Delayed diagnosis and treatment of adolescents and young women with suspected endometriosis.

STUDY OBJECTIVE: Early diagnosis and treatment of endometriosis in adolescents and young women is considered essential for improving their quality of life and for prevention of long-term complications. In adult women with endometriosis, significant delays in diagnosis and medical or surgical treatment have been described. Our study aimed to investigate the delay in diagnosis and treatment of adolescents and young women with suspected endometriosis. METHODS: A retrospective study of adolescents and young women (12-22 years-old) who were evaluated for suspected endometriosis at the endometriosis clinic in the Shamir medical center between January 2017 and December 2022. All patients were referred by their primary care gynecologists. The evaluation in the endometriosis clinic included targeted history, physical exam and a focused ultrasound survey for endometriosis (performed trans-abdominally in all cases, and trans-vaginally in sexually active women). RESULTS: Out of 400 women with suspected endometriosis evaluated in our endometriosis clinic during the study period, 68 were adolescents and young women <22 years old. Their mean age at time of evaluation for endometriosis was 18 ± 2.5 years, and the mean time-period from onset of symptoms to the endometriosis evaluation was 4.0 ± 2.9 years. Their most common symptoms were dysmenorrhea (in 61 cases, 89.7 %), followed by gastrointestinal symptoms (in 32 cases, 47.1 %). In 30 (44.1 %) cases, hormonal treatment was prescribed by the primary care gynecologist prior to their appointment in the endometriosis clinic. On comparison of patients with delay of <4 years (N = 31) versus ≥4 years (N = 37) from symptom onset to the endometriosis evaluation, patients with shorter duration of symptoms were more likely to decline any hormonal treatment for endometriosis while patients with longer duration of symptoms were more likely to accept the recommendation for hormonal treatment (16.2 % versus 0 %, p = 0.02, and 83.8 % versus 100 %, p = 0.03, respectively). CONCLUSION: Adolescents and young women with suspected endometriosis may experience significant delays in diagnosis and medical care, similar to adult patients.

Expression Changes and Impact of the Extracellular Matrix on Etoposide Resistant Human Retinoblastoma Cell Lines.

Retinoblastoma (RB) represents the most common malignant childhood eye tumor worldwide. Several studies indicate that the extracellular matrix (ECM) plays a crucial role in tumor growth and metastasis. Moreover, recent studies indicate that the ECM composition might influence the development of resistance to chemotherapy drugs. The objective of this study was to evaluate possible expression differences in the ECM compartment of the parental human cell lines WERI-RB1 (retinoblastoma 1) and Y79 and their Etoposide resistant subclones via polymerase chain reaction (PCR). Western blot analyses were performed to analyze protein levels. To explore the influence of ECM molecules on RB cell proliferation, death, and cluster formation, WERI-RB1 and resistant WERI-ETOR cells were cultivated on Fibronectin, Laminin, Tenascin-C, and Collagen IV and analyzed via time-lapse video microscopy as well as immunocytochemistry. We revealed a significantly reduced mRNA expression of the proteoglycans Brevican, Neurocan, and Versican in resistant WERI-ETOR compared to sensitive WERI-RB1 cells. Also, for the glycoproteins α1-Laminin, Fibronectin, Tenascin-C, and Tenascin-R as well as Collagen IV, reduced expression levels were observed in WERI-ETOR. Furthermore, a downregulation was detected for the matrix metalloproteinases MMP2, MMP7, MMP9, the tissue-inhibitor of metalloproteinase TIMP2, the Integrin receptor subunits ITGA4, ITGA5 and ITGB1, and all receptor protein tyrosine phosphatase ß/ζ isoforms. Downregulation of Brevican, Collagen IV, Tenascin-R, MMP2, TIMP2, and ITGA5 was also verified in Etoposide resistant Y79 cells compared to sensitive ones. Protein levels of Tenascin-C and MMP-2 were comparable in both WERI cell lines. Interestingly, Fibronectin displayed an apoptosis-inducing effect on WERI-RB1 cells, whereas an anti-apoptotic influence was observed for Tenascin-C. Conversely, proliferation of WERI-ETOR cells was enhanced on Tenascin-C, while an anti-proliferative effect was observed on Fibronectin. In WERI-ETOR, cluster formation was decreased on the substrates Collagen IV, Fibronectin, and Tenascin-C. Collectively, we noted a different ECM mRNA expression and behavior of Etoposide resistant compared to sensitive RB cells. These findings may indicate a key role of ECM components in chemotherapy resistance formation of RB.

Psychosocial benefits of insulin pump therapy in children with diabetes type 1 and their families: The pumpkin multicenter randomized controlled trial.

OBJECTIVE: Continuous subcutaneous insulin infusion (CSII) is on the rise among pediatric patients with type 1 diabetes mellitus. Metabolic effects alone cannot explain this rising popularity. From the patient's perspective, the main benefits of CSII may be found in subjective psychosocial health outcomes (patient-reported outcomes [PRO]). SUBJECTS AND METHODS: In a multicenter open randomized controlled trial, children and adolescents aged 6 to16 years currently treated with multiple daily injections (MDI) were randomized 1:1, stratified by center, to either starting with CSII immediately after the baseline interview or to continuing MDI while waiting 6 months for transmission to CSII. The primary outcomes were patient-reported diabetes-specific health-related quality of life (DHRQOL) and diabetes burden of the main caregiver. Secondary outcomes were caregiver stress, fear of hypoglycemia, satisfaction with treatment, and HbA1c. RESULTS: Two-hundred and eleven patients were randomized between February 2011 and October 2014, and 186 caregivers and 170 patients were analyzed using the intention-to-treat principle for primary outcomes. Children 8 to 11 years in the CSII group reported improved DHRQOL at follow-up compared to MDI (median difference [MD] 9.5, 95% confidence interval [CI] 3.6-16.7, P = 0.004). There were no treatment differences in the adolescent age-group 12 to 16 years (MD 2.7; 95% CI -3.2-9.5; P = 0.353). The main caregivers of the CSII group reported a significant decline of overall diabetes burden at follow-up compared to the MDI group (MD 0; 95% CI -1-0; P = 0.029). Secondary PROs also were in favor of CSII. CONCLUSIONS: CSII has substantial psychosocial benefits. PROs demonstrate these benefits. Registered as NCT01338922 at clinicaltrials.gov.