External validation of the barcelona magnetic resonance imaging predictive model for detecting significant prostate cancer including men receiving 5-alpha reductase inhibitors.

PURPOSE: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). MATERIALS AND METHODS: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. RESULTS: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783-0.842) and 0.849 (0.806-0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. CONCLUSIONS: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.

Interplay of the Mediterranean diet and genetic hypertension risk on blood pressure in European adolescents: Findings from the HELENA study.

Early-life onset of high blood pressure is associated with the development of cardiovascular diseases in adulthood. In adolescents, limited evidence exists regarding the association between adherence to the Mediterranean Diet (MedDiet) and normal blood pressure (BP) levels, as well as its potential to modulate genetic predisposition to HTN. This study investigated the interaction between a MedDiet score and a recently developed HTN-genetic risk score (HTN-GRS) on blood pressure levels in a European adolescent cohort. The MedDiet score was derived from two non-consecutive 24-h dietary recalls and ranged from 0 (indicating low adherence) to 9 (indicating high adherence). Multiple linear regression models, adjusted for covariates, were employed to examine the relationship between the MedDiet score and BP z-scores and to assess the interaction effects between the MedDiet score and HTN-GRS on BP z-scores. MedDiet score showed a negative association with z-systolic BP (SBP) (ß = -0.40, p < 0.001) and z-diastolic BP (DBP) (ß = -0.29, p = 0.001). Additionally, a significant interaction effect was identified between the MedDiet score and HTN-GRS on z-SBP (ß = 0.02, p < 0.001) and z-DBP (ß = 0.02, p < 0.001). The modulatory effect of the MedDiet was more pronounced in females than in males, and HTN-GRS exhibited a stronger influence on DBP than on SBP.   Conclusion: The study suggests that higher adherence to the MedDiet is associated with reduced BP levels in adolescents and provides evidence of a genetic-diet interaction influencing BP in adolescents. What is Known: • Adherence to the Mediterranean diet may reduce BP levels. What is New: • It is the first study to assess the connection between adherence to a Mediterranean diet, a hypertension genetic risk score, and how they interact in influencing blood pressure. • It is conducted within a multicenter cohort of European adolescents.

Prostate Cancer and the Mevalonate Pathway.

Antineoplastic therapies for prostate cancer (PCa) have traditionally centered around the androgen receptor (AR) pathway, which has demonstrated a significant role in oncogenesis. Nevertheless, it is becoming progressively apparent that therapeutic strategies must diversify their focus due to the emergence of resistance mechanisms that the tumor employs when subjected to monomolecular treatments. This review illustrates how the dysregulation of the lipid metabolic pathway constitutes a survival strategy adopted by tumors to evade eradication efforts. Integrating this aspect into oncological management could prove valuable in combating PCa.

The body mass index increases the genetic risk scores' ability to predict risk of hepatic damage in European adolescents: The HELENA study.

BACKGROUND: Hepatic disorders are often complex and multifactorial, modulated by genetic and environmental determinants. During the last years, the hepatic disease has been progressively established from early stages in life. The use of genetic risk scores (GRS) to predict the genetic susceptibility to a particular phenotype among youth has gained interest in recent years. Moreover, the alanine aminotransferase (ALT) blood biomarker is often considered as hepatic screening tool, in combination with imaging techniques. The aim of the present study was to develop an ALT-specific GRS to help in the evaluation of hepatic damage risk in European adolescents. METHODS: A total of 972 adolescents (51.3% females), aged 12.5-17.5 years, from the Healthy Lifestyle in Europe by Nutrition in Adolescence study were included in the analyses. The sample incorporated adolescents in all body mass index (BMI) categories and was divided considering healthy/unhealthy ALT levels, using sex-specific cut-off points. From 1212 a priori ALT-related single nucleotide polymorphisms (SNPs) extracted from candidate gene selection, a first screening of 234 SNPs univariately associated was established, selecting seven significant SNPs (p < .05) in the multivariate model. An unweighted GRS (uGRS) was developed by summing the number of reference alleles, and a weighted GRS (wGRS), by multiplying each allele to its estimated coefficient. RESULTS: The uGRS and wGRS were significantly associated with ALT (p < .001). The area under curve was obtained integrating BMI as clinical factor, improving the predictive ability for uGRS (.7039) and wGRS (.7035), using 10-fold internal cross-validation. CONCLUSIONS: Considering BMI status, both GRSs could contribute as complementary tools to help in the early diagnosis of hepatic damage risk in European adolescents.

