Search

The UV light densitometer was developed to measure concentration of gases having absorption in the ultraviolet region using UV absorption method. The developed densitometer was applied to monitor temporal variation of concentration of ALD precursor TEMAZ introduced into a chamber, where TEMAZ was introduced alternately with purge Ar gas to simulate ALD process. We could successfully capture temporal variation of gas concentration such as time delay in arrival of gas in the chamber due to presence of gas flow. Such phenomenon cannot be measured by the pressure gauge.

Yasushi Hibino,1 Shohei Matsumoto,2 Hisamitsu Nagase,3 Takamasa Nakamura,4,5 Yoshihito Kato,4,6 Tatsuya Isomura,4,5 Michiko Hori4,7 1Gifu Prefecture Pharmacists Association, Gifu, Japan; 2Ogaki Pharmacists Association, Gifu, Japan; 3Faculty of Pharmacy, Gifu University of Medical Science, Gifu, Japan; 4Japan Selfcare Promotion Association, Tokyo, Japan; 5Clinical Study Support, Inc, Nagoya, Japan; 6Kowa Company, Ltd, Nagoya, Japan; 7SIC Co., Ltd, Tokyo, JapanCorrespondence: Tatsuya Isomura, Japan Selfcare Promotion Association, Showayakubou Bldg. 5F, 3-4-18 Nihonbashi-honcho, Chuo-ku, Tokyo, 103-0023, Japan, Tel +81-3-6271-8941, Fax +81-3-6271-8942, Email info@jspa-nsc.comPurpose: Contributing to public health by supporting people’s health is the social mission of community pharmacists. This multicenter, prospective case series study aimed to evaluate changes in people’s behavior and health states through community pharmacists’ self-care support for healthy lifestyles.Methods: The participants were recruited from voluntary adults aged ≥ 20 years who agreed to participate in the study, at community pharmacies in Gifu, Japan, between June and September 2021. Participants self-managed their lifestyles for six months while recording their health data, including blood pressure (BP), daily using devices (home BP monitor, body composition monitor, and activity meter) and a diet-recording app. They received lifestyle modification support at pharmacies at least once per month. Participants’ subjective health status, attitudes, and behavioral changes were evaluated using self-report questionnaires. Due to the exploratory nature of this study, data were primarily analyzed descriptively.Results: Fifty-four participants aged 20 to 77 (mean age: 49.6 years; female participant proportion: 55.6%) participated in this study. Their mean weekly BP shifted almost horizontally from baseline to week 24 (systolic BP: 118.8 to 121.5 mmHg; diastolic BP: 76.1 to 77.5 mmHg). At six months, 38.9% and 35.2% of the participants reported better overall health and mental health, respectively, than at baseline. Over 85% of the participants became more proactive in improving their lifestyles regarding salt intake, diet, weight loss, and exercise, although drinking and smoking habits were more challenging to change. All the participants reported that they intended to continue to improve their lifestyle.Conclusion: The participants’ responses suggested that community pharmacists’ support helped increase participants’ health awareness and promote their health-enhancing behaviors. However, its impact on health parameters should be further examined in future studies. More vigorous, tailored self-care support may be worth considering in developing a more effective, community-fitted health/well-being support system in Japan.Keywords: community pharmacies, self-care, behavioral change, lifestyle modification, blood pressure, Japan

Background: During hormone replacement therapy (HRT) to optimize endometrial growth for thawed-frozen embryo transfer (FET), patients normally undergo estrogen administration for 14 days (day 14 group). However, if optimal endometrial thickness is not achieved in 14 days, estrogen treatment is continued for seven more days at a higher dose (day 21 group). This study aimed to determine the effects of this extended estrogen administration regimen on pregnancy outcomes. Methods: A retrospective analysis was performed using our patient database from November 2016 to March 2018. We analyzed 303 cycles of blastocyst-FET and compared patient background characteristics and pregnancy outcomes between day 14 and day 21 groups. Results: In day 21 group, the pregnancy rate tended to be lower while the miscarriage rate and ectopic pregnancy rate were higher than those in day 14 group. However, the differences between the groups were not statistically significant. Conclusions: Delayed endometrial growth resulted in poorer pregnancy outcomes in FET, but the differences were not statistically significant. Thus, it could be meaningful to add estrogen administration for 7 days to avoid the poor outcomes caused by a thin endometrium.

