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1.
J Huntingtons Dis ; 13(2): 119-131, 2024.
Article in English | MEDLINE | ID: mdl-38968054

ABSTRACT

The field of Huntington's disease research covers many different scientific disciplines, from molecular biology all the way through to clinical practice, and as our understanding of the disease has progressed over the decades, a great deal of different terminology has accrued. The field is also renowned for its collaborative spirit and use of standardized reagents, assays, datasets, models, and clinical measures, so the use of standardized terms is especially important. We have set out to determine, through a consensus exercise involving basic and clinical scientists working in the field, the most appropriate language to use across disciplines. Nominally, this article will serve as the style guide for the Journal of Huntington's Disease (JHD), the only journal devoted exclusively to HD, and we lay out the preferred and standardized terminology and nomenclature for use in JHD publications. However, we hope that this article will also serve as a useful resource to the HD research community at large and that these recommended naming conventions will be adopted widely.


Subject(s)
Huntington Disease , Terminology as Topic , Huntington Disease/classification , Huntington Disease/diagnosis , Humans , Biomedical Research/standards
2.
Ann Plast Surg ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38833665

ABSTRACT

INTRODUCTION: Some patients pursuing gender-affirming mastectomy prefer to forgo autologous nipple and areolar reconstruction, instead choosing a "no nipple" option. The objective of this study is to evaluate the motives and influences contributing to this decision. METHODS: A retrospective survey-based study of patients undergoing gender-affirming mastectomy over a 4.6-year period was conducted. All patients were offered nipple and areolar reconstruction. A survey was distributed to those who elected to forgo nipple and areolar reconstruction exploring the factors influencing that choice and postoperative satisfaction. RESULTS: Five hundred thirty-six patients underwent gender-affirming mastectomy and 13% chose to forgo nipple and areolar reconstruction. The survey response rate was 72%. Most respondents identified as nonbinary (48%) or transmasculine (42%). Body image, defined in the context of this study as an improvement in body image satisfaction due to achievement of a more gender-congruent appearance, was the most highly cited and most heavily weighted decision-making factor. Concerns about nipple graft outcomes were frequently cited as important but carried less weight. There were no differences between transmasculine and nonbinary patients in terms of motivations for choosing this surgical option. Fifty-eight percent of respondents pursued or planned to pursue chest tattoos, whereas 42% preferred no further chest modifications. Patient satisfaction was high postoperatively (98%), and 82% of respondents would choose to forgo nipple and areolar reconstruction again even if surgical outcomes of free nipple grafts were improved. CONCLUSIONS: Gender-affirming mastectomy without nipple and areolar reconstruction was requested by 13% of patients presenting for gender-affirming chest surgery over the study period and had high postoperative satisfaction among patients who chose this option. This modification of gender-affirming mastectomy is a variation that surgical teams should be aware of. Many reasons to forgo nipple preservation were cited, most of which related to body image. Secondary factors were easier recovery and/or concern about outcomes of free nipple grafts. Many patients wished information about this surgical option was more widely available.

3.
Curr Opin Urol ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38898789

ABSTRACT

PURPOSE OF REVIEW: To review findings related to phantom genital sensation, emphasizing phantom sensation in the transgender and gender diverse (TGD) population. We discuss prevalence, presentation and potential implications for sensory outcomes in genital gender-affirming surgery. RECENT FINDINGS: There is a high prevalence of phantom genital sensations in the TGD population. The prevalence varies by body part, approaching 50% in the most frequently reported transgender phantom - the phantom penis. Unlike genital phantoms that occur after trauma or surgery which are often painful, transgender phantoms are typically neutral and often erogenous in experience. Phantom sensation in the TGD population can be an affirming experience and important part of sexual well being and embodiment. SUMMARY: Recent studies have begun to characterize the prevalence and presentations of phantom genital sensations in TGD people, informing our evolving understanding of the sensory experiences of the transgender and gender diverse population. Targeting integration of these centrally-mediated phantom genital sensations with the peripherally generated sensation from genital stimulation may represent one potential avenue to improve sensation and embodiment following genital gender-affirming surgical procedures. Additionally, emerging techniques in modern peripheral nerve surgery targeting phantom pain may offer potential treatment options for painful phantom sensation seen after cases of genital surgery or trauma.

