Giant Midline Prostatic Cyst: An Unusual Cause of Acute Urinary Retention.

Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a comparison of congenital intraprostatic midline cysts, namely, Müller's cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm2 cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm2 cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report.

Giant Midline Prostatic Cyst: An Unusual Cause of Acute Urinary Retention

Midline prostatic cysts are infrequent and mostly asymptomatic. We presented a striking case of a giant midline cyst and detailed its diagnosis, evolution, and treatment. From this case, we offered a comparison of congenital intraprostatic midline cysts, namely, Müller’s cysts and utricle cysts. A 40-year-old male experienced recurrent urinary retention. A 10 × 11 mm2 cyst in the mid-prostatic region was diagnosed through transrectal ultrasound, leading to a transperineal puncture as a minimally invasive intervention. Seven years later, the cyst recurred, manifesting obstructive symptoms such as a weak urinary stream, frequent urination, and residual urine sensation. Laparoscopic surgery was then performed for the confirmed 98 × 13 mm2 cystic recurrence. The postoperative course was favourable with no complications. Symptoms were completely resolved, which was maintained over a three-year follow-up period. The therapeutic approach to midline cysts targets symptomatic cases or infertility, ranging from cyst puncture to transurethral endoscopic treatment. Recurrence after minimally invasive interventions is a challenge, with laparoscopic surgery as an alternative post-failed conservative approach. Although total cyst removal risks adjacent structure damage, marsupialisation improves the clinical outcomes. In summary, symptomatic midline prostatic cysts present challenges owing to recurrences after minimally invasive approaches. Enhanced laparoscopic techniques offer a solution, particularly in highly symptomatic cases requiring definitive treatment, as illustrated by this outstanding case report. (AU)

Results of fusion prostate biopsy comparing with cognitive and systematic biopsy.

PURPOSE: Our study aims to determine whether there are differences in the degree of detection of prostate cancer (PCa) and CsPCa between fusion prostate biopsy (FPB), cognitive biopsy (PCB), and randomized, systematic biopsy (SB). METHODS: A retrospective analysis was carried out of 195 patients with suspected PCa at the San Cecilio University Clinical Hospital in Granada who underwent a prostate biopsy between January and December 2021. Patients were divided into three groups: group 1, patients undergoing FPB transperineally with ultrasound BK 3000 (N = 87); group 2, PCB (N = 59) transperineally; and group 3, transrectal SB (N = 49), the latter two, with an ultrasound BK Specto. RESULTS: We found differences in favor of image-directed biopsies (FPB and PCB) with a percentage of positive biopsies of 52.8% and 50%, respectively, compared to 41.4% with SB, but without these differences being significant. Given the controversy in performing prostate biopsies in PI-RADS 3 lesions reported in the literature, a subanalysis was performed excluding the FPB performed for PI-RADS 3 lesions (PI-RADS 4 and 5 are included), finding significant differences when comparing FPB with PCB and SB (group 1, 64% vs group 2, 45.8%; p = 0.05) (group 1, 64% vs group 3, 42.9%; p = 0.035). CONCLUSION: With the results obtained in our series, we conclude that the finding of a PI-RADS 3 lesion in mpMRI should not be an absolute criterion to indicate prostate biopsy. On the other hand, for PI-RADS 4 and 5 lesions, FPB is recommended, which in this case turns out to be superior to PCB and SB.

Adjuvant intravesical treatment in patients with intermediate and high-risk non-muscle-invasive bladder cancer with BCG versus MMC applied with COMBAT or EMDA. Results of a prospective study.

