Abstract: Throwing-related shoulder and elbow pain continues to be reported among adolescent baseball players. Few prospective studies have specifically examined the association between throwing-related shoulder and elbow pain and physical and developmental changes. Purpose: To evaluate the changes in physical and developmental characteristics during 1 year with respect to throwing-related shoulder and elbow pain in adolescent baseball players. Study Design: Case-control study; Level of evidence, 3. Methods: This 1-year prospective follow-up study investigated 164 baseball players aged 7 to 13 years. Player data (age, height, weight, field position, and pitch count), lower extremity muscle tightness, and range of motion (ROM) of the shoulder, elbow, and hip joints were assessed during the 2016 and 2017 preseason medical examinations. After the 2016 season, the participants completed questionnaires related to throwing-related shoulder and elbow pain, defined as an inability to play for ≥1 week because of elbow or shoulder difficulties. For study participants with and without throwing-related shoulder or elbow pain during the 2016 season, we conducted univariate and multivariate logistic regression analysis to identify risk factors for throwing-related shoulder or elbow pain. Results: Overall, 21 players (12.8%) reported a shoulder pain episode, 56 players (34.1%) had an elbow pain episode, and 70 players (42.7%) reported having experienced shoulder and/or elbow pain during the 2016 season. In multivariate logistic regression analysis, (1) shoulder pain was associated with 2016 preseason height (odds ratio [OR], 1.06; 95% CI, 1.01-1.11; P = .01) and change in dominant-side elbow extension ROM from 2016 to 2017 (OR, 1.12; 95% CI, 1.02-1.24; P = .02); (2) elbow pain was associated with change in weight from 2016 to 2017 (OR, 1.21; 95% CI, 1.04-1.41; P = .014); and (3) throwing-related shoulder and/or elbow pain was associated with greater 2016 preseason height (OR, 1.04; 95% CI, 1.003-1.68; P = .03) and an increase in height from 2016 to 2017 (OR, 1.17; 95% CI, 1.01-1.35; P = .03). Conclusion: Our results indicated that adolescent baseball players who were taller in the preseason and those with an increase in height over the 1-year study period faced significant risks for developing throwing-related shoulder and/or elbow pain.

Abstract: Shoulder and elbow injuries are major problems in baseball players. Tightness of the upper extremities has been reported as a risk factor for shoulder and elbow injuries in elementary and junior high school baseball players. However, few studies have been conducted on the relationship between decreased hip range of motion (ROM) and shoulder and elbow injuries. Purpose/Hypothesis: This study aimed to prospectively examine the relationship between hip ROM and throwing-related shoulder and elbow injuries in elementary and junior high school baseball players. The hypothesis was that players with unrestricted ROM in the hip would have a reduced risk of upper extremity injuries. Methods: The study included 263 baseball players (mean ± SD age, 10.5 ± 1.3 years; range, 7-14 years). The following physical parameters were assessed: (1) hip flexion ROM measured in the supine position and (2) hip internal and external rotation in the prone position. After the season, players completed questionnaires regarding shoulder and/or elbow injuries. For comparison, the players were classified as injured (not able to play for ≥8 days because of shoulder and/or elbow problems) or noninjured. Results: During the season, 52 players had shoulder and/or elbow injuries. When the injured and noninjured groups were compared, hip flexion on the dominant side (121.5° ± 12.0° vs 126.7° ± 9.8°, respectively; P 〈 .01), hip flexion on the nondominant side (119.6° ± 11.7° vs 126.0° ± 9.9°, respectively; P 〈 .01), and internal rotation on the dominant side (52.5° ± 11.3° vs 56.8° ± 10.8°, respectively; P = .01) were significantly reduced in the injured group. Conclusion: We identified preseason decreases in flexion bilaterally and internal rotation on the dominant side as risk factors for shoulder and elbow injuries in elementary and junior high school baseball players. Further studies are required to prevent disabilities in elementary and junior high school baseball players through development of prevention and intervention programs.

