Nihon University Itabashi Hospital Research Articles

The Time Course of Catecholamine Dose Reduction in Septic Shock as a Predictor of Bacterial Susceptibility to Empiric Antimicrobial Therapy: A Retrospective Observational Study.

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. In this study, we investigate whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy or not. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted to the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant groups based on the bacteria's susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from the peak to the end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: the time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 h (p = 0.0057), and to 0%, it was 29 vs. 54 h (p = 0.0475). The time to reduce the dose from the maximum NEE to 75% was 8 vs. 12.5 h (p = 0.0733), and to 50% it was 13 vs. 21.5 h (p = 0.1081). Conclusions: In septic shock with bacteraemia, a faster catecholamine dose reduction indicates bacterial susceptibility to the initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of the appropriate initial empiric therapy.

Validity study of the Japanese version of the Nijmegen Questionnaire for verifying dysfunctional breathing in Japanese asthma patients

Dysfunctional breathing (DB) is a clinical condition characterized by irregular breathing patterns presenting a sensation of dyspnea and a feeling of chest tightness. DB is a known comorbidity of asthma that is difficult to control, leading to poor quality of life, so early diagnosis and therapeutic intervention are essential to improve the clinical condition of asthma. The Nijmegen Questionnaire (NQ), developed to screen for DB and translated into various languages, is used worldwide. However, a Japanese NQ (JNQ) is unavailable, so DB has not been clinically verified in people with asthma in Japan. This study aimed to prepare a JNQ, verify its reliability and validity, and demonstrate its clinical benefits in asthma treatment. The JNQ was prepared by back-translating the NQ with the author's consent. The answers to self-administered questionnaires, including the JNQ, Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), and Patient Health Questionnaire 9 (PHQ-9), were obtained with the consent of 68 people with asthma (average age ± SD, 52.04± 12.43 years) who visited Nihon University Itabashi Hospital. The reliability of the JNQ was analyzed by the Cronbach alpha coefficient. Acomparative test was conducted for each questionnaire (ACT, ACQ, Mini-AQLQ, PHQ-9), considering a JNQ score of 23 as the cutoff value. Patients with a score of 23 or more were assigned to the DB group, whereas patients with a score of less than 23 were assigned to the non-DB group. We analyzed the correlation between the JNQ and each questionnaire. The JNQ showed sufficient reliability (Cronbach alpha= 0.875). Correlation analysis between the JNQ score and each questionnaire revealed negative correlations with the ACT score (r= 0.262) and Mini-AQLQ score (r= -0.453) and positive correlations with the ACQ score (r= 0.337) and PHQ-9 score (r= 0.539). All of these correlations were statistically significant. As a result of the comparative test, the DB and non-DB groups showed a significant difference in Mini-AQLQ (P= .023) and PHQ-9 (P= .003) scores. No significant difference was observed between ACT (P= .294) and ACQ (P= .177) scores. The JNQ validates DB in Japanese people with asthma and reflects the deterioration of asthma control, decreased quality of life, and depression. Using the JNQ, early diagnosis and therapeutic intervention (eg, breathing exercises and a psychosomatic approach) for DB in people with asthma may help suppress the severity of asthma in Japan.

Augmenting Blood Test and Periodontal Examination Data with Generative Adversarial Networks for Enhanced Dementia Risk Prediction.

This study investigates the effectiveness of data augmentation to improve dementia risk prediction using deep neural networks (DNNs). Previous research has shown that basic blood test data were cost-effective and crucial in predicting cognitive function, as indicated by mini-mental state examination (MMSE) scores. However, creating models that can accommodate various conditions is a significant challenge due to constraints related to blood test and MMSE results, such as high costs, limited sample size, and missing data from specific tests not conducted in certain facilities. Periodontal examinations have also emerged as a cost-effective tool for mass screening. To address these issues, this study explores the use of generative adversarial networks (GANs) for generating synthesised data from blood test and periodontal examination results. We used DNNs with four hidden layers to compare prediction accuracy between real and GAN-synthesised data from 108 participants at Nihon University Itabashi Hospital. The GAN-synthesised DNNs achieved a mean absolute error (MAE) of 1.91±0.30 compared to 2.04±0.37 for real data, indicating improved accuracy with synthesised data. Importantly, synthesised data showcased enhanced robustness against missing important variables including age information, and better managed data imbalances. Considering the difficulties in amassing extensive medical data, the augmentation approach is promising in refining dementia risk prediction.