BACKGROUND: Bacillus Calmette-Guerin (BCG) maintenance therapy is the standard adjuvant treatment of high- and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). However, the problems of shortages and the adverse effects, both local and systemic, that it causes lead to the search for alternatives with devices that improve the penetration of intravesical chemotherapeutics. MATERIALS AND METHODS: Prospective observational study was conducted from August 2018 to August 2022. Patients diagnosed with intermediate and high-risk NMIBC without CIS who received one of the following three treatments were included: BCG in induction protocol with six weekly instillations and maintenance with three weekly instillations at months 3, 6, and 12. MMC was applied by Physionizer® 30 device with a current of 20 mA for 30 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (EMDA group). MMC was applied by COMBAT BRS System V2.0 device at 43 ± 0.5 â„ƒ for 60 min was used in an induction protocol of 6 weekly instillations followed by 6 monthly instillations as maintenance (HIVEC group). The primary objective was to compare the 24-month recurrence-free rate between the three groups. The secondary objectives were to evaluate the rate free of progression at 24 months and the degree of toxicity of the treatments. RESULTS: One hundred and eighty-three patients divided into a HIVEC group with sixty-one patients, EMDA group with fifty-nine patients, and BCG group with sixty-three patients. After a mean follow-up of 25 months (IQR 13-36), the 24-month recurrence-free rate was 82.1% for HIVEC, 80% for EMDA, and 84.6% for BCG (p > 0.05), and a progression-free rate at 24 months of 95.6% for HIVEC, 98.3% for EMDA, and 92.9% for BCG (p > 0.05). No statistically significant differences were found between the three groups with respect to the degree of reported adverse events. CONCLUSION: Adjuvant treatment with BCG or MMC applied with COMBAT or EMDA does not present differences in the recurrence-free rate and progression at 24 months in our population of patients with intermediate- and high-risk NMBC without CIS.

Conductive hyperthermic chemotherapy versus electromotive drug administration of mitomycin C as intravesical adjuvant treatment of patients with intermediate or high-risk non-muscle invasive bladder cancer.

BACKGROUND: Devices that increase the penetration of intravesical chemotherapeutic agents have been developed as alternatives to the use of bacillus Calmette-Guérin, in short supply at a time of increasing global incidence of non-muscle invasive bladder cancer (NMIBC). We performed a prospective observational study to compare 2 of these devices in the treatment of patients with high- and intermediate-risk NMIBC. The primary endpoint was the recurrence-free rate. Secondary endpoints were the rate of progression and adverse events. METHODS: After undergoing transurethral bladder resection, 98 patients were selected to receive 1 of 2 treatments: hyperthermic intravesical chemotherapy (HIVEC) treatment with 40 mg of mitomycin C (MMC) using Combat BRS System V2.0 at 43 ± 0.5°C and 200 ml/min for 60 minutes (56 patients) or electromotive drug administration (EMDA) with 40 mg of MMC at 20 mA for 30 minutes (42 patients). The treatment schemes were similar: 6 weekly instillations as induction and 6-monthly instillations as maintenance. The recurrence rates were evaluated at 6 and 12 months and the progression rates at 12 months. RESULTS: The recurrence-free rate at 12 months was 91,1% in the HIVEC group and 88.1% in the EMDA group (P ≥ 0.05). After the 12-month follow-up, only 1 progression occurred in each treatment group. In terms of adverse events, no significant differences were found between the treatments. CONCLUSIONS: HIVEC and EMDA techniques are comparable in terms of recurrence, progression and adverse events at 12 months in the treatment of patients with high- and intermediate-risk NMIBC.

[Adaptation of surgery practice during the Covid-19 pandemic. Ureteroscopy in outpatient surgery.] / Ureterorrenoscopias en régimen ambulatorio. Adaptación del protocolo por la pandemia Covid-19.