Abstract: Background: Isocitrate dehydrogenase (IDH)-1 and -2 are TCA cycle-involved enzymes which convert isocitrate to alpha-ketoglutarate. Mutations that alter the enzymatic activity causes accumulation of a mal-metabolite D-2-hydroxyglutarate, which results in inhibition of DNA methylation and tumorigenesis. IDH-1 and IDH-2 mutation are present in approximately 7-10% and 10% of patients with acute myeloid leukemia (AML), respectively. Recently, whole exome sequencing has been used for the next-generation sequencing of AML, and certain gene mutations have been identified in patients with AML. The treatment strategies for leukemia have undergone drastic changes with the rapid development of new drugs. However, the proper use of newly developed agents poses a major challenge in AML treatment. Genome profiling analysis can be used to select the optimal treatment for patients with newly diagnosed AML. IDH mutant-specific inhibitors such as ivosidenib and enasidenib were already approved in the US, and combination treatment with venetoclax and Azacitidine was recently approved in Japan. Methods and Results: We lunched an actionable mutation profiling multicenter study named Hematologic Malignancies (HM)-SCREEN-Japan 01 (UMIN000035233), in which a comprehensive genomic assay was performed by Foundation One Heme (F1H) panel. The primary outcome was the frequency of each genomic alteration, as determined using F1H, which is a comprehensive genome profiling test based on next-generation sequencing, in the AML specimens. The secondary outcome was the association between each genomic alteration and the clinicopathological characteristics, prognosis, and quality of specimens used in the genetic analysis. The eligibility criteria were as follows: 1) histological diagnosis of AML through bone marrow aspiration; 2) fulfillment of either of the following conditions: i) newly diagnosed AML unfit for standard treatment (ND-unfit AML) or ii) R/R-AML; 3) sufficient sample collection via bone marrow aspiration; 4) Age of participants 20 years or above during registration; 5) provision of written informed consent by participants. Paraffin-embedded bone marrow samples were gathered from 17 Japanese faculties and the F1H reports were returned to the patients. The median turnaround time was 13 days (minimum 8 days). We found 13 patients (7.3%) with IDH1 mutation and 17 patients (9.6%) with IDH2 mutation out of 177 patients who joined this study and the F1H report was successfully returned. Only one patient had both mutations, and each mutation was mutually exclusive in all the other patients (Figure 1). The major amino acid alteration of IDH1 and IDH2 were R132C/G/H/L and R140Q/W, respectively. Frequently co-occurring mutations include FLT3 (44.8%), NPM1 (34.5%), DNMT3A (31.0%) and RUNX1 mutation (20.7%). Mutations of RAS pathway-related genes (e.g., KRAS, NRAS and PTPN11) were seen in 6 patients (20.7%). Any gene alterations didn't show statistically significant co-occurrence with IDH1 and IDH2 mutation. Serial genome profiling analyses were performed to evaluate the time-dependent changes in the genome profiles of patients administered FLT3 inhibitors, gilteritinib, and quizartinib for treating FLT3-mutated AML. Also in this cohort, we are examining the properties and distribution of IDH1/2 mutations during treatment with FLT3 inhibitors. In the several patients, expansion and persistence of IDH mutated clones seemed to be cause of resistance (Figure 2 as the representative result). The detailed