Different effects of crizotinib treatment in two non-small cell lung cancer patients with SDC4::ROS1 fusion variants.

The possibility of stratifying patients according to differences in ROS proto-oncogene 1 (ROS1) fusion partners has been discussed. This study aimed to clarify the clinicopathological differences between two SDC4::ROS1 positive NSCLC cases who had different responses to crizotinib. Cytology and pathology samples from two NSCLC cases with SDC4::ROS1 who were diagnosed and treated with crizotinib at Nihon University Itabashi Hospital were obtained. Case 1 has been well-controlled with crizotinib for over 5 years, but case 2 was worse and overall survival was 19 months. Sequencing analysis of ROS1 fusion genes was performed by reverse-transcription-PCR and Sanger's sequencing methods. In addition, thyroid transcription factor (TTF)-1, ROS-1, Ki67, and phosphorylated extracellular signal-regulated kinase (pERK)1/2 expression were investigated using immunohistochemistry. Sequencing analysis showed SDC4 exon2::ROS1 exon 32 (exon33 deleted) in case 1, and coexistence of SDC4 exon2::ROS1 exon 34 and SDC4 exon2::ROS1 exon35 in case 2. The Ki67 index was not different, but ROS1 and pERK1/2 expression levels tended to be higher in the tumor cells of case 2 than in case 1. Therapeutic response to crizotinib and patients' prognosis in ROS1 rearranged NSCLC may be related to the activation of ROS1 signaling, depending on ROS1 and pERK1/2 overexpression status, even if the ROS1 fusion partner is the same.

Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries.

Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179). The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p＜0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p＜0.0001, macrophage: ATAs, 0.29% [0.095 - 1.1%] versus PTAs, 0.12% [0.029 - 0.36%]; p＜0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p＜0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs. Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.

Sodium-glucose co-transporter 2 inhibitors in acute heart failure: real-world prescription trends and outcomes analysis.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown potential therapeutic benefits in heart failure (HF). However, data on their real-world usage and benefits in acute decompensated heart failure (ADHF) are limited. We conducted a post hoc analysis of real-world data from 1108 patients with ADHF admitted to Nihon University Itabashi Hospital (Tokyo, Japan) between 2018 and 2022. Patients were divided into two groups based on the prescription of SGLT2 inhibitors during hospitalization: an SGLT2 inhibitor group (SGLT2i group) (n=289) and a non-SGLT2i group (n=819). The primary endpoints were death and rehospitalization for HF after discharge. The median age was 76 [interquartile range (IQR): 66, 83] years, and 732 patients (66%) were male. Data showed an increasing trend in the prescription of SGLT2 inhibitors since 2021. During a median follow-up period of 366days (IQR: 116, 614), 458 (41.3%) patients reached the primary endpoint. The Kaplan-Meier analysis showed that the SGLT2i group had a significantly lower rate of composite events than the non-SGLT2i group, both overall (log-rank test, P<0.001) and in the following left ventricular ejection fraction (LVEF) subgroups: HF with reduced ejection fraction (EF) (n=413), HF with mildly reduced EF (n=226), and HF with preserved EF (n=466) (log-rank test; P=0.044, P=0.013, and P=0.001, respectively). Furthermore, patients starting SGLT2 inhibitors during hospitalization had a significantly lower rate of composite events than those not using SGLT2 inhibitors (log-rank test, P<0.001). This association was also significant in the LVEF subgroups (P=0.005, P=0.032, and P=0.004, respectively). The prescription and initiation of SGLT2 inhibitors during hospitalization are associated with improved post-discharge outcomes in patients with ADHF, irrespective of LVEF.

COVID-19 Pandemic and Medical Contribution at Nihon University Itabashi Hospital

COVID-19 Pandemic and Medical Contribution at Nihon University Itabashi Hospital

Saline suppression to distinguish the primary aldosteronism subtype: a diagnostic study.

