Kawasaki Medical School Research Articles

A-100 Clinical Utility of Measuring Creatine Concentration in Erythrocyte

Abstract Background Shortened erythrocyte lifespan characterizes hemolytic anemia and impacts HbA1c values. Recently, erythrocyte creatine concentration (EC) measurement emerged as a new method to assess erythrocyte lifespan. However, literature reports conflicting findings regarding the association between erythrocyte lifespan and EC concentration. In our study, we noted low EC concentrations in renal diseases, typically linked to short erythrocyte lifespan, while iron deficiency anemia exhibited high EC concentrations. This contradicts established relationships, prompting a reevaluation of EC concentration assessment. The aim is to evaluate the clinical utility of EC concentration measurements by correlating them with various clinical parameters, including hematopoietic status. Methods EC concentrations were measured in 522 subjects (252 females, 270 males) aged 19 to 95 at Kawasaki Medical School Hospital. Medical records and laboratory test results from around one month before and after blood collection were used to create a database. Box-and-whisker plots illustrated EC concentration distribution for each disease, and scatter plots compared EC concentrations with laboratory parameters. Results EC concentrations were lower in renal diseases like Diabetes and Chronic Kidney Disease but higher in iron deficiency anemia (Fig. 1). Moreover, EC concentrations rose as hemoglobin concentrations declined, unaffected by CKD grade (Fig. 2). Conclusions While conventionally, high EC concentrations imply a short erythrocyte lifespan, our study noted the opposite trend. EC concentrations might not indicate erythrocyte lifespan but instead reflect hemoglobin synthesis. Investigating EC concentration's relationship with factors like iron and vitamin B12 involved in hemoglobin synthesis may unveil new clinical applications.

Pathology of Ketoacidosis in Emergency of Diabetic Ketoacidosis and Alcoholic Ketoacidosis: A Retrospective Study.

This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, β-hydroxybutyric acid, and β-hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.

Identifying key predictors for uterine manipulator use in robotic simple hysterectomy: a retrospective cohort analysis.

Robotic simple hysterectomy (RSH) is the most common robotic gynecologic surgery in the United States. Uterine manipulators are commonly used to handle the uterus during laparoscopic surgery, but few studies have examined their necessity in RSH. This study retrospectively compares RSH cases with and without the use of manipulators, and identifies predictors for their intraoperative use. This retrospective cohort study included patients undergoing RSH for benign pathologies at Kawasaki Medical School from October 2020 to December 2022. Patients with malignancies were excluded. The robotic surgeries were performed by three skilled surgeons using the four-arm da Vinci Xi surgical system. Data on perioperative and operative parameters were collected, including age, body mass index (BMI), history of abdominal surgery, disease type, presence of ovarian cysts, and operative time. Statistical analyses were performed using EZR software, with multivariate logistic regression to identify predictive factors for uterine manipulator use. The study included 113 patients who underwent RSH without a uterine manipulator and 58 with one. Patients without a manipulator were older, while those with a manipulator had higher BMIs and a higher prevalence of ovarian chocolate cysts and Douglas obliteration. Operating time was shorter without a manipulator. Independent predictors for manipulator use were higher BMI, presence of ovarian endometrioid cysts, and Douglas obliteration. RSH without a uterine manipulator is feasible and can reduce the need for surgical assistants. Predictors for manipulator use include higher BMI, ovarian cysts, and Douglas obliteration. The use of a fourth robotic arm can enhance surgical independence and resource efficiency. Further research is needed to assess the long-term cost-effectiveness and outcomes of this approach.

Structural and functional differences in auto-antibody positive compared to auto-antibody negative hypothyroid patients with chronic thyroiditis

