A spiral CT scan was performed at 6 months to detect presence of endoleaks. MMP-3 and MMP-9 levels were measured before EVG (nϭ30) and OSR (nϭ15) treatments and at 1, 3, and 6 months of follow-up by a sandwich ELISA technique. Healthy volunteers (nϭ10) were used as control subjects. Immunohistochemical staining for MMP-9 and MMP-3 was performed on tissue samples from surgical cases. Both MMP-9 and MMP-3 mean basal levels were significantly higher in patients affected by AAA than in control subjects (32.3Ϯ20.7 ng/mL for EVG and 28Ϯ9.9 ng/mL for OSR versus 8.9Ϯ2.5 ng/mL, 2PϽ0.05; 18.3Ϯ9.7 ng/mL and 26.7Ϯ10.8 ng/mL versus 8.2Ϯ5.3 ng/mL, 2PϽ0.001).In the OSR group, both MMP-9 and MMP-3 mean levels decreased after surgery (28Ϯ9.9 ng/mL at basal versus 14.7Ϯ6.6 ng/mL at 6 months, 2PϽ0.001; 26.7Ϯ10.8 versus 12Ϯ5.3 ng/mL; 2PϽ0.001). In the EVG group, a statistically significant difference at 6-month follow-up in MMP-9 and MMP-3 mean plasma values was detected in patients who had endoleakage in comparison with patients without endoleakage (44.3Ϯ20.7 versus 14.6Ϯ7.0 ng/mL, 2PϽ0.005; 25Ϯ11.5 versus 10.3Ϯ5.4 ng/mL, 2PϽ0.005). Conclusions-After EVG exclusion, MMP-9 and MMP-3 levels decreased to a level similar to that of patients undergoing OSR. In addition, a lack of decrease in MMP levels after EVG exclusion may help in identifying patients who will have endoleakage and consequent aneurysm expansion caused by continuous sac pressurization during follow-up.
Reliable biomarkers are needed to avoid diagnostic delay and its devastating effects in patients with primary central nervous system (CNS) lymphoma (PCNSL). We analysed the discriminating sensitivity and specificity of myeloid differentiation primary response (88) (MYD88) L265P mutation (mut-MYD88) and interleukin-10 (IL-10) in cerebrospinal fluid (CSF) of both patients with newly diagnosed (n = 36) and relapsed (n = 27) PCNSL and 162 controls (118 CNS disorders and 44 extra-CNS lymphomas). The concordance of MYD88 mutational status between tumour tissue and CSF sample and the source of ILs in PCNSL tissues were also investigated. Mut-MYD88 was assessed by TaqMan-based polymerase chain reaction. IL-6 and IL-10 messenger RNA (mRNA) was assessed on PCNSL biopsies using RNAscope technology. IL levels in CSF were assessed by enzyme-linked immunosorbent assay. Mut-MYD88 was detected in 15/17 (88%) PCNSL biopsies, with an 82% concordance in paired tissue-CSF samples. IL-10 mRNA was detected in lymphomatous B cells in most PCNSL; expression of IL-6 transcripts was negligible. In CSF samples, mut-MYD88 and high IL-10 levels were detected, respectively, in 72% and 88% of patients with newly diagnosed PCNSL and in 1% of controls; conversely, IL-6 showed a low discriminating sensitivity and specificity. Combined analysis of MYD88 and IL-10 exhibits a sensitivity and specificity to distinguish PCNSL of 94% and 98% respectively. Similar figures were recorded in patients with relapsed PCNSL. In conclusion, high detection rates of mut-MYD88 and IL-10 in CSF reflect, respectively, the MYD88 mutational status and synthesis of this IL in PCNSL tissue. These biomarkers exhibit a very high sensitivity and specificity in detecting PCNSL both at initial diagnosis and relapse. Implications of these findings in patients with lesions unsuitable for biopsy deserve to be investigated.
Introduction There is currently neither a clinically useful, reliable and inexpensive assay to measure circulating levels of free testosterone (T) in the range observed in women, nor is there agreement on the serum free T threshold defining hypoandrogenism that is associated with female-impaired sexual function. Aim Following the Clinical and Laboratory Standards Institute guidelines, we generated clinically applicable ranges for circulating androgens during specific phases of the menstrual cycle in a convenience sample of 120 reproductive-aged, regularly cycling healthy European Caucasian women with self-reported normal sexual function. Methods All participants were asked to complete a semistructured interview and fill out a set of validated questionnaires, including the Female Sexual Function Index, the Female Sexual Distress Scale, and the 21-item Beck's Inventory for Depression. Between 8 am and 10 am, a venous blood sample was drawn from each participant during the midfollicular (day 5 to 8), the ovulatory (day 13 to 15), and the midluteal phase (day 19 to 22) of the same menstrual cycle. Main Outcome Measures Serum levels of total and free testosterone, Δ4-androstenedione, dehydroepiandrosterone sulphate and sex hormone-binding globulin during the midfollicular, ovulatory and midluteal phase of the same menstrual cycle. Results Total and free T levels showed significant fluctuations, peaking during the ovulatory phase. No significant variation during the menstrual cycle were observed for Δ4-androstenedione and dehydroepiandrosterone sulphate. Despite the careful selection of participants that yielded an homogeneous group of women without sexual disorders, we observed a wide range of distribution for each of the circulating androgens measured in this study. Conclusions This report provides clinically applicable ranges for androgens throughout the menstrual cycle in reproductive-aged, regularly cycling, young healthy Caucasian European women with self-reported normal sexual function.
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