Introduction: Intraperitoneal retention of surgical instrument fragments may lead to severe complications. Therefore, such foreign bodies must be detected before surgery completion. We present a case with intraoperative breakage of a laparoscopic needle holder confirmed by a routine postoperative abdominal X-ray and review the literature regarding intraoperative laparoscopic instrument breakage. Case Report: A 58-year-old woman with stage IB1 cervical adenocarcinoma underwent a laparoscopic radical hysterectomy. Surgery was completed without major complications; however, an abdominal X-ray as a routine postoperative examination revealed a radiopaque shadow of approximately 3 mm corresponding to a broken part of the tissue-pad of the laparoscopic needle holder tip. It was successfully removed using laparoscopy with fluoroscopic guidance without further complications. According to the literature review, most of the instrument breakage were noticed during surgery as they were either obvious or impaired function. In our case, since the detached foreign body was extremely small and did not significantly affect needle holder function, it remained unnoticed until the postoperative X-ray was taken. Conclusion: Postoperative abdominal X-rays identify instrumental fragments infrequently; however, they may help detect intraperitoneal retention of foreign bodies and avoid serious complications following laparoscopic surgery.

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature37 °C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

Obesity leads to an increase in the incidence and severity of asthma. Adipokines, such as leptin, secreted by adipocytes induce systemic inflammation, causing airway inflammation. We previously reported that leptin activates both inflammatory and structural cells, including lung fibroblasts. However, little is known about the differential leptin expression and responsiveness to leptin in asthmatic individuals and healthy controls (HC). In this study, we investigated the expression and origin of leptin in asthmatic airways. We also compared the effect of leptin on asthmatic and HC fibroblasts.Lung specimens from asthmatic and non-asthmatic patients were analyzed by immunohistochemical staining using anti-leptin and anti-CD163 antibodies. Leptin mRNA and protein levels in human monocytes were detected by real-time PCR and western blotting and ELISA, respectively. We used flow cytometry to analyze asthmatic and HC lung fibroblasts for leptin receptor (Ob-R) expression. Further, we determined cytokine levels using cytometric bead array and ELISA and intracellular phosphorylation of specific signaling molecules using western blotting.Asthma specimens displayed accumulation of leptin-positive inflammatory cells, which were also positive for CD163, a high-affinity scavenger receptor expressed by monocytes and macrophages. Leptin expression was observed at both transcript and protein levels in human blood-derived monocytes. No significant differences were observed between asthmatic and HC lung fibroblasts in Ob-R expression, cytokine production, and intracellular phosphorylation of p38 mitogen-activated protein kinase.Our findings reveal similar responsiveness of control and asthmatic fibroblasts to leptin. However, the accumulation of inflammatory leptin-producing monocytes in the airway may contribute to the pathogenesis of asthma.

Palatine tonsillectomy is a surgical procedure that novice otolaryngologists should master early and is taught at many medical institutions. Unfortunately, however, the transoral procedure cannot provide a large enough field of view to doctors other than the one performing the operation. Therefore, it is difficult to share the surgical field and provide real-time teaching. Dissection of the wrong layer can cause postoperative bleeding and pain. Our department uses a 70-degree, 4-mm rigid endoscope for palatine tonsillectomy, which makes it possible for preceptors to teach tonsillectomy in real time and to evaluate the condition of the postoperative wound in detail. We classified the postoperative state after tonsillectomy into three stages, based on the degree of residual subcapsular connective tissue. We assessed the association between the amount of residual subcapsular connective tissue and the underlying disease that required indication for tonsillectomy, the postoperative course, and the operation time in 33 patients who had undergone palatine tonsillectomy at our institution between May 2017 and November 2020. We found that the more the subcapsular connective tissue that remained, the less the postoperative pain and bleeding. This association suggests that conserving the subcapsular connective tissue is important. Bringing the endoscope closer to the surgical field to observe the field without blind areas enables adequate hemostasis and easy sharing of the surgical field; therefore, this method is also effective for teaching tonsillectomy to surgical trainees.