Most primary hypothyroidism in adults is caused by chronic thyroiditis. Autoantibodies such as anti-thyroglobulin antibody (TgAb) and anti-thyroid peroxidase antibody (TPOAb) are involved in the pathogenesis of chronic thyroiditis. On the other hand, the clinical features of antibody-negative hypothyroidism are not clear. In this study, we aimed to determine the prevalence of thyroid-related autoantibodies in patients with primary hypothyroidism and to evaluate the differences in thyroid structure between antibody-positive and antibody-negative hypothyroidism. Among 804 patients who attended Kawasaki Medical School Hospital for thyroid hormone abnormalities or thyroid gland enlargement between January 1, 2010 and December 31, 2021, 237 patients with primary hypothyroidism who underwent thyroid antibody measurement and thyroid ultrasound examination were included. Participants were divided into groups according to antibody positivity/negativity, and differences in antibody positivity and thyroid structure were evaluated. In this study, 34.6% of patients had antibody-negative hypothyroidism. The positive rate of each antibody was 62.0% for TgAb and 49.4% for TPOAb. The participants with antibody-positive hypothyroidism had significantly larger thyroid gland on thyroid ultrasound examination (p < 0.05). Thyroid-stimulating hormone was significantly higher in participants with antibody-positive compared to antibody-negative hypothyroidism. The present study reveals a positive rate of thyroid-related autoantibodies in patients with hypothyroidism and the differences in thyroid structure between patients with and without antibodies. This study clearly show that the prevalence of antibody-negative chronic thyroiditis is quite high among hypothyroid patients, although this point needs confirmation by further investigations. The data in this study would be useful for the treatment of antibody-negative hypothyroid patients.

Simple standing test without furosemide is useful in the diagnosis of primary aldosteronism

Primary aldosteronism (PA) is a well-known cause of secondary hypertension. We have long performed the simple standing test in patients with PA. On the other hand, there are few reports on the usefulness of the simple standing test in PA. This study is a single-center, retrospective, observational study. A total of 173 patients with hypertension or adrenal tumor admitted to Kawasaki Medical School were included. Eighty patients who met the exclusion criteria were excluded, and 31 patients without PA (non-PA), 26 patients with unilateral PA, and 36 patients with bilateral PA were included in the study. The simple standing test was performed after 120 min of standing or sitting followed, and the aldosterone/renin ratio (ARR) and percentage of increase plasma aldosterone concentration (%increase of PAC) was calculated. The mean ARR in the simple standing test in unilateral PA (1143 (528–2200)) and bilateral PA subjects (521 (374–765)) were significantly higher compared to non-PA subjects (152 (102–240)) (p < 0.0001, p = 0.0013, respectively). The percentage increase of PAC after standing loading was significantly lower in unilateral PA subjects (110 (96–140)) compared to non-PA subjects (187 (155–244)) (p = 0.0003), with no difference between non-PA and bilateral PA subjects (p = 0.99). The cutoff value of the ARR in the simple standing test for diagnosis of PA in this study was 364 (AUC = 0.948, sensitivity = 83.8%, specificity = 93.5%, false positive rate = 3.7%, false negative rate = 25.6%, p < 0.001), which was not inferior to the diagnostic performance of the captopril loading test. The diagnostic performance of the simple standing test for PA was not inferior to that of the captopril loading test. The percentage increase of PAC in unilateral PA subjects was significantly lower compared to bilateral PA subjects. These results demonstrate the usefulness of the simple standing test, which can be performed simultaneously with general screening tests of PA.

Spinal Instability as a Prognostic Factor in Patients With Spinal Metastasis of Castration-resistant Prostate Cancer.

To evaluate the Spinal Instability Neoplastic Score (SINS) for prediction of survival in patients with spinal column metastasis of castration-resistant prostate cancer (CRPC). A retrospective study of spinal instability was performed in patients with CRPC using SINS. Overall survival was evaluated starting from the time of SINS evaluation. The subjects were 42 patients with CRPC among 261 cases diagnosed with metastatic spinal tumors by radiologists, among 42,152 cases that underwent a body computed tomography scan at Kawasaki Medical School Hospital within 32 months from December 2013 to July 2016. The median age was 78 (range=55-91 years), the median prostate-specific antigen (PSA) level at SINS evaluation was 42.1 (0.1-3,121.6) ng/ml, and 11 patients had visceral metastasis. The median periods from diagnosis of bone metastasis and development of CRPC to SINS evaluation were 17 (0-158) and 20 (0-149) months, respectively. The spine was stable in 32 cases (group S) and potentially unstable or unstable in 10 (24%) (group U). The median observation period was 17.5 (0-83) months and 36 patients died. The median survival period after SINS evaluation was longer in group S than that in group U (20 vs. 10 months, p=0.0221). In multivariate analysis, PSA level, visceral metastasis, and spinal instability were significant prognostic factors. The hazard ratio for patients in group U was 2.60 (95%CI=1.07-5.93, p=0.0345). Spinal stability evaluated using SINS is a new prognostic factor for survival of patients with spinal metastasis of CRPC.