Postnatal catch-up growth in term newborns with altered fetal weight patterns. The GROWIN study.

BACKGROUND: Small for gestational age (SGA) perform a postnatal catch-up growth to recover their genetic trajectory. We studied the postnatal catch-up growth pattern of fetuses born with an appropriate-for-gestational-age (AGA) weight but with fetal growth deceleration (FGD) to explore whether they catch up. METHODS: Nine hundred and sixty-six newborns at Villalba University General Hospital (HUGV), were followed from 34 to 37 weeks to birth. Z-scores, adjusted for sex and age, of weight, length, and BMI at 3, 6, 9, and 12 months were calculated. We define catch-up as an increase in z-score greater than 0.67 SD in the growth curves. RESULTS: AGA FGD had lower mean weight and length than AGA non-FGD at all time points; BMI was lower until 3 months. AGA FGD had a lower weight, length, and BMI z-score (until 9, 6 months, and at birth, respectively) than AGA non-FGD. AGA FGD newborns had a significantly increased likelihood of weight catch-up at 3 months (OR 1.79; 95% CI: 1.16, 2.78; p = 0.009) and BMI in all investigated periods (OR 1.90; 95% CI 1.30, 2.78; p < 0.001 at 3 months), compared to AGA non-FGD newborns. CONCLUSIONS: AGA FGD newborns perform catch-up growth, especially in weight and BMI, in the first year of life, compared to AGA non-FGD. IMPACT: Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a lower weight and height, during the first year of life, compared to AGA non-FGD. Appropriate-for-gestational-age (AGA) newborns with fetal growth deceleration (FGD), between the third trimester of pregnancy and delivery, present a higher likelihood of weight catch-up in the first 3 months of life and of BMI in the first year compared to AGA non-FGD. AGA FGD experienced early weight and BMI catch-up, especially in the first 3 months of life, like SGA. This finding should be considered in the future follow-up.

Yield, Chemical Composition and Bioactivity of Essential Oils from Common Juniper (Juniperus communis L.) from Different Spanish Origins.

Essential oils (EOs) obtained from Juniperus communis L. are frequently used in the production of bioproducts. However, there are no studies regarding industrial crops' production, allowing for better control of the quality and production of juniper EOs. To select the plant material for developing future crops of this species in northern Spain, four locations where this shrub species grows in the wild were selected and samples of both genera were collected. The EOs were obtained by steam distillation, and their chemical composition and bioactivity were evaluated. The results showed that the yield of EOs from male and female samples were within the usual reported ranges, varying between 0.24 and 0.58% (dry basis, d.b.). However, limonene content in three locations varied between 15 and 25%, which is between 100% and 200% higher than the values usually reported for other European countries. The antibacterial activity was determined by broth microdilution and showed that gram-positive bacteria were more susceptible to the tested EOs since, in general, lower MIC values were obtained compared to gram-negatives. The EOs from location 1 (L1F) and 2 (L2M) inhibited the growth of six out of the eight clinical strains tested. Samples from location 1 were particularly effective, exhibiting MBC against two gram-negative (E. coli and P. mirabilis) and one gram-positive bacteria (E. faecalis). Moreover, the majority of the EOs tested showed anti-inflammatory activity. Cytotoxic effect has been demonstrated in tumor cell lines, with the best results observed against gastric carcinoma (AGS) cells (GI50 between 7 to 77 µg/mL). Although generally presenting higher GI50, most samples also inhibited the growth of non-tumoral cells, particularly hepatocytes (PLP2 cells). Therefore, its use for their anti-proliferative activity should consider specific conditions to avoid damaging normal cells. Finally, the results and conclusions obtained led to the selection of the female shrubs from location 1 (L1F) as the plant material to be propagated in order to produce plants for a future juniper crop.

