1.Relationship between Treatment Choices according to the Modified Osteoporotic Fracture Score and Posttreatment Radiographic Outcomes
Shinya TOKUNAGA ; Toshiyuki TAKAHASHI ; Koki MITANI ; Tomoo INOUE ; Ryo KANEMATSU ; Manabu MINAMI ; Izumi SUDA ; Sho NAKAMURA ; Junya HANAKITA
Asian Spine Journal 2024;18(2):251-259
		                        		
		                        			 Methods:
		                        			Consecutive patients diagnosed with OFs at Fujieda Heisei Memorial Hospital were divided into three groups: nonsurgical therapy, balloon kyphoplasty (BKP), and open surgery groups. The mOF score was calculated, and the levels of independence and posttreatment imaging data were compared between patients treated and not treated according to the mOF score-based treatment recommendation. 
		                        		
		                        			Results:
		                        			In total, 118 patients were included (nonsurgical therapy, n=57; BKP, n=48; open surgery, n=13), of whom 100 (85%) received treatment consistent with the mOF score-based treatment recommendation. In the BKP and open surgery groups, the mOF scorebased treatment recommendations were consistent with the actual treatment in 93% of the patients. However, in the nonsurgical group, the mOF score-based treatment recommendation was not consistent with the actual treatment in 25% of the patients. In this group, patients not treated according to the mOF score had significantly shorter vertebral body height, greater local kyphosis, and smaller sacral slope after treatment than patients treated according to the mOF score-based treatment recommendation. 
		                        		
		                        			Conclusions
		                        			In the BKP and open surgery groups, the mOF scores were consistent with actual clinical selection. In the nonsurgical therapy group, patients not treated according to the mOF score-based treatment recommendation exhibited severe vertebral body deformity and a less well-balanced spine shape after treatment. The mOF score may help in selecting suitable treatments for OFs. 
		                        		
		                        		
		                        		
		                        	
2.Verification of grip strength as an evaluation tool for locomotive syndrome in rheumatoid arthritis
Yasumori SOBUE ; Mochihito SUZUKI ; Yoshifumi OHASHI ; Ryo SATO ; Hironobu KOSUGIYAMA ; Yusuke OHNO ; Junya HASEGAWA ; Takaya SUGIURA ; Kenya TERABE ; Shuji ASAI ; Shiro IMAGAMA
Osteoporosis and Sarcopenia 2024;10(3):119-125
		                        		
		                        			 Objectives:
		                        			Locomotive syndrome (LS) leads to reduced physical function and a high risk of becoming bedridden.Grip strength serves as an indicator of upper limb and overall physical function. Rheumatoid arthritis (RA) patients with reduced grip strength frequently show finger and wrist joint inflammation. The purpose of this study was to verify grip strength as an evaluation tool for physical function and LS in RA patients. 
		                        		
		                        			Methods:
		                        			As part of an ongoing multicenter observational study, 591 consecutive RA patients whose background information was available, including data for the 25-question Geriatric Locomotive Function Scale (GLFS-25) and grip strength, were examined. LS was defined as a GLFS-25 score ≥ 16 points. Finger and wrist joint inflammation were defined as tender or swollen joints. 
		                        		
		                        			Results:
		                        			Among the 591 patients, 244 (41.3%) patients had LS, and 167 (28.3%) were male. Receiver operating characteristic curve analysis yielded cut-off values of grip strength for LS of 24 kg (specificity 72.2%; sensitivity 62.7%) for males and 17 kg (specificity 65.7%; sensitivity 67.6%) for females. Multivariable logistic regression analysis revealed a significant association of grip strength with LS, even after adjusting for finger and wrist joint inflammation. 
		                        		
		                        			Conclusions
		                        			LS was significantly associated with grip strength, even after adjusting for the presence of finger and wrist joint inflammation. We recommend adopting grip strength measurement as a screening tool for evaluating LS and guiding interventions. 
		                        		