The Impact of Potassium Binders on Mortality in Patients with Hyperkalemia: A Single-Center Study

Hyperkalemia is associated with an increased risk of mortality and is a common complication in patients with chronic kidney disease (CKD). Despite the prevalence of hyperkalemia, current real-world data suggest that serum potassium levels are not effectively managed in clinical practice. The potential benefit of potassium binders in reducing the risk of death has not been thoroughly investigated. Therefore, this retrospective cohort study aimed to investigate the potential impact of potassium binders on mortality risk in patients with CKD by analyzing electronic medical records. The study included 1689 patients with CKD and hyperkalemia (serum potassium level &gt; 5.0 mEq/L), who visited Kawasaki Medical School Hospital between January 2014 and December 2018. The patients were divided into two groups: those without CPS (calcium polystyrene sulphonate) treatment (CPS_OFF) and those with CPS treatment (CPS_ON). The results showed that the incidence of death was significantly higher in the CPS_OFF group than in the CPS_ON group (22.3% vs. 19.6%, p &lt; 0.001). After propensity score matching, the CPS_ON group had a higher survival rate than the CPS_OFF group (log-rank test, p = 0.020). These results suggest that potassium binders may reduce the risk of death in patients with CKD and hyperkalemia. We hope that the results of this cohort study will be confirmed in future RCTs.

748-P: GLP-1 Receptor Agonists Dulaglutide and Semaglutide in Japanese Patients with Type 2 Diabetes—Randomized, Parallel-Group, Multicenter, Open-Label Trial

The clinical usefulness of once weekly GLP-1 receptor agonists, dulaglutide (D) and semaglutide (S), on domestically approved doses in Japan, was assessed by the multicenter RCT to compare the efficacy, safety and patient satisfaction of D at a dose of 0.75mg and S at a dose of 0.25-1.0mg in patients with type 2 diabetes. The study protocol was approved by the IRB of Kawasaki Medical School (No.5276-01). A total 120 patients eligible for the criteria with HbA1c of 7% or more were randomly assigned to groups D and S (D:S = 59:61), and 107 subjects completed the trial for 24 weeks (D:S=53:54). Backgrounds of 107 subjects were age 62.7 ± 10.7 years, disease duration 13.9 ± 7.4 years, BMI 29.3 ± 5.9 kg/m2, HbA1c 8.0 ± 0.6%. There were no differences in these parameters between 2 groups. Dose of S was escalated by 4 weeks from 0.25mg to adequate dose for each, and average dose was 0.63±0.24mg. The primary endpoint was the difference of HbA1c level between 2 groups at 24 weeks. The HbA1c level at 24 weeks was significantly lower in S than D (D: 8.1±0.6→7.4±0.8 vs S: 7.9±0.5→ 6.7±0.5%, p&amp;lt;0.0001). Reduction in BMI and VFA levels were also more significant in S (D vs. S), BMI: 29.2→28.8 vs. 29.4→28.1 kg/m2, VFA: 174.5→164.6 vs. 175.8→153.2cm2, respectively (p&amp;lt; 0.05). The achievement rate of HbA1c &amp;lt;7% was higher in S (D vs S; 30.8% vs 70.4%, p&amp;lt;0.0001). The parameters such as LDL-C, ALT, γGTP, and apo B/A1 were decreased, and the L/S ratio was increased only in S. Compared the changes in L/S ratio less than 0.9 at baseline, which is diagnosed as NAFLD by CT, between two groups, the ratio was significantly elevated only in the S, but not in D at 24weeks. Gastrointestinal symptoms were observed in 13.2% of D and 46.3% of S (p&amp;lt;0.01). DTR-QoL scores related to pain and gastrointestinal symptoms were superior in D. This prospective trial demonstrated that S has more pronounced effects on glucose and BMI lowering, as well as a reduction in liver fat percentage and visceral fat area. Disclosure T. Kimura: Speaker's Bureau; Sanwa Kagaku Kenkyusho, Kowa Research Institute, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Sanofi, MSD Life Science Foundation, Lilly, Daiichi Sankyo, Novo Nordisk. Y. Katakura: Speaker's Bureau; Abbott. M. Shimoda: Speaker's Bureau; Sanofi, Lilly, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., MSD Life Science Foundation, Mitsubishi Tanabe Pharma Corporation. F. Kawasaki: None. M. Yamabe: Speaker's Bureau; Novo Nordisk, Eli Lilly Japan K.K., Abbott Japan Co., Ltd., Sanofi, Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Ono Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Sumitomo Dainippon Pharma Co., Ltd., Terumo Corporation. F. Tatsumi: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., Novo Nordisk. M. Matsuki: None. Y. Iwamoto: Speaker's Bureau; Kowa Company, Ltd. T. Anno: None. Y. Fushimi: None. S. Kamei: None. Y. Kimura: None. J. Sanada: Speaker's Bureau; Lilly, Kowa Company, Ltd. Y. Hirata: None. S. Nakanishi: Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Kowa Company, Ltd., Abbott, Mitsubishi Tanabe Pharma Corporation. T. Mune: None. K. Kaku: Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Novo Nordisk. Consultant; Sanwa Kagaku Kenkyusho. Speaker's Bureau; Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. H. Kaneto: Research Support; Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan, Inc. Speaker's Bureau; Lilly, Sanofi, Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd. Research Support; Abbott.