Assessment of the Use of Common Juniper (Juniperus communis L.) Foliage following the Cascade Principle.

Juniperus communis L. is a species commonly grown in regions of the Northern Hemisphere, and is a good candidate to be cultivated in marginal lands. Plants coming from a pruning performed in a natural population located in Spain were used to assess the yield and quality of different products obtained following the cascade principle. A total of 1050 kg of foliage biomass were crushed, steam-distilled, and separated into fractions to produce biochar and absorbents for the pet industry using pilot plants. The obtained products were analysed. The essential oil, with a yield of 0.45% dry basis and a qualitative chemical composition similar to that described for the berries in international standards or monographs, showed antioxidant activity with promising CAA results (inhibition of 89% of the cell's oxidation). However, regarding antibacterial and antifungal activities, it only inhibited the growth of microorganisms at the maximum concentration tested, 2.5%. Concerning the hydrolate, it did not show bioactivity. Regarding the biochar, whose yield was 28.79% dry basis, interesting results were obtained for its characterisation as a possible soil improver for agronomic purposes (PFC 3(A)). Finally, promising results were obtained regarding the use of common juniper as absorbent, taking into account the physical characterisation and odour control capacity.

Mortality and Causes of Death After Liver Transplantation: Analysis of Sex Differences in a Large Nationwide Cohort.

In the last few years, several studies have analyzed sex and gender differences in liver transplantation (LT), but none have performed a disaggregated analysis of both mortality and causes of death. Data from 15,998 patients, 11,914 (74.5%) males and 4,069 (25.5%) females, transplanted between 2000 and 2016 were obtained from the Liver Transplantation Spanish Registry. Survival analysis was applied to explore recipient sex as a risk factor for death. The causes of death at different follow-up duration were disaggregated by recipient sex for analysis. Short-term survival was higher in males, whereas long-term survival was higher in females. Survival at 1, 5 and 10 years post-transplant was 87.43%, 73.83%, and 61.23%, respectively, in males and 86.28%, 74.19%, and 65.10%, respectively, in females (p = 0.05). Post-LT mortality related to previous liver disease also presented sex differences. Males had 37% increased overall mortality from acute liver failure (p = 0.035) and 37% from HCV-negative cirrhosis (p < 0.001). Females had approximately 16% increased mortality when the liver disease was HCV-positive cirrhosis (p = 0.003). Regarding causes of death, non-malignancy HCV+ recurrence (6.3% vs. 3.9% of patients; p < 0.001), was more frequently reported in females. By contrast, death because of malignancy recurrence (3.9% vs. 2.2% of patients; p = 0.003) and de novo malignancy (4.8% vs. 2.5% of patients; p < 0.001) were significantly more frequent in male recipients. Cardiovascular disease, renal failure, and surgical complications were similar in both. In summary, male patients have lower short-term mortality than females but higher long-term and overall mortality. In addition, the post-LT mortality risk related to previous liver disease and the causes of mortality differ between males and females.

Genomic analysis revealed conserved acid tolerance mechanisms from native micro-organisms in fermented feed.

