Whole-body non-forensic fetal virtopsy using postmortem magnetic resonance imaging at 7 Tesla vs classical autopsy.

OBJECTIVE: To determine the diagnostic accuracy of virtual autopsy using whole-body postmortem ultra-high field magnetic resonance imaging (MRI) at 7 Tesla (T), using a short T2-weighted imaging (T2-WI) protocol, compared with classical autopsy, for detecting structural abnormalities in small second-trimester fetuses. METHODS: Thirty consecutive fetuses at 13-19 weeks' gestation (weight, 17-364 g) were included following spontaneous pregnancy loss or termination of pregnancy. After fixation in 10% formaldehyde solution (48 h to 1 week), all fetuses were scanned using a two-dimensional turbo high-resolution T2-WI protocol with multislice relaxation time, followed by an invasive autopsy. The diagnostic accuracy of virtual autopsy vs classical autopsy was calculated for 990 anatomical structures (30 fetuses × 33 items). Sensitivity, specificity, positive and negative predictive values and Cohen's κ coefficient of agreement, with their 95% CIs, as well as the McNemar test, were used to evaluate the accuracy and agreement of the two diagnostic methods. Analysis was stratified by anatomical segment (nervous, pulmonary, cardiovascular, digestive, renal, facial and skeletal) and across three gestational-age intervals (13-14, 15-16 and 17-19 weeks). RESULTS: Considering classical autopsy as the gold standard, virtual autopsy had a sensitivity of 92.04% (95% CI, 85.42-96.29%) and a specificity of 97.87% (95% CI, 94.64-99.42%), with a positive predictive value of 96.30% (95% CI, 90.78-98.56%) and a negative predictive value of 95.34% (95% CI, 91.61-97.45%), achieving a diagnostic accuracy of 95.68% (95% CI, 92.73-97.68%) for detecting structural abnormalities in second-trimester fetuses. Cohen's κ for virtual vs classical autopsy was 0.907. The diagnostic ability of virtual autopsy at 7 T for malformed fetuses was superior to that of classical autopsy for analyzing the nervous system in small fetuses with pronounced autolysis, equivalent to that of classical autopsy when analyzing pulmonary, cardiovascular and renal systems and inferior when evaluating the fetal intestines. The sensitivity of virtual autopsy at 7 T for describing structural abnormalities increased with gestational age. CONCLUSION: Virtual fetal autopsy using 7-T MRI and a turbo high-resolution T2-WI protocol with multislice relaxation time is a feasible postmortem diagnostic tool for the identification of fetal structural anomalies. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

THE ROLE OF HIGH FOLLICULAR LEVELS OF ANGIOTENSIN II AND VASCULAR ENDOTHELIAL GROWTH FACTOR IN ANTICIPATING THE DEVELOPMENT OF SEVERE OVARIAN HYPERSTIMULATION SYNDROME IN PATIENTS WITH PROPHYLACTIC CABERGOLINE THERAPY UNDERGOING AN IN VITRO FERTILIZATION PROCEDURE.

BACKGROUND AND AIMS: Severe Ovarian Hyperstimulation Syndrome (OHSS) forms with very aggressive clinical evolution are still common, despite prophylactic measures. Besides the Vascular Endothelial Growth Factor (VEGF), there are other angiogenic factors, like Renin-Angiotensin-Aldosterone System (RAS), that might be associated with this disorder. Our study aims to evaluate the role of VEGF and Angiotensin II (ANG II) in the development of early severe OHSS, in high risk patients under prophylactic Cabergoline therapy. MATERIAL AND METHODS: We recruited 192 patients undergoing in vitro fertilization (IVF) procedures with high risk for OHSS development. Out of these, 106 patients with OHSS were enrolled in the study, of which 28 subjects had a severe form of disease (group I), and 78 patients had a mild/moderate form (group II). We collected blood and follicular fluid from our study participants and determined serum and follicular VEGF and ANG II levels using Enzyme-Linked Immunosorbent Assay (ELISA) technique. RESULTS: Follicular VEGF, ANG II, and serum VEGF levels were significantly higher in group I versus group II. Serum VEGF titers were 645.97 versus 548.62 (p = 0.0008), follicular VEGF titers were 2919.52 versus 1093.68 (p < 0.0001), and follicular ANG II levels were 281.64 versus 65.76 (p < 0.0001). No significant differences have been shown between the two groups for serum ANG II levels. CONCLUSION: Our study results provide evidence of a OHSS phenotype that is more prone to undergo severe clinical forms of disease, despite treatments with VEGF receptor blockers, and show that ANG II appears to play a major role alongside VEGF, in the development of these severe forms of disease.

Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

OBJECTIVES: EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. METHODOLOGY: 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. RESULTS: The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. CONCLUSIONS: Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors.

OBJECTIVES: EWS/FLI-1 fusion mainly appears in Ewing's sarcoma or the primitive neuroectodermal tumors and represents a genomic marker for these tumors. However, it can appear with lower frequency in other soft tissue tumors. The paper investigates the presence of EWS/FLI-1 fusion in clinically diagnosed sarcoma belonging to different non-Ewing connective tissue tumors in order to search for a possible new biomarker valuable for investigators. METHODOLOGY: 20 patients with soft tissue tumors, who underwent surgery, were tested. Intra-operative samples of normal and tumor tissue were collected for histopathological diagnosis and genetics determinations. The patients' RNA from tumor and normal peritumoral tissue was extracted and EWS/FLI-1 fusion screened by quantitative real-time PCR. The relative expression of the fusion in the tumor sample was compared to the similar expression in normal tissue. RESULTS: The amplification in the threshold zone was shown by 5 samples (25%): 2 clear cell sarcoma, 1 fibrosarcoma, 1 malignant tumor of nerve sheath, 1 metastatic adenocarcinoma. We differentiated between the unspecific amplification and concluded that these are weak positive results. CONCLUSIONS: Genomic investigation may establish the tumor malignancy and its possible affiliation earlier than histopathology. It can support the screening of EWS/FLI-1 fusion in a larger variety of clinically diagnosed soft tissue tumors.

CD28 T-cell costimulatory molecule expression in pemphigus vulgaris.

BACKGROUND: CD28 superfamily of immune costimulatory molecules could play an important role in autotolerance control. CD28 costimulation seems to be necessary for regulatory T cell (Treg) activation and successive suppressive activities involved in autoimmunity protection. This study investigates CD28 expression, especially inducible costimulator fraction, on T lymphocytes in pemphigus vulgaris (PV) patients. METHODS: CD28 expression on T lymphocytes was assessed in 16 PV patients during acute attack. All patients and 10 healthy control subjects were tested for lymphocyte populations, T-cell subpopulations (T-CD4+, T-CD8+), Treg and CD28 expression on T-cell subpopulations. RESULTS: T, B and natural killer cells average values in PV patients were close to the control group values. Compared with control group, PV values showed lower Treg (2.2% compared with 4.7%), slightly decreased CD4+ CD28+ T cells (91% compared with 95%), higher CD4+ CD28- T cells (9% compared with 5%), decreased CD8+ CD28+ T cells (57% and 73%, respectively) and significantly enhanced CD8+ CD28- T cells (43% compared with 27%). CONCLUSIONS: These data suggest that Treg-mediated suppressor T-cell effects could be diminished in PV, together with an abnormal or ineffective subsequent helper T-cell suppression. CD28 high expression on helper T cells and low expression on suppressor T cells are arguments for a potential CD28 role in PV autoimmune response mechanism.