RESUMO
PURPOSE: We describe the outcomes of intraocular lens (IOL) explantation in a cluster of opaque multifocal Lentis LS-313 following refractive lens exchange (RLE). METHODS: Single-centre, single-surgeon, retrospective case series. RESULTS: The study enrolled 10 eyes of 10 patients, 6 male and 4 female. All patients had uneventful RLE with multifocal IOL implantation. The mean patient age at the time of RLE was 53 years ± 2.52 (SD). Two eyes had YAG laser capsulotomy prior to explantation. The mean interval between the initial RLE and IOL explantation was 5.4 years ± 1.4 (SD). IOL exchange was performed in all eyes in one procedure. Five eyes had in the bag hydrophobic acrylic IOL (3 multifocal and 2 monofocal), three eyes had 3-piece hydrophobic acrylic IOL in the ciliary sulcus and two had an anterior chamber IOL. Intraoperatively one patient had weak zonules and two patients had zonular dehiscence and required anterior vitrectomy. The mean preoperative CDVA was 0.25 ± 0.15 (SD) logMAR and at the final follow-up, improved to 0.00 ± 0.07 (SD) logMAR (p < 0.01). Light microscopy with von Kossa stain confirmed IOL calcification. No postoperative complications were recorded. CONCLUSIONS: IOL exchange appears to be a feasible and safe surgical option for multifocal IOL opacification. However, patients must be warned of additional intraoperative risks including zonular dialysis, vitreous loss, retinal detachment and need for potential scleral or iris fixated IOL or anterior chamber IOL (ACIOL) with its associated sequel of complications. Moreover, YAG laser capsulotomy should be considered carefully as it increases the chances of intraoperative complications and restricts the surgical options of secondary IOL insertion such as in-the-bag IOL exchange with MFIOL.
Assuntos
Lentes Intraoculares , Lentes Intraoculares Multifocais , Feminino , Humanos , Implante de Lente Intraocular/métodos , Masculino , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Acuidade VisualRESUMO
BACKGROUND: Secondary oligo/amenorrhoea occurs in 3%-5% of women of reproductive age. The two most common causes are polycystic ovary syndrome (PCOS) (2%-13%) and functional hypothalamic amenorrhoea (FHA) (1%-2%). Whilst both conditions have distinct pathophysiology and their diagnosis is supported by guidelines, in practice, differentiating these two common causes of menstrual disturbance is challenging. Moreover, both diagnoses are qualified by the need to first exclude other causes of menstrual disturbance. AIM: To review clinical, biochemical and radiological parameters that could aid the clinician in distinguishing PCOS and FHA as a cause of menstrual disturbance. RESULTS: FHA is uncommon in women with BMI > 24 kg/m2 , whereas both PCOS and FHA can occur in women with lower BMIs. AMH levels are markedly elevated in PCOS; however, milder increases may also be observed in FHA. Likewise, polycystic ovarian morphology (PCOM) is more frequently observed in FHA than in healthy women. Features that are differentially altered between PCOS and FHA include LH, androgen, insulin, AMH and SHBG levels, endometrial thickness and cortisol response to CRH. Other promising diagnostic tests with the potential to distinguish these two conditions pending further study include assessment of 5-alpha-reductase activity, leptin, INSL3, kisspeptin and inhibin B levels. CONCLUSION: Further data directly comparing the discriminatory potential of these markers to differentiate PCOS and FHA in women with secondary amenorrhoea would be of value in defining an objective probability for PCOS or FHA diagnosis.