AIMS: Fermented feed is an agricultural practice used in many regions of the world to improve the growth performance of farm animals. This study aimed to identify and evaluate the lactic acid bacteria and yeast involved in the production of fermented feed. METHODS AND RESULTS: We isolated and described two micro-organisms from autochthonous microbiota origin present in a regional feed product, Lactobacillus paracasei IBR07 (Lacticaseibacillus paracasei) and Kazachstania unispora IBR014 (Saccharomyces unisporum). Genome sequence analyses were performed to characterize both micro-organisms. Potential pathways involved in the acid response, tolerance and persistence were predicted in both genomes. Although L. paracasei and K. unispora are considered safe for animal feed, we analysed the presence of virulence factors, antibiotic resistance and pathogenicity islands. Furthermore, the Galleria mellonella model was used to support the safety of both isolates. CONCLUSIONS: We conclude that IBR07 and IBR014 strains are good candidates to be used as starter cultures for feed fermentation. SIGNIFICANCE AND IMPACT OF THE STUDY: The data presented here will be helpful to explore other biotechnological aspects and constitute a starting point for further studies to establish the consumption benefit of fermented feed in farm animal production.

Predictive Value of Genetic Risk Scores in the Development of Colorectal Adenomas.

INTRODUCTION: Unlike colorectal cancer (CRC), few studies have explored the predictive value of genetic risk scores (GRS) in the development of colorectal adenomas (CRA), either alone or in combination with other demographic and clinical factors. METHODS: In this study, genomic DNA from 613 Spanish Caucasian patients with CRA and 829 polyp-free individuals was genotyped for 88 single-nucleotide polymorphisms (SNPs) associated with CRC risk using the MassArray™ (Sequenom) platform. After applying a multivariate logistic regression model, five SNPs were selected to calculate the GRS. Regression models adjusted by sex, age, family history of CRC, chronic use of NSAIDs, low-dose ASA, and consumption of tobacco were built in order to study the association between GRS and CRA risk. We evaluated the discriminatory capacity using the area under the receiver operating characteristic curve (AUC). The interactions between demographic information and GRS were also analyzed. RESULTS: Significant associations between high GRS values and risk of CRA for analyzed models were observed. In particular, patients with higher GRS values had 2.3-2.6-fold increase in risk of CRA compared to patients with middle values. Combining sex and age with the GRS significantly increased the discriminatory accuracy of the univariate model with GRS alone. The best model achieved an AUC value of 0.665 (95% CI: 0.63-0.69). The GRS showed a different behavior depending on sex and age. CONCLUSION: Our findings showed that, besides sex and age, GRS is an important risk factor for development of CRA and may be useful for CRC risk stratification and adaptation of screening programs.

Reduced Growth in Non-Small for Gestational Age Fetuses from 35 Weeks of Gestation to Birth and Perinatal Outcomes.

OBJECTIVE: This study aimed to assess reduced fetal growth between 35 weeks of gestation and birth in non-small for gestational age fetuses associated with adverse perinatal outcomes (APOs). MATERIAL AND METHOD: It is a retrospective cohort study of 9,164 non-small for gestational age fetuses estimated by ultrasound at 35 weeks. The difference between the birth weight percentile and the estimated percentile weight (EPW) at 35 weeks of gestation was calculated, and we studied the relationship of this difference with the appearance of APO. APOs were defined as cesarean or instrumental delivery rates for nonreassuring fetal status, 5-min Apgar score <7, arterial cord blood pH <7.10, and stillbirth. Fetuses that exhibited a percentile decrease between both moments were classified into 6 categories according to the amount of percentile decrease (0.01-10.0, 10.01-20.0, 20.01-30.0, 30.01-40.0, 40.01-50.0, and >50.0 percentiles). It was evaluated whether the appearance of APO was related to the amount of this percentile decrease. Relative risk (RR) was calculated in these subgroups to predict APOs in general and for each APO in particular. Receiver operating characteristic and area under curves (AUC) for the difference in the percentile was calculated, used as a continuous parameter in the entire study population. RESULTS: The median gestational age at delivery in uncomplicated pregnancies was 40.0 (39.1-40.7) and in pregnancies with APOs 40.3 (49.4-41.0), p < 0.001. The prevalence of APOs was greater in the group of fetuses with a decrease in percentile (7.6%) compared to those with increased percentile (4.8%) (p < 0.001). The RR was 1.63 (95% CI: 1.365-1.944, p < 0.001). Although the differences were significant in all decreased percentile groups, RRs were significantly higher when decreased growth values were >40 points (RR: 2.036, 95% CI: 1.581-2.623, p < 0.001). The estimated value of the AUC for percentile decrease was 0.58 (0.56-0.61, p < 0.001). CONCLUSION: Fetuses with a decrease in the EPW between the ultrasound at 35 weeks of gestation and birth have a higher risk of APOs, being double in fetuses with a decrease of >40 percentile points.

