AIMSThe aims of this article are to provide an overview of the technique of phalloplasty by radial forearm free flap in the context of female-to-male gender reassignment surgery, with a specific ...focus on surgical technical details and the prevention of postoperative complications. METHODSIn the light of our 30 years of experience in caring for female-to-male transgender individuals and conducting a critical review of the literature, we exhaustively present our technique of radial forearm free flap phalloplasty in female-to-male gender reassignment surgery. RESULTSThe technique of radial forearm free flap phalloplasty, utilizing a one-stage approach for neourethral and neophallus construction based on the "tube within a tube" principle, not only achieves an aesthetically pleasing appearance of the neophallus resembling a normal penis with tactile and erogenous sensitivities but also yields a functional neourethra and satisfactory penile rigidity using implants for standing voiding and sexual intercourse. This intricate surgical procedure demands not only meticulous execution of all surgical maneuvers but also high-level postoperative care. Despite refinements in technique over recent decades, aesthetic sequelae at the donor site of the flap remain subject to criticism, and postoperative complications, particularly of vascular and urological nature, remain significant. CONCLUSIONFuture optimization of the surgical technique for this procedure will be imperative to minimize postoperative complications and establish a true technical "gold standard" for phalloplasty in female-to-male transgender individuals.
We studied age-related ultrastructural reorganization in acinar cells and intercalary ducts of the lacrimal gland acini in 3-, 15-, and 24-month-old Wistar rats. Ultrastructural changes in the ...lacrimal gland progressed with age and led to dramatic ultrastructural reconstruction of the lacrimal gland at the age of 24 months. These changes mainly included complete destruction of acinar cells and increase in the number of enlarged branched ducts that fi lled the greater part of gland volume; these dusts were lined with epithelial cells with altered ultrastructure. Acinar cells in the acini communicate via special connecting intermembrane complexes formed by desmosomes and mitochondria adjacent to them in each contacting cell. It is assumed that association of mitochondria with desmosomes found in the acini is a special functional complex indicating that every single acinus is a functional formation. This assumption is indirectly confi rmed by the fact that the destruction never occurred in a single cell, but always involved all cells constituting the acini. The revealed ultrastructural changes refl ect age-related deterioration of the secretory function of the lacrimal gland.
L’objectif de cet article est de faire un point sur la technique de phallopoièse par lambeau antébrachial radial libre dans le cadre de la chirurgie de réassignation sexuelle femme à homme avec un ...accent particulier sur les détails techniques chirurgicaux et sur la prévention des complications postopératoires.
À l’aune de nos 30 dernières années d’expérience de prise en charge des personnes transgenres femme à homme et d’une lecture critique de la littérature, nous présentons de manière exhaustive notre technique de phallopoièse par le lambeau antébrachial radial libre dans la chirurgie de réassignation sexuelle femme à homme.
La technique de phallopoièse par lambeau antébrachial radial libre réalisant la construction du néo-urètre et du néo-phallus en un temps opératoire selon le principe de « tube dans un tube » permet d’obtenir non seulement un aspect esthétique du néo-phallus ressemblant à une verge normale avec des sensibilités tactiles et érogènes mais également un néo-urètre fonctionnel et une rigidité pénienne satisfaisante à l’aide d’implants permettant d’uriner debout et d’avoir des rapports sexuels. C’est une procédure chirurgicale complexe nécessitant non seulement une grande qualité d’exécution des tous les gestes chirurgicaux mais également des soins postopératoires de haut niveau. Malgré les raffinements techniques apportés durant ces dernières décennies, les séquelles esthétiques au niveau du site donneur du lambeau restent critiquables et les complications postopératoires, notamment vasculaires et urologiques, demeurent élevées.
Une optimisation de la technique chirurgicale de ce procédé sera nécessaire dans le futur afin de minimiser les complications postopératoires et d’établir un véritable « gold standard » technique de la phallopoièse pour les personnes transgenres femme à homme.
The aims of this article are to provide an overview of the technique of phalloplasty by radial forearm free flap in the context of female-to-male gender reassignment surgery, with a specific focus on surgical technical details and the prevention of postoperative complications.
In the light of our 30 years of experience in caring for female-to-male transgender individuals and conducting a critical review of the literature, we exhaustively present our technique of radial forearm free flap phalloplasty in female-to-male gender reassignment surgery.