Assuntos
Síndrome do Ovário Policístico , Amenorreia/diagnóstico , Androgênios , Hormônio Antimülleriano , Feminino , Humanos , Distúrbios Menstruais , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnósticoRESUMO
BACKGROUND: Hypogonadotropic hypogonadism (HH) is hypogonadism due to either hypothalamic or pituitary dysfunction. While gonadotropin-releasing hormone (GnRH) can directly test pituitary function, no specific test of hypothalamic function exists. Kisspeptin-54 (KP54) is a neuropeptide that directly stimulates hypothalamic GnRH release and thus could be used to specifically interrogate hypothalamic function. Congenital HH (CHH) is typically due to variants in genes that control hypothalamic GnRH neuronal migration or function. Thus, we investigated whether KP54 could accurately identify hypothalamic dysfunction in men with CHH. METHODS: Men with CHH (n = 21) and healthy eugonadal men (n = 21) received an intravenous bolus of either GnRH (100 µg) or KP54 (6.4 nmol/kg), on 2 occasions, and were monitored for 6 h after administration of each neuropeptide. RESULTS: Maximal luteinizing hormone (LH) rise after KP54 was significantly greater in healthy men (12.5 iU/L) than in men with CHH (0.4 iU/L; p < 0.0001). KP54 more accurately differentiated CHH men from healthy men than GnRH (area under receiver operating characteristic curve KP54: 1.0, 95% CI 1.0-1.0; GnRH: 0.88, 95% CI 0.76-0.99). Indeed, all CHH men had an LH rise <2.0 iU/L following KP54, whereas all healthy men had an LH rise >4.0 iU/L. Anosmic men with CHH (i.e., Kallmann syndrome) had even lower LH rises after KP54 than did normosmic men with CHH (p = 0.017). Likewise, men identified to have pathogenic/likely pathogenic variants in CHH genes had even lower LH rises after KP54 than other men with CHH (p = 0.035). CONCLUSION: KP54 fully discriminated men with CHH from healthy men. Thus, KP54 could be used to specifically interrogate hypothalamic GnRH neuronal function in patients with CHH.
Assuntos
Hormônio Liberador de Gonadotropina/farmacologia , Hipogonadismo/sangue , Hipogonadismo/congênito , Hipogonadismo/diagnóstico , Kisspeptinas/farmacologia , Hormônio Luteinizante/sangue , Hormônio Luteinizante/efeitos dos fármacos , Adulto , Hormônio Liberador de Gonadotropina/administração & dosagem , Humanos , Síndrome de Kallmann/sangue , Síndrome de Kallmann/diagnóstico , Kisspeptinas/administração & dosagem , MasculinoRESUMO
BACKGROUND: The aim of this study was to evaluate the clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) in vitrectomized eyes. METHODS: A multi-surgeon, retrospective case series of previously vitrectomized eyes that underwent DMEK between 2013 and 2018 at Moorfields Eye Hospital. Patients' demographics, preoperative, intraoperative and postoperative data were collected. RESULTS: In total, 14 eyes of 13 patients, aged 63 ± 14.6 years were included. Three eyes had intraoperative posterior dislocation of the DMEK graft into the vitreous cavity, two of these were aphakic and one had an unstable PCIOL. Postoperatively, one graft had a total detachment and required repeat keratoplasty for primary failure, two grafts had visually significant partial detachment and needed rebubbling. Three patients developed high intraocular pressure (IOP) and one required an urgent glaucoma drainage device 1-month post-DMEK. The mean corrected distance visual acuity was 0.81 ± 0.42 logMAR preoperatively, and postoperatively was 0.6 ± 0.51 at 3 months (p = 0.414); 0.69 ± 0.81 at 6 months (p = 0.684); and 0.7 ± 0.8 at 12 months (p = 0.658). CONCLUSIONS: DMEK in vitrectomized eyes has unique challenges that necessitate careful preoperative planning. We observed a significant proportion of dislocated grafts in vitrectomized eyes with either unstable IOL or aphakic. Moreover, vitrectomized eyes with secondary glaucoma may be particularly vulnerable to uncontrolled IOP postoperatively and close monitoring is essential to prevent worsening of visual acuity. We recommend that DMEK may not be a feasible option in eyes that are prone to collapse, in particular aphakic vitrectomized eyes, as opposed to DSAEK or penetrating keratoplasty.