clinical outcomes of AML patients with IDH1/2 mutations are under investigation. Conclusions: In our evaluation of the suitability of F1H for HM-SCREEN-Japan 01, we successfully identified IDH-1/2 mutation that can be used as therapeutic targets in AML, which have rarely been identified thus far. Figure 1 Figure 1. Disclosures Shibayama: Eisai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Ono: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Nippon Shinyaku: Honoraria; Daiichi Sankyo: Honoraria; Novartis: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer: Honoraria; Fujimoto: Honoraria; AbbVie: Honoraria, Research Funding; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Mundi Pharma: Honoraria; Essentia Pharma Japan: Research Funding. Yamauchi: Otsuka: Research Funding; Ono Pharmaceutical: Honoraria; Pfizer: Honoraria, Research Funding; Chugai: Honoraria; Abbie: Research Funding; Astellas: Research Funding; Daiichi Sankyo: Research Funding; Solasia Pharma: Research Funding. Kondo: Otsuka Pharmaceutical: Consultancy, Honoraria, Research Funding; Novartis Pharma KK: Honoraria; Bristol-Myers Squibb Company: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Sanwa Kagaku Kenkyusho CO.,LTD: Consultancy; Pfizer: Honoraria; Astellas Pharma Inc.: Consultancy, Honoraria; Abbvie: Honoraria. Yamamoto: AbbVie: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Bristol-Myers Squibb/Celgene: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Daiichi Sankyo: Honoraria; Eisai: Honoraria, Research Funding; IQIVA/Incyte: Research Funding; IQIVA/HUYA: Honoraria; HUYA: Consultancy; Janssen: Honoraria; Kyowa Kirin: Honoraria; Meiji Seika Pharma: Consultancy, Honoraria, Research Funding; MSD: Honoraria; Mundipharma: Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Sanofi: Honoraria; Solasia Pharma: Research Funding; SymBio: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Yakult: Honoraria, Research Funding; Zenyaku: Honoraria, Research Funding; Micron: Honoraria; IQIVA/Genmab: Research Funding; ADC Therapeutics: Honoraria. Kuroda: Taiho Pharmaceutical: Research Funding; Fujimoto Pharmaceutical: Current Employment, Honoraria, Research Funding; Asahi Kasei: Research Funding; Shionogi: Research Funding; Nippon Shinyaku: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Sysmex: Research Funding; Eisai: Honoraria, Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Abbvie: Consultancy, Honoraria; MSD: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Astellas Pharma: Honoraria, Research Funding; Otsuka Pharmaceutical: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Dainippon Sumitomo Pharma: Honoraria, Research Funding; Chugai Pharmaceutical: Honoraria, Research Funding; Bristol-MyersSquibb: Consultancy, Honoraria, Research Funding; Janssen Pharmaceutical K.K: Consultancy. Usuki: Astellas: Research Funding, Speakers Bureau; Abbvie: Research Funding; Gilead: Research Funding; Symbio: Research Funding, Speakers Bureau; Daiichi Sankyo: Research Funding, Speakers Bureau; Sumitomo Dainippon: Research Funding; Otsuka: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Brisol-Myers Squibb: Research Funding, Speakers Bureau; Ono: Research Funding, Speakers Bureau; Janssen: Research Funding; Celgene: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; Nippon Boehringer Ingelheim: Research Funding; Astellas-Amgen-Biopharma: Research Funding; Nippon shinyaku: Research Funding, Speakers Bureau; Kyowa Kirin: Research Funding, Speakers Bureau; Pfizer: Research Funding; Alexion: