Prostate Imaging for Local Recurrence Reporting and Data System for Biparametric Magnetic Resonance Imaging: A Proposal.

We investigated a novel dedicated Prostate Imaging for Local Recurrence Reporting and Data System (PI-RRADS) in biochemical recurrence after radiotherapy (RT) and rad- ical prostatectomy (RP) evaluating biparametric magnetic resonance imaging (bpMRI) exams, at 3T MRI of 55 patients. Associating bpMRI and biochemical recurrence data, we calculated bpMRI diagnostic accuracy. Four probability categories, from 1 (very low) to 4 (very high), were distinguished. In 20 patients with radiotherapy, 25% and 75% of lesions were reported as PI-RRADS 3, and 4, respectively. In 35 patients with radi- cal prostatectomy, 7.7% of lesions were included in PI-RRADS 1-2, whereas 40.4% and 51.9% in PI-RRADS 3 and 4 categories, respectively. Excellent agreement and significant correlation between bpMRI and biochemical recurrence were found. BpMRI showed sensitivity, specificity, positive predictive value, negative predictive value, false-posi- tive value, false-negative value, and total diagnostic accuracy of 96.15%, 86.7%, 97.4 %, 81.25%, 13.3%, 3.8% and 94.6%, respectively. BpMRI-based PI-RRADS allows the detection and localization local recurrence in biochemical recurrence after RT and RP contributing in clinical management and treatment.

Biochemical and Anthropometric Parameters for the Early Recognition of the Intrauterine Growth Restriction and Preterm Neonates at Risk of Impaired Neurodevelopment.

BACKGROUND: S100B and Tau are implicated with both brain growth and injury. Their urinary levels in 30-to-40-day-old full-term, preterm, IUGR, and preterm-IUGR subjects were measured to investigate their possible relationship with future delayed neurodevelopment. METHODS: Values were related to the neuro-behavioral outcome at two years of age, as well as to brain volumes and urinary NGF assessed at the same postnatal time point. RESULTS: Using the Griffiths III test, cognitive and motor performances were determined to establish subgroups characterized by either normal or impaired neuro-behavior. The latter included preterm, IUGR, and preterm-IUGR individuals who exhibited significantly higher and lower S100B and Tau levels, respectively, along with markedly reduced cerebral volumes and urinary NGF, as previously demonstrated. Contrary to NGF, however, Tau and S100B displayed a weak correlation with brain volumes. CONCLUSIONS: Delayed cognitive and motor performances observed in two-year-old preterm and IUGR-born individuals were also found to be associated with anomalous urinary levels of S100B and Tau, assessed at 30-40 days of the postnatal period, and their changes did not correlate with brain growth. Thus, our data suggests that, in addition to cerebral volumes and NGF, urinary S100B and Tau can also be considered as valuable parameters for the early detection of future neurodevelopmental abnormalities.

S-PI-RADS and PI-RRADS for Biparametric MRI in the Detection of Prostate Cancer and Post-treatment Local Recurrence.

The application of biparametric magnetic resonance imaging (bpMRI) [T2-weighted (T2W) and diffusion weighted imaging (DWI)/apparent diffusion coefficient (ADC)] using dedicated structured methods, such as Simplified Prostate Imaging Reporting and Data System (S-PI-RADS) for the detection, categorization, and management of prostate cancer (PCa) is reported. Also, Prostate Imaging Reporting for Local Recurrence and Data System (PI-RRADS) for the detection and assessment of the probability of local recurrence after radiotherapy (RT) or radical prostatectomy (RP) in patients with biochemical recurrence (BCR) is proposed. Both S-PI-RADS and PI-RRADS assign to DWI/ADC a main role for the above purpose. S-PI-RADS identifies four categories and, on the basis of the qualitative and quantitative analysis of the restricted diffusion on ADC map and lesion volume, distinguishes two categories of lesions: category 3 (moderately homogeneous hypointense on ADC map) and category 4 (markedly homogeneous or inhomogeneous hypointense on ADC map). Ιn category 3, two subcategories (3a: volume <0.5 cm3 and 3b: volume ≥0.5 cm3) suggesting clinical management. PI-RRADS distinguishes four assessment categories and suggests the stratification of the probability (ranging from very low for category 1 to very high for category 4) of local disease recurrence. In clinical practice, S-PI-RADS and PI-RRADS, based on bpMRI represent a potential valid approach that may facilitates the detection and management of PCa and for detecting local recurrence after treatment improving communication with other professionals.