Background The phase 3 VELIA trial evaluated veliparib with carboplatin/paclitaxel and as maintenance in patients with high-grade serous ovarian carcinoma. Methods Patients with previously untreated stage III–IV high-grade serous ovarian carcinoma were randomized 1:1:1 to control (placebo with carboplatin/paclitaxel and placebo maintenance), veliparib-combination-only (veliparib with carboplatin/paclitaxel and placebo maintenance), or veliparib-throughout (veliparib with carboplatin/paclitaxel and veliparib maintenance). Randomization stratification factors included geographic region (Japan versus North America or rest of the world). Primary end point was investigator-assessed median progression-free survival. Efficacy, safety, and pharmacokinetics were evaluated in a subgroup of Japanese patients. Results Seventy-eight Japanese patients were randomized to control (n = 23), veliparib-combination-only (n = 30), and veliparib-throughout (n = 25) arms. In the Japanese subgroup, median progression-free survival for veliparib-throughout versus control was 27.4 and 19.1 months (hazard ratio, 0.46; 95% confidence interval, 0.18–1.16; p = 0.1 [not significant]). In the veliparib-throughout arm, grade 3/4 leukopenia, neutropenia, and thrombocytopenia rates were higher for Japanese (32%/88%/32%) versus non-Japanese (17%/56%/28%) patients. Grade 3/4 anemia rates were higher in non-Japanese (65%) versus Japanese (48%) patients. Early introduction of olanzapine during veliparib monotherapy maintenance phase may help prevent premature discontinuation of veliparib, via its potent antiemetic efficacy. Conclusions Median progression-free survival was numerically longer in Japanese patients in the veliparib-throughout versus control arm, consistent with results in the overall study population. Pharmacokinetics were comparable between Japanese and non-Japanese patients. Data for the subgroup of Japanese patients were not powered to show statistical significance but to guide further investigation.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Background Accelerated tumor growth during immunotherapy in pre-existing measurable lesions, hyperprogressive disease (HPD), has been reported. However, progression of non-measurable lesions and new lesions are frequently observed in patients with advanced gastric cancer (AGC). Methods This retrospective study involved AGC patients at 24 Japanese institutions who had measurable lesions and received nivolumab after ≥ 2 lines of chemotherapy. HPD was defined as a ≥ two-fold increase in the tumor growth rate of measurable lesions. The pattern of disease progression was classified according to new lesions in different organs and ascites appeared/increase of ascites. Results Of 245 patients, 147 (60.0%) showed progressive disease (PD) as the best response and 41 (16.7%) showed HPD during nivolumab monotherapy. There was no significant difference in overall survival (OS) between patients with HPD and those with PD other than HPD (median OS 5.0 vs 4.8 months; hazard ratio [HR] 1.0, 95% confidence interval [CI] 0.6–1.5; p = 1.0). Fifty-three patients developed new lesions in different organs and 58 had appearance/increase of ascites; these patients showed shorter OS than those without each of these features (median OS 3.3 vs 7.1 months, HR 1.8, 95% CI 1.2–2.7, p = 0.0031 for new lesions, and 3.0 vs 7.8 months, HR 2.6, 95% CI 1.8–3.8, p Conclusions New lesions in different organs and appearance/increase of ascites, rather than the original definition of HPD, are the patterns of disease progression associated with poor prognosis in AGC patients receiving nivolumab whose best response was PD.

