Introduction La lipodystrophie congénitale liée aux mutations de la cavine-1/PTRF (CGL4) est caractérisée par une lipoatrophie généralisée, une insulino-résistance, une hypertriglycéridémie, une ...stéatose hépatique et une dystrophie musculaire. La cavine-1/PTRF, partenaire des cavéolines, est un composant des cavéoles membranaires impliquées dans le trafic cellulaire, le transport et le métabolisme lipidiques. Par ailleurs, les cavéolines modulent l'autophagie, un processus contrôlant la dégradation lysosomale des composants intracellulaires qui participe à l'adipogenèse et à la régulation des gouttelettes lipidiques adipocytaires. Nous avons voulu explorer l'hypothèse d'une implication de l'autophagie dans la physiopathologie de la CGL4. Patients et Méthodes Nous avons recherché des mutations de la cavine-1/ PTRF dans deux familles présentant une lipodystrophie congénitale généralisée et étudié les fibroblastes des deux sujets index. Nous avons analysé la sensibilité à l'insuline et la différenciation adipocytaire dans des fibroblastes témoins et mutés cavin-1/PTRF et dans des pré-adipocytes murins 3T3-F442A après inhibition de l'expression de cavin-1/PTRF et/ou du processus d'autophagie par transfection de siRNA spécifiques d'ATG5. Résultats Nous avons identifié deux nouvelles mutations inactivatrices de la cavine-1/PTRF chez quatre patients issus des deux familles. Dans les fibroblastes des deux cas index, nous observons une diminution de l'expression de la cavine-1/PTRF et de ses partenaires cavéolines-1/2. Nous montrons également une augmentation du flux autophagique et une altération du signal insulinique. Nous retrouvons les mêmes altérations lorsque l'expression de la cavine-1/PTRF est réprimée dans les fibroblastes humains et dans la lignée pré-adipocytaire 3T3-F442A. De plus, le défaut de cavine-1/PTRF inhibe la différenciation des préadipocytes en adipocytes in vitro. Enfin, l'inhibition de l'autophagie par transfection d'un siRNA ATG5 améliore l'insulino-sensibilité et restaure la différenciation adipocytaire. Conclusions Les mutations inactivatrices de la cavine-1/PTRF, responsables d'une forme de lipodystrophie généralisée congénitale, entraînent une activation anormale de l'autophagie qui participe au défaut de différenciation adipocytaire et à l'insulino-résistance. Ce mécanisme physiopathologique pourrait ouvrir de nouvelles perspectives thérapeutiques.
Objectif La dyslipidémie est un facteur de risque important des complications macroangiopathiques chez les patients diabétiques. La réduction du LDL-cholestérol (LDLc) permet de diminuer la ...morbimortalité cardiovasculaire. Les recommandations de la Société Européenne de Cardiologie (ESC) concernant les objectifs de concentrations de LDLc ont été mises à jour en 2011. Notre objectif est d'évaluer la proportion des patients atteignant les objectifs de LDLc en fonction des recommandations européennes notamment en prévention secondaire et en cas de néphropathie diabétique (objectifs de LDLc < 0,7 g/L). Patients et Méthodes Nous avons collecté les données des patients diabétiques ( n = 5 760) ayant consulté au Centre Universitaire du Diabète et de ses Complications de l'hôpital Lariboisière entre septembre 2014 et août 2015. Nous avons analysé les résultats de 3 539 patients pour lesquels le LDLc était disponible et calculable (triglycéridémie < 4 g/L). Résultats Notre cohorte inclut des diabétiques à haut risque cardiovasculaire (les données sont exprimées en médiane (Q1-Q3)) : homme 57,8 % ; âge 58 ans (18-80) ; IMC 27,5 kg/m2 (16,42-50,22) ; obèses 33 % ; durée de diabète 13 ans (0-59) ; HbA1c 7,4 % (4,6-14) ; hypertension 68 % ; tabac 16,3 % ; néphropathie 39,6 % ; prévention cardiovasculaire secondaire 39 %. Chez les patients avec néphropathie, le LDLc est de 0,89 g/L (0,25-2,13) vs 1,01 g/L (0,35-2,06) chez ceux sans néphropathie ( p < 10-4), 21,8 % sont dans les objectifs, 77,2 % sont traités par hypolipémiants. Chez les patients en prévention secondaire, le LDLc est de 0,79 g/L (0,31-1,9), 35,8 % sont dans les objectifs, 91,7 % sont traités par hypolipémiants. Chez les patients en prévention primaire, le LDLc est à 1,01 g/L (0,2-2,59), 49 % sont dans les objectifs, 61 % sont traités par hypolipémiants. Conclusions Dans notre cohorte de patients diabétiques, le LDLc atteint rarement les objectifs de l'ESC. Une insuffisance de prescription peut expliquer ces résultats en prévention primaire alors qu'en prévention secondaire le problème de l'efficacité et/ou de la dose choisie peut se poser.