4.
Ann Surg ; 2024 May 10.
Article in English | MEDLINE | ID: mdl-38726665

ABSTRACT

OBJECTIVE: Despite politically charged media coverage and legislation surrounding gender affirming care (GAC), many organizations have released position statements to provide scientifically backed clinical practice standards, combat misinformation, and inform medicolegal policies. The purpose of this study is to objectively assess the availability and the content of the official position statements of relevant medical professional organizations regarding GAC. SUMMARY BACKGROUND DATA: A list of U.S. medical professional organizations with likely involvement in GAC based on medical or surgical specialties was compiled. METHODS: For included organizations, we evaluated the availability, content, and publication year of positions on GAC through October 2023. When available, formal positions were categorized as supportive or unsupportive. RESULTS: A total of 314 professional medical organizations were screened for our study based on specialty, relevance to GAC, and issuance of patient guidelines or position statements. Inclusion criteria were met by 55 organizations. Most organizations (35, 63.6%) had formal position statements on GAC. Support for GAC was described in 97.1% (n=34). Further, 94.2% (n=33) of available statements explicitly addressed GAC in individuals less than 18 years old and were largely supportive (96.9%, n=32). CONCLUSIONS: This cross-sectional analysis demonstrates that a majority of multidisciplinary professional medical organizations with relevance to GAC have issued formal position statements on the topic. Available positions were overwhelmingly supportive of individualized access to gender-affirming therapies in adult and adolescent populations. However, silence from some organizations continues to represent a modifiable disparity in the provision of GAC.

5.
J Clin Med ; 13(10)2024 May 08.
Article in English | MEDLINE | ID: mdl-38792302

ABSTRACT

Gender-affirming vaginoplasty (GAV) comprises the construction of a vulva and a neovaginal canal. Although technical nuances of vulvar construction vary between surgeons, vulvar construction is always performed using the homologous penile and scrotal tissues to construct the corresponding vulvar structures. Therefore, the main differentiating factor across gender-affirming vaginoplasty techniques is the tissue that is utilized to construct the neovaginal canal. These tissue types vary markedly in their availability, histology, and ease of harvest and have different advantages and disadvantages to their use as neovaginal lining. In this narrative review, the authors provide a comprehensive overview of the tissue types and associated operative approaches used for construction of the neovagina in GAV. Tissue choice is guided by several factors, such as histological similarity to natal vaginal mucosa, tissue availability, lubrication potential, additional donor site morbidity, and the specific goals of each patient. Skin is used to construct the neovagina in most cases with a combination of pedicled penile skin flaps and scrotal and extra-genital skin grafts. However, skin alternatives such as peritoneum and intestine are increasing in use. Peritoneum and intestine are emerging as options for primary vaginoplasty in cases of limited genital skin or revision vaginoplasty procedures. The increasing number of gender-affirming vaginoplasty procedures performed and the changing patient demographics from factors such as pubertal suppression have resulted in rapidly evolving indications for the use of these differing vaginoplasty techniques. This review sheds light on the use of less frequently utilized tissue types described for construction of the neovaginal canal, including mucosal tissues such as urethral and buccal mucosa, the tunica vaginalis, and dermal matrix allografts and xenografts. Although the body of evidence for each vaginoplasty technique is growing, there is a need for large prospective comparison studies of outcomes between these techniques and the tissue types used to line the neovaginal canal to better define indications and limitations.

7.
Dev Psychopathol ; : 1-9, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38584251

ABSTRACT

Previous studies show aggression-related structural alterations in frontal and limbic brain regions. Most studies have focused on overall aggression, instead of its subtypes, and on specific regions instead of networks. This study aims to identify both brain networks and regions that are associated with reactive and proactive subtypes of aggression. Structural MRI data were collected from 340 adolescents (125 F/215 M) with a mean age of 16.29 (SD = 1.20). Aggression symptomology was indexed via the Reactive Proactive Aggression Questionnaire (RPQ). Freesurfer was used to estimate Cortical Volume (CV) from seven networks and regions within specific networks associated with aggression. Two multivariate analyses of covariance (MANCOVAs) were conducted on groups for low versus higher reactive and proactive RPQ scores. Our reactive aggression MANCOVA showed a main effect in CV [F(14,321) = 1.935, p = 0.022,ηp2 = 0.078] across all the 7-Networks. Unpacking this main effect revealed significant volumetric differences in the right Limbic Network (LN) (p = 0.029) and the Temporal Pole (p = 0.011), where adolescents in the higher reactive aggression group showed higher cortical volumes. Such findings are consistent with region/voxel-specific analyses that have associated atypical structure within the LN and reactive aggression. Moreover, the temporal pole is highly interconnected with regions important in the regulation and initiation of reactive aggression.