886-P: Protective Effects of DPP-4 Inhibitor and SGLT2 Inhibitor on Pancreatic ß-Cell Function—Randomized, Parallel-Group, Multicenter, Open-Label Study (SECRETE-I)

Aims: Effects of DPP-4 inhibitor or SGLT2 inhibitor on human β-cell function are not well understood, and there is no report showing the difference between the two agents. The aim of this study is to compare the effects of these drugs on β-cell function in patients with type 2 diabetes. Methods: The study protocol was approved by the IRB of Kawasaki Medical School (No. jRCTs061190008). A total of 103 patients met the inclusion criteria (age; 20 to 79 years, HbA1c; ≥7.0% and &amp;lt;9.0%). Subjects were randomly assigned to luseogliflozin (L) group (n=49) or teneligliptin (T) group (n=54) and received 24 wks of intervention followed by 1-2 wks of drug washout. The primary endpoint was the change in log-transformed (Ln) disposition index (DI) 0-120 from baseline. Subjects underwent 75gOGTT before and after treatment. Results: The main baseline backgrounds of L and T groups were as follows; age: 60.8±11.1 vs. 62.6±11.2 years (p=0.4), diabetes duration: 10.1±7.9 vs. 9.2±7.6 years (p=0.6), BMI: 27.0±4.2 vs. 27.2±5.4 kg/m2 (p=0.8), HbA1c: 7.6±0.4 vs. 7.5±0.5 % (p=0.5), DI 0-120: 0.80±0.60 vs. 0.92±0.59 (p=0.1). HbA1c levels were significantly decreased in both groups, but the amount of change was greater in the T group (-0.2%, p=0.02). Body weight was significantly decreased only in the L group, with a group difference of -2.5 kg (p&amp;lt;0.001). Ln DI 0-120 were improved in both groups: -0.46±0.66 to -0.15±0.59 (p=0.01) in L group and -0.26±0.60 to -0.02±0.60 (p=0.003) in T group. The change in Ln serum proinsulin/CPR ratio, a marker of β-cell dysfunction, was reduced in L group (1.63±0.63 to 1.56±0.68, p=0.16), but rather increased in T group (1.70±0.75 to 1.90±0.51, p=0.01), with significant difference between the 2 groups (-0.27; p=0.004). Conclusion: Improvement effects on DI 0-120 were almost identical between luseogliflozin and teneligliptin. On the other hand, burden on β-cells was mitigated only in luseogliflozin group. Disclosure M.Shimoda: Speaker's Bureau; Sanofi, Lilly, AstraZeneca, Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., MSD Life Science Foundation, Mitsubishi Tanabe Pharma Corporation. A.Obata: None. T.Kimura: Speaker's Bureau; Sanwa Kagaku Kenkyusho, Kowa Research Institute, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Boehringer Ingelheim Japan, Inc., Sumitomo Dainippon Pharma Co., Ltd., Sanofi, MSD Life Science Foundation, Lilly, Daiichi Sankyo, Novo Nordisk. F.Kawasaki: None. F.Tatsumi: Speaker's Bureau; Abbott Japan Co., Ltd., Kowa Company, Ltd., Novo Nordisk. S.Nakanishi: Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sanofi, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Daiichi Sankyo, Kowa Company, Ltd., Abbott, Mitsubishi Tanabe Pharma Corporation. T.Mune: None. K.Kaku: Advisory Panel; Novo Nordisk, Consultant; Sanwa Kagaku Kenkyusho, Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. H.Kaneto: Research Support; Sumitomo Dainippon Pharma Co., Ltd., Taiho Pharmaceutical Co. Ltd., Boehringer Ingelheim Japan, Inc., Abbott, Speaker's Bureau; Lilly, Sanofi, Boehringer Ingelheim Japan, Inc., Novo Nordisk, Sumitomo Dainippon Pharma Co., Ltd. Y.Katakura: Speaker's Bureau; Abbott. M.Iwamoto: Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Boehringer Ingelheim Inc., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd. Y.Kimura: None. T.Anno: None. H.Isobe: None. Y.Iwamoto: Speaker's Bureau; Kowa Company, Ltd. Y.Fushimi: None. J.Sanada: Speaker's Bureau; Lilly, Kowa Company, Ltd. Funding Taisho Pharmaceutical Holdings Co., Ltd.