OBJECTIVE: The World Health Organizationdeclared a pandemic status due to the COVID-19 disease caused by the new coronavirus SARS-Cov-2 in March 2020. This caused high health pressure that hashad an impact on the Spanish National Health System and Granada has been one of the most affected provincesnationwide. The high healthcare pressure derived from it has had an impact on the National Health System throughout the Spanish territory, with Granada beingone of the most affected provinces nation wide. The increase in the admissions of patients with COVID-19 in such a short time has forced us to optimize hospital resources, prioritizing them in patients with COVID-19 and oncological or urgent pathology. In this context, the increasingly frequent and recurrent lithiasis is treated conservatively. However, the prolongation of the pandemic situation poses the challenge of offering definitive treatment to these patients. MATERIAL AND METHODS: We present the rearrangement performed in our Lithotripsy Unit with the aim of developing a comprehensive and alternative protocol for performing ureteroscopies on an outpatient basis, assuming the patient from admission to hospital discharge, with the collaboration of the Anesthesiology service. RESULTS: In this new protocol, 35 ureteroscopies were performed without noticing intraoperative complications or during the recovery period developed in the Day Hospital integrated within the Lithotripsy Unit. CONCLUSIONS: The redistribution of our resources has allowed us to continue performing ureterorenoscopies on an outpatient basis without the need to use hospital beds and reducing the traffic of patients within the hospital itself with an adequate safety profile.

OBJETIVO: En marzo de 2020, la organización mundial de la salud declaró el estado de pandemia por la enfermedad COVID-19 ocasionada por el nuevo coronavirus SARS-Cov-2. La alta presión asistencial derivada de la misma, ha repercutido en el Sistema Nacional de Salud en todo el territorio español, siendo Granada una de las provincias más afectadas a nivel nacional. El aumento de ingresos de pacientes con esta enfermedad en tan corto periodo de tiempo, nos ha obligado a optimizar los recursos hospitalarios priorizándolos en los pacientes afectos de COVID-19 y patología oncológica o urgente. En este contexto, la enfermedad litiásica, cada vez más frecuente y recurrente es manejada de forma conservadora. Sin embargo, la prolongación en el tiempo de la situación de pandemianos plantea el reto de ofrecer un tratamiento definitivoa estos pacientes. MATERIAL Y MÉTODOS: Exponemos la reordenaciónrealizada en nuestra Unidad de Litotricia con el objetivode desarrollar un protocolo integral y alternativo derealización de ureteroscopias en régimen ambulatorioasumiendo el paciente desde su ingreso hasta su altahospitalaria, con la colaboración del servicio de Anestesiologíay Reanimación. RESULTADOS: Se realizan 35 ureteroscopias en estenuevo protocolo sin advertir complicaciones intraoperatoriasni durante el periodo de recuperación desarrolladoen el Hospital de Día integrado dentro de la Unidadde Litotricia. CONCLUSIONES: La redistribución de nuestros recursosnos ha permitido continuar realizando de maneraordinaria ureterorrenoscopias en régimen ambulatoriosin necesidad de usar camas de hospitalización y disminuyendoel tránsito de pacientes dentro del propiohospital con un adecuado perfil de seguridad.

[Assessment of radiopaque kidney stone treatment: Combination of extracorporeal shock wave lithotripsy and Fagolitos Plus®. Preliminary case control description.] / Evaluación del tratamiento de litiasis renal radiopaca mediante la combinación de litotricia extracorpórea por ondas de choque y Fagolitos Plus®. Estudio preliminar de casos y controles.

