenchuto for critically ill patients with EFI. Using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2018, we identified mechanically ventilated patients in intensive care units (ICUs) who had EFI during mechanical ventilation. We defined EFI as receipt of intravenous metoclopramide during mechanical ventilation. Patients who started Daikenchuto within 2 days of EFI onset were defined as the Daikenchuto group, and the remaining patients were defined as the control group. Propensity score-matched analyses were performed to compare the outcomes between the 2 groups. A total of 61,454 patients were included. Of these, 8842 patients (14%) were in the Daikenchuto group. One-to-one propensity score matching created 8701 matched pairs. After propensity score matching, the total number of days receiving enteral nutrition within 28 days of EFI onset was significantly longer in the Daikenchuto group than in the control group (risk difference, 0.9 days; 95% CI, 0.5-1.3 days). There were no significant differences in 28-day in-hospital mortality, hospital-acquired pneumonia, ventilator-free days, length of ICU stay, time to discharge alive, and adverse complications. This nationwide observational study suggested that use of Daikenchuto may increase the total number of days receiving enteral nutrition in mechanically ventilated patients with EFI.

Growth stimulation of Bifidobacterium from human colon using daikenchuto in an in vitro model of human intestinal microbiota

Daikenchuto (DKT) is a Japanese traditional herbal (Kampo) medicine containing ginseng, processed ginger, and Japanese or Chinese pepper. We aimed to determine how DKT affects human colonic microbiota. An in vitro microbiota model was established using fecal inocula collected from nine healthy volunteers, and each model was found to retain operational taxonomic units similar to the ones in the original human fecal samples. DKT was added to the in vitro microbiota model culture at a concentration of 0.5% by weight. Next-generation sequencing of bacterial 16S rRNA gene revealed a significant increase in the relative abundance of bacteria related to the Bifidobacterium genus in the model after incubation with DKT. In pure cultures, DKT significantly promoted the growth of Bifidobacterium adolescentis, but not that of Fusobacterium nucleatum or Escherichia coli. Additionally, in pure cultures, B. adolescentis transformed ginsenoside Rc to Rd, which was then probably utilized for its growth. Our study reveals the in vitro bifidogenic effect of DKT that likely contributes to its beneficial effects on the human colon.

The Japanese Herbal (Kampo) Medicine Hochuekkito Attenuates Lung Inflammation in Lung Emphysema.

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder. It often causes weight loss, which is considered a poor prognostic factor. A Japanese herbal Kampo medicine, Hochuekkito (TJ-41), has been reported to prevent systemic inflammation and weight loss in COPD patients, but the underlying biological mechanisms remain unknown. In the present study, we investigated the role of TJ-41 in vivo using a mouse model of lung emphysema. We used lung epithelium-specific Taz conditional knockout mice (Taz CKO mice) as the lung emphysema model mimicking the chronic pulmonary inflammation in COPD. Acute inflammation was induced by intratracheal lipopolysaccharide administration, simulating COPD exacerbation. Mice were fed a diet containing 2% TJ-41 or a control diet. Taz CKO mice showed increased numbers of inflammatory cells in the bronchoalveolar lavage fluid compared to control mice. This effect was reduced by TJ-41 treatment. In the acute exacerbation model, TJ-41 mitigated the increased numbers of inflammatory cells in the bronchoalveolar lavage fluid and attenuated lung inflammation in histopathological studies. Additional in vitro experiments using the human macrophage cell line U-937 demonstrated that lipopolysaccharide-induced tumor necrosis factor-alpha expression was significantly downregulated by TJ-41. These results suggest that TJ-41 has anti-inflammatory effects in lung emphysema both in the chronic phase and during an acute exacerbation. In conclusion, our study sheds light on the anti-inflammatory effects of TJ-41 in lung emphysema. This establishes its potential as a new anti-inflammatory therapy and a preventive medicine for exacerbations during the long-time maintenance of COPD patients.

Effect of Japanese herbal Kampo medicines on live birth rate in women with recurrent pregnancy loss.

To determine the effectiveness of Japanese Kampo medicines on the overall live birth rate among patients with recurrent pregnancy loss (RPL) in a real-world setting. In the current retrospective cohort study, we used the JMDC Claims Database to extract information on women diagnosed with RPL between January 1, 2005 and August 31, 2018. Eligible women were divided into two groups according to Kampo medicines administered as treatments for RPL. The primary outcome was the live birth rate during the study period. Propensity score matching, Kaplan-Meier cumulative incidence plots, log-rank test, and Cox proportional-hazards regression model were used to compare the primary outcome between patients with and without Japanese herbal Kampo medicines. Among 5517 eligible patients, 1652 used Kampo medicines and 3865 did not. After propensity score matching, the live birth rate at 2.0years was 15.7% in the Kampo group and 11.2% in the non-Kampo group. At 4.0years, the difference between the two groups had slightly increased. The overall live birth rate differed significantly between the two groups (hazard ratio 1.32, 95% confidence interval 1.13-1.53; P<0.001). Japanese herbal Kampo medicines may improve the live birth rate in patients with RPL.