Lesion Volume in a Bi- or Multivariate Prediction Model for the Management of PI-RADS v2.1 Score 3 Category Lesions.

OBJECTIVE: This study aimed at improving the discrimination of Prostate Imaging - Reporting and Data System version 2.1 (PI-RADS v2.1) score 3 suspicious prostate cancer lesions using lesion volume evaluation. MATERIAL AND METHODS: Two hundred five PI-RADS v2.1 score 3 lesions were submitted to transperineal MRI/TRUS fusion-targeted biopsy. The lesion volumes were estimated on diffusion-weighted imaging sequence and distributed in PI-RADS 3a (LV < 0.5 mL) and PI-RADS 3b (LV ≥ 0.5 mL) subcategories, using a 0.5 mL cutoff value. Data were retrospectively matched with histopathological findings from the biopsy. Assuming that lesions with LV < or ≥ 0.5 mL were respectively not eligible (benign and indolent PCa lesions) or eligible for biopsy (significant PCa lesions), the diagnostic accuracy of lesion volume in determining clinically significant PCa at biopsy was evaluated using a bi- or multivariate model. RESULTS: About 55.1% and 44.9% of lesions were distributed in subcategories 3a and 3b, respectively. The overall PI-RADS score 3 detection rate was 273%. 3.5% (1.95% of total), and 25% (11.7% of total) significant PCa were found in PI-RADS 3a and 3b subcategory, respectively. The method showed 85.2% sensitivity, 61.2% specificity, 25% positive predictive value, and 96.5% negative predictive value and avoided 55.1% of unnecessary biopsies. The diagnostic accuracy in determining significant PCa at biopsy was 73.2% or 86.5% depending on whether lesion volume was used alone or in combination with prostate volume and patient age in a multivariate model. CONCLUSION: 0.5 mL lesion volume cutoff value significantly discriminates fusion-targeted biopsy need in PI-RADS v2.1 score 3 lesions and its diagnostic accuracy improves when it combines with prostate volume and age in a multivariate model.

Brain 3D-echographic early predictors of neuro-behavioral disorders in infants: a prospective observational study.

BACKGROUND: Prematurity, low birth weight (LBW), very low birth weight (VLBW), and intrauterine growth restriction (IUGR) are risk factors of long-term poor neuro-development outcomes and associate with reduction of regional brain volumes. OBJECTIVE: To evaluate the possible role of 3D ultrasound sonography (3DUS) regional brain volumes, measured at 30-40 days of postnatal period, as early predictors of long-term risk of neuro-behavioral disorders. METHODS: A highly selected population, which included: full-term, preterm, IUGR, and preterm-IUGR born individuals, was followed longitudinally from 30 to 40 days of postnatal period to the second year of life. The population was mostly composed of bichorionic twins to ensure a, theoretically, major intracategory homogeneity. Preterm and IUGR subjects were characterized by a gestational age (GA) and birth weight (BW)>32 weeks and >1500 g, respectively, whereas the full-term neonates were of 37 weeks GA. At enrollment, the assessment of the volumetric measurements was performed using the 3DUS. The evaluation of neuro-development was performed at 2 years using the Griffiths Mental Development Scales. RESULTS: The 3DUS measurements of whole brain, thalamus, frontal cortex, and cerebellum volumes, assessed at 30-40 days of postnatal period, were significantly reduced in infants characterized by negative outcome. In addition, the respective areas of the ROC curves, made by comparing values of normal and abnormal neuro-development groups, were indicative of a strong diagnostic accuracy. CONCLUSION: Data found suggest that the 3DUS regional brain volumes may assume a significant role as early indicators of neonates at major risk of neuro-behavioral disorders in later life. Further and larger studies in this direction are needed to validate this significant perspective.

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.

Simplified PI-RADS (S-PI-RADS) for biparametric MRI to detect and manage prostate cancer: What urologists need to know.