Assuntos
Lâmina Limitante Posterior , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/efeitos adversos , Endotélio Corneano , Sobrevivência de Enxerto , Humanos , Ceratoplastia Penetrante , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
PURPOSE: To assess the safety, efficacy, and complication rate of phacoemulsification and intraocular lens (IOL) implantation in patients with congenital uveal coloboma and to evaluate the role of pupilloplasty. METHODS: A retrospective review of 41 eyes (31 patients) with congenital coloboma that underwent phacoemulsification and IOL implantation between September 2012 and September 2018. Preoperative, intraoperative, and postoperative data were collected for analysis. RESULTS: The mean patient age at surgery was 53.9 years (range 15-82). The primary indication for surgery was cataract removal for visual improvement, and lens subluxation was additionally present in two eyes (5%) preoperatively. The mean preoperative corrected distance visual acuity (CDVA) was 0.90 LogMAR. Phacoemulsification surgery was performed in all cases and nine eyes (22%) had pupilloplasty for pupil reconstitution at the time of the procedure. Surgeon grade varied from trainee surgeon under supervision to consultant. Eight patients (19.5%) had posterior capsular rupture (PCR) with or without vitreous loss requiring anterior vitrectomy. Of these, 2 cases (5%) had dropped nuclear fragments requiring subsequent pars plana vitrectomy and lens fragment removal. The mean postoperative CDVA was 0.62 LogMAR (p = 0.0003). CONCLUSION: Patients with iridolenticular choroidal coloboma appear to be more at risk of complications, as were cases performed by non-consultant surgeons. Contrary, patients with phakodonesis, preoperative anterior chamber vitreous, dense cataracts, and cases were iris hooks used had no significant difference at PCR rate. The risk of postoperative glare and pupilloplasty needs to be considered in cases with good visual potential to avoid a possible second procedure.
Assuntos
Extração de Catarata , Catarata , Coloboma , Facoemulsificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Catarata/complicações , Coloboma/complicações , Coloboma/diagnóstico , Coloboma/cirurgia , Humanos , Implante de Lente Intraocular , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Vitrectomia , Adulto JovemRESUMO
BACKGROUND: Despite advances in cardiopulmonary resuscitation, functional survival remains low after out-of-hospital cardiac arrest (OOHCA). Intra-aortic balloon pump (IABP) therapy has recently been shown to augment cerebral blood flow. Whether IABP therapy in the post-resuscitation period improves functional outcomes is unknown. METHODS: We analysed 174 consecutive patients who were successfully resuscitated from an OOHCA between 2011-2013 at Harefield Hospital, London. We analysed functional status at discharge and mortality up to one year. RESULTS: A total of 55 patients (32.1%) received IABP therapy. Comparing those receiving IABP with those not receiving IABP, there was no difference in favourable functional status at discharge (49.1% vs. 57.1%, p=0.321); and mortality at one year (45.5% vs. 35.5%, p=0.164). Multivariable analyses identified IABP therapy as a strong independent predictor for favourable functional status at discharge (OR=7.51, 95% CI: 2.15-26.14, p=0.002) and this association was maintained in propensity-score adjusted analyses (OR=9.90, 95% CI: 2.11-46.33, p=0.004) and inverse probability treatment weighted analyses (OR=10.84, 95% CI: 2.75-42.69, p<0.001). However, IABP therapy was not an independent predictor for mortality at one year (HR=0.93, 95% CI: 0.52-1.65, p=0.810) and this was confirmed in both propensity-score adjusted and inverse probability treatment weighted analyses. CONCLUSIONS: In this observational analysis of patients surviving an OOHCA, the use of IABP therapy in the post-resuscitation period was associated with improved functional outcomes. This warrants further evaluation in larger prospective studies.
