Adolescents diagnosed with polycystic ovary syndrome under the Rotterdam criteria but not meeting the diagnosis under the updated guideline.

STUDY QUESTION: What are the characteristics of adolescents diagnosed with polycystic ovary syndrome (PCOS) based on the 2003 Rotterdam criteria, but who do not meet the diagnosis according to the international evidence-based guideline? SUMMARY ANSWER: Adolescents who had features of PCOS but did not meet the evidence-based guideline adolescent criteria exhibited unfavorable metabolic profiles compared to controls and shared considerable metabolic and hormonal features with adolescents who did meet the adolescent criteria. WHAT IS KNOWN ALREADY: The international evidence-based PCOS guideline recommended that ultrasound should not be used for the diagnosis of PCOS in girls with a gynecological age of <8 years. Thus far, few studies have evaluated the clinical characteristics of the girls diagnosed with PCOS based on the Rotterdam criteria but who do not meet the diagnosis according to the updated guideline. STUDY DESIGN, SIZE, DURATION: This is a retrospective study, and subjects attended for care from 2004 to 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Adolescent girls with PCOS diagnosed according to the 2003 Rotterdam criteria and healthy controls. All participants were between 2 and 8 years since menarche. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 315 girls diagnosed with PCOS according to the Rotterdam criteria, those with irregular menstruation (IM)/hyperandrogenism (HA)/polycystic ovary (PCO), IM/HA, HA/PCO, and IM/PCO phenotypes accounted for 206 (65.4%), 30 (9.5%), 12 (3.8%), and 67 (21.3%) participants, respectively. According to the evidence-based guideline, 79 girls (25.1%) with the HA/PCO or IM/PCO phenotypes were not diagnosed with PCOS, and aligned to the international guideline; they were designated as the 'at-risk' group. As expected, the girls meeting the evidence-based guideline adolescent criteria showed the worst metabolic profiles (degree of generalized or central obesity, frequency of insulin resistance, prediabetes or diabetes, and metabolic syndrome) and higher hirsutism scores than the at-risk group or controls. Approximately 90% of the at-risk group were not overweight or obese, which was similar to the controls. However, they showed worse metabolic profiles, with higher blood pressure, triglyceride, and insulin resistance parameters than controls; furthermore, these profiles were similar to those of the girls meeting the adolescent criteria. The at-risk group showed similarly elevated serum LH levels and LH/FSH ratio with the girls meeting adolescent criteria. LIMITATIONS, REASONS FOR CAUTION: We could not evaluate hormonal or ultrasound parameters in controls. WIDER IMPLICATIONS OF THE FINDINGS: Compared to the conventional Rotterdam criteria, the recent international evidence-based guideline-avoiding ultrasound in PCOS diagnosis in adolescents-still gives the opportunity to identify young girls at risk, aligned to the findings in this study. A practical approach to this adolescent population would involve establishing IM or HA (with ultrasound not indicated) and designating 'at-risk' PCOS status with regular check-ups for newly developed or worsening PCOS-related symptoms or metabolic abnormalities, with subsequent reassessment including ultrasound or anti-Müllerian hormone, once 8 years post-menarche. STUDY FUNDING/COMPETING INTEREST(S): No funding was received in support of this study. The authors have no conflicts of interest to disclose. TRIAL REGISTRATION NUMBER: N/A.

Aerobic Exercise Improves Radiation Therapy Efficacy in Non-Small Cell Lung Cancer: Preclinical Study Using a Xenograft Mouse Model.

The "oxygen effect" improves radiation efficacy; thus, tumor cell oxygen concentration is a crucial factor for improving lung cancer treatment. In the current study, we aimed to identify aerobic exercise-induced changes in oxygen concentrations in non-small cell lung cancer (NSCLC) cells. To this end, an NSCLC xenograft mouse model was established using human A549 cells. Animals were subsequently subjected to aerobic exercise and radiation three times per week for 2 weeks. Aerobic exercise was performed at a speed of 8.0 m/m for 30 min, and the tumor was irradiated with 2 Gy of 6 MV X-rays (total radiation dose 12 Gy). Combined aerobic exercise and radiation reduced NSCLC cell growth. In addition, the positive effect of aerobic exercise on radiation efficacy through oxygenation of tumor cells was confirmed based on hypoxia-inducible factor-1 and carbonic anhydrase IX expression. Finally, whole-transcriptome analysis revealed the key factors that induce oxygenation in NSCLC cells when aerobic exercise was combined with radiation. Taken together, these results indicate that aerobic exercise improves the effectiveness of radiation in the treatment of NSCLC. This preclinical study provides a basis for the clinical application of aerobic exercise to patients with NSCLC undergoing radiation therapy.