8.
J Huntingtons Dis ; 13(1): 91-101, 2024.
Article in English | MEDLINE | ID: mdl-38517798

ABSTRACT

Background: Perivascular spaces (PVS) are fluid-filled cavities surrounding small cerebral blood vessels. There are limited reports of enlarged PVS across the grey matter in manifest Huntington's disease (HD). Little is known about how PVS morphometry in the white matter may contribute to HD. Enlarged PVS have the potential to both contribute to HD pathology and affect the distribution and success of intraparenchymal and intrathecally administered huntingtin-lowering therapies. Objective: To investigate PVS morphometry in the global white matter across the spectrum of HD. Relationships between PVS morphometry and disease burden and severity measures were examined. Methods: White matter PVS were segmented on 3T T2 W MRI brain scans of 33 healthy controls, 30 premanifest HD (pre-HD), and 32 early manifest HD (early-HD) participants from the Vancouver site of the TRACK-HD study. PVS count and total PVS volume were measured. Results: PVS total count slightly increased in pre-HD (p = 0.004), and early-HD groups (p = 0.005), compared to healthy controls. PVS volume, as a percentage of white matter volume, increased subtly in pre-HD compared to healthy controls (p = 0.044), but not in early-HD. No associations between PVS measures and HD disease burden or severity were found. Conclusions: This study reveals relatively preserved PVS morphometry across the global white matter of pre-HD and early-HD. Subtle morphometric abnormalities are implied but require confirmation in a larger cohort. However, in conjunction with previous publications, further investigation of PVS in HD and its potential impact on future treatments, with a focus on subcortical grey matter, is warranted.


Subject(s)
Huntington Disease , White Matter , Humans , Huntington Disease/complications , White Matter/diagnostic imaging , White Matter/pathology , Disease Progression , Magnetic Resonance Imaging , Gray Matter/diagnostic imaging , Brain/diagnostic imaging , Brain/pathology
9.
Transl Androl Urol ; 13(2): 274-292, 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38481864

ABSTRACT

Background and Objective: The vulva is the external portion of a gender-affirming vaginoplasty or vulvoplasty procedure-the "visible" result of surgery. The vulvar appearance can play a major role in how individuals feel about their surgical results and new genital anatomy. Therefore, optimizing the aesthetics of the vulva is an important component of surgical care. Although there is no one "ideal" vulvar appearance, aesthetics are optimal when each major sub-unit of the vulva is reconstructed to create a proportional and cohesive vulvar unit. In this article we perform a narrative review of the literature and discuss clinical approaches to improve aesthetic satisfaction such as patient education, re-defining the "ideal" vulva, aesthetic surgery tenets and technical strategies based on our collective experience of over 630 gender-affirming vulvar constructions. Methods: A narrative review of the literature was completed accessing PubMed, EMBASE, Google Scholar using search terms "Vaginoplasty OR Vulvoplasty". Articles were removed if not pertaining to gender affirmation surgery, were not in English language, were not accessible or did not discuss aesthetics in the body of the text. Key Content and Findings: A total of 1,042 articles were identified from initial search criteria. Of those, 905 were excluded as they did not involve gender affirmation as an indication. An additional 112 papers were excluded as they were not accessible, not in English, focused on non-vulvar outcomes or did not comment on vulvar aesthetics. Ultimately 25 articles were included for narrative review; 21 of these included technical descriptions of vulva and 13 had direct aesthetic discussion. The anatomy and aesthetics of the transfeminine vulva are reviewed according to the previously described principle of anatomic vulvar sub-units: the labia majora, labia minora, clitoris, urethra and the introitus. Conclusions: Ultimately, creating the optimal vulva for each individual patient will demand flexible surgical decisions based on individual anatomy and available tissues. This narrative review provides an overview of current approaches to aesthetics in gender-affirming vulvar construction and technical insights based on our institutional experience of performing over 630 gender-affirming vaginoplasty and vulvoplasty procedures.