A Prospective Randomized Study on the Preventive Effect of Japanese Herbal Kampo Medicine Goreisan for Recurrence of Chronic Subdural Hematoma.

Although the recurrence of chronic subdural hematoma (CSDH) after surgical treatment significantly affects the patients’ quality of life, the recurrence rate has not improved in decades. Goreisan, a Japanese herbal Kampo medicine, promotes the hydragogue effect and has been empirically used in the treatment of CSDH in Japan. We conducted a prospective randomized study to investigate whether Goreisan treatment decreases the recurrence rate of CSDH. Between March 2013 and December 2018, a total of 224 patients who underwent initial burr hole surgery for CSDH were randomly assigned to receive Goreisan for 3 months (Group G) or no medication (Group N). The primary endpoint was symptomatic recurrence within 3 months postoperatively, and the secondary endpoint was complications, including the adverse effects of Goreisan. Of 224 randomized patients, 208 were included in the final analysis (104 in Group G and 104 in Group N). The overall recurrence rate was 9.1% (19/208). The recurrence rate of Group G was lower than that of Group N (5.8% vs 12.5%, P = 0.09), but the difference was not statistically significant. However, a significant preventive effect of Goreisan was found in 145 patients with high-risk computed tomography (CT) features, namely, homogeneous and separated types (5.6% vs 17.6%, P = 0.04). Although the present study did not prove the beneficial effect of Goreisan treatment, it suggested the importance of selecting patients with an increased risk of recurrence. A subset of patients whose hematoma showed homogeneous and separated patterns on CT image might benefit from Goreisan treatment.

Safety and effectiveness of Japanese herbal Kampo medicines for treatment of hyperemesis gravidarum.

To investigate whether Japanese Kampo medicines, including Sho-hange-kabukuryou-to, Touki-syakuyaku-san, and Hange-kouboku-to, are safe for fetuses, and whether these medicines reduce hospitalizations and medical costs in pregnant women with hyperemesis gravidarum. We used the Japan Medical Data Center database to extract data for pregnant women (aged ≥19years) admitted to obstetric clinics or hospitals for delivery between January 1, 2005, and December 31, 2016. Eligible patients were classified into three groups: Kampo medicines for hyperemesis gravidarum, other medicines for hyperemesis gravidarum, and without hyperemesis gravidarum. Safety outcome measures were neonatal outcomes (congenital anomalies, low birthweight, and preterm birth), and effectiveness measures were mother's unplanned hospitalization for hyperemesis gravidarum and total medical costs within 20weeks of gestation. We identified 121287 eligible mothers. No significant differences in the safety measures were observed among the groups. The Kampo medication group had a significantly lower proportion of mothers with unplanned hospital admission (odds ratio 0.80, 95% confidence interval [CI] 0.69-0.92) and lower total costs (coefficient [US$] 12.8, 95% CI -23.2 to -2.4) than the other medication group. Kampo medicines may reduce unplanned admissions and medical costs among pregnant women with hyperemesis gravidarum. UMIN Clinical Trials Registry: R000037298 UMIN000032706.

Reduction in exacerbation of COPD in patients of advanced age using the Japanese Kampo medicine Dai-kenchu-to: a retrospective cohort study.

PurposePatients with symptomatic COPD are recommended to use inhaled bronchodilators containing long-acting muscarinic receptor antagonists (LAMAs). However, bronchodilators may cause gastrointestinal adverse effects due to anticholinergic reactions, especially in advanced-age patients with COPD. Dai-kenchu-to (TU-100, Da Jian Zhong Tang in Chinese) is the most frequently prescribed Japanese herbal Kampo medicine and is often prescribed to control abdominal bloating and constipation. The purpose of this study was to evaluate the role of Dai-kenchu-to as a supportive therapy in advanced-age patients with COPD.Patients and methodsWe used the Japanese Diagnosis Procedure Combination inpatient database and identified patients aged ≥75 years who were hospitalized for COPD exacerbation. We then compared the risk of re-hospitalization for COPD exacerbation or death between patients with and without Dai-kenchu-to using 1-to-4 propensity score matching. A Cox proportional hazards model was used to compare the two groups. We performed subgroup analyses for patients with and without LAMA therapy.ResultsPatients treated with Dai-kenchu-to had a significantly lower risk of re-hospitalization or death after discharge; the HR was 0.82 (95% CI, 0.67–0.99) in 1-to-4 propensity score matching. Subgroup analysis of LAMA users showed a significant difference in re-hospitalization or death, while subgroup analysis of LAMA non-users showed no significant difference.ConclusionOur findings indicate that Dai-kenchu-to may have improved the tolerability of LAMA in advanced-age patients with COPD and, therefore, reduced the risk of re-hospitalization or death from COPD exacerbation. Dai-kenchu-to may be recommended as a useful supportive therapy for advanced-age patients with COPD.

Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice

Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. Brain water content of 4h MCAO mice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema.