Although anti-PD-1 antibody monotherapy (PD-1) is commonly used to treat advanced acral melanoma (AM), its efficacy is limited. Further, data on the efficacy of PD-1 plus anti-CTLA-4 antibody (PD-1+CTLA-4) for the treatment of AM are limited. Therefore, we compared the efficacy of PD-1+CTLA-4 and PD-1 in the treatment of Japanese patients with advanced AM.This retrospective study evaluated patients with advanced AM who were treated with PD-1 or PD-1+CTLA-4 as first-line immunotherapy in 24 Japanese institutions between 2014 and 2020. Treatment efficacy focussing on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) was compared between the two groups.In total, 254 patients (palm and sole melanoma [PSM], n = 180; nail apparatus melanoma [NAM], n = 74) were included. Among the patients with PSM, the ORR (19% vs. 31%; P = 0.44), PFS (5.9 vs. 3.2 months; P = 0.74), and OS (23.1 vs. not reached; P = 0.55) did not differ significantly between the PD-1 and PD-1+CTLA-4 groups. Among the patients with NAM, the ORR (61% vs. 10%; P 0.001) was significantly higher and PFS was longer (6.4 vs. 3.8 months; P = 0.10) in the PD-1+CTLA-4 group than in the PD-1 group. Cox multivariate analysis demonstrated that PD-1+CTLA-4 is an independent predictor of a favourable PFS in patients with NAM (P = 0.002).The efficacy of PD-1+CTLA-4 is not superior to that of PD-1 for the treatment of advanced PSM. However, PD-1+CTLA-4 may be more efficacious than PD-1 for the treatment of advanced NAM.

Objective: Robot-assisted surgery is a minimally invasive approach for repairing the mitral valve. This study aimed to assess its safety and clinical efficacy when compared with conventional sternotomy, partial sternotomy, and right minithoracotomy. Methods: A systematic review of peer-reviewed studies comparing robot-assisted mitral valve repair with conventional sternotomy, partial sternotomy, and right minithoracotomy was conducted following Cochrane Collaboration guidelines. Meta-analyses were performed where possible. Results: The search strategy yielded 15 primary studies, of which 12 compared robot-assisted with conventional sternotomy, 2 compared robot-assisted with partial sternotomy, and 6 compared robot-assisted with right minithoracotomy. The overall quality of evidence was low, and there was a lack of data on long-term outcomes. Individual studies and pooled data demonstrated that robotic procedures were comparable to conventional sternotomy and other minimally invasive approaches with respect to the rates of stroke, renal failure, reoperation for bleeding, and mortality. Robot-assisted mitral valve repair was superior to conventional sternotomy with reduced atrial fibrillation, intensive care unit and hospital stay, pain, time to return to normal activities, and physical functioning at 1 year. However, robot-assisted mitral valve repair had longer cardiopulmonary, aortic cross-clamp, and procedure times compared with all other surgical approaches. Conclusions: Based on current evidence, robot-assisted mitral valve repair is comparable to other approaches for safety and early postoperative outcomes, despite being associated with longer operative times. Ideally, future studies will be randomized controlled trials that compare between robot-assisted surgery, conventional surgery, and other minimally surgery approaches focusing on hard clinical outcomes and patient-reported outcomes.

Cervical cancer remains a major threat to women's health, especially in countries with limited medical resources, and new drugs are needed to improve patient survival and minimize adverse effects. Here, we examine the effects of a triphenylphosphonium (TPP)-conjugated pyrrole-imidazole polyamide (CCC-h1005) targeting the common homoplasmic mitochondrial DNA (mtDNA) cancer risk variant (ATP6 8860AG) on the survival of cervical cancer cell lines, cisplatin-resistant HeLa cells and patient-derived cervical clear cell carcinoma cells as models of cervical cancer treatment. We found that CCC-h1005 induced death in these cells and suppressed the growth of xenografted HeLa tumors with no severe adverse effects. These results suggest that PIP-TPP designed to target mtDNA cancer risk variants can be used to treat many cervical cancers harboring high copies of the target variant, providing a foundation for clinical trials of this class of molecules for treating cervical cancer and other types of cancers.

Activating mutations of the KRAS occurs in90% of pancreatic ductal adenocarcinoma (PDAC) cases. However, direct pharmacological targeting of the activated KRAS protein has been challenging. We previously reported that KR12, a DNA-alkylating pyrrole-imidazole polyamide designed to recognize the KRAS G12D/V mutation, showed an anti-tumor effect in colorectal cancer. In this study, we evaluated the anti-tumor effect of KR12 in PDAC.KR12 was synthesized by an automated peptide synthesizer PSSM-8 and tested for anti-tumor effect in PDAC mouse models.KR12 inhibited tumor growth in a spontaneous PDAC mouse model, although the anti-tumor activity appeared to be limited in a human PDAC xenograft model. We developed a pyrrole-imidazole polyamide screening process based on the hypothesis that genetic elements otherwise unaffected by KR12 could exert attenuating effects on KRAS-suppression-resistant PDAC. We identified RAD51 as a potential therapeutic target in human PDAC cells. A RAD51 inhibitor showed an inhibitory effect on cell growth and affected the cytotoxic activity of KR12 in PDAC cells.These data suggested that the simultaneous inhibition of RAD51 and mutant KRAS blockage would be an important therapeutic strategy for PDAC.