The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA), while adrenal vein sampling (AVS) is used to subtype PA as unilateral or bilateral. Criteria that can accurately identify those with bilateral PA based on SST results could reduce the need for AVS. We previously demonstrated that a combination of plasma aldosterone concentration (PAC) < 300 pmol L-1 and a reduction in aldosterone-to-renin ratio (ARR) following recumbent SST had high specificity for predicting bilateral PA in an Australian cohort of 92 patients with PA who have undergone AVS. We sought to validate our predictive criteria in larger, independent cohorts of patients with PA. An international, multi-centre cohort study. Data from 55 patients at Monash Health, Victoria, Australia, 106 patients from the First Affiliated Hospital of Chongqing Medical University, China, and 105 patients from Nihon University Itabashi Hospital, Japan were analysed. A combination of PAC <300 pmol L-1 and a reduction in ARR following recumbent SST predicted bilateral PA with specificities of 88.2%, 97.0%, and 100.0% in Australian, Chinese, and Japanese cohorts, respectively. This criterion could allow 22%-38% of patients with PA to bypass AVS and proceed directly to medical treatment. In patients undergoing the recumbent SST, a post-saline PAC <300 pmol L-1 together with a reduction in ARR can predict bilateral PA with high specificity and may allow targeted treatment to be commenced without AVS in up to a third of patients.

Differences in psychosocial factors and sleep study findings between delayed sleep-wake phase disorder and hypersomnia in teenagers.

Central hypersomnia (HS) and delayed sleep-wake phase disorder (DSWPD) appear commonly in adolescents, and they severely reduce quality of life and have an enormous impact on academic performance and other aspects of development. Although these disorders are thought to be considerably different in etiology, it is sometimes difficult to distinguish them because of their similar clinical features. This study aimed to compare psychosocial factors and sleep study findings between HS and DSWPD in teenagers. The clinical data of 89 teenagers who visited the psychiatric section of the Sleep Medicine Center of Nihon University Itabashi Hospital from January 2013 to December 2019 were analyzed. Psychosocial factors were evaluated at the first visit, and polysomnography (PSG) and the multiple sleep latency test (MSLT) were performed for patients deemed to require definitive diagnosis. Compared with patients with HS, those with DSWPD had a higher rate of mother's employment, introversion, adjustment problems, events that triggered the disorder, concurrent mental disorders, habitual lateness, and difficulty attending school or work. PSG did not show any differences in sleep parameters between the two disorders, except for sleep latency. On the MSLT, sleep latency was shorter in those with HS on the second, third, and fourth tests. The present results suggest that focusing on psychosocial factors could be useful for differential diagnosis of the two disorders that appear commonly in adolescents.

Retrospective Analysis of the Incidence of Drug-Induced Interstitial Lung Disease by Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Survival in Patients Aged 75 Years or Older with Lung Cancer.

To date, the appropriate epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients aged ≥75 years with advanced EGFR mutation-positive, nonsmall cell lung cancer remain unknown. This study included a total of 89 patients aged ≥75 years who were diagnosed with EGFR mutation-positive, nonsmall cell lung cancer and treated with EGFR-TKIs at the Tokyo Metropolitan Geriatric Hospital and Nihon University ITABASHI Hospital from 2009 to 2020. The patients were classified into five groups based on their treatment: gefitinib (n = 23), erlotinib (n = 4), afatinib (n = 3), first-line osimertinib (n = 23), and TKI to TKI (n = 36). The efficacy and safety of each EGFR-TKI were analyzed. No significant differences in the overall survival and progression-free survival were observed among the groups. However, a significantly higher incidence of drug-induced interstitial lung disease (ILD) was detected with osimertinib than with the first-generation EGFR-TKIs (p = 0.008). In older patients with EGFR mutation-positive lung cancer, the incidence of drug-induced ILD was significantly increased during osimertinib treatment. This outcome should be noted when treating older patients with osimertinib who may not always want to live longer but want to live better.

Association between unintentional splenic radiation and lymphopenia and high neutrophil/lymphocyte ratio after radiotherapy in patients with esophageal cancer.