Impact of nutritional guidance on various clinical parameters in patients with moderate obesity: A retrospective study.

This study aims to investigate whether there is adequate provision of nutritional guidance through interventions by registered dietitians, especially for patients with moderate obesity. This is particularly important as such interventions may prove to be more effective for Japanese patients. In Japan, since there is a system of nutritional guidance with a registered dietitian for patients with a BMI over 30 kg/m2, we recruited 636 patients with obesity who had a BMI over 30 kg/m2 admitted to the Kawasaki Medical School General Medical Center between April 2018 and March 2020 through a review of their medical records. Second, we recruited 153 patients who underwent a blood examination before receiving nutritional guidance and at least one time every 3 to 6 months thereafter after receiving it. We aimed to evaluate whether continued nutritional guidance and follow-up interventions for patients with obesity were effective. We compared the BMI and metabolic markers of the patients who received nutritional guidance from a registered dietitian against those who did not. A total of 636 patients with obesity who have a BMI over 30 kg/m2 were included in this study. A total of 164 patients with obesity received nutritional guidance from a registered dietitian at least one time, but 472 patients did not. Most interventions on nutritional guidance conducted by a registered dietitian were ordered from internal medicine (81.1%). However, internal medicine was the most common department that did not perform these interventions; however, less than half of the (49.2%) received them. In the second analysis, we compared two groups of patients with obesity. The first group (n = 70) who underwent blood examinations received nutritional guidance from a registered dietitian, while the second group (n = 54) did not receive such guidance. We found that there was no significant difference in body weight and BMI between the two groups of patients. We observed a significant decrease in dyslipidemia-associated metabolic markers among the patients who received nutritional guidance compared to those who did not [total cholesterol, -9.7 ± 29.3 vs. 2.3 ± 22.0 mg/dL (p = 0.0208); low-density lipoprotein cholesterol, -10.4 ± 30.5 vs. -2.0 ± 51.0 mg/dL (p = 0.0147), respectively]. Other metabolic markers also tended to decrease, although they did not reach statistical significance. It is rare for patients with only obesity to receive nutritional guidance. However, when nutritional guidance from a registered dietitian is provided, improvements in BMI and metabolic parameters can be expected.

A global bibliometric analysis on Kawasaki disease research over the last 5 years (2017-2021).