INTRODUCTION: The nutritional supplement called Fagolitos plus® contains hydroxycitric acid as main component, in addition to zinc, magnesium, vitamin A and vitamin B6. It is necessary to study new molecules as chemolytic treatment in calcium lithiasis or that facilitate its fragmentation with the help of other instrumental treatments. OBJECTIVE: The objective of this study is to evaluate the effectiveness of the combined treatment of Fagolitos plus® and extracorporeal lithotripsy in the fragmentation of the lithiasis. MATERIAL AND METHODS: Retrospective case-control study includes 88 patients with lithiasis. Group 1: Treated with 1 session of extracorporeal lithotripsy and Fagoliths plus®. Group 2: Treated with 1 session of extracorporeal lithotripsy. The variables analyzed were: Age, sex, body mass index, maximum diameter of the stone, area of the stone, hounsfield units of the stone measured by axial tomography, location of the stone, result after 1 session of extracorporeal wave lithotripsy shock [complete fragmentation, partial fragmentation (presence of a fragment greater than 5 mm) and absence of fragmentation (same size of the lithiasis)], adverse effects that occurred after taking Fagolitos plus®, days of treatment with Fagolitos plus® and energy shock wave applied to lithiasis. Results were analyzed with SPSS 20.0, p≤0.05. RESULTS: The mean age of the patients included in the study is 53.81 ± 12.62 years in group 1 compared to 56.53 ± 12.37 years in group 2, p=0.31. According to the distribution by sex, there were no statistically significant differences (p=0.5), including 24 men and 24 women in group 1 and 23 men and 17 women in group 2. The mean of body mass index of the patients in group 1 was 28.39 ± 2.27 kg/m2 in group 1 versus 28.39 ± 3.03 kg/m2 in group 2, p=0.9. The maximum diameter of the stone was 11.5 ± 3.91 mm in group 1 compared to 13.15 ± 5.49 mm in group 2, p=0.1. The area of the lithiasis measured by tomography was 104.74 ± 70.56 mm2 in group 1 compared to 141.91 ± 80.95 mm2 in group 2, p=0.3. The Hounsfield units measured by tomography of the lithiasis in group 1 was 1061.98 ± 213.68 compared to 1143.15 ± 172.24 in group 2, p=0.06. Relation to fragmentation, complete fragmentation was observed in 66.7% of group 1 patients, compared to 41% of group 2 patients (p=0.02), between 20-30 days after the first session of Extracorporeal Lithotripsy evaluated by means of a simple X-ray of the Abdomen. CONCLUSIONS: The administration of Fagolitos plus® concomitant to extracorporeal lithotripsy could increase its effectiveness in lithiasis fragmentation, requiring clinical trials and prospective studies to confirm these findings.

INTRODUCCIÓN: El complemento nutricional denominado Fagolitos plus® contiene como principal componente ácido hidroxicítrico, además de zinc, magnesio, vitamina A y vitamina B6. Es necesario estudiar nuevas moléculas como tratamiento quimiolítico en litiasis cálcica o que faciliten su fragmentación con la ayuda de otros tratamientos instrumentales. OBJETIVO: El objetivo de este estudio es evaluar la efectividad del tratamiento combinado de Fagolitos plus® y Litotricia extracorpórea en la fragmentación de la litiasis.MATERIAL Y MÉTODOS: Estudio retrospectivo de casos y controles, incluye 88 pacientes con litiasis. Grupo 1: Tratados con 1 sesión de litotricia extracorpórea y Fagolitos plus®. Grupo 2: Tratados con 1 sesión de litotricia extracorpórea. Las variables analizadas fueron: Edad, sexo, índice de masa corporal, diámetro máximo de la litiasis, área de la litiasis, unidades hounsfield de la litiasis medida por Tomografía axial, localización de la litiasis, resultado tras 1 sesión de Litotricia extracorpórea por ondas de choque [fragmentación completa, fragmentación parcial (presencia de un fragmento mayor a 5 mm) y ausencia de fragmentación (mismo tamaño de la litiasis)], efectos adversos acontecidos tras la toma de Fagolitos plus®, días de tratamiento con Fagolitos plus® y energía de ondas de choque aplicada a la litiasis. Se analizaron resultados con SPSS 20.0, p≤0,05. RESULTADOS: La edad media de los pacientes incluidos en el estudio es de 53,81 ± 12,62 años en el grupo 1 frente a 56,53 ± 12,37 años en el grupo 2, p=0,31. Según la distribución por sexos, tampoco existen diferencias estadísticamente significativas (p=0,5), incluyendo 24 hombres y 24 mujeres en el grupo 1 y 23 hombres y 17 mujeres en el grupo 2. El índice de masa corporal medio de los pacientes del grupo 1 fue de 28,39 ± 2,27 kg/m2 en el grupo 1 frente a 28,39 ± 3,03 kg/m2 en el grupo 2, p=0,9. El diámetro máximo de la litiasis fue de 11,5 ± 3,91 mm en el grupo 1 frente a 13,15 ± 5,49 mm en el grupo 2, p=0,1. El área de la litiasis medida por tomografía computarizada fue de 104,74 ± 70,56 mm2 en el grupo 1 frente a 141,91 ± 80,95 mm2 en el grupo 2, p=0,3. Las unidades Hounsfield medidas por tomografía de la litiasis en el grupo 1 fue de 1061,98 ± 213,68 frente a 1143,15 ± 172,24 en el grupo 2, p=0,06. En relación con la fragmentación, se observó fragmentación completa en el 66,7% de los pacientes del grupo 1, frente al 41% de los pacientes del grupo 2 (p=0,02) entre 20-30 días tras la primera sesión de Litotricia Extracorpórea evaluado mediante Radiografía simple de Abdomen. CONCLUSIONES: La administración de Fagolitos plus® concomitante a la Litotricia extracorpórea podría aumentar su efectividad en la fragmentación de la litiasis, siendo necesarios ensayos clínicos y estudios prospectivos que confirmen estos hallazgos.