Outcomes with and without bevacizumab as first-line chemotherapy in Japanese-only ovarian cancer patients have not been reported. In this study, we report a retrospective study conducted at the Tohoku Gynecologic Cancer Unit.The study included 453 patients with stage III/IV ovarian, fallopian tube, and primary peritoneal cancer who received first-line platinum-based chemotherapy. The patients were divided into two groups: bevacizumab (168 patients) and without bevacizumab (285 patients). The primary endpoint was the rate of platinum-resistant recurrence and the secondary endpoints were the antitumor response, progression-free survival, overall survival, and adverse events.The objective response rates for patients with measurable diseases treated with and without bevacizumab were 84.5% and 73.0%, respectively (P = 0.0066). Platinum-resistant recurrence in the groups treated with and without bevacizumab was noted in 31 (18.4%) and 111 (38.6%) patients, respectively (P 0.0001). The median progression-free survival for the bevacizumab and without bevacizumab groups was 23 and 15 months, respectively (P = 0.0002), and the median overall survival was not reached and 49 months, respectively (P = 0.0005). Hypertension of grade 3 or higher was observed in 21 patients (12.5%) in the bevacizumab group (P 0.001), and proteinuria was observed in 18 patients (10.7%) and 1 patient (0.3%) in the bevacizumab and without bevacizumab groups, respectively (P 0.001). Intestinal perforation was observed in only one patient (0.6%) in the bevacizumab group.Combination and maintenance with bevacizumab in primary chemotherapy for advanced ovarian, fallopian tube, and primary peritoneal cancer was effective in reducing platinum-resistant recurrence rates and prolonging progression-free and overall survival.

BackgroundAcute exacerbation is a life-threatening event in patients with fibrosing interstitial lung diseases (ILDs). Although nintedanib reduces acute exacerbation incidence, its effectiveness during acute exacerbation is unclear.MethodsUsing data from the Diagnosis Procedure Combination database (September 2015–March 2020) in Japan, we identified patients with fibrosing ILDs who received intravenous injection of high-dose corticosteroid within 3 days post-admission and analysed their first hospitalisation. We performed overlap propensity score weighting to compare in-hospital outcomes between patients who received nintedanib within 14 days post-admission and those who did not. The primary and secondary outcomes were in-hospital mortality and length of hospitalisation in the patients discharged alive, respectively.ResultsAmong the 6235 identified patients, 353 patients received nintedanib within 14 days post-admission. In-hospital mortality occurred in 13.7% and 6.0% patients in the control (n=5882) and nintedanib-treated (n=353) patients, respectively. The mean length of hospitalisation was 39.9 and 30.4 days in the control and nintedanib-treated patients, respectively. After overlap propensity score weighting, nintedanib treatment was significantly associated with lower in-hospital mortality in the adjusted cohort (OR 0.43, 95% CI 0.27–0.70; p=0.001). The mean length of hospitalisation in nintedanib-treated patients (30.7 days) was significantly shorter than that in the control group (37.5 days; pConclusionsNintedanib initiation during acute exacerbation was significantly associated with a lower risk of in-hospital death and shorter length of hospitalisation in patients with fibrosing ILDs. Our results elucidate the potential role of nintedanib in the treatment of acute exacerbation in patients with fibrosing ILDs. Further prospective studies are warranted.

Fragment-based ligand discovery was successfully applied to histone deacetylase HDAC2. In addition to the anticipated hydroxamic acid- and benzamide-based fragment screening hits, a low affinity (∼1 mM) α-amino-amide zinc binding fragment was identified, as well as fragments binding to other regions of the catalytic site. This alternative zinc-binding fragment was further optimized, guided by the structural information from protein-ligand complex X-ray structures, into a sub-μM, brain penetrant, HDAC2 inhibitor (