BackgroundUnintentional irradiation of the spleen may reduce absolute lymphocyte count (ALC), which can affect tumor immunity. Therefore, in the present study, we evaluated spleen dose-volume parameters associated with ALC and neutrophil/lymphocyte ratio (NLR) in patients with esophageal cancer.MethodsThis retrospective study evaluated patients who were diagnosed with stage I–IV esophageal cancer and who received radiotherapy at Nihon University Itabashi Hospital between January 2015 and March 2020. Spleen V5, V10, V20, and V30 and mean spleen dose, which are dose-volume histogram parameters correlated with ALC and NLR, were analyzed.ResultsIn total, 89 esophageal cancer patients with a median age of 72 years (range, 51–92 years) were included in this research. Results showed that spleen V5, V10, and V20 and mean splenic dose were significantly correlated with a low ALC. Meanwhile, a significant association was observed between spleen V5 and V10 and a high NLR (P<0.05). In the linear regression analysis, spleen V5 and V10 were remarkably associated with a low ALC (P=0.006 and 0.008). Further, a correlation was noted between spleen V5 and a high NLR (P=0.019). Spleen V5 and V10 were remarkably associated with greater than grade 3 lymphopenia (P=0.024 and P=0.031).ConclusionsA correlation was observed between the irradiated volume of the spleen and ALC and NLR in patients with esophageal cancer. Furthermore, the spleen should be regarded as a high-risk organ, and the use of techniques in reducing spleen V5, V10 for the preservation of tumor immunity may be beneficial.

A Novel Protocol for Rituximab Administration with Reduced Incidence of Severe Infusion-Related Adverse Reactions in Patients with B-Cell Non-Hodgkin Lymphoma

Introduction: Rituximab is widely used as the standard treatment for most types of B-cell non-Hodgkin lymphomas (B-NHL). However, infusion-related reactions (IRRs), such as fever, chills, nausea, rashes, rigors, or hypotension, are a significant burden to patients and oncology practitioners. Thus, we developed a novel protocol on the rituximab administration to avoid severe IRRs during a short-time infusion in the outpatient chemotherapy center of Nihon University Itabashi Hospital.Methods: This observational study aimed to establish an effective dosing schedule for safely administering rituximab within a short time for patients with various B-NHL types. Rituximab was diluted to a concentration of 1 mg/mL and intravenously administered to patients at a dose of 375 mg/m 2. Before the rituximab administration, prophylactic premedications were given per guidelines. We stratified patients into low (n = 0), moderate (n = 1), or high risk (n = 2) groups according to the observed number of risk factors for IRRs identified in our previous study, i.e., indolent histology and presence of bulky disease (>10cm) (Hayama et al. 2017, PMID: 28144804). In the low- and moderate-risk groups, the infusion rate of rituximab was set at 25 mg/h (first 1h), 100 mg/h (next 1h), and a maximum of 200 mg/h thereafter (conventional infusion #1, approx. 4.3h). In the high-risk group, the infusion rate of rituximab was set at 25 mg/h (first 1h) and a maximum of 100 mg/h thereafter (long infusion, approx. 6.8h). The second infusion of rituximab was dependent on the occurrence of IRRs in the first cycle. If a patient in the low-risk group did not have IRRs in the first cycle, the infusion rate of rituximab in the second cycle was then started at 100 mg/h for the first 30min and increased by 100 mg/h every 30min to a maximum of 400 mg/h thereafter (short infusion, approx. 2.3h). Also, for a patient in the moderate-risk group without any grade of IRRs in the first cycle, the infusion rates of second rituximab was set at 100 mg/h (first 1h) and a maximum of 200 mg/h thereafter (conventional infusion #2, approx. 3.5h). Finally, a patient in the high-risk group without IRRs in the first cycle received the second rituximab as per the conventional infusion #1. If patients experienced any grades of IRR in the first cycle, the next rituximab was administered on the same schedule as the first cycle. The infusion procedure for the third cycle was at the discretion of attending physicians (Figure). The primary endpoint was the incidence of IRRs during the first and second doses of rituximab in each risk group. The secondary endpoints were; overall incidence of IRRs in the first and second doses of rituximab; infusion rates of rituximab at the IRRs; conversion rate of the short infusion at the third cycle in each group; overall conversion rate of the short infusion at the third cycle.Results: A total of 81 B-NHL patients treated with rituximab in 2018 and 2019 at Nihon University Itabashi Hospital was evaluated. The incidence of IRRs during the first and second cycles in each risk group was 31%, 20%, and 57% in the low- (n = 39), moderate- (n = 35), and high-risk (n = 7) groups, respectively, with no significant difference among the three risk groups (p = 0.1407). The overall incidence of IRRs was 28% without grade 3 or higher severity. The IRRs occurred most frequently at the infusion rate of 100 mg/h (n = 16). Conversion rates to the short infusion at the third cycle of rituximab were 82%, 29%, and 29%, in the low-, moderate-, and high-risk groups, respectively, with a significant imbalance between the groups (p <0.0001). The overall conversion rate of the short infusion in the third cycle was 54%, without any grades of IRRs (Table).Conclusions: Our step-by-step infusion protocol of rituximab provided a safe and comfortable drug administration for both patients and oncology practitioners. In addition, the protocol can reduce unexpected, severe adverse reactions to rituximab that typically require hospital admission and medical expenses (UMIN-CTR, UMIN000032309). [Display omitted] DisclosuresMiura: Chugai: Honoraria; Kyowa Kirin: Honoraria. Hatta: Pfizer Japan Inc.: Honoraria; Novartis KK: Honoraria; Bristol-Myers Squibb: Honoraria; Otsuka Pharmaceutical.: Honoraria.