Evaluación del tratamiento de litiasis renal radiopaca mediante la combinación de litotricia extracorpórea por ondas de choque y fagolitos plus. Estudio preliminar de casos y controles / Evaluation of the treatment of radiopaque renal lithiasis through the combination of extracorporeal lithotripsy by shock waves and phagoliths plus. Preliminary case-control study

Objetivo: El objetivo de este estudio es evaluar la efectividad del tratamiento combinado de Fagolitos plus® yLitotricia extracorpórea en la fragmentación de la litiasis.Material y métodos: Estudio retrospectivo de casosy controles, incluye 88 pacientes con litiasis. Grupo 1:Tratados con 1 sesión de litotricia extracorpórea y Fagolitos plus ®. Grupo 2: Tratados con 1 sesión de litotriciaextracorpórea. Las variables analizadas fueron: Edad, sexo, índice de masa corporal, diámetro máximo dela litiasis, área de la litiasis, unidades hounsfield de lalitiasis medida por Tomografía axial, localización de lalitiasis, resultado tras 1 sesión de Litotricia extracorpóreapor ondas de choque [fragmentación completa, fragmentación parcial (presencia de un fragmento mayor a5 mm) y ausencia de fragmentación (mismo tamaño dela litiasis)], efectos adversos acontecidos tras la toma deFagolitos plus ®, días de tratamiento con Fagolitos plus ®y energía de ondas de choque aplicada a la litiasis. Seanalizaron resultados con SPSS 20.0, p≤0,05. Resultados: La edad media de los pacientes incluidos en el estudio es de 53,81 ± 12,62 años en elgrupo 1 frente a 56,53 ± 12,37 años en el grupo 2,p=0,31. Según la distribución por sexos, tampoco existen diferencias estadísticamente significativas (p=0,5),incluyendo 24 hombres y 24 mujeres en el grupo 1 y23 hombres y 17 mujeres en el grupo 2. El índice demasa corporal medio de los pacientes del grupo 1 fuede 28,39 ± 2,27 kg/m 2 en el grupo 1 frente a 28,39± 3,03 kg/m2 en el grupo 2, p=0,9. El diámetro máximo de la litiasis fue de 11,5 ± 3,91 mm en el grupo1 frente a 13,15 ± 5,49 mm en el grupo 2, p=0,1.El área de la litiasis medida por tomografía computarizada fue de 104,74 ± 70,56 mm 2 en el grupo 1frente a 141,91 ± 80,95 mm2 en el grupo 2, p=0,3.Las unidades Hounsfield medidas por tomografía de lalitiasis en el grupo 1 fue de 1061,98 ± 213,68 frentea 1143,15 ± 172,24 en el grupo 2, p=0,06...(AU)