Summary Introduction The optimal treatment of proximal hypospadias remains controversial. Several techniques have been described, but the best approach remains unsettled. Objective To evaluate and ...compare the complication rates of proximal hypospadias with and without ventral curvature (VC), according to three different surgical techniques: tubularized incised plate (TIP) uretroplasty, dorsal inlay graft TIP (DIG), and staged preputial repair (SR). It was hypothesized that SR performs better than TIP and DIG for proximal hypospadias. Methods Single-center, retrospective chart review of all patients with primary proximal hypospadias reconstructed between 2003 and 2013. The DIG was selectively employed in cases with narrow urethral plate (UP) and deficient spongiosum. Extensive urethral plate (UP) mobilization (UPM), dorsal plication (DP) and/or deep transverse incisions of tunica albuginea (DTITA) were selectively performed when attempting to spare transecting the UP. Division of UP and SR was favored in cases with severe VC (>50°), which was often concurrently managed with DTITA if intrinsic curvature was present. For SR, tubularization of the graft was performed 6 months later. Results A total of 140 patients were included. Tubularized incised plate (TIP), DIG, and SR techniques were performed in 57, 23, and 60 patients, respectively. The TIP and DIG techniques achieved similar success rates, although DIG was performed in cases of narrow and spongiosum-deficient plates. Reoperation rates with TIP and DIG techniques was 52.6% and 52.1% (NS). Urethro-cutaneous fistulas were seen in 31.5% and 13% of TIP and DIG techniques, respectively. Staged repair accomplished better results than both TIP and DIG techniques, despite being performed in the most unfavorable cases (reoperation rate 28%). After technical modifications, the DIG technique achieved similar outcomes of SR. Conclusions Proximal hypospadias remains challenging, regardless of the technique utilized for its repair. Urethro-cutaneous fistulas were more commonly seen after long TIP repairs. Approximately half of the patients undergoing long TIP and DIG procedures needed re-intervention, although the percentage decreased significantly with late modifications in the DIG group. Recurrence of VC after TIP and DIG techniques seemed to be a significant and under-reported complication. Staged repairs, despite being performed for the most severe cases, resulted in overall better outcomes.
Purpose Surgical management of the high urogenital sinus remains challenging. The anterior sagittal transrectal approach provides optimal exposure, facilitates vaginal dissection and separation from ...the urethra, and allows reconstruction of the bladder neck musculature. In this study we report our initial experience with this technique. Materials and Methods We performed a retrospective review of a 6-year multi-institutional experience treating patients with a urogenital sinus anomaly using the anterior sagittal transrectal approach without preoperative colostomy or prolonged postoperative fasting. Variables analyzed included patient age, associated malformations, the need for additional procedures and surgical outcomes. Results A total of 23 children with a mean age of 2.3 years (range 3 months to 17 years) who underwent surgery between 2003 and 2010 were included in the study. Mean followup was 3.4 years (range 14 months to 7 years). All children had a high urogenital sinus with (16) or without (7) congenital adrenal hyperplasia. There were 3 isolated cases treated with additional procedures. Only 1 anterior sagittal transrectal approach related complication was encountered when a perineal infection developed in a child and required temporary diverting colostomy without compromising the repair. There were no postoperative urethrovaginal fistulas. All toilet trained patients were continent for feces and most were voiding normally per urethra (21), except for 2 with associated urological malformations. There were 15 patients who underwent followup examination under anesthesia, and demonstrated separate urethral and vaginal openings. Conclusions The anterior sagittal transrectal approach provides excellent exposure for the management of a high urogenital sinus, facilitating the separation of urogenital structures. Good outcomes in terms of urinary/fecal continence as well as the absence of urethrovaginal fistulas were achieved in the majority of cases, supporting its consideration for the surgical management of this congenital abnormality.
Estimation of the quality of the urethral plate (UP) seems to be important when assessing postoperative outcomes of hypospadias repair, but its evaluation remains subjective. We developed an ...objective model aiming to standardize this assessment, proposing a methodology that could be adopted in future studies designed to evaluate outcomes in the treatment of hypospadias.
To evaluate the inter and intra observer reliability of a method to assess the quality of the urethral plate (UP) in hypospadias (POST - Plate Objective Scoring Tool) based on elements of glans characteristics. The reliability of such scoring methodology was compared to an analog accepted tool: the Glans-Urethral Meatus-Shaft (GMS) score. A secondary goal was to compare some characteristics of the UP in GMS score to POST values; aiming to find the threshold between favorable and unfavorable plates.
Data were prospectively obtained from prepubertal boys who underwent primary hypospadias repair between January 2018 and November 2019. Intrinsic elements of the glanular UP (A: distal midline mucocutaneous junction; B: Glanular knob where the mucosal edges of the UP's edge change direction; C: Glanular/coronal junction) were marked and the AB/BC ratio calculated. The “G” and “M” components of the GMS score were measured electronically three times by four different reviewers with variable pediatric urology experience and blinded to each other values. Favorable UP, according to the GMS score was compared to measurements obtained by POST (AB/BC ratio).