Prediction of Large for Gestational Age by Ultrasound at 35 Weeks and Impact of Ultrasound-Delivery Interval: Comparison of 6 Standards.

OBJECTIVE: The aim of the study was to assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks to predict large for gestational age (LGA) at term delivery according to 6 growth standards, including population, population-customized, and international references. The secondary objectives were to determine its predictive ability to detect adverse perinatal outcomes (APOs) and whether the ultrasound-delivery interval influences the detection rate of LGA newborns. METHODS: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks, and pregnancy and perinatal outcomes were used to calculate EPWs to predict LGAs at delivery according to the customized and the non-customized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC Fetal Medicine Foundation (FMF), the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) standards. RESULTS: For a 10% false-positive rate, detection rates for total LGAs at delivery ranged from 31.2% with the WHO (area under the curve [AUC] 0.77; 95% confidence interval [CI], 0.76-0.79) to 56.5% with the FMF standard (AUC 0.85; 95% CI, 0.84-0.86). Detection rates and values of AUCs to predict LGAs by ultrasound-delivery interval (range 1-6 weeks) show higher detection rates as the interval decreases. APO detection rates ranged from 2.5% with the WHO to 12.6% with the Figueras standard. CONCLUSION: The predictive ability of ultrasound estimated fetal weight at 35 weeks to detect LGA infants is significantly greater for FMF and MSUH NC standards. In contrast, the APO detection rate is significantly greater for customized standards. The shorter ultrasound-delivery interval relates to better prediction rates.

Active Surveillance in Prostate Cancer: Role of Available Biomarkers in Daily Practice.

Prostate cancer (PCa) is the most commonly diagnosed cancer in men. The diagnosis is currently based on PSA levels, which are associated with overdiagnosis and overtreatment. Moreover, most PCas are localized tumours; hence, many patients with low-/very low-risk PCa could benefit from active surveillance (AS) programs instead of more aggressive, active treatments. Heterogeneity within inclusion criteria and follow-up strategies are the main controversial issues that AS presently faces. Many biomarkers are currently under investigation in this setting; however, none has yet demonstrated enough diagnostic ability as an independent predictor of pathological or clinical progression. This work aims to review the currently available literature on tissue, blood and urine biomarkers validated in clinical practice for the management of AS patients.

Influence of the Storage of Cistus ladanifer L. Bales from Mechanised Harvesting on the Essential Oil Yield and Qualitative Composition.

Cistus ladanifer is a Mediterranean native plant from which valuable products, such as essential oil, are obtained. Manual harvesting of the plants in wild shrublands is usual during short periods of time. Their mechanised harvesting could increase the volume of harvested plants and prevent fires, further storage of the plants collected being necessary. The objective of this work is to study the influence of the storage period of mechanically harvested bales on the essential oil yield and qualitative composition. The harvesting trials were carried out with an adapted commercial harvester baler and the storage of the bales was performed indoors during 1-7 days, 15-30 days and 100-120 days. Afterwards, the bales were crushed (30 mm) and distilled in a 30 litre stainless steel still with saturated steam (0.5 bar). The essential oil components were identified by GC-MS and quantified by GC-FID. The storage of mechanically harvested Cistus ladanifer does not decrease the oil yield of steam distillation on a pilot scale. However, it leads to differences in the quantitative composition of the essential oils, decreasing the total monoterpene compounds content and increasing that of oxygenated sesquiterpenes, especially when the biomass is stored for 100-120 days, without affecting its qualitative composition.