Objetive: The objective of this study is to evaluatethe effectiveness of the combined treatment of Fagolitosplus® and extracorporeal lithotripsy in the fragmentationof the lithiasis.Material and methods: Retrospective case-control study includes 88 patients with lithiasis. Group 1:Treated with 1 session of extracorporeal lithotripsy andFagoliths plus ® . Group 2: Treated with 1 session of extracorporeal lithotripsy. The variables analyzed were:Age, sex, body mass index, maximum diameter of thestone, area of the stone, hounsfield units of the stonemeasured by axial tomography, location of the stone,result after 1 session of extracorporeal wave lithotripsy.shock [complete fragmentation, partial fragmentation(presence of a fragment greater than 5 mm) and absence of fragmentation (same size of the lithiasis)], adverse effects that occurred after taking Fagolitos plus ® ,days of treatment with Fagolitos plus ® and energyshock wave applied to lithiasis. Results were analyzedwith SPSS 20.0, p≤0.05.Results: The mean age of the patients included in thestudy is 53.81 ± 12.62 years in group 1 compared to56.53 ± 12.37 years in group 2, p=0.31. Accordingto the distribution by sex, there were no statisticallysignificant differences (p=0.5), including 24 men and24 women in group 1 and 23 men and 17 women ingroup 2. The mean of body mass index of the patientsin group 1 was 28.39 ± 2.27 kg/m 2 in group 1 versus 28.39 ± 3.03 kg/m 2 in group 2, p=0.9. The maximum diameter of the stone was 11.5 ± 3.91 mm ingroup 1 compared to 13.15 ± 5.49 mm in group 2,p=0.1. The area of the lithiasis measured by tomography was 104.74 ± 70.56 mm 2 in group 1 comparedto 141.91 ± 80.95 mm 2 in group 2, p=0.3. TheHounsfield units measured by tomography of the lithiasis in group 1 was 1061.98 ± 213.68 compared to1143.15 ± 172.24 in group 2, p=0.06.Relation to fragmentation, complete fragmentation wasobserved in 66.7% of group 1 patients, compared to...(AU)

The Effect of Maternal Obesity on Breast Milk Fatty Acids and Its Association with Infant Growth and Cognition-The PREOBE Follow-Up.

This study analyzed how maternal obesity affected fatty acids (FAs) in breast milk and their association with infant growth and cognition to raise awareness about the programming effect of maternal health and to promote a healthy prenatal weight. Mother-child pairs (n = 78) were grouped per maternal pre-pregnancy body mass index (BMI): normal-weight (BMI = 18.5-24.99), overweight (BMI = 25-29.99) and obese (BMI > 30). Colostrum and mature milk FAs were determined. Infant anthropometry at 6, 18 and 36 months of age and cognition at 18 were analyzed. Mature milk exhibited lower arachidonic acid (AA) and docosahexaenoic acid (DHA), among others, than colostrum. Breast milk of non-normal weight mothers presented increased saturated FAs and n6:n3 ratio and decreased α-linolenic acid (ALA), DHA and monounsaturated FAs. Infant BMI-for-age at 6 months of age was inversely associated with colostrum n6 (e.g., AA) and n3 (e.g., DHA) FAs and positively associated with n6:n3 ratio. Depending on the maternal weight, infant cognition was positively influenced by breast milk linoleic acid, n6 PUFAs, ALA, DHA and n3 LC-PUFAs, and negatively affected by n6:n3 ratio. In conclusion, this study shows that maternal pre-pregnancy BMI can influence breast milk FAs and infant growth and cognition, endorsing the importance of a healthy weight in future generations.

The Impact of Maternal Pre-Pregnancy Body Weight and Gestational Diabetes on Markers of Folate Metabolism in the Placenta.