Absence of coronary angioscopy-derived in-stent thrombi is associated with major bleeding events in acute myocardial infarction

Background and aimsThe optimal duration of dual antiplatelet therapy for acute myocardial infarction is controversial because the bleeding risk outweighs the thromboembolic risk. We hypothesized that an in-stent thrombus (IS-thrombus) detected by coronary angioscopy (CAS) after stent implantation would be associated with high bleeding risk. MethodsThis study included 208 patients who underwent CAS at 2 weeks after stent implantation for an acute myocardial infarction. The study was approved by the ethics committee at the Nihon University Itabashi Hospital (reference number RK-200714-10). ResultsIn 84 patients, in whom no IS-thrombus was identified in the culprit vessel using CAS, the major bleeding event rate was significantly higher than that in patients with IS-thrombi (n = 124). However, no difference was detected in major adverse cardiovascular events (MACE; stroke, hospitalization for a non-fatal myocardial infarction/unstable angina, target lesion revascularization, and cardiovascular death). After adjustments by the propensity score based on patient characteristics, the absence of IS-thrombi remained an independent predictor of major bleeding events (hazard ratio 4.73, 95% confidence interval 2.04–11.00, p < 0.001). ConclusionsThe absence of CAS-detected IS-thrombi in the subacute phase was independently associated with future major bleeding events, but not with MACE. These findings may help optimize the duration of dual antiplatelet therapy.

Clinical Significance of the Controlling Nutritional Status (CONUT) Score in Patients with Infective Endocarditis.

Risk stratification of patients with infective endocarditis (IE) is difficult. The Controlling Nutritional Status (CONUT) score is an index of immune function and nutritional status. We investigated the prognostic value of the CONUT score in IE and whether its prognostic value differed between IE patients with and without indications for surgery.Clinical records were retrospectively evaluated for 92 patients with IE treated at Nihon University Itabashi Hospital and Nihon University Hospital between January 2014 and May 2019. The CONUT score was determined upon admission, and patients were divided into two groups at the median score (≤ 7 [n = 50] and ≥ 8 [n = 42]). The primary outcome was all-cause mortality at 90 days after admission.The high CONUT group had significantly higher C-reactive protein and N-terminal pro-brain natriuretic peptide levels, as well as a significantly lower hemoglobin and estimated glomerular filtration rate (all P < 0.05), and considerably more valve perforation (26% versus 8%, P < 0.05). Kaplan-Meier analysis revealed that mortality was significantly higher in the high CONUT group (P < 0.001). Even after adjusting for the propensity score based on IE risk factors, a higher CONUT score was still associated with mortality. A receiver-operating characteristic analysis revealed that a CONUT score ≥ 8 had a sensitivity of 86% and specificity of 76% for predicting all-cause mortality. A CONUT score ≥ 8 was most strongly associated with mortality in patients with surgical indications (P < 0.001).In patients with IE, a higher CONUT score was significantly associated with inflammation, heart failure, renal dysfunction, anemia, valve dysfunction, and short-term mortality, especially in patients with surgical indications.