The technique of radial forearm free flap phalloplasty, utilizing a one-stage approach for neourethral and neophallus construction based on the “tube within a tube” principle, not only achieves an aesthetically pleasing appearance of the neophallus resembling a normal penis with tactile and erogenous sensitivities but also yields a functional neourethra and satisfactory penile rigidity using implants for standing voiding and sexual intercourse. This intricate surgical procedure demands not only meticulous execution of all surgical maneuvers but also high-level postoperative care. Despite refinements in technique over recent decades, aesthetic sequelae at the donor site of the flap remain subject to criticism, and postoperative complications, particularly of vascular and urological nature, remain significant.
Future optimization of the surgical technique for this procedure will be imperative to minimize postoperative complications and establish a true technical “gold standard” for phalloplasty in female-to-male transgender individuals.
L’objectif de cet article est de décrire de manière exhaustive la technique du lambeau péritonéal prélevé par voie cœlioscopique dans la chirurgie d’affirmation de genre homme-à-femme (HtF), en ...particulier dans les cas de défauts de profondeur vaginale post-vaginoplastie par lambeau pénien inversé.
Nos résultats à court terme révèlent que la vaginoplastie par lambeau péritonéal, adaptée de la procédure de Davydov, montre un potentiel significatif pour l’amélioration des résultats fonctionnels et esthétiques, y compris la création d’un néo-vagin autolubrifiant. Cependant, la complexité de la procédure nécessite une expertise chirurgicale avancée et des soins postopératoires adaptés. La sélection des patientes joue également un rôle essentiel, car toutes les patientes ne sont pas des candidates idéales pour cette procédure.
Malgré ses promesses, l’adoption généralisée de la technique du lambeau péritonéal dans la chirurgie d’affirmation du genre HtF est entravée par plusieurs défis, notamment la nécessité d’une formation chirurgicale spécialisée et les complications postopératoires potentielles. Ainsi, cette technique doit être considérée comme une alternative ou un complément aux méthodes traditionnelles, en fonction des facteurs propres aux patientes. Des recherches plus approfondies et des essais cliniques plus étendus sont nécessaires pour bien comprendre son potentiel et ses limites afin d’améliorer l’arsenal des options chirurgicales efficaces pour la chirurgie d’affirmation de genre HtF.œ
The aim of this article is to provide a comprehensive description of the peritoneal flap technique in male-to-female (MtF) gender affirmation surgery, particularly in cases of insufficient depth after penile inversion vaginoplasty.
Our short-term results reveal that the peritoneal flap vaginoplasty, adapted from the Davydov procedure, has shown significant potential for improving functional and aesthetic outcomes, including the creation of a self-lubricating neovagina. However, the complexity of the procedure requires advanced surgical expertise and appropriate postoperative care. Patient selection also plays an essential role as not all patients are ideal candidates for this procedure.
Despite its promises, the widespread adoption of the peritoneal flap technique in male-to-female (MtF) gender affirmation surgery is hindered by several challenges, including the need for specialized training and potential postoperative complications. Thus, this technique should be considered as an alternative or complement to traditional methods, depending on individual patient factors. Further research and extensive clinical trials are needed to better understand its potential and limitations in order to enhance the arsenal of effective surgical options for MtF gender affirmation surgery.
Abstract
Background
Ulcerative colitis (UC) patients show high variations in disease phenotype and response to therapy. Intestinal epithelia play a key role in UC pathogenesis, and therefore ...patient-derived epithelial model to study this variation are warranted. Few studies suggest that colonoids derived from UC patients retain some disease-related transcriptional and epigenetic changes, but they also raise questions regarding their persistence in culture. Here, we aimed to characterize if UC epithelial dysfunctions and response to inflammatory signals retained in colonoid culture.
Methods
Rectal biopsies were used to generate epithelial organoids (colonoids) that were grown through 5–10 passages using L-WRN conditioned medium. Media and total RNA were collected for measuring CXCL1 secretion using ELISA and qPCR, respectively.