Speakers Bureau; Eisai: Speakers Bureau; MSD: Speakers Bureau; PharmaEssentia: Speakers Bureau; Yakult: Speakers Bureau; Mundipharma: Research Funding. Yoshimitsu: Novartis: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Ishitsuka: Asahi kasei: Research Funding; Eli Lilly: Research Funding; MSD: Research Funding; Daiichi Sankyo: Consultancy, Other: Personal fees; Kyowa Kirin: Other: Personal fees, Research Funding; Ono Pharmaceutical: Other: Personal fees, Research Funding; Celgene: Honoraria, Other: Personal fees; Chugai Pharmaceutical: Honoraria, Other: Personal fees, Research Funding; BMS: Other; Takeda: Other: Personal fees, Research Funding; Mundipharma: Other: Personal fees; Taiho Pharmaceuticals: Other: Personal fees, Research Funding; Janssen Pharmaceuticals: Other: Personal fees; Huya Japan: Other: Personal fees; Novartis: Other: Personal fees; Pfizer: Other: Personal fees; Astellas Pharma: Other: Personal fees, Research Funding; Genzyme: Other: Personal fees; Sumitomo Dainippon Pharma: Other: Personal fees, Research Funding; Eisai: Other: Personal fees, Research Funding; Mochida: Other: Personal fees, Research Funding; Shire: Other; Otsuka Pharmaceutical: Other: Personal fees; Teijin Pharma: Research Funding. Ono: Pfizer Japan Inc.: Honoraria; Bristol-Myers Squibb Company: Honoraria; Celgene: Honoraria, Research Funding; Otsuka Pharmaceutical Co., Ltd.: Honoraria; Janssen Pharmaceutical K.K: Honoraria; Eisai Co., Ltd.: Honoraria; Astellas Pharma Inc.: Honoraria; Takeda Pharmaceutical Company Limited.: Honoraria; ONO PHARMACEUTICAL CO., LTD.: Honoraria, Research Funding; DAIICHI SANKYO COMPANY, LIMITED.: Honoraria; Novartis Pharma KK: Honoraria; Chugai Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Kyowa Kirin Co., Ltd.: Honoraria, Research Funding; Mundipharma K.K.: Honoraria; TAIHO PHARMACEUTICAL CO., LTD.: Research Funding; Merck Sharp & Dohme: Honoraria, Research Funding. Takahashi: Toyamakagaku: Research Funding; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Otsuka Pharmaceutical: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Chugai: Research Funding; Kyowahakko-Kirin: Research Funding; Ono: Research Funding; Asahikasei: Research Funding; Eizai: Research Funding. Iyama: Alexion Pharmaceuticals: Honoraria, Research Funding; Astellas: Honoraria; CSL Behring: Honoraria; Daiichi Sankyo: Honoraria; Otsuka Pharmaceuticals Factory: Honoraria; Otsuka Pharmaceuticals Factory: Honoraria; MSD: Research Funding; Nippon Shinyaku: Honoraria; Novartis: Honoraria; Otsuka: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; SymBio Pharmaceuticals: Research Funding. Izutsu: Genmab: Honoraria, Research Funding; Daiichi Sankyo: Honoraria, Research Funding; Fuji Film Toyama Chemical: Honoraria; Eisai: Honoraria, Research Funding; Incyte: Research Funding; Huya Biosciences: Research Funding; Chugai: Honoraria, Research Funding; Symbio: Honoraria; Solasia: Research Funding; Pfizer: Research Funding; Ono Pharmaceutical: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; MSD: Research Funding; Kyowa Kirin: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Beigene: Research Funding; Bayer: Research Funding; AstraZeneca: Honoraria, Research Funding; Allergan Japan: Honoraria; AbbVie: Honoraria; Takeda: Honoraria, Research Funding; Yakult: Research Funding. Minami: Novartis Pharma KK: Honoraria; Ono: Research Funding; Pfizer Japan Inc.: Honoraria; Astellas: Honoraria; Takeda: Honoraria; Bristol-Myers Squibb Company: Honoraria; CMIC: Research Funding.