Kawasaki disease (KD) is a systemic vasculitis of unknown etiology that mainly affects children. We aim to conduct a bibliometric analysis to explore the latest research hotspots and trends of KD. By using the keywords "Kawasaki disease," "Kawasaki syndrome", and "Mucocutaneous Lymph Node Syndrome," the Web of Science (WOS) and Scopus databases were searched for publications related to KD from 2017 to 2021. Author, country and journal submissions were classified and evaluated using Biblioshiny software (using R language). VOSviewer (version 1.6.18) was used to visualize the relevant network relationships. According to the search strategy, 5,848 and 6,804 KD studies were published in WOS and Scopus, respectively. The results showed an overall increasing trend in the number of publications and citations during the study period. The three most influential institutions in the WOS were St. Marianna University, Kawasaki Medical School and The University of Tokyo in Japan, while in Scopus, Harvard Medical School, University of California and Tehran University of Medical Sciences were the most influential institutions. The most influential authors of the two databases are Goodman SG, Kazunori Kataoka, and Takeshi Kimura of the WOS and Marx Nikolau and Wang Y, Burns JC, and Newburger JW of the Scopus, respectively. And Scientific Reports and Frontiers in Pediatrics were the most critical journals. The most cited documents were the WOS document by McCrindle et al. and the Scopus document by Benjamin et al. published in 2017, while the keywords in the last few years were focused on "COVID-19," "multisystem inflammatory syndrome," and "pandemic." This bibliometric analysis summarizes for the first time the research progress in KD (2017-2021), providing a qualitative and quantitative assessment of KD research bibliometric information. In the field, researchers mainly from Japan and USA are dominant, followed by China. It is recommended to pay close attention to the latest hot spots, such as "COVID-19" and "multisystem inflammatory syndrome." These results provide a more intuitive and convenient way for researchers to obtain the latest information on KD.

Laparoscopic Adenomyomectomy under Real-Time Intraoperative Ultrasound Elastography Guidance: A Case Series and Feasibility Study.

This study aimed to examine the clinical characteristics of 11 patients undergoing laparoscopic adenomyomectomy guided by intraoperative ultrasound elastography and this technique's feasibility. Eleven patients undergoing laparoscopic adenomyomectomy using ultrasound elastography for adenomyosis at Kawasaki Medical School Hospital in Okayama, Japan between March 2020 and February 2021 were enrolled. Operative outcomes included operative time, operative bleeding, resected weight, operation complications, percent change in hemoglobin (Hb) values, and uterine volume pre- and postoperatively. Dysmenorrhea improvement was evaluated by changes in visual analog scale (VAS) scores pre- and 6- and 12-months postoperatively. The median operative time and bleeding volume was 125 min (range, 88-188 min) and 150 mL (10-450 mL), respectively. The median resected weight was 5.0 g (1.5-180 g). No intraoperative or postoperative blood transfusions or perioperative complications were observed. The median changes in uterine volume, Hb value, and VAS score were -49% (-65 to -28%), -3% (-11 to 35%), and -80% (-100 to -50%), respectively. The median follow-up period post-surgery was 14 months (7-30 months). Adenomyosis recurrence was not observed in the patients during the follow-up period. Laparoscopic adenomyomectomy using ultrasound elastography guidance is minimally invasive and resects as many adenomyotic lesions as possible.

Kawasaki Medical School Microsurgery Training Program

Kawasaki Medical School Microsurgery Training Program

Characteristics of Patients with Trephine Syndrome: A Retrospective Study.

ABSTRACTObjectives:This study retrospectively investigated the prevalence and clinical features of trephine syndrome, which is a late complication of craniectom, in patients who underwent craniectomy decompression.Methods:Trephine syndrome was defined as an increase of ≥2 points in the functional independent measure (FIM) score at 7 days after cranioplasty compared with that 3 days before cranioplasty. Patients who underwent craniectomy at Kawasaki Medical School Hospital between January 1, 2010, and March 15, 2020, were included in the study.Results:During the observation period, 102 patients underwent craniectomy decompression; 71 of them later underwent cranioplasty. In total, 12 and 59 patients were assigned to the trephine and non-trephine syndrome groups, respectively. The patients in the trephine syndrome group were significantly younger than those in the non-trephine syndrome group (P<0.05). The mean durations±standard deviations (in days) from craniectomy decompression to cranioplasty were 57.1±38.9 and 83.6±69.3 for the trephine and non-trephine syndrome groups, respectively (P<0.05). Improvements in the FIM motor scores were greater than the improvements in the cognitive scores for all but one case (P<0.05). The frequency with which patients experienced exacerbation (worsened consciousness and sudden anisocoria) after hospitalization was significantly higher in the trephine syndrome group than in the non-trephine syndrome group (P<0.05).Conclusions:Performing cranioplasty as early as possible in young patients may lead to functional improvement. In the trephine syndrome group, the improvement in motor FIM score was greater than that of the cognitive score. Moreover, post-hospitalization exacerbation was more frequent in the trephine syndrome group.

