Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age.

(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22-49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients.

Fetal pulmonary hemodynamics: Doppler reference values in low risk pregnancies.

OBJECTIVE: To investigate fetal pulmonary hemodynamics in normal pregnancy using pulsed and color Doppler ultrasonography and to define Doppler reference ranges values in the whole fetal pulmonary circulation during different gestational ages. MATERIALS AND METHODS: A prospective observational study was conducted to evaluate 190 healthy singleton pregnancies between 20 and 38 weeks of gestation, including 10 cases for each gestational age. The main pulmonary artery, right pulmonary artery, left pulmonary artery, ductus arteriosus and pulmonary veins waveforms were evaluated. The waveform profile was studied for each pulmonary vessel investigated. We calculated the normal distribution of data of 12 Doppler parameters, their values were expressed as 5th, 25th, 50th, 75th and 95th centile. RESULTS: We report several pulmonary hemodynamic changes with the progression of pregnancy. We focused on the hemodynamic values of the parameters most useful in clinical practice and that would better describe the hemodynamic events of this vascular district. CONCLUSION: This study reports a complete description of the fetal pulmonary hemodynamics at different gestational ages. Many hemodynamic parameters show a typical change during gestation. The reference ranges described in this study may help in situations where is indicated to evaluate the pulmonary hemodynamics and to identify healthy fetuses from those affected by pathological conditions related mainly to fetal cardiovascular anomalies and/or feto-maternal pathologic conditions.

3-D Echo Brain Volumes to Predict Neurodevelopmental Outcome in Infants: A Prospective Observational Follow-up Study.

Prematurity and intra-uterine growth restriction (IUGR) are risk factors for long-term poor neurodevelopmental outcomes and are associated with reductions in regional brain volumes. In this study, the aim was to determine the possible role of 3-D ultrasonography (3-DUS) volumes of whole brain, thalamus, frontal cortex and cerebellum, measured at postnatal days 30-40, as early predictors of long-term risk for neurobehavioral disorders. To this purpose, a heterogeneous population of full-term, preterm, IUGR and preterm IUGR (pre-IUGR) born individuals (n = 334), characterized by gestational age and birth weight in the ranges 24-41 wk and 860-4000 g, respectively, was followed from postnatal days 30-40 to the second year of life. At enrollment, brain volumes were measured using 3-DUS, whereas neurodevelopment was assessed at 2 y using the Griffiths III test. Cerebral volumes were strictly and significantly lower in infants characterized by a negative outcome and had excellent diagnostic accuracy. The 3-DUS volume of whole brain, thalamus, frontal cortex or cerebellum may be an early predictor of neonates at major risk for neurobehavioral disorders in later life.

Urinary Nerve Growth Factor in full-term, preterm and intra uterine growth restriction neonates: Association with brain growth at 30-40 days of postnatal period and with neuro-development outcome at two years. A pilot study.

Nerve Growth Factor (NGF) and Brain Derived Neurotrophic Factor (BDNF) are crucial for the peripheral and central nervous system development, respectively, and differential brain and blood levels in Intra Uterine Growth Restriction (IUGR) and prematurity have been found. As reduced growth of brain regions, measured at 30-40 days of postnatal period, has been demonstrated in preterm and IUGR neonates who showed impaired neuro-development at two years of age, in this study, the levels of NGF and BDNF were evaluated in the urine samples of 30-40 day-old subjects who were full-term, preterm and IUGR and showed a normal or an abnormal neuro-development at follow up after two years. Neurotrophins were measured concurrently with volumes of whole brain, thalamus, frontal cortex and cerebellum. Values were then correlated with later neuro-developmental outcome. Biochemical parameters and cerebral volumes were assessed using colorimetric ELISA kits and three-dimensional ultra-sonography (3DUS), respectively. Neuro-development was estimated using the Griffiths-II test. Urinary NGF and brain volumes significantly correlated and were lower in preterm and IUGR subjects characterized by poor neuro-development. No differences were seen in the case of BDNF. The present investigation demonstrates, for the first time, the strong and direct association of NGF with brain growth at the initial phase of the postnatal period and with neuro-developmental outcome in later life. Remarkably, urinary NGF may be suggested as an early prognostic indicator of high long-term risk of motor and cognitive impairment in IUGR and preterm neonates.