10.
Hum Genomics ; 18(1): 32, 2024 Mar 26.
Article in English | MEDLINE | ID: mdl-38532526

ABSTRACT

BACKGROUND: Advanced paternal age (APA) is associated with adverse outcomes to offspring health, including increased risk for neurodevelopmental disorders. The aim of this study was to investigate the methylome and transcriptome of the first two early embryonic tissue lineages, the inner cell mass (ICM) and the trophectoderm (TE), from human blastocysts in association with paternal age and disease risk. High quality human blastocysts were donated with patient consent from donor oocyte IVF cycles from either APA (≥ 50 years) or young fathers. Blastocysts were mechanically separated into ICM and TE lineage samples for both methylome and transcriptome analyses. RESULTS: Significant differential methylation and transcription was observed concurrently in ICM and TE lineages of APA-derived blastocysts compared to those from young fathers. The methylome revealed significant enrichment for neuronal signaling pathways, as well as an association with neurodevelopmental disorders and imprinted genes, largely overlapping within both the ICM and TE lineages. Significant enrichment of neurodevelopmental signaling pathways was also observed for differentially expressed genes, but only in the ICM. In stark contrast, no significant signaling pathways or gene ontology terms were identified in the trophectoderm. Despite normal semen parameters in aged fathers, these significant molecular alterations can adversely contribute to downstream impacts on offspring health, in particular neurodevelopmental disorders like autism spectrum disorder and schizophrenia. CONCLUSIONS: An increased risk for neurodevelopmental disorders is well described in children conceived by aged fathers. Using blastocysts derived from donor oocyte IVF cycles to strategically control for maternal age, our data reveals evidence of methylation dysregulation in both tissue lineages, as well as transcription dysregulation in neurodevelopmental signaling pathways associated with APA fathers. This data also reveals that embryos derived from APA fathers do not appear to be compromised for initial implantation potential with no significant pathway signaling disruption in trophectoderm transcription. Collectively, our work provides insights into the complex molecular mechanisms that occur upon paternal aging during the first lineage differentiation in the preimplantation embryo. Early expression and epigenetic markers of APA-derived preimplantation embryos highlight the susceptibility of the future fetus to adverse health outcomes.


Subject(s)
Autism Spectrum Disorder , Humans , Male , Aging , Blastocyst/metabolism , Epigenesis, Genetic , Fathers , Middle Aged , Female
11.
J Plast Reconstr Aesthet Surg ; 90: 105-113, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38367407

ABSTRACT

Gender-affirming phalloplasty involves flap tubularization, placing unique stresses on the vascularity of the flap. Tubularization renders the flap susceptible to postoperative edema that can lead to excessive turgor that, if left untreated, can compromise perfusion and threaten the viability of the phallic reconstruction. This phenomenon has not been formally described in our literature. We aim to define this entity, described here as "Excessive Phallic Turgor" (EPT), and to outline its incidence, frequency of its underlying etiologies, and sequelae. We conducted a single-center, retrospective review of all phalloplasty operations involving flap transfer performed from December 2016 to May 2023. All patients requiring emergent intervention (bedside suture release, reoperation, or both) due to excessive phallic swelling and impending flap compromise were considered to have EPT. Variables compared between groups included underlying etiology (categorized as congestion, hematoma or swelling), patient demographics, flap type and size, management, length of stay, and postoperative outcomes. Over the study period, 147 phalloplasty operations involving flap transfer for shaft creation were performed. Of those, 15% developed EPT. Age, BMI, flap length, flap circumference, flap surface area, single vs multistage operation, flap tubularization (shaft-only vs tube-within-tube), and flap donor site were not significantly different between the cohort that developed EPT and that which did not. Development of EPT was associated with higher rates of phallic hematoma, surgical site infection, shaft fistula requiring repair, and longer inpatient stays. When EPT develops, prompt diagnosis and alleviation of intraphallic pressure are paramount for mitigating short- and long-term morbidity.


Subject(s)
Sex Reassignment Surgery , Humans , Male , Sex Reassignment Surgery/adverse effects , Phalloplasty , Urethra/surgery , Surgical Flaps/surgery , Hematoma/surgery , Penis/surgery
13.
Am J Psychiatry ; 181(4): 291-298, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38419495