Epidemiology of urinary tract infections in children: Causative bacteria and antimicrobial therapy.

Urinary tract infections (UTIs) are the most common bacterial infections in children. This study aimed to review characteristics of causative bacteria and the effectiveness of antimicrobial therapy in children with febrile UTIs. Clinical records of 108 patients (130 episodes) with febrile UTIs admitted to the Kawasaki Medical School Hospital between July 2009 and October 2016 were retrospectively reviewed. The characteristics of the causative bacteria, antibacterial therapy, and therapeutic effect were verified. Patients were aged between 0 and 183months (median age: 3months). Seventy-three (67.6%) were males. Sixty-three episodes (48.5%) were diagnosed with complicated UTIs. Forty-seven episodes (36.2%) were observed in patients aged <3months; 15 of them had complicated UTIs. Escherichia coli (E.coli) was the most common pathogen, followed by Enterococcus faecalis (E.faecalis). Blood cultures were positive in three episodes. Among the 130 episodes, 62 (47.7%) were treated with a combination of ampicillin and third-generation cephalosporins, followed by third-generation cephalosporins (31 episodes, 23.8%) and sulbactam sodium / ampicillin sodium (15 episodes, 11.5%). In case of patients with uncomplicated/complicated UTIs and patients aged <3 and ≥3 months, the most common pathogen was E.coli, followed by E. faecalis. There was no difference in therapeutic effects between "combination ampicillin and third-generation cephalosporins" and "third-generation cephalosporin monotherapy" administered for the treatment of UTIs caused by E.coli. Escherichia coli is the most common pathogen among pediatric UTIs. For antibacterial therapy, third-generation cephalosporin monotherapy is effective and may not require combination therapy with ampicillin.

Combination of type IV collagen 7S, albumin concentrations, and platelet count predicts prognosis of non-alcoholic fatty liver disease.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and affects approximately 25% of the general global adult population. The prognosis of NAFLD patients with advanced liver fibrosis is known to be poor. It is difficult to assess disease progression in all patients with NAFLD; thus, it is necessary to identify patients who will show poor prognosis.AIMTo investigate the efficacy of non-invasive biomarkers for predicting disease progression in patients with NAFLD.METHODSWe investigated biomarkers associated with mortality in patients with NAFLD who visited the Kawasaki Medical School General Medical Center from 1996 to 2018 and underwent liver biopsy and had been followed-up for > 1 year. Cumulative overall mortality and liver-related events during follow-up were calculated using the Kaplan-Meier analysis and compared using log-rank testing. We calculated the odds ratio and performed receiver operating characteristic curve analysis with logistic regression analysis to determine the optimal cut-off value with the highest prognostic ability.RESULTSWe enrolled 489 patients who were followed-up for a period of 1-22.2 years. In total, 13 patients died (2.7% of total patients enrolled); 7 patients died due to liver-related causes. Poor prognosis was associated with liver fibrosis on histological examination but not with inflammation or steatosis. Blood biomarkers associated with mortality were platelet counts, albumin levels, and type IV collagen 7S levels. The optimal cutoff index for predicting total mortality was a platelet count of 15 × 104/μL, albumin level of 3.5 g/dL, and type IV collagen 7S level of 5 mg/dL. In particular, only one-factor patients with NAFLD presenting with platelet counts ≤ 15 × 104/μL, albumin levels ≤ 3.5 g/dL, or type IV collagen 7S ≥ 5 mg/dL showed 5-year, 10-year, and 15-year survival rates of 99.7%, 98.3%, and 94%, respectively. However, patients with two factors had lower 5-year and 10-year survival rates of 98% and 43%, respectively. Similarly, patients with all three factors showed the lowest 5-year and 10-year survival rates of 53% and 26%, respectively.CONCLUSIONA combination of the three non-invasive biomarkers is a useful predictor of NAFLD prognosis and can help identify patients with NAFLD who are at a high risk of all-cause mortality.

