Safety and Efficacy Study of Collagenase Clostridium Histolyticum Applied With an Intensive Protocol in the Treatment of Peyronie's Disease.

INTRODUCTION: Collagenase clostridium histolyticum (CCH) is a treatment for Peyronie's disease (PD) whose efficacy and safety has been demonstrated using a classic protocol and a shortened protocol. AIM: To evaluate the efficacy and safety of an even more intense protocol in which a CCH injection is applied for 3 separate cycles of 1 week. METHODS: Prospective, nonrandomized, clinical study of a cohort of 13 patients with PD and non-ventral curvatures, between 30 and 90 degrees and with stable disease were included. Under local anesthesia, 0.9 mg of CCH is infiltrated in 3 parallel and equidistant transverse bands across the plaque in 3 sessions separated by 1 week. Between sessions the patient is instructed to perform home modeling and penis stretching. MAIN OUTCOME MEASURES: The measurements collected were from girth, length of the penis and length of the plaque. Side and degree of curvature. Ultrasound evaluation of the plaque characteristics and assessing the interface between the tunica albuginea and Buck's fascia. Furthermore, questionnaires were collected: International Index of Erectile Function (IIEF) and 15-question and Peyronie's Disease Questionnaire (PDQ). All these parameters were evaluated before and after treatment. RESULTS: An improvement in curvature was obtained in 76.9% of patients, reaching an improvement in the angle of curvature after the treatment cycles by an average of 19 ° (range 0-35 °) from the beginning. There are also improvements in the results of the IIEF and PDQ questionnaires. Length, penis girth, and plate length measurements hardly changed after treatment. Reported adverse effects are mild and limited to the penis. CONCLUSIONS: We demonstrate the safety and efficacy of CCH in the treatment of PD using a more intense protocol than the previous ones. In addition, reducing the overall duration of allows for greater adherence and compliance of patients. Melgarejo-Segura MT, Funes-Padilla C, Morales-Martínez A, et al. Safety and Efficacy Study of Collagenase Clostridium Histolyticum Applied With an Intensive Protocol in the Treatment of Peyronie's Disease. Sex Med 2021;9:100375.

[Medical management of uric acid renal stones, case description.] / Manejo médico de los cálculos renales de ácido úrico, a próposito de un caso.

Uric acid renal stones are a frequent and important part of our clinical practice. Conservative treatment through diet and urine alkalinization with citrate and teobromina seem a promising combination for treatment of those stones. We show on our cases a complete resolution of staghorn stone at 12 weeks of allopurinol and lit-control pH Up treatment, without adverse events and avoiding surgical treatment.

Los cálculos urinarios de ácido úrico corresponden a una patología frecuente e importante en nuestra práctica clínica. El tratamiento conservador mediante medidas higiénico-dietéticas y la correcta alcalinización urinaria mediante citrato y teobromina parece ser una combinación prometedora para el tratamiento y resolución de estas litiasis. Así lo pone de manifiesto uno de nuestros casos, donde se observa la resolución completa de una litiasis coraliforme de ácido úrico durante 12 semanas de tratamiento con Alopurinol y Lit-Control pH Up sin observar reacciones adversas y evitando la necesidad de medidas quirúrgicas invasivas.

Urinary stone epidemiology in Spain and worldwide. / Epidemiología de la litiasis urinaria en el mundo y en España.

Urinary stones is a pathology whose incidence and prevalence are increasing in developed and underdeveloped countries. Overall, in the United States the prevalence has been increased from 3.2% in 1980 to 10.1% in 2014. In Spain, this increase has also been significant, from 5% in 2005 to 14.6% in 2016. In the rest of the world happens in a similar way, where an average increase is observed in the last 15-20 years of approximately 5-7%. The decade of life between 40-60 years is usually the highest incidence of stones. Regarding sex, in recent years there has been a growing in women, associated with a change in diet and obesity, and currently there are no differences between sex. It is a more frequent disease in the Western world,although there are countries in the Middle East such as Saudi Arabia where the prevalence is very high, around 20%. Respect the lithiasis composition, calcium oxalate continues to be the most frequent around 70-80%, with an increase in uric acid lithiasis in recent years and a decrease in infective lithiasis. In relation to the appearance of this pathology in children, it is rare in the first years of life, being more prevalent from 12-13 years of age and increasing in adolescence. It is usually more common in girls than in boys and in the Caucasian racecompared to African Americans. There are no differences in lithiasic composition with respect to adults, calcium oxalate being the most frequent composition, but with a prevalence of 50-60%. However, the causes and etiopathogenic factors in children are less studied and well known than in adults.