ABSTRACT

OBJECTIVE: The authors investigated the neural impact of intranasal oxytocin on emotion processing areas in youths with severe irritability in the context of disruptive mood and behavior disorders. METHODS: Fifty-two participants with severe irritability, as measured by a score ≥4 on the Affective Reactivity Index (ARI), with diagnoses of disruptive behavior disorders (DBDs) and/or disruptive mood dysregulation disorder (DMDD) were randomly assigned to treatment with intranasal oxytocin or placebo daily for 3 weeks. Assessments were conducted at baseline and at the end of the trial; the primary outcomes were measures of irritability on the ARI and ratings on the Clinical Global Impressions severity scale (CGI-S) focusing on DBD and DMDD symptoms, and secondary outcomes included the CGI improvement scale (CGI-I) and ratings of proactive and reactive aggressive behavior on the Reactive-Proactive Aggression Questionnaire. Forty-three participants (22 in the oxytocin group and 21 in the placebo group) completed pre- and posttreatment functional MRI (fMRI) scans with the affective Stroop task. RESULTS: Youths who received oxytocin showed significant improvement in CGI-S and CGI-I ratings compared with those who received placebo. In the fMRI data, blood-oxygen-level-dependent (BOLD) responses to emotional stimuli in the dorsomedial prefrontal cortex and posterior cingulate cortex were significantly reduced after oxytocin compared with placebo. These BOLD response changes were correlated with improvement in clinical severity. CONCLUSIONS: This study provides initial and preliminary evidence that intranasal oxytocin may induce neural-level changes in emotion processing in youths with irritability in the context of DBDs and DMDD. This may lead to symptom and severity changes in irritability.


Subject(s)
Irritable Mood , Oxytocin , Adolescent , Humans , Attention Deficit and Disruptive Behavior Disorders , Irritable Mood/drug effects , Irritable Mood/physiology , Mood Disorders/diagnosis , Oxytocin/pharmacology , Oxytocin/therapeutic use
14.
Transl Psychiatry ; 14(1): 54, 2024 Jan 23.
Article in English | MEDLINE | ID: mdl-38263400

ABSTRACT

BACKGROUND: Suicide is the second leading cause of death for adolescents in the United States. However, relatively little is known about the forms of atypical neuro-cognitive function that are correlates of suicidal ideation (SI). One form of cognitive/affective function that, when dysfunctional, is associated with SI is emotion regulation. However, very little work has investigated the neural correlates of emotion dysregulation in adolescents with SI. METHODS: Participants (N = 111 aged 12-18, 32 females, 31 [27.9%] reporting SI) were recruited shortly after their arrival at a residential care facility where they had been referred for behavioral and mental health problems. Daily reports of SI were collected during the participants' first 90-days in residential care. Participants were presented with a task-fMRI measure of emotion regulation - the Affective Number Stroop task shortly after recruitment. Participants were divided into two groups matched for age, sex and IQ based on whether they demonstrated SI. RESULTS: Participants who demonstrated SI showed increased recruitment of regions including dorsomedial prefrontal cortex/supplemental motor area and parietal cortex during task (congruent and incongruent) relative to view trials in the context of emotional relative to neutral distracters. CONCLUSIONS: Participants with SI showed increased recruitment of regions implicated in executive control during the performance of a task indexing automatic emotion regulation. Such data might suggest a relative inefficiency in the recruitment of these regions in individuals with SI.


Subject(s)
Emotional Regulation , Suicide , Female , Humans , Adolescent , Suicidal Ideation , Emotions , Executive Function
15.
J Control Release ; 367: 27-44, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38215984

ABSTRACT

Efficient delivery of therapeutics to the central nervous system (CNS) remains a major challenge for the treatment of neurological diseases. Huntington disease (HD) is a dominantly inherited neurodegenerative disorder caused by a CAG trinucleotide expansion mutation in the HTT gene which codes for a toxic mutant huntingtin (mHTT) protein. Pharmacological reduction of mHTT in the CNS using antisense oligonucleotides (ASO) ameliorates HD-like phenotypes in rodent models of HD, with such therapies being investigated in clinical trials for HD. In this study, we report the optimization of apolipoprotein A-I nanodisks (apoA-I NDs) as vehicles for delivery of a HTT-targeted ASO (HTT ASO) to the brain and peripheral organs for HD. We demonstrate that apoA-I wild type (WT) and the apoA-I K133C mutant incubated with a synthetic lipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine, can self-assemble into monodisperse discoidal particles with diameters <20 nm that transmigrate across an in vitro blood-brain barrier model of HD. We demonstrate that apoA-I NDs are well tolerated in vivo, and that apoA-I K133C NDs show enhanced distribution to the CNS and peripheral organs compared to apoA-I WT NDs following systemic administration. ApoA-I K133C conjugated with HTT ASO forms NDs (HTT ASO NDs) that induce significant mHTT lowering in the liver, skeletal muscle and heart as well as in the brain when delivered intravenously in the BACHD mouse model of HD. Furthermore, HTT ASO NDs increase the magnitude of mHTT lowering in the striatum and cortex compared to HTT ASO alone following intracerebroventricular administration. These findings demonstrate the potential utility of apoA-I NDs as biocompatible vehicles for enhancing delivery of mutant HTT lowering ASOs to the CNS and peripheral organs for HD.