Inflammatory Cell Numbers in the Stomach of Japanese Subjects with Endoscopically Normal Mucosa without Helicobacter pylori Infection

Introduction: Since inflammatory cells, such as lymphocytes and plasma cells, normally inhabit the stomach, the border between normal and mild inflammation is difficult to visually determine using the updated Sydney system scale of gastritis. Additionally, eosinophils in the gastric mucosa must be counted to diagnose eosinophilic gastritis. We aimed to determine the normal number of inflammatory cells in patients with endoscopically normal mucosa and without Helicobacter pylori infections. Methods: We assessed patients aged 20–79 years, who had undergone upper gastrointestinal endoscopy at Kawasaki Medical School Hospital between January 2010 and December 2014. Inflammatory cells were counted in 1,000 μm² fields of pyloric and fundic gland mucosal biopsy specimens. We finally included 325 (male, n = 141; female, n = 184; average age = 49.3 years) patients without inflammation who had H. pylori-negative endoscopic results and negative histological findings interpreted based on the updated Sydney System and the Kyoto classification of gastritis. Results: The average numbers of nucleated cells were 83.3 ± 14.2 and 65.4 ± 12.6/mm² in the pyloric and fundic gland mucosae, respectively. Inflammatory cells were significantly more abundant in the pyloric mucosa than in the fundic gland mucosa (p < 0.05). Age and sex distribution did not significantly differ. Eosinophils were absent or scanty in the gastric mucosae of both glands in all patients. Conclusion: We determined the absolute values of inflammatory cells, including eosinophils, in normal mucosae of pyloric and fundic glands. These findings could be important in defining gastric mucosal inflammation, including eosinophilic gastritis diagnosis.

Pulmonary Cryptococcosis Complicated by Pneumococcal Pneumonia Co-Infection with Influenza AVirus

A 73-year-old man visited Kawasaki Medical School Hospital with complaints of cough and fever persisting for five days. He was diagnosed with myasthenia gravis in 2010 and had received immunosuppressive treatment for eight years. He presented with infiltration shadows in the bilateral middle and lower lung fields. Because both influenza A virus antigen and urinary pneumococcal pneumonia antigen were positive in laboratory findings, he was diagnosed with pneumococcal pneumonia co-infection with influenza a on admission. We administered peramivir and sulbactam/ampicillin after admission. Although the inflammatory response improved, infiltration shadows did not improve. We performed bronchoscopic examination and obtained the diagnosis of the complication of pulmonary cryptococcosis by transbronchial lung biopsy. He was treated with fluconazole for six months for pulmonary cryptococcosis and he showed improvement without adverse reactions. We report an interesting immunocompromised patient with pulmonary cryptococcosis complicated by pneumococcal pneumonia co-infection with influenza A.

Analysis of risk factors for multidrug-resistant pathogens and appropriate treatment indications for pneumonia in children with neurologic impairment

IntroductionThe features of pneumonia in children with neurologic impairment (NI) resemble those of healthcare-associated pneumonia is defined as pneumonia occurring in the community associated with healthcare risk factors. There are currently no guidelines for the treatment of pneumonia in children with NI. Here, we assessed whether the guidelines applicable for treating pneumonia in adults could be applied to children with NI. MethodsBetween 2008 and 2019, we enrolled children with NI who developed pneumonia and were treated in the pediatric ward of Kawasaki Medical School Hospital. We evaluated patient characteristics, the frequency of isolation of multidrug-resistant (MDR) pathogens, and clinical outcomes. ResultsMDR pathogens were more frequently isolated from patients receiving tube feeding (TF) and/or with tracheostomy than from patients without these risk factors. Other risk factors, including a history of antibiotic therapy and methicillin-resistant Staphylococcus aureus isolation, recent hospitalization, residence in a nursing home or extended care facility, and low-dose, long-term macrolide therapy, did not significantly affect the frequency of MDR pathogen isolation. In patients receiving TF and/or with tracheostomy, treatment success was achieved in all cases treated with broad-spectrum antibiotics and 72.2% of cases treated with non-broad-spectrum antibiotics (P = 0.007). Conversely, among patients without these risk factors, no such difference was observed. ConclusionsOur findings indicate that the guideline to select antibiotics for treating pneumonia in children with NI should be simpler and more useful than the current guidelines for adult pneumonia, based on risk factor assessment for MDR pathogens.

Kawasaki Medical School Hospital

Kawasaki Medical School Hospital