Assuntos
Balão Intra-Aórtico , Parada Cardíaca Extra-Hospitalar/mortalidade , Parada Cardíaca Extra-Hospitalar/cirurgia , Período Pós-Operatório , Ressuscitação/métodos , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ressuscitação/efeitos adversos , Taxa de SobrevidaRESUMO
OBJECTIVE: To quantify how representative a single measure of reproductive hormone level is of the daily hormonal profile using data from detailed hormonal sampling in the saline placebo-treated arm conducted over several hours. DESIGN: Retrospective analysis of data from previous interventional research studies evaluating reproductive hormones. SETTING: Clinical Research Facility at a tertiary reproductive endocrinology centre at Imperial College Hospital NHS Foundation Trust. PATIENTS: Overall, 266 individuals, including healthy men and women (n = 142) and those with reproductive disorders and states (n = 124 [11 with functional hypothalamic amenorrhoea, 6 with polycystic ovary syndrome, 62 women and 32 men with hypoactive sexual desire disorder, and 13 postmenopausal women]), were included in the analysis. INTERVENTIONS: Data from 266 individuals who had undergone detailed hormonal sampling in the saline placebo-treated arms of previous research studies was used to quantify the variability in reproductive hormones because of pulsatile secretion, diurnal variation, and feeding using coefficient of variation (CV) and entropy. MAIN OUTCOME MEASURES: The ability of a single measure of reproductive hormone level to quantify the variability in reproductive hormone levels because of pulsatile secretion, diurnal variation, and nutrient intake. RESULTS: The initial morning value of reproductive hormone levels was typically higher than the mean value throughout the day (percentage decrease from initial morning measure to daily mean: luteinizing hormone level 18.4%, follicle-stimulating hormone level 9.7%, testosterone level 9.2%, and estradiol level 2.1%). Luteinizing hormone level was the most variable (CV 28%), followed by sex-steroid hormone levels (testosterone level 12% and estradiol level 13%), whereas follicle-stimulating hormone level was the least variable reproductive hormone (CV 8%). In healthy men, testosterone levels fell between 9:00 am and 5:00 pm by 14.9% (95% confidence interval 4.2, 25.5%), although morning levels correlated with (and could be predicted from) late afternoon levels in the same individual (r2 = 0.53, P<.0001). Testosterone levels were reduced more after a mixed meal (by 34.3%) than during ad libitum feeding (9.5%), after an oral glucose load (6.0%), or an intravenous glucose load (7.4%). CONCLUSION: Quantification of the variability of a single measure of reproductive hormone levels informs the reliability of reproductive hormone assessment.
Assuntos
Hormônio Foliculoestimulante , Hormônio Luteinizante , Masculino , Humanos , Feminino , Estudos Retrospectivos , Reprodutibilidade dos Testes , Testosterona , Estradiol , GlucoseRESUMO
Obesity-related hypogonadotropic hypogonadism is a well-characterized condition in men (termed male obesity-related secondary hypogonadism; MOSH); however, an equivalent condition has not been as clearly described in women. The prevalence of polycystic ovary syndrome (PCOS) is known to increase with obesity, but PCOS is more typically characterized by increased gonadotropin-releasing hormone (GnRH) (and by proxy luteinizing hormone; LH) pulsatility, rather than by the reduced gonadotropin levels observed in MOSH. Notably, LH levels and LH pulse amplitude are reduced with obesity, both in women with and without PCOS, suggesting that an obesity-related secondary hypogonadism may also exist in women akin to MOSH in men. Herein, we examine the evidence for the existence of a putative non-PCOS "female obesity-related secondary hypogonadism" (FOSH). We précis possible underlying mechanisms for the occurrence of hypogonadism in this context and consider how such mechanisms differ from MOSH in men, and from PCOS in women without obesity. In this review, we consider relevant etiological factors that are altered in obesity and that could impact on GnRH pulsatility to ascertain whether they could contribute to obesity-related secondary hypogonadism including: anti-Müllerian hormone, androgen, insulin, fatty acid, adiponectin, and leptin. More precise phenotyping of hypogonadism in women with obesity could provide further validation for non-PCOS FOSH and preface the ability to define/investigate such a condition.