Subject(s)
Huntington Disease , Oligonucleotides, Antisense , Mice , Animals , Oligonucleotides, Antisense/therapeutic use , Apolipoprotein A-I/genetics , Huntington Disease/drug therapy , Huntington Disease/genetics , Oligonucleotides/therapeutic use , Brain/metabolism , Huntingtin Protein/genetics , Huntingtin Protein/metabolism , Huntingtin Protein/therapeutic use , Disease Models, Animal
18.
Lancet Neurol ; 23(3): 243-255, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38280392

ABSTRACT

BACKGROUND: Laquinimod modulates CNS inflammatory pathways thought to be involved in the pathology of Huntington's disease. Studies with laquinimod in transgenic rodent models of Huntington's disease suggested improvements in motor function, reduction of brain volume loss, and prolonged survival. We aimed to evaluate the safety and efficacy of laquinimod in improving motor function and reducing caudate volume loss in patients with Huntington's disease. METHODS: LEGATO-HD was a multicentre, double-blind, placebo-controlled, phase 2 study done at 48 sites across ten countries (Canada, Czech Republic, Germany, Italy, Netherlands, Portugal, Russia, Spain, UK, and USA). Patients aged 21-55 years with a cytosine-adenosine-guanine (CAG) repeat length of between 36 and 49 who had symptomatic Huntington's disease with a Unified Huntington's Disease Rating Scale-Total Motor Score (UHDRS-TMS) of higher than 5 and a Total Functional Capacity score of 8 or higher were randomly assigned (1:1:1:1) by centralised interactive response technology to laquinimod 0·5 mg, 1·0 mg, or 1·5 mg, or to matching placebo, administered orally once daily over 52 weeks; people involved in the randomisation had no other role in the study. Participants, investigators, and study personnel were masked to treatment assignment. The 1·5 mg group was discontinued before recruitment was finished because of cardiovascular safety concerns in multiple sclerosis studies. The primary endpoint was change from baseline in the UHDRS-TMS and the secondary endpoint was percent change in caudate volume, both comparing the 1·0 mg group with the placebo group at week 52. Primary and secondary endpoints were assessed in the full analysis set (ie, all randomised patients who received at least one dose of study drug and had at least one post-baseline UHDRS-TMS assessment). Safety measures included adverse event frequency and severity, and clinical and laboratory examinations, and were assessed in the safety analysis set (ie, all randomised patients who received at least one dose of study drug). This trial is registered with ClinicalTrials.gov, NCT02215616, and EudraCT, 2014-000418-75, and is now complete. FINDINGS: Between Oct 28, 2014, and June 19, 2018, 352 adults with Huntington's disease (179 [51%] men and 173 [49%] women; mean age 43·9 [SD 7·6] years and 340 [97%] White) were randomly assigned: 107 to laquinimod 0·5 mg, 107 to laquinimod 1·0 mg, 30 to laquinimod 1·5 mg, and 108 to matching placebo. Least squares mean change from baseline in UHDRS-TMS at week 52 was 1·98 (SE 0·83) in the laquinimod 1·0 mg group and 1·2 (0·82) in the placebo group (least squares mean difference 0·78 [95% CI -1·42 to 2·98], p=0·4853). Least squares mean change in caudate volume was 3·10% (SE 0·38) in the 1·0 mg group and 4·86% (0·38) in the placebo group (least squares mean difference -1·76% [95% CI -2·67 to -0·85]; p=0·0002). Laquinimod was well tolerated and there were no new safety findings. Serious adverse events were reported by eight (7%) patients on placebo, seven (7%) on laquinimod 0·5 mg, five (5%) on laquinimod 1·0 mg, and one (3%) on laquinimod 1·5 mg. There was one death, which occurred in the placebo group and was unrelated to treatment. The most frequent adverse events in all laquinimod dosed groups (0·5 mg, 1·0 mg, and 1·5 mg) were headache (38 [16%]), diarrhoea (24 [10%]), fall (18 [7%]), nasopharyngitis (20 [8%]), influenza (15 [6%]), vomiting (13 [5%]), arthralgia (11 [5%]), irritability (ten [4%]), fatigue (eight [3%]), and insomnia (eight [3%]). INTERPRETATION: Laquinimod did not show a significant effect on motor symptoms assessed by the UHDRS-TMS, but significantly reduced caudate volume loss compared with placebo at week 52. Huntington's disease has a chronic and slowly progressive course, and this study does not address whether a longer duration of laquinimod treatment could have produced detectable and meaningful changes in the clinical assessments. FUNDING: Teva Pharmaceutical Industries.