Investigator Initiated Clinical Trial of Valganciclovir, An Antiviral Drug for Symptomatic Congenital Cytomegalovirus Disease, Started at Nihon University Itabashi Hospital

Investigator Initiated Clinical Trial of Valganciclovir, An Antiviral Drug for Symptomatic Congenital Cytomegalovirus Disease, Started at Nihon University Itabashi Hospital

Cerebral Autoregulation During Active Standing Test in Juvenile Patients with Instantaneous Orthostatic Hypotension.

Instantaneous orthostatic hypotension (INOH) is one of the main types of orthostatic dysregulation in children and adolescents. In patients with INOH arterial pressure drops considerably after active standing and is slow to recover. We investigated changes in cerebral oxygenation in the bilateral prefrontal cortex during an active standing test in juvenile INOH patients to evaluate changes in cerebral oxygen metabolism. We enrolled 82 INOH patients (mean age 13.8±2.2years, 52 mild and 30 severe patients) at Nihon University Itabashi Hospital from October 2013 to April 2018. We measured cerebral oxygenated hemoglobin, deoxygenated hemoglobin, and total hemoglobin levels in the bilateral prefrontal cortex using near-infrared spectroscopy during an active standing test. In severe INOH patients, cerebral oxygenation of the right prefrontal cortex remained constant when blood pressure dropped; however, de-oxy-Hb significantly increased. These findings confirm that there is asymmetrical autoregulation between the right and left prefrontal cortex.

&lt;p&gt;Hospital–pharmacy cooperative training and drug-taking compliance in outpatients with chronic pain: a case–control study&lt;/p&gt;

Purpose: Chronic pain is a common symptom that is suffered by 20% of the overall population in Japan. Although pharmacotherapy is critical for the treatment of chronic pain, there are no reports on the pharmacies. In the present study, we examined the effect of hospital–community pharmacy cooperative training on improving drug-taking compliance, pain relief, anxiety, insomnia, and motor function in patients with chronic pain.Patients and methods: The subject sample included 87 patients with chronic pain who were examined for the first time at the outpatient services department of Nihon University Itabashi Hospital. Patients were interviewed to obtain information regarding drugs used before and after the treatment, habitually used community pharmacies, presence of cooperative training with Itabashi Hospital, drug-taking compliance, and side effects. We compared treatment outcomes before and after consultation using the Brief Pain Inventory (BPI), Hospital Anxiety and Depression Scale (HADS), EuroQol Group measure (EQ-5D) for quality of life, Athens Insomnia Scale, and Locomo 25 scale for motor function.Results: In patients who used community pharmacies that perform training, drug-taking compliance was significantly better, and a significant improvement was observed in the scores of BPI, HADS Anxiety, Athens Insomnia, and Locomo 25.Conclusion: Pharmacotherapy is essential for the treatment of chronic pain. To this end, appropriate drugs with proper drug management guidance are indispensable. In this study, the use of community pharmacies that have undergone cooperative training with hospitals improves pain and anxiety. This is achieved through proper drug management guidance, shared awareness of drug information, and achievement of better drug-taking compliance. To improve the quality of treatment for chronic pain, involvement of community pharmacies such as by providing accurate information is essential. In the future, expanding cooperative training with hospitals may further help reassure patients, facilitate drug-taking, and improve the quality of treatment for chronic pain.