Assuntos
Hipogonadismo , Síndrome do Ovário Policístico , Feminino , Masculino , Humanos , Hormônio Luteinizante , Obesidade/complicações , Hipogonadismo/etiologia , Androgênios , Síndrome do Ovário Policístico/complicações , Hormônio Liberador de Gonadotropina , Hormônio FoliculoestimulanteRESUMO
Distressing low sexual desire, termed Hypoactive Sexual Desire Disorder (HSDD), affects approximately 10% of women and 8% of men. In women, the 'top-down' theory of HSDD describes hyperactivity in higher-level cognitive brain regions, suppressing lower-level emotional/sexual brain areas. However, it is unknown how this neurofunctional disturbance compares to HSDD in men. To investigate this, we employed task-based functional MRI in 32 women and 32 men with HSDD to measure sexual-brain processing during sexual versus non-sexual videos, as well as psychometric questionnaires to assess sexual desire/arousal. We demonstrate that women had greater activation in higher-level and lower-level brain regions, compared to men. Indeed, women who had greater hypothalamic activation in response to sexual videos, reported higher psychometric scores in the evaluative (r = 0.55, P = 0.001), motivational (r = 0.56, P = 0.003), and physiological (r = 0.57, P = 0.0006) domains of sexual desire and arousal after watching the sexual videos in the scanner. By contrast, no similar correlations were observed in men. Taken together, this is the first direct comparison of the neural correlates of distressing low sexual desire between women and men. The data supports the 'top-down' theory of HSDD in women, whereas in men HSDD appears to be associated with different neurofunctional processes.
Assuntos
Encéfalo , Libido , Imageamento por Ressonância Magnética , Disfunções Sexuais Psicogênicas , Humanos , Feminino , Masculino , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Disfunções Sexuais Psicogênicas/psicologia , Disfunções Sexuais Psicogênicas/fisiopatologia , Libido/fisiologia , Caracteres Sexuais , Adulto Jovem , Comportamento Sexual/psicologia , Comportamento Sexual/fisiologia , Mapeamento Encefálico , Inquéritos e Questionários , Pessoa de Meia-IdadeRESUMO
PURPOSE: The aim of this study was to report the first case of successful use of corneal collagen cross-linking (CXL) to halt the progression of keratoconus in a patient with concurrent iridocorneal endothelial (ICE) syndrome. METHODS: A 30-year-old White man was referred to our subspecialty corneal clinic for further investigation of right corectopia. The patient was asymptomatic and was otherwise fit. Slit-lamp examination revealed a right oval-shaped pupil decentered superiorly, a transillumination defect at the 5-o'clock position, minimal gutta-like changes in the corneal endothelium, and few inferior peripheral anterior synechiae. Dilated fundoscopy was normal in both eyes, with healthy optic discs, maculae, and peripheral retinae. Specular microscopy and slit-lamp findings suggested ICE syndrome. Subsequent investigation with corneal tomography showed progressive signs of inferior corneal ectasia with steepening, and thinning in the right eye, consistent with keratoconus. The left eye was unremarkable. RESULTS: Epithelium-off accelerated corneal CXL was performed in the affected eye. Early post-CXL follow-up (1 week) was unremarkable, and further follow-ups were arranged at 3, 6, 12, and 24 months, respectively. In subsequent reviews, the patient's vision and corneal tomography findings were stable. CONCLUSIONS: We describe the first case of corneal CXL for progressive keratoconus with ICE syndrome. co-existing keratoconus and ICE syndrome can occur, and corneal cross-linking was used successfully in this case to halt keratoconus progression. However, further studies will need to establish the impact of epithelium-off corneal cross-linking, especially in more severely affected eyes.