Subject(s)
Huntington Disease , Quinolones , Adult , Male , Humans , Female , Huntington Disease/drug therapy , Treatment Outcome , Quinolones/therapeutic use , Germany , Double-Blind Method
19.
Urology ; 183: e320-e322, 2024 01.
Article in English | MEDLINE | ID: mdl-38167597

ABSTRACT

OBJECTIVE: To present 2 clitoroplasty techniques-the preputial skin and urethral flap-and describe our rationale for using each technique to construct the clitoro-urethral complex in gender-affirming vaginoplasty. METHODS: For uncircumcised patients or circumcised patients with greater than 2 cm of inner preputial skin and at least 8 cm of shaft skin proximal to the circumcision scar, we use the preputial skin clitoroplasty, a modification of the Ghent style clitoroplasty. The entire corona is used after medial glans and urethral mucosa is excised. The corona is brought together 1 cm from midline to create the visible ovoid clitoris; the remaining coronal tissue remains lateral to the clitoris for erogenous sensation as clitoral corpora. The clitoris is anchored to the proximal tunica, positioned at the level of the adductor longus tendon. The folded neurovascular bundle is fixed in the suprapubic area. The ventral urethral is spatulated and urethral flap approximated to the clitoris. Preputial skin is sutured proximally as tension allows. The clitoro-urethral complex is inset into an opening created in the penile skin flap. For patients with less skin, we use the urethral flap clitoroplasty. More corpus spongiosum is used, as the urethra creates the clitoral hood; this is described in the literature and attributed to Pierre Brassard. The clitoris is inset following a dorsal urethrotomy, with a small collar of preputial skin sewn to the spongiosum and urethral mucosa. The urethra is transected about 1 cm distally. The ventral urethra is then spatulated and the urethroplasty completed. RESULTS: We prefer the preputial skin flap technique for its' greater coronal tissue volume for erogenous sensation and better esthetics, in our opinion. Circumcised patients should have at least 2 cm of skin distal to the circumcision scar. To avoid using skin graft for the introitus-a risk for introital stenosis-shaft skin proximal to the circumcision line should be at least 8 cm. CONCLUSION: We present 2 technical options for clitoroplasty and construction of the clitoro-urethral complex in gender-affirming vaginoplasty.


Subject(s)
Plastic Surgery Procedures , Urethra , Male , Female , Humans , Urethra/surgery , Cicatrix , Surgical Flaps , Penis/surgery
20.
Plast Reconstr Surg Glob Open ; 12(1): e5512, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38204876

ABSTRACT

Symptomatic neuromas of the superficial radial nerve (SRN) can cause debilitating pain. Traditional surgical management options have demonstrated inconsistent outcomes prompting a search for alternatives. Recent reports have emerged on the use of targeted muscle reinnervation (TMR) for neuromas of the SRN using donors that are well established in hand surgery, such as the brachioradialis (BR) or extensor capri radialis longus or brevis. Use of the brachioradialis or extensor capri radialis longus motor targets can require surgery at or above the level of the antecubital fossa, and denervation of these muscle groups may be undesirable in cases of complex upper extremity injury where these donors may be needed for tendon or nerve transfer. The supinator is an expendable and often overlooked donor nerve that has not been assessed as a target for TMR of the SRN. In this case series, three patients with SRN neuromas whose conservative management failed and who did not have an SRN lesion amenable to reconstruction were managed with TMR to the nerves to supinator. At latest follow-up (9-22 months), no patients had deficits in supination or evident donor site morbidity. Two patients reported complete resolution of their SRN neuroma pain, and one patient reported partial improvement. This case series reports early results of TMR of the SRN using nerves to supinator in cases of SRN neuromas not amenable to reconstruction, demonstrating technical feasibility, improvements in neuroma pain, and no discernible donor morbidity.

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