Abstract: Youth baseball players who experience elbow pain during the season frequently exhibit radiographic elbow abnormalities. However, it is unknown whether asymptomatic elbow abnormalities are risk factors for in-season elbow injuries. Purpose: To determine whether the preseason presence of asymptomatic medial epicondyle apophysitis is a risk factor for in-season elbow injuries in youth baseball players. Study Design: Cohort study; Level of evidence, 2. Methods: Youth baseball players (N = 210; age range, 7-12 years) with no pain or history of injury in their throwing arms underwent preseason evaluations that included shoulder and elbow range of motion measurements, shoulder muscle strength testing, and ultrasound elbow scans with a multifrequency 13-MHz linear array transducer. Over 1 year of play, the players and their parents maintained daily elbow pain diaries. Elbow injuries were defined as medial elbow symptoms that prevented ball throwing for ≥8 days. Results: The preseason ultrasound evaluation revealed medial epicondyle apophysitis in 59 players. In the year following, elbow injuries occurred in 17 (28.8%) players with preseason medial epicondyle apophysitis and 18 (11.9%) players without apophysitis. Independent predictors of elbow injuries were preseason medial epicondyle apophysitis (odds ratio [OR], 2.488; 95% confidence interval [CI] , 1.152-5.376; P = .02) and deficits of abduction (ABD) and external rotation of the dominant shoulder (OR, 0.963; 95% CI, 0.936-0.992; P = .012). Conclusion: Asymptomatic medial epicondyle apophysitis and ABD and external rotation deficits in the dominant shoulder were risk factors for elbow injuries in 7- to 12-year-old youth baseball players. These findings may aid in the design of programs to prevent elbow injuries in this population.

Abstract: We aimed to examine the relationship between hip range of motion (ROM) and abduction strength and throwing-related shoulder/elbow injuries in high school baseball pitchers. The study included 135 baseball pitchers. We asked them to fill out a questionnaire at the checkups, that included the dominant arm and the years of baseball experience. To avoid a confirmation bias, the examiners were blinded to the participants’ hand dominance. All players underwent physical function measurements, such as height, weight, shoulder and hip strength, and shoulder and hip ROM. Shoulder and elbow injury was defined as shoulder and elbow pain that the patient had been aware of in the past 3 years. The results of injured and non-injured pitchers were compared. Eighty-five pitchers had experienced a shoulder or elbow injury in the past 3 years. The shoulder ROM and strength in the injured and non-injured groups did not differ to a statistically significant extent. The hip external rotation ROM on the dominant side, the hip abduction strength on the non-dominant side, and the hip abduction strength on the dominant side were significantly lower in the injured group than in the non-injured group. The results may contribute to reducing the incidence of these injuries.

Abstract: Background. Accurate identification of neuropathic pain is necessary for appropriate treatment; however, the relationship between nontraumatic shoulder disorders and neuropathic pain remains unknown. Therefore, this retrospective observational study aimed to investigate the relationship, features, background factors, and prevalence of neuropathic pain among patients with nontraumatic shoulder disorders. Methods. We evaluated 198 patients who visited our outpatient clinic, which specializes in shoulder disorders, from April 2015 to March 2016. The patients’ age, sex, affected side, diagnosis, and pain duration were recorded, and the results of physical examination, including passive range of motion, impingement sign, and muscular strength assessments, were analyzed. The presence of neuropathic pain was assessed using the painDETECT questionnaire. Participants were divided into two groups according to the presence of neuropathic pain. Pain intensity was assessed using a visual analog scale, and the patient’s mental status was assessed using the short-form McGill Pain Questionnaire and Hospital Anxiety and Depression Scale. The scores were compared between the groups. Results. Neuropathic pain was observed in 7.6% of patients. The visual analog scale score for pain, short-form McGill Pain Questionnaire score, and Hospital Anxiety and Depression Scale score were significantly associated with the presence of neuropathic pain in the univariate analysis. Patient background factors and physical function were not associated with the presence of neuropathic pain. The prevalence of neuropathic pain in patients with frozen shoulder was 33.3%, which was significantly higher than that in patients with other shoulder disorders. Conclusion. The occurrence of neuropathic pain may aggravate pain in patients with nontraumatic shoulder disorders. Neuropathic pain was not a rare condition in patients with nontraumatic shoulder disorders, particularly in those with frozen shoulder. The coexistence of neuropathic pain cannot be determined from background factors or physical function. Accurate diagnosis of neuropathic pain is essential in patients with nontraumatic shoulder disorders.