Assuntos
Síndrome Endotelial Iridocorneana , Ceratocone , Fotoquimioterapia , Masculino , Humanos , Adulto , Ceratocone/tratamento farmacológico , Crosslinking Corneano , Substância Própria , Raios Ultravioleta , Acuidade Visual , Reagentes de Ligações Cruzadas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Riboflavina/uso terapêutico , Topografia da Córnea , Fotoquimioterapia/métodosRESUMO
CONTEXT: Limited data exist regarding whether the endocrine response to the gonadotropin-releasing hormone receptor agonist (GnRHa) triptorelin differs in women with polycystic ovary syndrome (PCOS) compared with healthy women or those with hypothalamic amenorrhea (HA). OBJECTIVE: We compared the gonadotropin response to triptorelin in healthy women, women with PCOS, or those with HA without ovarian stimulation, and in women with or without polycystic ovaries undergoing oocyte donation cycles after ovarian stimulation. METHODS: The change in serum gonadotropin levels was determined in (1) a prospective single-blinded placebo-controlled study to determine the endocrine profile of triptorelin (0.2 mg) or saline-placebo in healthy women, women with PCOS, and those with HA, without ovarian stimulation; and (2) a retrospective analysis from a dose-finding randomized controlled trial of triptorelin (0.2-0.4 mg) in oocyte donation cycles after ovarian stimulation. RESULTS: In Study 1, triptorelin induced an increase in serum luteinizing hormone (LH) of similar amplitude in all women (mean peak LH: healthy, 52.3; PCOS, 46.2; HA, 41.3 IU/L). The AUC of change in serum follicle-stimulating hormone (FSH) was attenuated in women with PCOS compared with healthy women and women with HA (median AUC of change in serum FSH: PCOS, 127.2; healthy, 253.8; HA, 326.7 IU.h/L; P = 0.0005). In Study 2, FSH levels 4 hours after triptorelin were reduced in women with at least one polycystic morphology ovary (n = 60) vs normal morphology ovaries (n = 91) (34.0 vs 42.3 IU/L; P = 0.0003). Serum anti-Müllerian hormone (AMH) was negatively associated with the increase in FSH after triptorelin, both with and without ovarian stimulation. CONCLUSION: FSH response to triptorelin was attenuated in women with polycystic ovaries, both with and without ovarian stimulation, and was negatively related to AMH levels.
Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Pamoato de Triptorrelina/uso terapêutico , Amenorreia/complicações , Estudos Retrospectivos , Estudos Prospectivos , Hormônio Luteinizante , Hormônio Foliculoestimulante , Hormônio AntimüllerianoRESUMO
Background: Free ionized calcium (Ca2+) is the biologically active component of total calcium (TCa) and hence responsible for its biological action. TCa is routinely adjusted for albumin using several formulae (e.g. James, Orell, Payne and Berry) to more closely reflect Ca2+. Here, we derive a novel formula to estimate Ca2+ and compare its performance to established formulae. Methods: Cohort for prediction of Ca2+: 2806 serum samples (TCa) taken contemporaneously with blood gas samples (Ca2+) at Imperial College Healthcare NHS Trust were used to derive formulae to estimate Ca2+ using multivariable linear regression. Cohort for prediction of PTH: Performance of novel and existing formulae to predict PTH in 5510 patients was determined by Spearman correlation. Results: Ca2+ prediction Cohort: Adjusted calcium (r2 = 0.269) was less strongly associated with Ca2+, than TCa (r2 = 0.314). Prediction of Ca2+ from a newly derived formula incorporating TCa, potassium, albumin, and hematocrit had an improved r2 of 0.327, whereas inclusion of all available parameters increased the r2 further to 0.364. Of the established formulae, James performed best in predicting Ca2+ (r2 = 0.27). PTH prediction cohort: Berry resulted in higher whereas Orell in lower adjusted calcium levels. Prediction of PTH was strongest in the setting of hypercalcemia, with James having the highest Spearman correlation coefficient (+0.496) similar to including all parameters (+0.499). Conclusion: Adjustment of calcium for albumin using established formulae does not always outperform unadjusted TCa in the reflection of Ca2+. Further prospective studies are needed to optimise adjustment of TCa and to establish bounds for validity.
Assuntos
Cálcio , Hipercalcemia , Humanos , Cálcio da Dieta , Albumina Sérica , Modelos LinearesRESUMO
Importance: The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior. Objective: To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD. Design, Setting, and Participants: This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021. Interventions: Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo. Main Outcomes and Measures: Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal. Results: Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). Conclusions and Relevance: Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire. Trial Registration: isrctn.org Identifier: ISRCTN17271094.