Essential Oils from Residual Foliage of Forest Tree and Shrub Species: Yield and Antioxidant Capacity.

Increasing applications and markets for essential oils could bring new opportunities for cost-effective and sustainable management of unused forestry biomass; however, better knowledge of the production and application of such essential oils is necessary. The objective of this work is to contribute to greater knowledge of the essential oil production on a pilot scale from foliage biomass of wild shrubs and tree residues produced in some forestry enhancement operations and to study their antioxidant capacity (ORAC-oxygen radical absorbance capacity). Fresh biomass (twigs) of seven species (E. globulus, E. nitens, P. pinaster, P. sylvestris, R. officinalis, C. ladanifer, and J. communis) was manually collected in Spain in two different periods and was ground at 30 mm and distilled in a 30 L stainless steel still with saturated steam. The essential oil components were identified by GC-MS and quantified by GC-FID, and their antioxidant activity was determined with the ORAC method. Promising results on essential oil yield were obtained with E. globulus, E. nitens, R. officinalis, and J. communis. All essential oils studied exhibited antioxidant capacity by the ORAC assay, particularly that from C. ladanifer. Moreover, oxygenated sesquiterpenes contents, one of the minor components of oils, were significantly correlated with ORAC values.

Chemical and Bioactive Characterization of the Essential Oils Obtained from Three Mediterranean Plants.

Cupressus sempervirens L., Juniperus communis L. and Cistus ladanifer L. are Mediterranean arboreal and shrub species that possess essential oils (EO) in their leaves and branches. This study aimed at characterizing the EOs obtained by steam distillation from the three species collected in different locations from Spain (Almazán, Andévalo, Barriomartín, Cerezal, Ermitas and Huéscar). For this purpose, volatiles composition was determined by GC-MS, and different bioactivities were evaluated. The highest content in terpenes was observed in C. sempervirens (Huéscar origin) followed by J. communis (Almazán origin), corresponding to 92% and 91.9% of total compounds, respectively. With exception of C. ladanifer from Cerezal that presented viridiflorol as the most abundant compound, all the three species presented in common the α-pinene as the major compound. The EOs from C. ladanifer showed high antibacterial potential, presenting MIC values from 0.3 to 1.25 mg/mL. Concerning other bioactivities, C. ladanifer EO revealed an oxidation inhibition of 83%, while J. communis showed cytotoxicity in the MCF-7 cell line, and C. sempervirens and C. ladanifer EOs exhibited the highest potential on NCI-H460 cell lines. Nevertheless, some EOs revealed toxicity against non-tumoral cells but generally presented a GI50 value higher than that of the tumor cell lines.

Machine Learning Algorithm to Predict Acidemia Using Electronic Fetal Monitoring Recording Parameters.

BACKGROUND: Electronic fetal monitoring (EFM) is the universal method for the surveillance of fetal well-being in intrapartum. Our objective was to predict acidemia from fetal heart signal features using machine learning algorithms. METHODS: A case-control 1:2 study was carried out compromising 378 infants, born in the Miguel Servet University Hospital, Spain. Neonatal acidemia was defined as pH < 7.10. Using EFM recording logistic regression, random forest and neural networks models were built to predict acidemia. Validation of models was performed by means of discrimination, calibration, and clinical utility. RESULTS: Best performance was attained using a random forest model built with 100 trees. The discrimination ability was good, with an area under the Receiver Operating Characteristic curve (AUC) of 0.865. The calibration showed a slight overestimation of acidemia occurrence for probabilities above 0.4. The clinical utility showed that for 33% cutoff point, missing 5% of acidotic cases, 46% of unnecessary cesarean sections could be prevented. Logistic regression and neural networks showed similar discrimination ability but with worse calibration and clinical utility. CONCLUSIONS: The combination of the variables extracted from EFM recording provided a predictive model of acidemia that showed good accuracy and provides a practical tool to prevent unnecessary cesarean sections.