Biparametric magnetic resonance imaging (bpMRI) of the prostate has emerged as an alternative to multiparametric MRI (mpMRI) for the detection of clinically significant prostate cancer (csPCa). However, while the Prostate Imaging Reporting and Data System (PI-RADS) is widely known for mpMRI, a proper PI-RADS for bpMRI has not yet been adopted. In this review, we report the current status and the future directions of bpMRI, and propose a simplified PI-RADS (S-PI-RADS) that could help radiologists and urologists in the detection and management of PCa.

Urinary Cystatin-C, a marker to assess and monitor neonatal kidney maturation and function: validation in twins.

BACKGROUND: Nephrogenesis is a complex process of nephron formation and maturation that can be compromised by preterm delivery and intrauterine growth restriction. This study aimed to evaluate and compare urinary Cys-C levels with renal volume in a cohort of preterm and term twins, adequate for gestational age or intrauterine growth restricted, to investigate their values in different conditions of nephrogenesis. METHODS: The study was performed on twins at 30-40 days of postnatal corrected age: renal volumes were measured by 3D ultrasound technology and urine samples were analyzed for Cystatin-C. A follow-up was performed by Cystatin-C. RESULTS: Renal volumes in preterm and intrauterine growth-restricted twins showed values significantly lower than those observed in term twins and were inversely correlated to urinary Cystatin-C levels. During the follow-up, intrauterine growth-restricted twins showed amplified levels of urinary Cystatin-C; in contrast, invariable or decreased levels were observed in adequate for gestational age twins. CONCLUSIONS: Urinary Cystatin-C, evaluated when intrauterine/extrauterine nephrogenesis could be considered completed, concurrently with renal volume assessment can improve the identification of neonates with initial kidney impairment. Its potential value as a useful marker in monitoring physiological/pathological renal conditions could be considered, mainly for neonates at elevated risk of developing long-term renal diseases. IMPACT: Urinary Cys-C levels are inversely correlated to renal volumes and reflect nephrogenesis conditions. No data in literature are reported regarding: (a) the concurrent assessment of renal volumes and urinary levels of Cystatin-C in preterm and term twins with different conditions of gestational life, i.e., AGA and IUGR and (b) the follow-up of IUGR and preterm neonates using the urinary Cys-C determination. The variations of urinary Cys-C levels, observed in the follow-up of preterm and/or IUGR neonates, support the usefulness of monitoring those neonates with altered nephrogenesis, who are later at risk for renal impairment and for long-term renal diseases.

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.

Prostate MRI and transperineal TRUS/MRI fusion biopsy for prostate cancer detection: clinical practice updates.

This narrative review summarizes the current knowledge about multiparametric and biparametric magnetic resonance imaging of the prostate. This is provided from both a radiological and a urological point of view analyzing the technical aspects of fusion-targeted biopsy using the transperineal approach. We report practical considerations concerning pure cognitive and software-assisted settings, discuss the principal transperineal fusion software now available, and debate the pros and cons of choosing one approach over the other.

Locally advanced rectal cancer: qualitative and quantitative evaluation of diffusion-weighted magnetic resonance imaging in restaging after neoadjuvant chemo-radiotherapy.

PURPOSE: To determine the added value of qualitative and quantitative evaluation of diffusion-weighted magnetic resonance imaging (DWI) in locally advanced rectal cancer (LARC) restaging after neoadjuvant chemo-radiotherapy (CRT). MATERIALS AND METHODS: A retrospective study was performed of 21 patients with LARC treated with CRT. All patients were evaluated with 1.5 T conventional magnetic resonance imaging (MRI) and DWI (0-1000 s/mm²) before starting therapy and after neoadjuvant CRT. All included patients underwent surgery after CRT: the histopathological evaluation of surgical specimens represented the reference standard for local staging after neoadjuvant therapy. The qualitative analysis was carried out by two operators in consensus, who reviewed the conventional MR image set [T1-weighted and T2-weighted morphological sequences + dynamic contrast-enhanced sequences (DCE)] and the combined set of conventional and DW images. For the quantitative analysis, the apparent diffusion coefficient (ADC) values were measured at each examination. For each lesion, the mean ADC value (ADCpre and ADCpost) and the ΔADC (ADCpost - ADCpre) were calculated, and values of the three groups of response [complete response (pCR), partial response (pPR), stable disease (pSD)] were compared. RESULTS: In LARC restaging, conventional MRI showed a sensitivity of 80% and a specificity of 50%, with a total diagnostic capacity of 71.40%, while by adding DWI sensitivity increased to 100%, specificity to 67%, and total diagnostic capacity to 90.40%. ΔADC correlates with treatment response and a cutoff of 1.35 × 10-3 mm²/s predicts the pCR with a sensitivity of 93.3% and a specificity of 83.3%. CONCLUSIONS: Adding DWI to conventional sequences may improve MRI capability to evaluate tumor response to CRT. The quantitative DWI assessment is promising, but larger studies are required.