Dietary methyl donors, including folate, may modify the placenta and size at birth but the influence of maternal body weight has not been widely investigated. We therefore examined whether maternal or fetal folate status, together with indices of placental folate transport, were modulated by either maternal pre-pregnancy body mass index (BMI i.e., overweight: 25 ≤ BMI < 30 or obesity: BMI ≥ 30 kg/m²) and/or gestational diabetes mellitus (GD). We utilised a sub-sample of 135 pregnant women participating in the Spanish PREOBE survey for our analysis (i.e., 59 healthy normal weight, 29 overweight, 22 obese and 25 GD). They were blood sampled at 34 weeks gestation, and, at delivery, when a placental sample was taken together with maternal and cord blood. Placental gene expression of folate transporters and DNA methyltransferases (DNMT) were all measured. Folate plasma concentrations were determined with an electro-chemiluminescence immunoassay. Food diaries indicated that folate intake was unaffected by BMI or GD and, although all women maintained normal folate concentrations (i.e., 5⁻16 ng/mL), higher BMIs were associated with reduced maternal folate concentrations at delivery. Umbilical cord folate was not different, reflecting an increased concentration gradient between the mother and her fetus. Placental mRNA abundance for the folate receptor alpha (FOLR1) was reduced with obesity, whilst DNMT1 was increased with raised BMI, responses that were unaffected by GD. Multi-regression analysis to determine the best predictors for placental FOLR1 indicated that pre-gestational BMI had the greatest influence. In conclusion, the placenta's capacity to maintain fetal folate supply was not compromised by either obesity or GD.

Maternal BMI and gestational diabetes alter placental lipid transporters and fatty acid composition.

INTRODUCTION: Placental fatty acid (FA) uptake and metabolism depend on maternal supply which may be altered when women have a high pre-pregnancy body mass index (BMI) or develop gestational diabetes (GDM). Consequently, an impaired FA transport to the fetus may negatively affect fetal development. While placental adaptation of maternal-fetal glucose transfer in mild GDM has been described, knowledge on placental FA acid metabolism and possible adaptations in response to maternal obesity or GDM is lacking. We aimed to analyze the FA composition and the expression of key genes involved in FA uptake and metabolism in placentas from women with pre-pregnancy normal weight (18.5 ≤ BMI<25 kg/m2), overweight (25 ≤ BMI<30 kg/m2), obesity (BMI ≥ 30 kg/m2), and lean pregnant women with GDM. METHODS: Placental FA content was determined by gas liquid chromatography. Placental mRNA expression of FA transport proteins (FATP1, FATP4, FATP6), FA binding proteins (FABP3, FABP4, FABP7), FA translocase (FAT/CD36) and enzymes (Endothelial lipase (EL) and lipoprotein lipase (LPL)) were quantified by qRT-PCR. RESULTS: High pre-pregnancy BMI and GDM were associated with decreased placental FATP1, FATP4, EL and increased FAT/CD36 and FATP6 expressions. LPL mRNA levels and placental total FA content were similar among groups. Specific FA, including some long-chain polyunsaturated FA, were altered. DISCUSSION: Our results demonstrate that high pre-pregnancy BMI or GDM independently alter mRNA expression levels of genes involved in FA uptake and metabolism and the placental FA profile, which could affect fetal development and long-term health.

Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome.

Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta's whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women. We identified 72 differentially regulated genes, with most being down-regulated in obesity (n = 61). Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women, including inflammation and immune responses, lipid metabolism, cancer pathways, and angiogenesis. In addition, we detected new molecular aspects of obesity-derived effects on the placenta, involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2, FSTL3, IGFBP1, MMP12, PRG2, PRL, QSOX1, SERPINE2 and TAC3. Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome.

Maternal PPARG Pro12Ala polymorphism is associated with infant's neurodevelopmental outcomes at 18 months of age.

BACKGROUND: Peroxisome proliferator activated receptors (PPARs) are ligand activated transcription factors with crucial functions in lipid homeostasis, glucose metabolism, anti-inflammatory processes, placental development, and are involved in cognitive functions and neurodegenerative diseases. Polymorphisms in PPAR genes are shown to influence the activity of these receptors. AIMS: 1) To examine the association of PPARG Pro12Ala polymorphism in pregnant women and their offspring on infant's neurodevelopmental outcomes during the first 18 months of life; 2) to determine the influence of Pro12Ala polymorphism on fatty acid concentrations in plasma phospholipids and placental tissue. STUDY DESIGN: 138 mother-infant pairs from the PREOBE observational study were genotyped for PPARG Pro12Ala. Plasma phospholipids and placental fatty acid concentrations were measured at delivery. Infants' neuropsychological assessment at 6 and 18 months of age was performed using Bayley III. RESULTS: The effect of Pro12Ala on infant's neurodevelopmental outcomes was detected at 18 months, but not at 6 months of age. 18 months old infants born to mothers with wild-type Pro12 genotype had better cognitive (OR=5.11, 95% CI: 1.379-18.96, p=0.015), language (OR=3.41, 95% CI: 1.35-11.24, p=0.044), and motor development scores (OR=4.77, 95% CI: 1.243-18.33, p=0.023) than the Ala allele carriers. Pro12Ala variants did not seem to affect fatty acids concentrations in blood nor in placenta at delivery. CONCLUSIONS: Infants born to mothers with Pro12 genotype have better neurodevelopmental outcomes at 18 months of age than Ala allele carriers, indicating a long-term transplacental action of PPARγ variants on foetal brain development.