Results
3 control and 5 UC patients-derived colonoids were generated. Median age was 17 years and 75% were females. Control patients were evaluated for loose stool, abdominal pain, and anemia, but had normal rectal mucosa endoscopically and histologically. UC included newly diagnosed and established patients. Colonoids were allowed to differentiate for 48 hours before applying different inflammatory cocktails to induce inflammation for 24 h with IFNγ+LPS, IFNγ+TNFα, and TNFα+LPS (20 ng/ml each trigger). UC organoids secreted significant higher levels of CXCL1 as detected in the media at baseline (p=0.02) and with IFNy+TNFa (p=0.01), but no difference was noted with TNFa+LPS (Fig. 1). In addition, CXCL1 mRNA showed significant higher levels after inflammatory triggering in UC vs. controls (Fig. 1) with IFNγ +LPS, (p=0.02), IFNγ+TNFα (p=0.003), and TNFα+LPS (p=0.016). Similarly, several other genes showed significant and substantial induction in UC organoids vs. controls, in some or all the inflammatory triggers (Fig. 2). The tight junction-associated protein, ZO1 showed substantially higher induction in UC compared to controls with the 3 inflammatory cocktails IFNγ +LPS, (p=0.03), IFNγ+TNFα (p=0.02), and TNFα+LPS (p=0.005). Significantly higher expression in UC organoid was further noted in comparison to control in IL8 levels upon IFNγ +LPS (p=0.002), in interferon inducible IDO1 with IFNγ+TNFα (p=0.001), and in goblet associated MUC2 (p=0.04) and bacterial sensing DUOX2 (p=0.001) with TNFα+LPS.
Conclusion
Our data suggest that UC colonoids retain some inflammatory response activity in-vitro even after several passages. We show that UC organoids secrete higher level of CXCL1. Additionally, we note higher transcriptional response to different inflammatory signals in UC organoids potentially implying an “immune” epithelial transcriptional memory that may contribute to UC chronicity.
Abstract
Background
Primary sclerosing cholangitis related to inflammatory bowel disease (PSC-IBD) diagnosed under the age of 6 years (i.e., VEO-IBD) may have unique characteristics and disease ...course. We aimed to analyze the characteristics and natural history of children with VEO PSC-IBD and compare them to children diagnosed with PSC-IBD at an older age.
Methods
This was a multicenter, retrospective, study evaluating patients diagnosed with both IBD and PSC before (VEO-PSC-IBD) or after the age of 6 years (PSC-IBD), followed at 14 centers affiliated with the Porto IBD Interest group of ESPGHAN. Demographic, clinical, laboratory, endoscopic, and imaging data were collected at baseline and every six months thereafter for a minimum follow-up of 12 months. IBD-related (clinical remission, need for systemic steroids, therapy escalation and surgery) and PSC-related outcomes (biliary and portal hypertensive complications, need for treatment escalation and liver transplantation, cholangiocarcinoma, and death) were analyzed at 1, 3, and 5 years.
Results
A total of 69 children with both IBD and PSC were included: 28 with VEO PSC-IBD median age 5.2 (3.7-5.9) years, 21 UC (75%), 4 IBDU (14%) and 3 (15%) CD and 41 with PSC-IBD median age 15.7 (13.3-16.9) years, 34 UC (83%), 6 IBDU (1.5%) and 1 (0.2%) CD. IBD was diagnosed prior to PSC in 28 of the 69 patients (40%), simultaneously in 30 (43%), and after PSC in 11 (16%), with no significant differences between VEO PSC-IBD and PSC-IBD. Most patients with UC presented with extensive disease at diagnosis (89% in VEO PSC-UC vs. 89% in PSC-UC, p = 0.72). Both groups presented most often with mild intestinal disease at diagnosis (mean PUCAI of VEO IBD-PSC 34±16, vs 31±19 of IBD-PSC, p=0.11; mean PCDAI 31±33 vs. 21±27, respectively, p=0.14). A higher number of VEO-IBD-PSC patients were diagnosed with autoimmune sclerosing cholangitis than older children 24 (86%) vs. 27 (66%) PSC-IBD, p=0.04, whereas no other differences were found for PSC-related variables. During follow-up, no significant differences were found in major IBD outcomes. The risk of developing biliary strictures and escalating therapy to vancomycin from ursodeoxycholic acid was lower in the VEO-PSC-IBD group (Figure 1 and 2, Log-rank p=0.02 and p=0.02), while no difference was found for portal hypertension and liver transplantation at 5-year follow-up. No cases of cholangiocarcinoma or death were reported.