Abstract OT3-02-01: Randomized phase II study of Hangeshashinto (TJ-14) for chemotherapy induced oral mucositis in patients with breast cancer (Hangesha-B study)

Abstract Background: Oral mucositis is a common complication of systemic chemotherapy for cancer, and is associated with higher risk of infection, pain, chemotherapy dose reduction. Severe mucositis impairs oral function and seriously affects nutrition and quality of life of the patients. Hangeshashinto (TJ-14) is a traditional Japanese herbal (Kampo) medicine reduces the level of prostaglandin E2 and affects the cyclooxygenase activity, and alleviates chemotherapy induced oral mucositis. We conducted a randomized phase II trial to investigate whether Hangeshashinto (TJ-14) prevents or controls chemotherapy induced oral mucositis. Patients and Methods: Patients who develop moderate to severe chemotherapy induced oral mucositis (WHO grade&amp;gt;1) during any cycle of chemotherapy are randomly assigned to receive either Hangeshashinto (TJ-14) (n=25) or placebo (n=25). Patients receive the administration of Hangeshashinto (TJ-14) or placebo for 3 weeks at the beginning of the next course of chemotherapy. The patients are advised to dissolve 2.5g of Hangeshashinto (TJ-14) or placebo in 50ml drinking water, and divide it into twice or three times in an oral cavity. Patients rinse their oral cavity with it three times daily. The signs of oral mucositis is assessed by the investigator during the screening cycle. The CTCAE v4.0 grading is used to assess the severity of oral mucositis. The primary endpoint is duration time of oral mucositis, and secondary endpoints include incidence of oral mucositis, incidence of diarrhea, blood levels of CRP, The change of body weight, and blood levels of albumin. Accrual: This study began in June 2015. The expected end of accrual of 50 patients will be the last quarter 2017. Citation Format: Iwamoto M, Umezaki N, Matsuda J, Kawaguchi K, Terasawa R, Sato N, Fyjioka H, Kimura K, Tanaka S, Uchiyama K. Randomized phase II study of Hangeshashinto (TJ-14) for chemotherapy induced oral mucositis in patients with breast cancer (Hangesha-B study). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-01.

Effect of Japanese Herbal Kampo Medicine Goreisan on Reoperation Rates after Burr-Hole Surgery for Chronic Subdural Hematoma: Analysis of a National Inpatient Database.

Goreisan is a herbal Kampo medicine used for treating chronic subdural hematoma (CSDH) in Japan. Experimental studies have suggested that Goreisan exerts a hydrogogue effect, but clinical evidence for the effectiveness of Goreisan in CSDH is currently lacking. Using a national Japanese inpatient database, we examined the association between Goreisan use and reoperation rates after burr-hole surgery for CSDH. We identified 36,020 patients, including 3,889 Goreisan users and 32,131 nonusers. Propensity scores of receiving Goreisan were calculated based on hospital characteristics and patient backgrounds (age, sex, body mass index, activities of daily living, consciousness level, comorbidities, antithrombotic agent use, mannitol infusion, and corticosteroid infusion). One-to-one propensity-score matching created 3,879 pairs of Goreisan users and nonusers. Propensity-matched analysis revealed that Goreisan use was significantly associated with a lower reoperation rate (4.8%) compared with nonuse (6.2%) (risk difference, −1.4%; 95% confidence interval (CI), −2.4% to −0.38%). The number needed to prevent one reoperation was 72 (95% CI, 41–265). Instrumental-variable analysis showed similar results to the propensity-matched analysis. These results suggest that Goreisan use reduced the need for reoperation after burr-hole surgery for CSDH.

In VivoAnti-Influenza Virus Activity of Japanese Herbal (Kampo) Medicine, “Shahakusan,” and Its Possible Mode of Action

Background. A Kampo medicine, Shahakusan (SHS), has been prescribed in late phase of infection that causes inflammations in the lung. But effect of SHS on viral infection in respiratory tract has never been reported. Objectives. To evaluate anti-influenza virus activity of SHS and its mode of actions through immune systems. Methods. SHS (0.3 g/kg/day) was orally administered to BALB/c miceforupper (URI) or lower respiratory tract infection (LRI) of influenza virus A/PR/8/34. The virus titer of nasal lavage fluid (NLF) at 5 or 2 day postinfection (p.i.) and cytokine mRNA expressions in mandibular lymph node or lung at 5 or 4 day p.i. were evaluated for URI or LRI, respectively. The histopathological examinations of lung tissue and NK cell activity in the splenocytes were also evaluated at 4 day p.i. on LRI. Results. When SHS was administered from 7 days before to 4 days p.i. for URI, the virus titer was significantly decreased in comparison with water-treated control, and IL-4, IL-1β, and IL-10 mRNA expression was decreased, but IL-12A mRNA expression was increased. Administration of SHS from one day before to one day p.i. for LRI significantly decreased the virus titer. SHS also decreased infiltration of inflammatory cells in the bronchoalveolar spaces and damage of desquamated mucosal epithelia of bronchiole, decreased IP-10 mRNA expression, and increased NK cell activity. Conclusion. SHS has no direct effect on influenza virus infection but exerts antiviral effect in mice by its immunomodulating activity through action of NK cells and anti-inflammatory activity in the lung.