La litiasis urinaria es una patología cuya incidencia y prevalencia van en aumento tanto en países desarrollados como países subdesarrollados. De forma global, en Estados Unidos se ha visto incrementada su prevalencia del 3,2% en 1980 hasta el 10,1% en 2014. En España, este aumento también ha sido significativo, desde el 5% en 2005 hasta el 14,6% en 2016. En el resto del mundo sucede de forma similar, donde se observa un incremento medio en los últimos 15-20 añosdel 5-7% aproximadamente. La década de la vida entre los 40-60 años suele ser la de mayor incidencia de litiasis. En cuanto a sexo, en los últimos años ha existid una tendencia cada vez mayor en la mujer, asociada al cambio de dieta y la obesidad, fundamentalmente y actualmente no existen prácticamente diferencias entre sexos. Es una enfermedad más frecuente en el mundo occidental, aunque existen países del Oriente Medio como Arabia Saudí en donde la prevalencia es muy elevada, en torno al 20%. En cuanto a la composición litiásica, la de oxalato cálcico sigue siendo la más frecuente en torno al 70-80% con un incremento en los últimos años de la litiasis de ácido úrico y un descenso en la litiasis infectiva. En relación a la aparición de esta patología en los niños, es poco frecuente en los primeros años de vida, siendo más prevalente a partir de los 12-13 años e incrementándose en la adolescencia. Suele ser más frecuente en niñas que en niños y en la raza caucásica respecto a los afroamericanos. No existen diferencias en cuanto a la composición litiásica con respecto a los adultos, siendo el oxalato cálcico elcompuesto más frecuente, pero con una prevalencia del 50-60%. Sin embargo, las causas y factores etiopatogénicos en los niños están peor estudiados y son menos conocidos que en los adultos.

Investigation of the impact of birth by cesarean section on fetal and maternal metabolism.

PURPOSE: Elective cesarean section (CS) was related to long-term adverse health effects in the offspring, but little is known about underlying mechanisms. Our study investigates the metabolic changes in both maternal and cord blood associated with CS in comparison to vaginal delivery (VD) to explore potential causal pathways. METHODS: Samples obtained from PREOBE study participants were subjected to LC-MS/MS-targeted metabolomics comprising > 200 metabolites. RESULTS: Elective CS showed an impact on both maternal and cord blood metabolomes. In maternal blood, the CS group showed lower levels of phospholipids (PL), principally ether-linked phosphatidylcholines (aaPC), pyruvic acid, branched chain keto-acids (BCKA), and other gluconeogenic substrates, but since the CS group showed different HDL levels in comparison to the VD group, we could not exclude contribution of the latter in the findings. In cord blood, the most remarkable finding in the CS group was the high levels of Cys; conversely, the lower levels of non-esterified fatty acids (NEFA), some tricarboxylic acid (TCA) cycle metabolites, gluconeogenic substrates, markers of ß-oxidation, and the sum of hexoses were lower in CS-born babies in addition to tendentially lower levels of PL. CONCLUSIONS: We speculate that lower levels of maternal and fetal corticosteroids in CS, due to less stressful condition, cause metabolic perturbations at birth initiating future negative health outcomes. This further supports the early programming hypothesis.

Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study.

