Inflammatory responses initiate rapid production of IL-1 family cytokines, including IL-18. This cytokine is produced at high levels in inflammatory diseases, including allergy and autoimmunity, and is known to induce IgE production in mice. Here we provide evidence that IL-18 is directly coupled to induction of self-reactive IgM and IgG antibody responses and recruitment of innate B2 B cells residing in the marginal zone of the spleen. Moreover, the data suggest that the B-cell activation occurs predominantly in splenic extrafollicular plasma cell foci and is regulated by natural killer T (NKT) cells that prevent formation of mature germinal centers. We also find evidence that NKT cells control this type of B-cell activation via cytotoxicity mediated by both the perforin and CD95/CD178 pathways. Thus, NKT cells regulate innate antibody responses initiated by an inflammatory stimulus, suggesting a general mechanism that regulates B-cell behavior in inflammation and autoreactivity.

BACKGROUND: Patient satisfaction and health-related quality of life are nowadays considered as the most important outcomes of pelvic organ prolapse treatment, and large, prospective clinical studies reporting the patient-reported surgical outcomes are needed. OBJECTIVE: To evaluate the effect of female pelvic organ prolapse surgery on health-related quality of life and patient satisfaction and to determine predictors of outcome. STUDY DESIGN: This prospective nationwide cohort study consisted of 3515 women undergoing surgery for pelvic organ prolapse in 2015. The outcomes were measured by validated health-related quality of life instruments (generic 15D, Pelvic Floor Distress Inventory-20, and Patient Global Impression of Improvement) at 6 months and 2 years postoperatively. The baseline predictors of outcomes were studied with logistic regression analysis. RESULTS: In total, 2528 (72%) women were eligible for analysis at 6 months and 2351 (67%) at 2 years. The mean change in the total 15D score suggested a clinically important improvement at 6 months but not at 2 years. However, an improvement in sexual activity, discomfort and symptoms, and excretion was observed during both follow-up assessments. Altogether, 77% and 72% of the participants reported a clinically significant improvement in Pelvic Floor Distress Inventory-20 at the 6month and 2-year follow-ups, respectively. A total of 84% were satisfied with the outcome and 90% reported an improvement in comparison with the preoperative state with Patient Global Impression of Improvement-I. The strongest predictive factors for a favorable outcome were advanced apical prolapse (adjusted odds ratio, 2.06; 95% confidence interval, 1.58e2.70) and vaginal bulge (1.90, 1.30e2.80). Smoking was associated with an unfavorable outcome as measured by Patient Global Index of Improvement-I (1.69, 1.02e2.81). CONCLUSION: Pelvic organ prolapse surgery improved health-related quality of life in 7 of 10 patients over a 2-year follow-up period, and patient satisfaction was high. Apical prolapse beyond the hymen and vaginal bulge were the most consistent predictors for improvement. Our results suggest that patients should be encouraged to stop smoking to avoid an unfavorable outcome.

BackgroundAlthough several validated generic health-related quality of life instruments exist, disease-specific instruments are important as they are often more sensitive to changes in symptom severity. It is essential to validate the instruments in a new population and language before their use. The objective of the study was to translate into Finnish the short forms of three condition-specific questionnaires (PFDI-20, PFIQ-7 and PISQ-12) and to evaluate their psychometric properties in Finnish women with symptomatic pelvic organ prolapse.MethodsA multistep translation method was used followed by an evaluation of validity and reliability in prolapse patients. Convergent and discriminant validity, internal consistency and reliability via test-retest were calculated.ResultsSixty-three patients waiting for prolapse surgery filled the three questionnaires within two weeks. Response rate for each item was high in PFDI-20 and PISQ-12 (99.8 and 98.9% respectively). For PFIQ-7 response rate was only 60%. In PFIQ-7, six respondents (9.5%) reached the minimum value of zero showing floor effect. None of the instruments had ceiling effect. Based on the item-total correlations both PFIQ-7 and PFDI-20 had acceptable convergent validity, while the convergent validity of PISQ-12 was lower, r = 0.138–0.711. However, in this instrument only three questions (questions 6, 10 and 11) had r < 0.3 while others had r ≥ 0.380. In the test-retest analysis all the three instruments showed good reliability (ICC 0.75–0.92). Similarly, the internal consistency of the instruments, measured by Cronbach’s α, was good (range 0.69–0.96) indicating high homogeneity.ConclusionsFinnish validated translation of the PFDI-20 and PISQ-12 have acceptable psychometric properties and can be used for both research purposes and clinical evaluation of pelvic organ prolapse symptoms. The Finnish version of PFIQ-7 displayed low response rate and some evidence of a floor effect, and thus its use is not recommended in its current form.Electronic supplementary materialThe online version of this article (doi:10.1186/s12955-017-0648-2) contains supplementary material, which is available to authorized users.

Introduction and hypothesis Patient-reported outcome measures are fundamental tools when assessing effectiveness of treatments. The challenge lies in the interpretation: which magnitude of change in score is meaningful for the patients? The minimal important difference (MID) is defined as the smallest difference in score that patients perceive as important. The Patient Acceptable Symptom State (PASS) represents the value of score beyond which patients consider themselves well. We aimed to determine the MID and PASS for Pelvic Floor Distress Inventory-20 (PFDI-20) and Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6) in pelvic organ prolapse (POP) surgery. Methods We used data from 2704 POP surgeries from a prospective, population-based cohort. MID was determined with three anchor-based and one distribution-based method. PASS was defined using two different methods. Medians of the estimates were identified. Results The MID estimates with (1) mean change, (2) receiver-operating characteristic (ROC) curve, (3) 75th percentile, and (4) distribution-based method varied between 22.9-25.0 (median 24.2) points for PFDI-20 and 9.0-12.5 (median 11.3) for POPDI-6. The PASS cutoffs with (1) 75th percentile and (2) ROC curve method varied between 57.7-62.5 (median 60.0) for PFDI-20 and 16.7-17.7 (median 17.2) for POPDI-6. Conclusion A mean difference of 24 points in the PFDI-20 or 11 points in the POPDI-6 can be used as a clinically relevant difference between groups. Postoperative scores ≤ 60 for PFDI-20 and ≤ 17 for POPDI-6 signify acceptable symptom state.