Effects of obesity and gestational diabetes mellitus on placental phospholipids.

Gestational diabetes mellitus (GDM) is associated with adverse effects in the offspring. The composition of placental glycerophospholipids (GPL) is known to be altered in GDM and might reflect an aberrant fatty acid transfer across the placenta and thus affect the foetal body composition. The aim of this study was to investigate possible effects of obesity and GDM, respectively, on placental GPL species composition. We investigated molecular species of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylserine (PS) in term placentas from controls (lean non-diabetic, body-mass-index [BMI] 18-24.9k g/m(2), n=31), obese non-diabetics (BMI ≥30 kg/m(2), n=17) and lean diabetics (n=15), using liquid chromatography - triple quadrupole mass spectrometry. PE(16:0/22:6) and PE(18:0/20:4) were increased in GDM and decreased species were PC(18:0/20:3), PC(18:1/20:3) and PS(18:0/18:2). A consistent difference between BMI related changes and changes caused by GDM was not observed. Arachidonic acid percentages of cord blood correlated with placental PC(16:0/20:4), whereas foetal docosahexaenoic acid correlated to placental PE species. Furthermore, a positive correlation of placental weight was found to levels of PE containing arachidonic acid. We demonstrated that obesity and GDM are associated with decreased dihomo-gamma-linolenic acid and increased arachidonic acid and docosahexaenoic acid contents of placental GPL, with unknown consequences for the foetus. PC(16:0/20:4) was identified as the major component for the supply of arachidonic acid to the foetal circulation, whereas PE containing arachidonic acid was found to be associated to the placental and infant growth.

Microbiota from the distal guts of lean and obese adolescents exhibit partial functional redundancy besides clear differences in community structure.

Recent research has disclosed a tight connection between obesity, metabolic gut microbial activities and host health. Obtaining a complete understanding of this relationship remains a major goal. Here, we conducted a comparative metagenomic and metaproteomic investigation of gut microbial communities in faecal samples taken from an obese and a lean adolescent. By analysing the diversity of 16S rDNA amplicons (10% operational phylogenetic units being common), 22 Mbp of consensus metagenome sequences (~70% common) and the expression profiles of 613 distinct proteins (82% common), we found that in the obese gut, the total microbiota was more abundant on the phylum Firmicutes (94.6%) as compared with Bacteroidetes (3.2%), although the metabolically active microbiota clearly behaves in a more homogeneous manner with both contributing equally. The lean gut showed a remarkable shift towards Bacteroidetes (18.9% total 16S rDNA), which become the most active fraction (81% proteins). Although the two gut communities maintained largely similar gene repertoires and functional profiles, improved pili- and flagella-mediated host colonization and improved capacity for both complementary aerobic and anaerobic de novo B(12) synthesis, 1,2-propanediol catabolism (most likely participating in de novo B(12) synthesis) and butyrate production were observed in the obese gut, whereas bacteria from lean gut seem to be more engaged in vitamin B(6) synthesis. Furthermore, this study provides functional evidence that variable combinations of species from different phyla could 'presumptively' fulfil overlapping and/or complementary functional roles required by the host, a scenario where minor bacterial taxa seem to be significant active contributors.