Conclusion
IBD-PSC has similar baseline characteristics whether diagnosed as VEO-IBD or thereafter. However, a milder disease course in terms of biliary complications and the need for PSC-related therapy escalation, with an overall mild intestinal disease at presentation in all patients, characterize this specific subcohort of patients.
Abstract
Background
Limited data are available on the use of Vedolizumab (VDZ) in paediatric Crohn’s Disease (CD) and Ulcerative Colitis (UC). We evaluated the effectiveness and safety of VDZ to ...induce remission at week 14 in the prospective, multicenter VEDOKIDS study.
Methods
We enrolled children (age 0–18 years) with CD or UC commenced on VDZ with a standardized dosing of 177mg/BSA up to 300mg at 0, 2, 6 and q8 weeks thereafter. Non-responders had their dose escalated to q4wks at the discretion of the local physician. Explicit demographic, clinical and safety data were prospectively recorded via REDcap. Clinical remission was defined as steroid- and EEN-free remission (i.e. wPCDAI<12.5 or PUCAI<10) without the need for new medications. Complete remission was defined as clinical remission with normal CRP and ESR. Predictors of response were explored by Logistic regression.
Results
128 children were enrolled, 60 (47%) with CD, and 68 (53%) with UC (58 (45%) males, mean age 13.8±3.6, 93 (73%) failed previous anti-TNF, median disease duration 2.3 years (IQR 0.9–4.7)). Using the ITT principle, clinical and complete remission rates for CD at week 14 were 30% and 20%, respectively, and for UC 50% and 38%, respectively (Fig 1). Clinical remission rates of those receiving VDZ as first line biologics versus second line were 57% and 34%, respectively (p=0.019; Fig 2); the corresponding complete remission rates were 49% and 23% (p=0.004).
In the UC group, disease activity at baseline measured by the PUCAI predicted clinical remission at week 14 (OR=0.95, 95%CI 0.93–0.98; median baseline PUCAI 15 (IQR 0–30) in those achieving remission and 45 (20–55) in those who did not; p=0.002). ESR (OR=0.94, 95%CI 0.89–0.98; p=0.009) and a trend towards extensive disease (L3 vs. L1 and L2; OR 0.14, 95%CI 0.18–1.036, p=0.054) predicted clinical remission in CD.
During the 14 weeks, 113 adverse events (AE) were recorded in 58 children: 28 AEs were possibly related to VDZ, all of which were mild-moderate and only 3 (11%) led to discontinuation of VDZ (leukocytoclastic vasculitis, myalgia and dyspnea). There were 18 serious AEs, only one was graded as possibly related to VDZ (headache). There were 18 non-serious cases (19%) of upper respiratory infections (pharyngitis, tonsilitis, parotitis, and otitis media) and one Campylobacter jejuni which was graded as serious.
Conclusion
In this prospective multicenter study, VDZ was safe and effective for inducing remission in a refractory cohort of paediatric IBD, more so in UC. Disease severity and extent at baseline may predict clinical response.
Involution of the thymus is one of the most expressed indices of aging of the immune system. The mechanisms of involution of the thymus are relatively well studied, whereas the reasons and mechanisms ...of accelerated involution of the thymus are less known. We have previously reported that premature aging in OXYS rats is associated with accelerated involution of the thymus. The aim of the present study was to examine morphofunctional conditions of epithelial cells in the thymus of OXYS rats. Immunohistochemical study revealed that in 3.5-month-old OXYS rats, i.e. in the initial period of age-related involution, the network of epithelial cells in the thymus was reduced, and the volume and area of the surface of epithelial cells in the cortical substance was lower compared to control Wistar rats. Electron microscopy found strong changes in the ultrastructure of epithelial cells, such as shrinkage of the cytoplasm volume, a clear decrease in the size and number of secretory vacuoles, and multiple autophagosomes and phagolysosomes. Our data show that a possible mechanism of the reduction of the epithelial network in the thymus of OXYS rats is an enhancement of autophagy, probably related to specific mitochondria dysfunction in these rats. The fact of age-related retardation of autophagy in some tissues is well known. In spite to this, based on the data from OXYS rats, we suppose that long-term deviation of intensity of this process from the physiological level may be directed not only to its attenuation but also to its activation and thus results in degenerative modifications of organs and the formation of the progeroid phenotype of the body.
The methods of calculation of duration of the metallic bricks heating and melting in liquid bath, taking into account variability of thermal-physical characteristics of metal due to temperature, is ...developed.
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