Assuntos
Ereção Peniana , Disfunções Sexuais Psicogênicas , Masculino , Humanos , Adulto , Kisspeptinas/farmacologia , Kisspeptinas/uso terapêutico , Comportamento Sexual , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Encéfalo/diagnóstico por imagemRESUMO
PURPOSE: We report, for the first time, 2 cases of corneal ulceration and perforation after treatment with dupilumab for atopic dermatitis. METHODS: A 30-year-old woman and a 44-year-old man developed unilateral severe corneal ulceration and perforation while on dupilumab therapy after 3 and 9 months, respectively. RESULTS: Corneal cultures were negative in both cases except for scanty growth of Staphylococcus species on enrichment. Both cases progressed to perforation despite intensive topical antibiotic treatment. The first case required a tectonic keratoplasty to restore globe integrity after failed attempts of corneal gluing and multilayer amniotic membrane transplantation, and the second case was managed successfully with a cyanoacrylate glue patch. CONCLUSIONS: Although there have been previous reports of conjunctival injection and dry eye after dupilumab, these are the first 2 reports of corneal ulceration with rapid progression to perforation in patients under treatment with dupilumab. The underlying pathophysiology for ulcerative keratitis in these cases remains unknown, but there is no doubt that cessation of dupilumab prevented progression of the melting. Severe ocular symptoms while on dupilumab require a prompt discussion with the dermatology team to potentially switch treatment and halt further keratitis progression.
Assuntos
Perfuração da Córnea , Úlcera da Córnea , Dermatite Atópica , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Perfuração da Córnea/induzido quimicamente , Úlcera da Córnea/induzido quimicamente , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/cirurgia , Dermatite Atópica/tratamento farmacológico , Feminino , Humanos , MasculinoRESUMO
PURPOSE: We present a no-touch Descemet membrane endothelial keratoplasty (DMEK) technique which assists in unfolding of tightly scrolled grafts from young donors. METHODS: The technique was developed following a wet-laboratory experiment using human corneas created to observe the behavior of the graft during spinning within the artificial anterior chamber. This approach involves injecting short bursts of balanced salt solution to make the scroll spin continuously in a 360-degree manner. Spinning of the graft over the surface is accompanied by rotation on its horizontal axis resulting in opening in the correct orientation. Unfolding is then completed with standard bimanual tapping maneuvers. The spinning technique was then performed in 4 patients who all had tight DMEK scrolls from young donors. RESULTS: The wet laboratory confirmed that directed jets of fluid to generate spinning and rotation open the graft in the correct orientation in most occasions. All 4 cases in this study received grafts from young donors (range 37-48 years old), and the technique achieved rapid unfolding with no complications. Two of our patients had glaucoma drainage devices, 1 had anterior chamber intraocular lens, and all other cases had clear corneas and good endothelial cell count after the 1-year follow-up. CONCLUSIONS: Our novel technique provides a safe and effective method to unscroll tight DMEK grafts that surgeons could incorporate into their armamentarium. Success is optimized by slightly undersizing the graft (7.5-8.0 mm).
Assuntos
Câmara Anterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Distrofia Endotelial de Fuchs/cirurgia , Acuidade Visual , Adulto , Idoso , Idoso de 80 Anos ou mais , Câmara Anterior/diagnóstico por imagem , Feminino , Distrofia Endotelial de Fuchs/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Doadores de TecidosRESUMO
PURPOSE: To evaluate the impact of surgery restrictions on cataract surgery performance. SETTING: Moorfields Eye Hospital, NHS Foundation Trust, London, United Kingdom. DESIGN: Retrospective, observational cross-sectional study. METHODS: A single-center, retrospective review of all patients who underwent phacoemulsification surgery at Moorfields Eye Hospital between September 2019 and January 2021 was conducted. The main outcome measure was posterior capsule rupture (PCR) rate before and after COVID-19-imposed restrictions to elective cataract surgery. RESULTS: A total of 15 688 surgeries were performed by 256 different surgeons in the study period. In the prerestriction period (September 2019 to March 2020), the PCR rate was 0.99%, whereas in the 19-week postrestriction period, the PCR rate spiked to 1.62% (odds ratio 1.65; P = .001; CI 1.24 to 2.20; relative risk: 1.64). CONCLUSIONS: The COVID-19 pandemic provided a unique opportunity to assess a large group of surgeons' performances after prolonged surgical abstinence. A 19-week restriction period in surgical activity showed an increased incidence of PCR complications. This is relevant because it can concern any surgeon on the extended time off from work such as sick, sabbatical, research, and parental leave. Supporting strategies should be implemented by associated regulators to minimize this negative impact.