Validation of a 2-gene mRNA urine test for the detection of ≥GG2 prostate cancer in an opportunistic screening population.

BACKGROUND: A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario. METHODS: We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis. RESULTS: In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa. CONCLUSIONS: In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.

How to implement magnetic resonance imaging before prostate biopsy in clinical practice: nomograms for saving biopsies.

PURPOSE: To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomograms for diagnosing different scenarios of aggressiveness of prostate cancer (PCa). METHODS: A cohort of 346 patients with suspicion of PCa because of abnormal finding in digital rectal examination (DRE) and/or high prostate specific antigen (PSA) level received mpMRI prior to prostate biopsy (PBx). A conventional 12-core transrectal PBx with two extra cores from suspicious areas in mpMRI was performed by cognitive fusion. Multivariate logistic regression analysis was performed combining age, PSA density (PSAD), DRE, number of previous PBx, and mpMRI findings to predict three different scenarios: PCa, significant PCa (ISUP-group ≥ 2), or aggressive PCa (ISUP-group ≥ 3). We validate models by ROC curves, calibration plots, probability density functions (PDF), and clinical utility curves (CUC). Cut-off probabilities were estimated for helping decision-making in clinical practice. RESULTS: Our cohort showed 39.6% incidence of PCa, 32.6% of significant PCa, and 23.4% of aggressive PCa. The AUC of predictive models were 0.856, 0.883, and 0.911, respectively. The PDF and CUC showed 11% missed diagnoses of significant PCa (35 cases of 326 significant PCa expected in 1000 proposed Bx) when choosing < 18% as the cutoff of probability for not performing PBx; the percentage of saved PBx was 47% (474 avoided PBx in 1000 proposed). CONCLUSION: We developed clinical and mpMRI-based nomograms with a high discrimination ability for three different scenarios of PCa aggressiveness (https://urostatisticalsolutions.shinyapps.io/MRIfusionPCPrediction/). Specific clinical cutoff points allow us to save a high number of PBx with a minimum of missed diagnoses.

Detection of Adverse Perinatal Outcomes at Term Delivery Using Ultrasound Estimated Percentile Weight at 35 Weeks of Gestation: Comparison of Five Fetal Growth Standards.

OBJECTIVE: To assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks of pregnancy to predict adverse perinatal outcomes (APOs) at term delivery according to 5 fetal growth standards, including population, population-customized, and international references. METHODS: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks and pregnancy and perinatal outcomes were used to calculate EPWs to predict APOs according to: the customized and noncustomized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) international standards. APOs were defined as the occurrence of cesarean or instrumental delivery for nonreassuring fetal status, 5-min Apgar score < 7, arterial cord blood pH <7.10, or stillbirth. The predictive ability of EPW for APOs was analyzed using the area under the curve (AUC), and sensitivities were calculated for different false-positive rates (FPRs). RESULTS: For a 10% FPR, detection rates for total APOs ranged between 12.7% with the customized MSUH (AUC 0.52; 95% CI 0.50-0.55) and 14.4% with the NC MSUH standard (AUC 0.55; 95% CI 0.53-0.57) for EPW by ultrasound; and from 22.0% with the customized MSUH standard (AUC 0.60; 95% CI 0.58-0.63) to 27.8% with the NC WHO (AUC 0.65; 95% CI 0.63-0.68) for EPW at delivery. CONCLUSIONS: The predictive capacity of the EPW for APOS is limited and similar, by both ultrasound and at delivery, for the 5 growth standards, without significant differences between customized and NC standards.