		                        		
		                        		
		                        	
3.Acquired Left Ventricle to Right Atrial Communication Following Infective Endocarditis of the Native Aortic Valve Diagnosed Using Cardiac Computed Tomography
Mizuho IKUCHI ; Kentaro HONDA ; Kota AGEMATSU ; Hideki KUNIMOTO ; Ryo NAKAMURA ; Koji TAJIMA ; Masahiro KANEKO ; Yoshiharu NISHIMURA
Japanese Journal of Cardiovascular Surgery 2023;52(1):14-17
		                        		
		                        			
		                        			Left ventricle to right atrial communication is a rare cardiac pathology, and it is either congenital or acquired. Recently, case reports of acquired left ventricle to right atrial communication have been increasing because of the increased numbers of cardiovascular procedures and improved cardiac diagnostic techniques. We report a case of acquired left ventricle to right atrial communication in a patient with native aortic valve infective endocarditis. A 52-year-old man with worsening dyspnea on exertion and lower leg edema was admitted to a hospital. Blood examination revealed elevated inflammatory marker levels, and transthoracic echocardiography (TTE) showed an aortic valve vegetation. The patient was subsequently transferred to our hospital for infective endocarditis with congestive heart failure. Medical treatment with antibiotics and diuretics was initiated. Cardiac computed tomography (CT) demonstrated left ventricle to right atrial communication. An urgent operation was performed wherein the defect was closed with autologous pericardial patches from both the right atrium and left ventricle. Aortic valve replacement was performed with a mechanical valve. The postoperative course was uneventful, and TTE showed no residual shunt. In our case, cardiac CT was useful for accurately diagnosing left ventricle to right atrial communication.
		                        		
		                        		
		                        		
		                        	
4.Study of the clinicopathological features of soluble PD-L1 in lung cancer patients
Takanobu SASAKI ; Ryo NONOMURA ; Toshiharu TABATA ; Naruo YOSHIMURA ; Shuko HATA ; Hiroki SHIMADA ; Yasuhiro NAKAMURA
Journal of Rural Medicine 2023;18(1):42-49
		                        		
		                        			
		                        			Objective: In recent years, an association between serum soluble immune checkpoint molecules (sICMs) and malignant tumors has been reported, which may become important biomarkers in the future. Although several reports have suggested a correlation between sICMs and prognosis, their origin is unclear. In this study, changes in serum soluble PD-L1 (sPD-L1) during the perioperative period and its origin were analyzed in patients with lung cancer.Patients and Methods: Patients with lung tumors (n=39) were included. Samples for sPD-L1 measurements were collected at five time points before and after surgery, and their changes over time were analyzed. ELISA was used to measure sPD-L1 levels.Results: Thirty-nine patients with lung tumors (31, males; 8, females; age, 74 (years) ± 7.7 (range: 51–89) years; malignancy/benign, 33/6) were enrolled. Eight cases of driver gene mutation-positive tumors were included. Twenty-eight (72%) patients were smokers, and their performance status was 0-1 in all 39 patients. PD-L1 TPS was ≥50%/1–49%/<1% in 8/10/14 patients. Stage I/II/III/IV/postoperative recurrence of lung cancer was observed in 21/0/6/5/1 patients, respectively. There were no significant correlations between sPD-L1 levels and clinicopathological features and no correlation with PD-L1 TPS. Comparing localized lesions (stages I–III) with advanced lesions (stage IV and postoperative recurrence), the distribution of sPD-L1 was slightly higher in advanced lesions, although the difference was not significant. No obvious changes in sPD-L1 expression were observed before and after surgery.Conclusion: sPD-L1 levels tended to be high in stage III and above lung cancer. There was no change in sPD-L1 levels before and after surgery. sPD-L1 levels did not correlate with the PD-L1 TPS.
		                        		