Forced oscillation technique may identify severe asthma

Background: Fixed airflow obstruction in severe asthma is usually assessed by spirometry. However, the role of the forced oscillation technique (FOT) in severe asthma is unknown. We hypothesised that FOT would be useful to diagnose severe asthma and discriminate it from non-severe asthma. Aims: In this cross-sectional study, we assessed the usefulness of FOT in diagnosing severe asthma. Methods: FOT (MostGraph) was performed in 48 patients with severe asthma and 207 with non-severe asthma who attended outpatient clinics at Shizuoka General Hospital or Nihon University Itabashi Hospital for routine check-ups between February 2013 and August 2016. Severe asthma patients fulfilled the definition of ERS/ATS severe asthma guidelines. Recursive partitioning analysis was performed to create classification tree. Demographic data, peripheral blood eosinophil and neutrophil counts, IgE, serum periostin, YKL-40, fractional exhaled nitric oxide, and spirometry were compared between the classes. Results: Recursive partitioning analysis revealed that resonant frequency (Fres: Hz) and resistance at 5 Hz (R5: cmH2O/L/s) were the significant parameters, suggesting the presence of airflow obstruction during tidal breathing (Figure 1). The accuracy of the diagnosis of severe asthma (class 4) was as follows: diagnostic odds ratio, 16.8; 95% confidence interval, 6.1 to 46.0; sensitivity 33.3%; and specificity, 97.1%. The patients in class 4 had lower FEV1, FVC, and FEV1/FVC, and higher BMI and YKL-40 than those in class 1. However, there was no difference in other parameters between classes 4 and 1. Conclusions: FOT may be useful in identifying severe asthma.

PB2055 HIGH PREVALENCE OF NON‐GERMINAL CENTER B‐CELL PHENOTYPE WITH MYC OVEREXPRESSION IN JAPANESE PATIENTS WITH INTRAVASCULAR LARGE B‐CELL LYMPHOMA

Background:Intravascular large B‐cell lymphoma (IVLBCL) is a rare subtype of B‐cell non‐Hodgkin lymphoma characterized by its unique disease progression within the lumen of multi vessels, nonspecific symptoms such as fever of unknown origin, and poor prognosis. Although recent studies have demonstrated some advances in understanding the pathogenesis of IVLBCL, clinicopathological features of the disease are still to be investigated especially in hemophagocytic syndrome (HPS)‐associated variant, formerly known as “Asian variant”.Aims:This study is conducted to identify the clinicopathological characteristics of IVLBCL, including HPS‐associated variant in the Japanese cohort.MethodsThis is a retrospective analysis of patients with de novo IVLBCL who were diagnosed in Nihon University Itabashi Hospital between 2004 and 2018. The diagnosis of IVLBCL required; no masses were found in lymph nodes nor extranodal sites; lymphoma cells were limited in the blood vessels in subcutaneous or solid organs, or bone marrow; and lymphoma cells were pathologically originated from mature, CD20‐positive B‐cells. HLH‐2004 criteria were used to determine whether patients were complicated with HPS. Immunohistochemistry analysis was performed using antibodies against MYC, BCL2, CD10, BCL‐6, MUM1, and CD5 according to the standard procedure. Cell‐of‐origin (COO) subtype was classified into germinal center B‐cell – like (GCB) or non‐GC type according to the Hans algorithm. As for MYC immunostaining, positivity of &lt;40%, ≥40%–69%, and ≥70% were defined negative (MYC−), positive (MYC+), and strongly positive (MYC + +), respectively. If the sample demonstrated concurrent positivity for MYC (≥40%) and BCL2 (≥50%), it was categorized into the double expressor lymphoma (DEL). Epstein‐Barr virus early RNA (EBER) in situ hybridization was also performed.Results:A total of 17 patients with a median 66‐years (range 43‐81) of age were analyzed. Of these patients, 10 (59%) were considered to be an HPS‐associated variant. All patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone based chemotherapies with or without CNS prophylaxis, resulting in 71% of complete remission (CR) rate and 26 months of median progression‐free survival (PFS). During the observation period, the central nervous system (CNS) relapse was found in 5 patients (29%). COO subtype was non‐GC type in all patients (100%). The numbers of patients with MYC−, MYC+, and MYC + + were 3 (18%), 7 (41%), 7 (41%), respectively. Nine patients (53%) were categorized into DEL. CD5 was positive in 5 patients (29%). EBER was negative in all patients (100%). These clinical or pathological findings were not significantly different between patients with and without HPS. Whereas the clinical outcome of 3 patients with MYC− was comparably favorable (all 3 patients achieved CR and had at least 6–16 months remission duration without CNS relapse), none of MYC positivity, CD5 positivity, nor DEL status was significantly associated with clinical outcomes such as CR rate, PFS duration, or CNS relapse rate.Summary/Conclusion:Our finding confirmed a high prevalence of non‐GC phenotype with MYC overexpression in IVLBCL both with and without HPS. These pathological characteristics may partially account for the clinical aggressiveness of the disease.