Typical Development of the Secondary Ossification Centers of the Acetabulum and Their Effects on Acetabular Coverage of the Femoral Head.

BACKGROUND: We investigated the normal development of the secondary ossification centers of the acetabulum, focusing on their location and the amount of acetabular coverage increased by them. METHODS: We enrolled 132 patients who were 7 to 16 years of age and had no pelvic deformity but did have ≥1 os ischium, os ilium, and/or os pubis on abdominal or pelvic computed tomographic (CT) scans. The locations of the ossification centers were evaluated by adopting an orientation using 0° for the superior acetabulum, 90° for the anterior acetabulum, 180° for the inferior acetabulum, and 270° for the posterior acetabulum, on a reconstructed 3-dimensional (3D) CT image. The acetabular coverage increase by the os ischium, os ilium, or os pubis was defined as the difference in the posterior acetabular sector angle (ΔPASA), posterosuperior acetabular sector angle (ΔPSASA), superior acetabular sector angle (ΔSASA), anterosuperior acetabular sector angle (ΔASASA), or anterior acetabular sector angle (ΔAASA) measured with and without each secondary ossification center. Patients were grouped into 3 age ranges: late childhood, preadolescence, and early adolescence. The location of each ossification center and the increase in acetabular coverage were compared between these groups. RESULTS: In the late-childhood group, the median start-to-end positions in right hips were 269° to 316° for the os ischium, 345° to 356° for the os ilium, and 81° to 99° for the os pubis. These positions tended to be wider in the early-adolescence group at 252° to 328° for the os ischium (p < 0.001), 338° to 39° for the os ilium (p = 0.005), and 73° to 107° for the os pubis (p = 0.049) in right hips. In right hips in the late-childhood group, the median values were 8.1° for ΔPASA, 14.0° for ΔPSASA, 9.9° for ΔSASA, 11.1° for ΔASASA, and 3.9° for ΔAASA; and in the early-adolescence group, the median values in right hips were 10.7° for ΔPASA, 12.9° for ΔPSASA, 8.4° for ΔSASA, 7.4° for ΔASASA, and 5.6° for ΔAASA. Only the median ΔPASA was larger in the early-adolescence group than in the late-childhood group (p = 0.026). Similar results were observed in left hips. CONCLUSIONS: In early adolescence, the secondary ossification centers appeared at more extended areas along the acetabular rim, and the increase in acetabular coverage by the secondary ossification centers tended to be larger in the posterior area but not in the anterior or superior area. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Diagnostic utility, disease activity, and disease phenotype correlation of serum ASCA, pANCA, and PR3-ANCA in pediatric inflammatory bowel disease

Abstract Objective: This study aimed to evaluate the diagnostic utility, disease activity, and phenotypic association of serum anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear anti-neutrophil cytoplasmic antibody (pANCA), PR3-ANCA, and MPO-ANCA in pediatric patients with inflammatory bowel disease (IBD). Methods: Pediatric patients diagnosed with IBD were recruited and classified as Crohn's disease (CD), ulcerative colitis (UC), and IBD-unclassified (IBD-U) through full investigation. The Paris classification was used to evaluate disease phenotypes of pediatric CD and UC. Results: In all, 229 pediatric patients with IBD (CD 147, UC 53, IBD-U 29) were included. The ASCA IgG seropositivity significantly differed among the three groups (CD 75.4%, UC 17.5%, and IBD-U 60.0%; p < 0.001). PR3-ANCA positive rates were the highest in UC (24.0%), followed by IBD-U (17.6%), and none in CD (p = 0.002); pANCA-positive rates were higher in IBD-U (33.6%), followed by UC (28.0%) than in CD (1.4%) (p < 0.001). Regarding disease phenotype, perianal disease revealed higher serum ASCA IgG titers (median 36.7 U/mL in P1 vs. 25.2 U/mL in P0, p = 0.019). Serum ASCA IgG and IgA cutoff values to distinguish CD were 32.7 (U/mL) and 11.9 (U/mL), respectively, with a specificity of 80.0%. Conclusion: Serological biomarkers of ASCA IgG and IgA were effective for differentiating CD in pediatric IBD patients, and serum pANCA and PR3-ANCA, but not MPO-ANCA, were effective in distinguishing UC and IBD-U. Furthermore, measuring serological titers of ASCA IgG and IgA may help differentiate CD and evaluate the disease activity and phenotype of pediatric IBD in practice.