		                        		
		                        		
		                        	
5.An Overview of Early Clinical Exposure for Undergraduate Medical Education in Japan
Ryo SUGAYA ; Akihisa NAKAMURA ; Yasushi MATSUYAMA ; Kazuhiko KOTANI
Medical Education 2023;54(3):267-271
		                        		
		                        			
		                        			Introduction: Early clinical exposure (ECE) is an educational methodology where medical students are exposed to the clinical settings in the undergraduate curriculum. This study aimed to examine the implementation status of ECE at medical schools in Japan. Methods: Based on published syllabi, we investigated the existence, location, and subjects (medical/non-medical staffs) of the training programs in medical schools. Results: Of 78 universities, 74 (95%) offered a total of 173 ECE practical training courses, and 51 (69%) combined on-campus and off-campus ECE training. Regarding the location and subjects, 81% of the on-campus ECE training was for medical personnel, 47% of the off-campus was for non-medical personnel, and 61% of the on- and off-campus was for both medical and non-medical personnel. Conclusions: More medical universities combined ECEs on-campus and off-campus and did not offer exposure only to medical staffs. The national trend can serve as a reference to discuss the circumstance of ECE and to plan ECE courses in the near future.
		                        		
		                        		
		                        		
		                        	
6.Interleukin-34 cancels anti-tumor immunity by PARP inhibitor
Takayoshi NAKAMURA ; Nabeel KAJIHARA ; Naoki HAMA ; Takuto KOBAYASHI ; Ryo OTSUKA ; Nanumi HAN ; Haruka WADA ; Yoshinori HASEGAWA ; Nao SUZUKI ; Ken-ichiro SEINO
Journal of Gynecologic Oncology 2023;34(3):e25-
		                        		
		                        			 Objective:
		                        			Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME). 
		                        		
		                        			Methods:
		                        			In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34. 
		                        		
		                        			Results:
		                        			We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34. 
		                        		
		                        			Conclusion
		                        			These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer. 
		                        		
		                        		
		                        		
		                        	
7.Subtype of Achalasia and Integrated Relaxation Pressure Measured Using the Starlet High-resolution Manometry System: A Multicenter Study in Japan
Tetsuya TATSUTA ; Hiroki SATO ; Yusuke FUJIYOSHI ; Hirofumi ABE ; Akio SHIWAKU ; Junya SHIOTA ; Chiaki SATO ; Masaki OMINAMI ; Yoshitaka HATA ; Hisashi FUKUDA ; Ryo OGAWA ; Jun NAKAMURA ; Yuichiro IKEBUCHI ; Hiroshi YOKOMICHI ; Shinsaku FUKUDA ; Haruhiro INOUE
Journal of Neurogastroenterology and Motility 2022;28(4):562-571
		                        		
		                        			 Background/Aims:
		                        			ManoScan and Sandhill high-resolution manometry (HRM) systems are used worldwide; however, the diagnosis of achalasia on the Starlet HRM system is not fully characterized. Furthermore, the impact of calcium channel blockers and nitrites in treating achalasia has not been investigated using HRM. Management of recurrent cases is a priority issue, although few studies have examined patient characteristics. 
		                        		
		                        			Methods:
		                        			We conducted a multicenter, large-scale database analysis. First, the diagnosis of treatment-naive achalasia in each HRM system was investigated. Next, patient characteristics were compared between type I-III achalasia, and the impact of patient characteristics, including calcium channel blocker and nitrite use for integrated relaxation pressure (IRP) values, were analyzed. Finally, patient characteristics with recurrent achalasia were elucidated. 
		                        		
		                        			Results:
		                        			The frequency of type I achalasia with Starlet was significantly higher than that with ManoScan and Sandhill HRM systems. In achalasia, multivariate analysis identified male sex, advanced age, long disease duration, obesity, type I achalasia, and sigmoid type as risk factors related to normal IRP values (< 26 mmHg). Calcium channel blockers and nitrites use had no significant impact on the IRP values, although achalasia symptoms were indicated to be alleviated. In recurrent cases, the IRP value was significantly lower, and advanced age, long disease duration, and sigmoid type were more common than in treatment-naive patients. 
		                        		
		                        			Conclusions
		                        			We should cautiously interpret the type of achalasia and IRP values in the Starlet HRM system. Symptoms of recurrent cases are related to disease progression rather than IRP values, which should be considered in decision making. 
		                        		