PF707 INCIDENCE AND OUTCOMES OF REFRACTORY IMMUNE THROMBOCYTOPENIC PURPURA IN CHILDREN; A SINGLE INSTITUTION EXPERIENCE

Background:The treatment of refractory immune thrombocytopenic purpura (ITP) in children is challenging. Although various medical approaches have been used to treat refractory ITP, few data are available on the long‐term incidence of outcomes in children with refractory ITP.Aims:In this study, we aimed to reveal the outcomes of 87 children with ITP in our institution during the last 19 years.Methods:We retrospectively reviewed the clinical data of children who were newly diagnosed with ITP from April 1998 to March 2017 at the Nihon University Itabashi Hospital. Patients aged below 16 years were included in this study. Patients with follow‐up duration of less than 3 months were excluded. In this study, refractory ITP was defined as a platelet count of &lt;50 × 109 /L, which did not respond to intravenous immunoglobulin (IVIG) and prednisolone (PSL). The definition of the treatment response was as follows: complete response (CR) or partial response (PR), platelet count sustaining more than 100 × 109/L or between 50 and 100 × 109/L at 6 months after change in the treatment approach, respectively. Since 2009, we have introduced cyclosporine (CSA) for refractory ITP; we have diagnosed refractory ITP as refractory thrombocytopenia, which is a subtype of refractory cytopenia of childhood, and then we have used CSA for such patients. In this study, we compared the incidence of CR plus PR in refractory ITP at 3 years after diagnosis in the 1998–2008 group and in the 2009–2017 group. This retrospective study was approved by the institutional review board.Results:A total of 87 children with ITP were identified (50 males and 37 females): 42 children (48%) in the 1998–2008 group and 45 children (52%) in the 2009–2017 group. There were 9 patients (21%) with refractory ITP in the 1998–2008 group and 8 patients (18%) in the 2009–2017 group. Treatment chart in 17 patients with refractory ITP are shown in Figure 1. We changed the diagnosis of ITP to refractory thrombocytopenia in the all patients with refractory ITP in the 2009–2017 group, and initiated treatment with CSA. CSA was started at a dose of 4–6 mg/kg/day (per oral), and the trough level was adjusted between 100 and 150 ng/ml. Two patients achieved CR by CSA therapy alone at 16 and 119 days after starting CSA therapy, respectively. One patient achieved PR with the addition of PSL. Five patients did not respond to CSA therapy alone and then received IVIG at the CSA trough level of more than 100 ng/ml. With this approach, 4 patients achieved CR at a median time of 21 days (range, 13–38) after starting CSA therapy. Overall, 7 out of the 8 patients with refractory ITP in the 2009–2017 group maintained CR plus PR at 3 years after diagnosis. No severe CSA‐associated adverse event was seen in any patients. In contrast, only 2 out of 9 patients with refractory ITP in the 1998–2008 group achieved CR spontaneously (without additional treatment) at 3 years after diagnosis. Moreover, 2 patients obtained CR after splenectomy, and the other 5 patients remained with thrombocytopenia.Summary/Conclusion:CSA with or without IVIG therapy was effective in most cases (88%) of childhood refractory thrombocytopenia. These findings indicate that childhood thrombocytopenia is partially mediated by T cells. Although splenectomy was a conventional treatment for refractory ITP, it surely increases the long‐term risks of venous and arterial thrombosis as well as sepsis from Streptococcus pneumoniae. Therefore, CSA with or without IVIG therapy is feasible in children with refractory ITP to avoid splenectomy.image