AIMS: Offspring of mothers suffering from obesity and/or gestational diabetes mellitus (GDM) were reported to be at risk of higher birth weight (BW), later obesity and diabetes. We hypothesize that infant anthropometry changes related to maternal pathological status are due to dysregulated infant metabolism. METHODS: First, we inspected differences in BMI z-scores (z-BMI) between three infant groups: born to normal weight (NW; n = 49), overweight/obese (OV/OB; n = 40) and GDM mothers (n = 27) at birth and 1 year. Then, we inspected associations between cord blood metabolites and 1-year Δ z-BMI in the three infant groups at birth and 1 year. RESULTS: No statistically significant difference was detected in z-BMI between the study groups at birth; however, GDM was associated with heavier infants at 1 year. Regarding the associations between the metabolites and z-BMI, phospholipids, especially those containing polyunsaturated fatty acids, were the species most impacted by the maternal metabolic status, since numerous phosphatidylcholines-PUFA were positively associated with z-BMI in NW but negatively in OV/OB and GDM groups at birth. Conversely, the sum of lysophosphatidylcholines was only positively associated with z-BMI in NW at birth but of no relation in the other two groups. At 1 year, most of the associations seen at birth were reversed in NW and lost in OV/OB and GDM groups. In the NW group, PC-PUFA were found to be negatively associated with Δ z-BMI at 1 year in addition to some medium-chain acylcarnitines, tricarboxylic acid metabolites, Asp and Asn-to-Asp ratio. In OV/OB and GDM groups, the non-esterified fatty acid (NEFA26:0) and His correlated with Δ z-BMI at 1 year in negative and positive directions, respectively. CONCLUSIONS: GDM was associated with overweight in offspring at 1 year, independent of the BW with lack of evidence on existing correlation of this finding with metabolic alterations detected in cord blood metabolome. Associations were found between cord blood metabolites and infant anthropometry at birth and were influenced by maternal OB and GDM. However, an extension of the findings monitored at birth among the three groups was not detected longitudinally showing a lack of predictive power of cord blood metabolome for later development at least 1 year.

Impact of maternal BMI and gestational diabetes mellitus on maternal and cord blood metabolome: results from the PREOBE cohort study.

AIMS: Maternal obesity and gestational diabetes mellitus (GDM) were frequently reported to be risk factors for obesity and diabetes in offspring. Our goal was to study the impact of maternal prepregnancy BMI (pBMI) and GDM on both maternal and cord blood metabolic profiles. METHODS: We used LC-MS/MS to measure 201 metabolites comprising phospholipids (PL), amino acids, non-esterified fatty acids (NEFA), organic acids, acyl carnitines (AC), and Krebs cycle metabolites in maternal plasma at delivery and cord plasma obtained from 325 PREOBE study participants. RESULTS: Several metabolites were associated with pBMI/GDM in both maternal and cord blood (p < 0.05), while others were specific to either blood sources. BMI was positively associated with leucine, isoleucine, and inflammation markers in both mother and offspring, while ß-hydroxybutyric acid was positively associated only in cord blood. GDM showed elevated levels of sum of hexoses, a characteristic finding in both maternal and cord blood. Uniquely in cord blood of offspring born to GDM mothers, free carnitine was significantly lower with the same tendency observed for AC, long-chain NEFA, PL, specific Krebs cycle metabolites, and ß-oxidation markers. CONCLUSIONS: Maternal BMI and GDM are associated with maternal and cord blood metabolites supporting the hypothesis of transgenerational cycle of obesity and diabetes.

The impacts of maternal iron deficiency and being overweight during pregnancy on neurodevelopment of the offspring.

Both maternal Fe deficiency (ID) and being overweight or obese (Ow/Ob, BMI≥25 kg/m2) may negatively affect offspring brain development. However, the two risk factors correlate and their independent effects on infant neurodevelopment are unclear. PREOBE is a prospective observational study that included 331 pregnant Spanish women, of whom 166 had pre-gestational Ow/Ob. Fe status was analysed at 34 weeks and at delivery, and babies were assessed using Bayley III scales of neurodevelopment at 18 months. In confounder-adjusted analyses, maternal ID at 34 weeks was associated with lower composite motor scores at 18 months (mean 113·3 (sd 9·9) v. 117·1 (sd 9·2), P=0·039). Further, the offspring of mothers with ID at delivery had lower cognitive scores (114·0 (sd 9·7) v. 121·5 (sd 10·9), P=0·039) and lower receptive, expressive and composite (99·5 (sd 8·6) v. 107·6 (sd 8·3), P=0·004) language scores. The negative associations between maternal ID at delivery and Bayley scores remained even when adjusting for maternal Ow/Ob and gestational diabetes. Similarly, maternal Ow/Ob correlated with lower gross motor scores in the offspring (12·3 (sd 2·0) v. 13·0 (sd 2·1), P=0·037), a correlation that remained when adjusting for maternal ID. In conclusion, maternal ID and pre-gestational Ow/Ob are both negatively associated with Bayley scores at 18 months, but independently and on different subscales. These results should be taken into account when considering Fe supplementation for pregnant women.

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