84 subjects were enrolled. The POST score had an excellent inter-observer agreement for the evaluation of the UP in distal hypospadias (Kappa = 0.832) while the “G” parameter of the GMS correlated poorly among the observers. The Inter-Class Correlation (ICC) analysis to examine the intra-rater agreement value was 0.914 (95% CI 0.87, 0.95.). AB/BC ratio values ranged from 0.6 to 1.6, with a mean of 1.12. The POST cut-off value for “favorable” UP was 1.2 (AUC = 0.62) 95% CI (0.52–0.84) (sensitivity 80% and specificity 60%).
The POST score has higher inter-observer reliability and functions favorably when compared to the GMS. In addition, it demonstrated a high intra-observer reliability among observers of variable experience. Our findings suggest that the POST score adds to evaluation of the UP and could be incorporated as an additional criterion to assess outcomes in distal hypospadias repairs. Display omitted
Purpose Hypospadias repair is a commonly performed procedure. Little is known about decisional regret in parents who agree to proceed with this surgical reconstruction. We present data on this ...previously underexplored issue. Materials and Methods We performed followup analysis of 100 couples prospectively evaluated after counseling for surgical correction of distal hypospadias in their son with assessment of complications and decisional regret 1 year after surgery. Findings were contrasted with baseline demographics, hypospadias knowledge and decisional conflict at the time of counseling. Results Decisional regret was found in 116 parents, including mild regret in 41.4% and moderate to severe regret in 8.6%. There was no statistically significant difference in paired regret analysis between mothers and fathers. Complications were strongly associated with decisional regret (p <0.001). On regression analysis postoperative complications (OR 14.7, 95% CI 1.6–131.6), parental desire to avoid circumcision (OR 7.4, 95% CI 1.1–49.4) and initial decisional conflict level (OR 1.06, 95% CI 1.02–1.09) were statistically significant predictors of moderate to strong decisional regret. These findings remained robust after imputation strategies to address missing data. The impact of decisional conflict and preference for circumcision were significant even after excluding families who experienced complications. Conclusions To our knowledge this is the first study demonstrating parental decisional regret after providing consent for surgical correction of distal hypospadias in their son. Based on the described risk factors efforts aimed at minimizing complications and counseling about foreskin preservation techniques may be prudent to ameliorate decisional regret. The novel association between decisional conflict and regret suggests that conflict assessment during counseling may help screen families at risk for postoperative regret.
•Successful separation, recycling and recovering of solid oxide cells components.•Air electrode LaxSr1-xCoO3 (x = 0.6), nickel oxide, and Zr1-xYxO(2-x)/2 (x = 0.08) recovered at high purity ...level.•Physical and electrochemical characterizations of recycled compounds.•Total recovered YSZ conductivity is close to commercial product.•90–92% of the total weight of initial Ni and YSZ recovered.
In this work, a strategy for recycling and recovery of anode supported Solid Oxide Fuel Cell (SOFC) ceramic components is presented. From commercial cells, electrodes and electrolyte are separated by mechanical scraping and grinding, followed by thermal and chemical treatments. Air electrode (LaxSr1-xCoO3), nickel oxide (NiO), which accounts for about 50% of the cell weight, and yttria-stabilized zirconia (YSZ), which is coming from both the fuel electrode and the electrolyte, were successfully separated, and 90–92% of the total weight of initial Ni and YSZ can be collected. The recovered materials are characterized by X-ray diffraction, scanning electron microscopy, (thermal, chemical) analysis and BET surface area measurement, and impurities amounts never excess 1 At.%. The conductivity level of the recycled YSZ materials was measured in air by electrochemical impedance spectroscopy and is found comparable with commercial YSZ material, with a total value exceeding 6.4 10−3 S cm−1 at 700 °C. The contributions of grain and grain boundary conductivities to the total conductivity are clearly distinguishable at lower temperatures.
Severity of penile curvature (PC) is commonly used to select the optimal surgical intervention for hypospadias, either alone or in conjunction with other phenotypic characteristics. Despite this, ...current literature on the accuracy and precision of different PC measurement techniques in hypospadias patients remains limited.
Assess the feasibility and validity of an artificial intelligence (AI)-based model for automatic measurement of PC.
Seven 3D-printed penile models with variable degrees of ventral PC were used to evaluate and compare interobserver agreement in estimation of penile curvatures using various measurement techniques (including visual inspection, goniometer, manual estimation via a mobile application, and an AI-based angle estimation app. In addition, each participant was required to complete a questionnaire about their background and experience.
Thirty-five clinical practitioners participated in the study, including pediatric urologists, pediatric surgeons, and urologists. For each PC assessment method, time required, mean absolute error (MAE), and inter-rater agreement were assessed. For goniometer-based measurement, the lowest MAE achieved was derived from a model featuring 86° PC. When using either UVI (unaid visual inspection), mobile apps, or AI-based measurement, MAE was lowest when assessing a model with 88° PC, indicating that high-grade cases can be quantified more reliably. Indeed, MAE was highest when PC angle ranged between 40° and 58° for all the investigated measurement tools. In fact, among these methodologies, AI-based assessment achieved the lowest MAE and highest level of inter-class correlation, with an average measurement time of only 22 s.
AI-based PC measurement models are more practical and consistent than the alternative curvature assessment tools already available. The AI method described in this study could help surgeons and hypospadiology researchers to measure PC more accurately. Display omitted