		                        		
		                        		
		                        	
8.Development of Dilated Esophagus, Sigmoid Esophagus, and Esophageal Diverticulum in Patients With Achalasia: Japan Achalasia Multicenter Study
Hiroki SATO ; Yusuke FUJIYOSHI ; Hirofumi ABE ; Hironari SHIWAKU ; Junya SHIOTA ; Chiaki SATO ; Hiroyuki SAKAE ; Masaki OMINAMI ; Yoshitaka HATA ; Hisashi FUKUDA ; Ryo OGAWA ; Jun NAKAMURA ; Tetsuya TATSUTA ; Yuichiro IKEBUCHI ; Hiroshi YOKOMICHI ; Shuji TERAI ; Haruhiro INOUE
Journal of Neurogastroenterology and Motility 2022;28(2):222-230
		                        		
		                        			 Background/Aims:
		                        			Patients with achalasia-related esophageal motility disorders (AEMDs) frequently present with dilated and sigmoid esophagus, anddevelop esophageal diverticulum (ED), although the prevalence and patients characteristics require further elucidation. 
		                        		
		                        			Methods:
		                        			We conducted a multicenter cohort study of 3707 patients with AEMDs from 14 facilities in Japan. Esophagography on 3682 patients were analyzed. 
		                        		
		                        			Results:
		                        			Straight (n = 2798), sigmoid (n = 684), and advanced sigmoid esophagus (n = 200) were diagnosed. Multivariate analysis revealed that long disease duration, advanced age, obesity, and type I achalasia correlate positively, whereas severe symptoms and integrated relaxation pressure correlate negatively with development of sigmoid esophagus. In contrast, Grade II dilation (3.5-6.0 cm) was the most common (52.9%), while grade III dilation (≥ 6 cm) was rare (5.0%). We found early onset, male, obesity, and type I achalasia correlated positively, while advanced age correlated negatively with esophageal dilation. Dilated and sigmoid esophagus were found mostly in types I and II achalasia, but typically not found in spastic disorders. The prevalence of ED was low (n = 63, 1.7%), and non-dilated esophagus and advanced age correlated with ED development. Patients with right-sided ED (n = 35) had a long disease duration (P = 0.005) with low integrated relaxation pressure values (P = 0.008) compared with patients with left-sided ED (n = 22). Patients with multiple EDs (n = 6) had lower symptom severity than patients with a single ED (P = 0.022). 
		                        		
		                        			Conclusions
		                        			The etiologies of dilated esophagus, sigmoid esophagus, and ED are considered multifactorial and different. Early diagnosis and optimal treatment of AEMDs are necessary to prevent these conditions. 
		                        		
		                        		
		                        		
		                        	
9.The Genotype-Based Morphology of Aldosterone-Producing Adrenocortical Disorders and Their Association with Aging
Xin GAO ; Yuto YAMAZAKI ; Yuta TEZUKA ; Kei OMATA ; Yoshikiyo ONO ; Ryo MORIMOTO ; Yasuhiro NAKAMURA ; Fumitoshi SATOH ; Hironobu SASANO
Endocrinology and Metabolism 2021;36(1):12-21
		                        		
		                        			
		                        			 Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with an increased incidence of cardiovascular events. PA itself is clinically classified into the following two types: unilateral PA, mostly composed of aldosteroneproducing adenoma (APA); and bilateral hyperaldosteronism, consisting of multiple aldosterone-producing micronodules (APMs) and aldosterone-producing diffuse hyperplasia. Histopathologically, those disorders above are all composed of compact and clear cells. The cellular morphology in the above-mentioned aldosterone-producing disorders has been recently reported to be closely correlated with patterns of somatic mutations of ion channels including KCNJ5, CACNA1D, ATP1A1, ATP2B3, and others. In addition, in non-pathological adrenal glands, APMs are frequently detected regardless of the status of the renin-angiotensin-aldosterone system (RAAS). Aldosterone-producing nodules have been also proposed as non-neoplastic nodules that can be identified by hematoxylin and eosin staining. These non-neoplastic CYP11B2-positive nodules could represent possible precursors of APAs possibly due to the presence of somatic mutations. On the other hand, aging itself also plays a pivotal role in the development of aldosterone-producing lesions. For instance, the number of APMs was also reported to increase with aging. Therefore, recent studies indicated the novel classification of PA into normotensive PA (RAAS-independent APM) and clinically overt PA. 
		                        		
		                        		
		                        		
		                        	
            

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