Renal Consequences of Gestational Diabetes Mellitus in Term Neonates: A Multidisciplinary Approach to the DOHaD Perspective in the Prevention and Early Recognition of Neonates of GDM Mothers at Risk of Hypertension and Chronic Renal Diseases in Later Life.

Fetal exposure to gestational diabetes mellitus (GDM) seems to stimulate a negative impact on the kidneys. Renal volumes and urinary biomarkers of renal function and tubular impairment and injury were evaluated in 30⁻40-day old newborns of GDM mothers (n = 139) who needed insulin therapy during pregnancy. We found that neonates of mothers who maintained strict control over normoglycemia (n = 65) during pregnancy and fulfilled the other criteria of the GDM management program showed no differences compared to control (n = 55). Conversely, those (n = 74), whose mothers did not maintain glycemic control and were not compliant to the management program, exhibited significantly lower levels of renal volumes and higher activity of N-acetyl-ß-D-glucosaminidase and cathepsin B. Differences due to maternal pre-gestational and gestational body mass index (BMI) as well as to maternal weight gain were demonstrated. Our findings indicate that a multidisciplinary approach, which involves an appropriate management of GDM, prevents the negative effects of GDM on the kidneys at 30⁻40 days of postnatal age, indicating the fundamental role of glycemic control, as well as of an adequate range of maternal weight gain. Total renal volume, cortical volume, and urinary activity of N-acetyl-ß-D-glucosaminidase and cathepsin B may be suggested as indicators for the early recognition of GDM neonates at long-term risk of hypertension and kidney disease.

COX inhibitors and bone: A safer impact on osteoblasts by NO-releasing NSAIDs.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain and inflammation. Although it is well known that NSAIDs can suppress bone growth, remodelling and repair, they are largely used post-operatively and post-traumatically to achieve analgesia and reduce inflammation in bone tissue. AIMS: The impact of two NO-releasing, non-selective NSAIDs, NCX-4016 and HCT-3012 (NO-derivatives of Aspirin and Naproxen, respectively) on osteoblasts were evaluated and compared to the non-selective, parent chemicals and to the COX-2-selective inhibitor Celecoxib. MAIN METHODS: Using MG-63 osteoblast-like cells, we considered proliferation, the early and late stage of differentiation, and the activity of proteinases thought to be involved in osteoid degradation, a preliminary fundamental event of bone remodelling. KEY FINDINGS: Unlike Aspirin, Naproxen and Celecoxib, the two NO-NSAIDs did not alter proliferation and differentiation of osteoblasts. They also reduced the activity of plasminogen activator, metalloproteinases, and cathepsin B. Similar inhibitory effects against these proteinases were recapitulated by the NO-donor sodium nitroprusside, thereby suggesting a NO-mediated mechanism. SIGNIFICANCE: Due to a differential effect on cell proliferation and differentiation, the two NO-NSAIDs exhibit a safer impact on osteoblast metabolism compared to Celecoxib and their parent compounds. This suggests an advantageous option for these drugs in individuals with a need of COX-inhibiting treatment, in general. In addition, their capability of modulating the proteinases involved in osteoid degradation may specifically suggest an additional safer use in comorbidity conditions of inflammation or pain with bone disorders characterized by high rate of remodelling, such as high-turnover osteoporosis in post-menopausal women.

Simplified Prostate Imaging Reporting and Data System for Biparametric Prostate MRI: A Proposal.

OBJECTIVE: We describe our institutional experience using a simplified Prostate Imaging Reporting and Data System (PI-RADS) based on biparametric prostate MRI. We discuss two important controversies: the use of gadolinium-based contrast agents and the management of PI-RADS category 3 lesions. CONCLUSION: Our simplified PI-RADS identifies four categories and suggests management strategies for each. The simplified PI-RADS can be an effective system to facilitate multidisciplinary cooperation and to improve the management of suspected prostate cancer.